SCI 발표논문
2007년 129편
- 692007
제1저자 김병수 · 교신저자 윤성수
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Combination of SK-7041, one of novel histone deacetylase inhibitors, and STI571-induced synergistic apoptosis in chronic myeloid leukemia.Anticancer Drugs. 2007;18(6):641-7.
PubMed IF 2 혈액종양내과Abstract
Although STI571 still plays a key role in the treatment of chronic myeloid leukemia, emergence of resistance to STI571 is a major obstacle to successful outcome. Therefore, new agents that increase the sensitivity of chronic myeloid leukemia cells to STI571 are urgently required. SK-7041 is a novel hybrid synthetic histone deacetylase inhibitor derived from the hydroxamic acid of trichostatin A and pyridyl ring of MS-275. Its cytotoxic effects were examined both as a single agent and in combination with STI571 in acute and chronic myeloid leukemia. SK-7041 exhibited growth inhibition of leukemia cells by downregulation of CDK4, cyclin E and cyclin B1 expression, and by upregulation of p21 expression with subsequent activation of the mitochondria-mediated caspase pathway. SK-7041 showed synergism on growth inhibition, cell cycle arrest and induction of apoptosis in chronic myeloid leukemia (K562) when combined with STI571. The synergistic effect was mediated through the same mechanism as in SK-7041 alone, involving reduction of cyclin D1 and induction of p21. Taken together, our findings suggest that SK-7041 is active against leukemia and offers new prospects for overcoming STI571 resistance in chronic myeloid leukemia.
- 682007
제1저자 최성희 · 교신저자 차봉수
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The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF rats.Diabetes Metab Res Rev. 2007;23(5):411-8.
PubMed IF 8.3 내분비대사내과Abstract
OBJECTIVE To investigate the effects of pioglitazone and metformin treatment during pre-diabetic period for the prevention of diabetes in a rat model.
METHODS OLETF rats aged 18-weeks, were treated with pioglitazone (10 mg/kg/day) and metformin (300 mg/kg/day) for 10 weeks from their pre-diabetic period. We measured weight, lipid profiles, fat distribution, glucose tolerance, and pancreatic insulin content.
RESULTS Prominent weight gain (mostly subcutaneous fat area) was observed in the pioglitazone-treated OLETF (O-P) rats versus significant weight loss was observed in the metformin-treated OLETF (O-M) rats. Pioglitazone reversed the serum triglyceride (TG) and FFAs levels to normal (TG 0.46 +/- 0.04 vs 0.88 +/- 0.05 mmol/l in LETO). At the age of 28 weeks, the O-P rats showed completely normal glucose tolerance, and the glucose disposal rate (GDR) was markedly improved (25.6 +/- 0.4 vs 20.6 +/- 0.5 mg/min/kg in O-C, p < 0.05). The O-M rats also showed an improved fasting glucose and GDR level, but not as much as those with O-P rats. The pancreas insulin contents were much improved in the O-P rats (22.9 +/- 1.2 vs 18.8 +/- 1.3 nmol/pancreas in O-M rats, p < 0.05) with histological improvement.
CONCLUSION The pre-diabetic treatment with pioglitazone, despite significant weight gain, completely prevents to develop diabetes and enhances beta cell function with preservation of islet cell changes. Metformin treatment was also effective, but mainly by ameliorating the insulin resistance with marked reduction in body weight. The reversal of dyslipidaemia and the fat redistribution might contribute to the greater improvement of pioglitazone treatment compared to metformin in OLETF rats.
- 672007
제1저자 허진,윤창환 · 교신저자 김효수
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Akt is a key modulator of endothelial progenitor cell trafficking in ischemic muscle.Stem Cells. 2007;25(7):1769-78.
PubMed IF 4.8 순환기내과Abstract
Trafficking of transplanted endothelial progenitor cells (EPCs) to ischemic tissue is enhanced by stromal-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF). However, it has not been studied how these cytokines modulate the local milieu to entrap EPCs. This study was performed to elucidate a molecular pathway of trafficking EPCs through Akt and to test its application as an adjuvant modality to increase EPC homing. In a mouse hind limb ischemia model, systemically administered 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled mouse EPCs showed three stages of homing to ischemic limb: adhesion to endothelial cells (ECs), incorporation to capillary, and transendothelial migration into extravascular space. As an underlying mechanism to control adhesion of EPCs to ECs, we found that Akt was activated in ECs of ischemic muscle by ischemia-induced VEGF and SDF-1. In vitro and in vivo experiments using adenoviral vector for constitutively active or dominant-negative Akt genes showed that activated Akt enhanced intercellular adhesion molecule 1 (ICAM-1) expression on ECs. Akt activation in ECs also enhanced EPC incorporation to ECs and transendothelial migration in vitro experiments. Activated Akt was sufficient for induction of EPC homing even in normal hind limb, where VEGF or SDF-1 was not increased. Finally, local Akt gene transfer to ischemic limb significantly enhanced homing of systemically administered EPCs, new vessel formation, blood flow recovery, and tissue healing. Akt plays a key role in EPC homing to ischemic limb by controlling ICAM-1 and transendothelial migration. Modulation of Akt in the target tissue may be an adjunctive measure to enhance homing of systemically administered stem cells, suggesting a possibility of cell-and-gene hybrid therapy. Disclosure of potential conflicts of interest is found at the end of this article.
- 662007
제1저자 김나영,조수정 · 교신저자 송인성
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The anti-cancer effect of COX-2 inhibitors on gastric cancer cells.Dig Dis Sci. 2007;52(7):1713-21.
PubMed IF 2.8 소화기내과Abstract
Epidemiologic studies have shown that nonsteroidal anti-inflammatory drugs could reduce the risk of cancer development including gastric cancer. This study was performed to identify the antineoplastic mechanism in gastric cancer cells affected by celecoxib, a selective COX-2 inhibitor. MTT assay, ELISA for prostaglandin E(2) (PGE(2)), cell-cycle analyses, immunofluorescent staining, and flow cytometry were performed after treating human gastric cancer cell lines (AGS and MKN-45) with celecoxib or indomethacin. The viabilities of celecoxib-treated cells decreased in a dose- and time-dependent manner compared with indomethacin. Drop of PGE(2) levels was more prominent in the presence of indomethacin than in that of celecoxib. Celecoxib arrested the cell cycle in the G(0)-G(1) phase, which reduced cell numbers in the S phase. Moreover, celecoxib increased the apoptotic cell proportions, a 4-fold increase over control cells. The anticancer effects of celecoxib on gastric cancer cells appear to be mediated by cell-cycle arrest and apoptosis, and not by COX-2 or PGE(2) suppression alone.
- 652007
제1저자 이은봉 · 교신저자 송영욱
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Evidence of potential interaction of chemokine genes in susceptibility to systemic sclerosis.Arthritis Rheum. 2007;56(7):2443-8.
PubMed IF 7.38 류마티스내과Abstract
OBJECTIVE To examine genetic polymorphisms in the chemokine pathway, and to assess their interactions in relation to susceptibility to systemic sclerosis (SSc).
METHODS To identify the risk of SSc conferred by genetic polymorphisms in the chemokine pathway, 10 single-nucleotide polymorphisms (SNPs) from 8 candidate genes were studied in 99 patients with SSc and 198 age- and sex-matched controls in a Korean population. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism or sequence-specific primer methods. Genetic associations between each SNP and SSc risk, calculated as odds ratios with 95% confidence intervals, were estimated using chi-square tests. Haplotypes for the 2 polymorphisms in the gene CCL5 (RANTES) were constructed, and their associations with SSc were tested. Gene-gene interactions were investigated using a recently described novel method, and the results were confirmed by conditional logistic regression. Adjustment for multiple testing was based on Bonferroni correction.
RESULTS There was significant evidence of gene-gene interaction between polymorphisms in the genes CXCL8 (interleukin-8) and CCL5, and both of these were associated with an increased risk of SSc. This SNP-SNP interaction was confirmed by 2 independent statistical methods. The associations remained significant after Bonferroni adjustment for multiple testing. No significant association between each individual SNP or haplotype and the risk of SSc was found.
CONCLUSION Crosstalk between the 2 chemokines CXCL8 and CCL5 may contribute to the susceptibility to SSc.
- 642007
제1저자 명선정 · 교신저자 윤정환
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Wnt signaling enhances the activation and survival of human hepatic stellate cells.FEBS Lett. 2007;581(16):2954-8.
PubMed IF 3.1 소화기내과Abstract
Wnt signaling was implicated in pulmonary and renal fibrosis. Since Wnt activity is enhanced in liver cirrhosis, Wnt signaling may also participate in hepatic fibrogenesis. Thus, we determined if Wnt signaling modulates hepatic stellate cell (HSC) activation and survival. Wnt3A treatment significantly activated human HSCs, while this was inhibited in secreted frizzled-related protein 1 (sFRP1) overexpressing cells. Wnt3A treatment significantly suppressed TRAIL-induced apoptosis in control HSCs versus sFRP1 over-expressing cells. Particularly, caspase 3 was more activated in sFRP1 over-expressing cells following TRAIL and Wnt3A treatment. These observations imply that Wnt signaling promotes hepatic fibrosis by enhancing HSC activation and survival.
- 632007
제1저자 오도연 · 교신저자 오도연
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Artificial nutrition and hydration in terminal cancer patients: the real and the ideal.Support Care Cancer. 2007;15(6):631-636.
PubMed IF 3.4 혈액종양내과Abstract
INTRODUCTION To better understand current practice relating to artificial nutrition/hydration in terminal cancer patients, we enrolled terminal cancer patients who were admitted at Seoul National University Boramae Hospital for supportive care only and who died with a duration of hospital stay to death of more than 1 week between 2003 and 2004. We detailed oral intake and intravenous nutrition/hydration status on admission, 1 week after admission, and 2 days before death. Administered calories and changes in these according to time and "DNR" (do-not-resuscitate) status were noted.
RESULTS Of the total 165 patients, oral intake was possible in 84 patients (50.9%) on admission, in 79 patients (47.8%) on 1 week after admission, and in 29 patients (17.5%) 2 days before death (p < 0.01). Intravenous nutrition/hydration was administered to 133 patients (80.6%) on admission, to 125 patients (75.7%) at 1 week, and to 137 patients (83.0%) 2 days before death (p = 0.7). The calories administered to the patient by oral intake were 393 kcal on admission, 353 kcal 1 week after admission, and 89 kcal 2 days before death. In addition, the calories delivered by intravenous fluid were 369, 386 and 465 kcal, respectively. Near to death, calories by oral intake continuously reduced (p < 0.01) and intravenous calories continuously increased (p = 0.04), but total administered calories reduced (p = 0.03). Intravenous nutrition/hydration stopped after the attainment of the advance directive of DNR in 9% of patients.
CONCLUSION This study showed the high prevalence of artificial nutrition/hydration, especially intravenous infusion, in Korean terminal cancer patients compared with situation in other countries. More studies are needed to verify the efficacy of artificial nutrition/hydration in terminal cancer patients.
- 622007
제1저자 박완범 · 교신저자 최강원
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Early modification of initial HAART regimen associated with poor clinical outcome in HIV patients.AIDS Res Hum Retroviruses. 2007;23(6):794-800.
PubMed IF 1 감염내과Abstract
Although the importance of the initial regimen in highly active antiretroviral therapy (HAART) has been emphasized, the effect on clinical outcome of early modification of the initial HAART regimen has not been well-defined. The analysis included antiretroviral-naive HIV patients who started HAART between 1999 and 2005 at a university hospital. Early modification was defined as any drug change within 2 months of starting HAART. The effect of early regimen modification on the occurrence of new AIDS-defining illness or death was assessed using Kaplan-Meier survival estimates, and hazard ratios were estimated using Cox's proportional hazards regression model. Of 398 patients beginning HAART, 21% experienced early modification of their regimen, the most common reason being gastrointestinal toxicity (49%). After adjusting for risk factors for occurrence of a new AIDS event or death, identified by univariate analysis, the hazards ratio contrasting early modification with maintenance of initial HAART regimen was 3.06 (95% confidence interval, 1.36-6.90; p = 0.007). There were significant differences between the AIDS event-free survival curves of patients in clinical categories B or C with or without early modification of initial HAART regimen (p = 0.0002), but no significant difference in patients in clinical category A (p = 0.706). A considerable proportion of patients who started HAART changed treatment regimen mainly due to intolerance early after start of HAART. Early modification of an initial HAART regimen was associated with poor clinical outcome in HIV patients in the advanced clinical categories.
- 612007
제1저자 나기영 · 교신저자 한진석
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Chronic furosemide or hydrochlorothiazide administration increases H+-ATPase B1 subunit abundance in rat kidney.Am J Physiol Renal Physiol. 2007;292(6):F1701-9.
PubMed IF 3.6 신장내과Abstract
Furosemide administration stimulates distal acidification. This has been attributed to the increased lumen-negative voltage in the distal nephron, but the aspect of regulatory mechanisms of H(+)-ATPase has not been clear. The purpose of this study is to investigate whether chronic administration of diuretics alters the expression of H(+)-ATPase and whether electrogenic Na(+) reabsorption is involved in this process. A 7-day infusion of furosemide or hydrochlorothiazide (HCTZ) lowered urine pH significantly. However, this effect of furosemide-induced distal acidification was not changed with amiloride-blocking electrogenic Na(+) reabsorption. On immunoblotting, a polyclonal antibody against the H(+)-ATPase B1 subunit recognized a specific approximately 56-kDa band in membrane fractions from the kidney. The protein abundance of H(+)-ATPase was significantly increased by furosemide and HCTZ infusion in both the cortex and outer medulla. Furosemide plus amiloride administration also increased the H(+)-ATPase protein abundance significantly. However, no definite subcellular redistribution of H(+)-ATPase was observed by furosemide +/- amiloride infusion with immunohistochemistry. Chronic furosemide +/- amiloride administration induced a translocation of pendrin to the apical membrane, while total protein abundance was not increased. The mRNA expression of H(+)-ATPase was not altered by furosemide +/- amiloride infusion. We conclude that chronic administration of diuretics enhances distal acidification by increasing the abundance of H(+)-ATPase irrespective of electrogenic Na(+) reabsorption. This upregulation of H(+)-ATPase in the intercalated cells may be the result of tubular hypertrophy by diuretics.
- 602007
제1저자 정수진 · 교신저자 이동호
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Eradication rates of helicobacter pylori infection with second-line treatment: non-ulcer dyspepsia compared to peptic ulcer disease.Hepatogastroenterology. 2007;54(76):1293-6.
PubMed IF 0.7 소화기내과Abstract
BACKGROUND/AIMS Initial proton pump inhibitor (PPI)-based triple therapy for Helicobacter pylori (H. pylori) infection is less effective in patients with nonulcer dyspepsia (NUD) than those with peptic ulcer disease (PUD). To date, there have been no studies on the difference in eradication rates in NUD compared to PUD with regard to second-line therapy. Therefore, we retrospectively analyzed the difference in eradication rates of a second-line quadruple therapy for NUD and PUD patients.
METHODOLOGY Between June 2003 and December 2005, patients who failed to respond to initial PPI-based triple therapy, received 7 days of quadruple therapy (PPI b.i.d., bismuth 300mg q.i.d., metronidazole 500mg t.i.d., tetracycline 500mg q.i.d.) as a second-line treatment regimen. Four weeks after the completion of the course of medication, a 13C-urea breath test was performed for detection of H. pylori.
RESULTS A total of 87 patients received second-line quadruple therapy. Of these, 43 patients had NUD and 44 patients had PUD (19 gastric ulcers, 23 duodenal ulcers, 2 both ulcers). The eradication rates were 76.7% (33/43) in the NUD group and 90.9% (40/44) in the PUD group by per-protocol analysis. Therefore, the eradication rates in the NUD group were significantly lower than those in the PUD group (p = 0.034).
CONCLUSIONS A 7-day bismuth-based second-line quadruple therapy for H. pylori infection was less effective in patients with NUD than those with PUD. Therefore, a more potent second-line treatment regimen or extension of treatment duration of quadruple therapy should be considered for the eradication of H. pylori in patients with NUD.
- 592007
제1저자 정우영 · 교신저자 조영석
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Effects of the early administration of heparin in patients with ST-elevation myocardial infarction treated by primary angioplasty.Circ J. 2007;71(6):862-7.
PubMed IF 5.8 순환기내과Abstract
BACKGROUND The effect of adjunctive heparin for primary angioplasty in patients with ST-elevation myocardial infarction (STEMI) is not well established, so the authors investigated the effect of early heparin administration in the emergency room (ER) on initial patency of the infarct-related artery (IRA) and on the clinical outcome in STEMI patients.
METHODS AND RESULTS One hundred and twenty consecutive patients who presented with STEMI less than 12 h from pain onset and who were eligible for primary percutaneous coronary intervention were allocated to an early heparin group (heparin administered in ER) or a late heparin group (heparin administered after angiography). In the early heparin group, unfractionated heparin (60 U/kg bolus IV, then 14 U . kg(-1) . h(-1) IV infusion) or enoxaparin (1 mg/kg bolus SC) were administered 144+/-95 min before angioplasty. No significant differences in baseline characteristics were observed between the early heparin group (n=56) and the late heparin group (n=64). However, initial Thrombolysis In Myocardial Infarction (TIMI) flow grade in the IRA was significantly different between the 2 groups (frequency of TIMI 0/1/2/3; 48/4/7/41% vs 70/8/11/11%, early vs late respectively, p=0.002). TIMI 2 or 3 flow was significantly more frequent in the early heparin group than in the late heparin group (48% vs 22%, p=0.002). However, no significant differences were noted between the 2 groups in terms of in-hospital major adverse cardiac events (7% vs 11%, p=0.472) and TIMI major bleeding (2% vs 3%, p=0.639).
CONCLUSIONS In STEMI patients, early heparin therapy administered in the ER improves coronary patency, despite not reaching clinical benefit.
- 582007
제1저자 박흥우 · 교신저자 조상헌
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Complementary roles of capsaicin cough sensitivity test and induced sputum test to methacholine bronchial provocation test in predicting response to inhaled corticosteroids in patients with chronic nonproductive cough.Ann Allergy Asthma Immunol. 2007;98(6):533-9.
PubMed IF 7.1 알레르기내과Abstract
BACKGROUND The capsaicin cough sensitivity test (CCST), methacholine bronchial provocation test (MBPT), and induced sputum test (IST) are widely used in the clinical evaluation of chronic nonproductive cough. However, little is known about their roles in predicting response to inhaled corticosteroids (ICSs) in patients with chronic nonproductive cough.
OBJECTIVE To test the hypothesis that the CCST and IST play complementary roles to the MBPT for predicting the response to ICS treatment in patients with chronic nonproductive cough.
METHODS A total of 43 patients with chronic nonproductive cough who showed isolated capsaicin cough hypersensitivity (CCST group) and 55 patients with chronic nonproductive cough who had methacholine airway hyperresponsiveness (MBPT group) were enrolled. These patients underwent the IST followed by treatment with ICSs for 4 weeks. Measurement of symptom improvement was recorded by the visual analog scale.
RESULTS The response rates to ICS treatment in the CCST and MBPT groups were similar (74.5% vs 86.0%; P = .21). Only the neutrophil count in the IST group was significantly different in responders and nonresponders after the ICS treatments (P = .005 for the CCST group and P = .006 for the MBPT group). Interestingly, the absence of sputum neutrophilia used as a criterion for subgroup analysis increased response rates in the patients with either methacholine airway hyperresponsiveness or capsaicin cough hypersensitivity.
CONCLUSIONS In the present study, we demonstrate that CCST and IST play complementary roles to MBPT. By combining the results of these tests, we are able to identify more patients with chronic nonproductive cough and treat patients more successfully with ICSs by improving the response rate to ICS treatment.
- 572007
제1저자 양재석 · 교신저자 안규리
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Molecular characterization of cDNA encoding porcine IP-10 and induction of porcine endothelial IP-10 in response to human TNF-alpha.Vet Immunol Immunopathol. 2007;117(1-2):124-8.
PubMed IF 1.8 신장내과Abstract
Donor-derived chemokines may play an important role in xenograft rejection, as well as allograft rejection. We have cloned the cDNA encoding porcine IP-10 (interferon-gamma-inducible protein 10), and evaluated its induction in miniature porcine endothelial cells in response to various human cytokines. The cloned sequence is 764 nucleotides long, and the open reading frame consists of 312 nucleotides. The deduced protein sequence includes a predicted mature protein of approximately 83 residues. The comparison of porcine IP-10, and its human, mouse, rat, goat, and sheep counterparts exhibited high similarity among different mammalian species. The sequences of important regulatory elements such as the interferon-stimulated response element (ISRE), and two NF-kappaB binding elements are conserved in the proximal promoter region of porcine IP-10, like other mammalian IP-10s. Human TNF-alpha induced the expression of IP-10 mRNA in porcine endothelial cells, while both human IFN-gamma and human IL-1beta failed. Together, the data of this study suggest that porcine IP-10 may interact with human leukocytes across the species barrier.
- 562007
제1저자 김주성 · 교신저자 송인성
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Helicobacter pylori eradication for low-grade gastric mucosa-associated lymphoid tissue lymphoma is more successful in inducing remission in distal compared to proximal disease.Br J Cancer. 2007;96(9):1324-8.
PubMed IF 7.8 소화기내과Abstract
A series of studies has shown that Helicobacter pylori eradication induces remission in most patients with low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, there have been few reports about the effect of bacterial treatment on the gastric MALT lymphoma in Korea, a well-known H. pylori endemic area. A total of 111 H. pylori-infected patients were prospectively enrolled in Seoul National University Hospital and 99 among them were completely followed up according to our protocol. After H. pylori eradication, tumoural response was evaluated by endoscopy and histopathology every 2-3 months till complete remission (CR) and every 6 months after achieving CR. Median follow-up period was 41 months (range, 11-125 months). Helicobacter pylori was successfully eradicated in all 99 patients and CR was obtained in 84 (84.8%) of 99 patients. The median time to reach CR was 3 months and 94% of CR is in continuous complete remission. Five patients with CR relapsed after 10-22 months without the evidence of H. pylori reinfection. Cumulative recurrence rate was 2.3, 7.7 and 9.3% at 1, 2 and 3 years, respectively. Tumours were mainly located in distal stomach (67.7%) and tumours in distal stomach were associated with more favourable response than those in proximal stomach (P=0.001). Majority of patients with low-grade gastric MALT lymphoma treated by exclusive H. pylori eradication have a favourable long-term outcome, offering a real chance of cure. Tumour location could be a predictive factor for remission following H. pylori eradication.
- 552007
제1저자 조영재 · 교신저자 임재준
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Clinical characteristics of tuberculosis in patients with liver cirrhosis.Respirology. 2007;12(3):401-5.
PubMed IF 7.2 호흡기내과Abstract
BACKGROUND AND OBJECTIVES Patients with liver cirrhosis are likely to be susceptible to tuberculosis (TB) because of immune system dysfunction. The aim of this study was to elucidate the clinical characteristics and treatment responses in TB patients with cirrhosis.
METHODS Cases were patients with TB detected during their follow up for liver cirrhosis over a 4-year period. Controls were randomly selected patients with TB but no liver disease, matched to cases by age and gender in a 3:1 ratio.
RESULTS Thirty-six cases and 108 controls were enrolled. Extrapulmonary TB was more common in cases than controls (31% vs 12%, P = 0.02). Clinical and radiographic manifestations and response to treatment did not differ between the two groups. The frequency of hepatotoxicity was higher in the cases than in the controls who were treated with a regimen containing rifampicin and isoniazid, although the difference was not statistically significant (27% vs 10%, P = 0.079).
CONCLUSIONS TB patients with liver cirrhosis show extrapulmonary involvement more frequently. Patients with pulmonary TB and cirrhosis usually respond well to anti-TB treatment although appear to present more frequently with treatment-related hepatotoxicity.
- 542007
제1저자 한세원 · 교신저자 김태유
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Intron 1 CA dinucleotide repeat polymorphism and mutations of epidermal growth factor receptor and gefitinib responsiveness in non-small-cell lung cancer.Pharmacogenet Genomics. 2007;17(5):313-9.
PubMed IF 1.6 혈액종양내과Abstract
OBJECTIVE Limited availability of tumoral tissue in non-small-cell lung cancer and presence of epidermal growth factor receptor mutation-independent responses call for investigation of other molecular predictive marker of gefitinib responsiveness. Therefore, CA repeat polymorphism in intron 1 was analyzed for its association with gefitinib responsiveness together with epidermal growth factor receptor mutation in Korean patients.
PATIENTS AND METHODS For 86 advanced non-small-cell lung cancer patients treated with gefitinib, epidermal growth factor receptor mutation was analyzed by direct sequencing (exons 18-21) from tumor tissue and CA repeat polymorphism was assessed by fragment length analysis from tumor and/or normal tissue.
RESULTS CA repeat status was identical in 33 patients with matched tumor and normal tissue. CA repeat was low (sum of both alleles < or =37) in 40 (46.5%) and high (sum > or =38) in 46 (53.5%) patients. Although epidermal growth factor receptor mutation was more frequent in high CA repeat patients [17.5% (7/40) in low vs. 28.3% (13/46) in high, P=0.18], response rate was higher in low CA repeat patients [25.0% (10/40) in low vs. 13.0% (6/46) in high, P=0.16]. In multivariate analysis, low CA repeat was associated with better objective response (odds ratio 7.1, 95% confidence interval 1.2-40.8; P=0.029) and time-to-progression (hazard ratio 0.54, 95% confidence interval 0.34-0.88; P=0.014), independent of the epidermal growth factor receptor mutational status. CA repeat status was not associated with epidermal growth factor receptor expression.
CONCLUSION Low number of CA repeats in intron 1 of epidermal growth factor receptor is associated with gefitinib responsiveness in non-small-cell lung cancer patients independent of epidermal growth factor receptor mutation.
- 532007
제1저자 송영욱 · 교신저자 송영욱
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Assessment of comparative pain relief and tolerability of SKI306X compared with celecoxib in patients with rheumatoid arthritis: a 6-week, multicenter, randomized, double-blind, double-dummy, phase III, noninferiority clinical trial.Clin Ther. 2007;29(5):862-873.
PubMed IF 3.7 류마티스내과Abstract
BACKGROUND SKI306X, which consists of biologically active ingredients from Clematis mandsburica, Tricbosantbes kirilowii, and Prunella vulgaris, was developed and tested in preclinical trials in Korea. Those studies found that SKI306X was associated with an anti-inflammatory and analgesic effect, and that it can delay the destruction of cartilage in rheumatoid arthritis (RA).
OBJECTIVE The aim of this study was to compare the pain relief and tolerability of SKI306X and celecoxib in patients with RA.
METHODS This study was a 6-week, multicenter, randomized, double-blind, double-dummy, Phase III, noninferiority clinical trial. Eligible patients were aged 18 to 80 years, had a history of RA with a disease duration of > or =3 months, and were functional American College of Rheumatology (ACR) class I, II, or III before entry. After a washout period of 2 weeks, patients were randomized to SKI306X 200 mg TID or celecoxib 200 mg BID for 6 weeks. The primary end point was a change in patient assessment of pain intensity using a visual analog scale (VAS). The secondary end points were a 20% improvement in response rate as defined by the ACR (ACR20) and the frequency of rescue medication use. Results after 3 and 6 weeks of treatment were compared with baseline and between treatment groups, and all patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs. AEs were identified based on spontaneous reports by patients during interviews conducted by the investigators and the study coordinator.
RESULTS Two hundred twenty-two Korean patients from 7 medical centers were assessed and 183 were enrolled and randomized to 1 of 2 treatment groups. Ninety-one patients (10 male, 81 female; mean [SD] age, 52.13 [12.64] years; mean [SD] duration of RA, 9.08 [10.23] years; no. [%] of ACR class I, II, and III, 13 [14.29], 44 [48.35] and 34 [37.36] patients, respectively) received SKI306X 200 mg TID and 92 patients (10 male, 82 female; mean [SD] age, 51.78 [10.94] years; mean [SD] duration of RA, 8.78 [7.78] years; no. [%] of ACR class I, II, and III, 14 [15.22], 44 [47.83], and 34 [36.96] patients, respectively) received celecoxib 200 mg BID. An analysis of the change in reported pain intensity as determined by VAS (mm) score between baseline and week 3 (mean [SD], 13.64 [16.62] vs 14.45 [15.89]), and between baseline and week 6 (18.4 [20.8] vs 17.9 [19.1], respectively) suggested that SKI306X was not inferior to celecoxib. The number of patients who achieved ACR20 response rate was not significantly different between the SKI306X group and the celecoxib group at week 3 (16/87 [18.4%] vs 24/87 [27.6%], respectively) and at week 6 (29/87 [33.3%] vs 29/87 [33.3%]). The frequency of rescue medication use was not significantly different between the SKI306X group and celecoxib group at week 3 (54/87 [62.1%] vs 47/87 [54.0%], respectively) or week 6 (57/87 [65.5%] vs 49/87 [56.3%]). Drug-related AEs were reported by 27 (29.7%) patients in the SKI306X group and 22 (23.9%) patients in the celecoxib group. The most frequent drug-related AEs were epigastric pain (9/91 [9.9%]) in the SKI306X group and glutamyltranferase elevation (4/92 [4.3%]) in the celecoxib group. No significant between-group differences were observed in the prevalence of drug-related clinical- or laboratory-determined AEs.
CONCLUSION The results of this study suggest that SKI306X was generally well tolerated and not inferior to celecoxib in regard to pain relief in these Korean patients with RA.
- 522007
제1저자 이준규 · 교신저자 김용태
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The efficacy of nonsurgical treatment of infected pancreatic necrosis.Pancreas. 2007;34(4):399-404.
PubMed IF 2.2 소화기내과Abstract
OBJECTIVES We conducted this study to evaluate the efficacy of nonsurgical treatment for patients with infected pancreatic necrosis (IPN).
METHODS Among 224 patients with acute pancreatitis from 2000 to 2004, there were 31 patients diagnosed as having IPN complication. The diagnostic criteria for IPN were either a positive culture or free gas in the pancreas of patients with acute pancreatic necrosis. Nonsurgical management including percutaneous drainage or endoscopic drainage (ED) followed by vigorous irrigation was initially attempted in all patients. Surgery was planned only when there was no clinical improvement after the initial nonsurgical treatment.
RESULTS Percutaneous drainage or ED was performed in 18 and 5 patients, respectively. Eight patients received antibiotics only. Four patients (12.9%) (3 from percutaneous drainage group and 1 from ED group) required surgery. Sepsis or fistula developed in 32% and 6% of patients, respectively, and was managed successfully. One patient (3.2%) died as a result of rapidly progressing multiorgan failure. The mean duration of hospitalization was 37 days. During the follow-up period, 7 patients were readmitted because of fever; they were managed by reposition of the drainage tube.
CONCLUSIONS Intensive nonsurgical treatment is very effective and safe and should be considered as an initial treatment modality for patients with IPN.
- 512007
제1저자 유병철 · 교신저자 이효석
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Twenty-four-week clevudine therapy showed potent and sustained antiviral activity in HBeAg-positive chronic hepatitis B.Hepatology. 2007;45(5):1172-8.
PubMed IF 18 소화기내과Abstract
UNLABELLED Clevudine is a pyrimidine analogue with potent and sustained antiviral activity against HBV. The present study evaluated the safety and efficacy of 30 mg clevudine once daily for 24 weeks and assessed the durable antiviral response for 24 weeks after cessation of dosing. A total of 243 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients were randomized (3:1) to receive clevudine 30 mg once daily (n=182) or placebo (n=61) for 24 weeks. Patients were followed for a further 24 weeks off therapy. Median serum HBV DNA reductions from baseline at week 24 were 5.10 and 0.27 log10 copies/mL in the clevudine and placebo groups, respectively (P<0.0001). Viral suppression in the clevudine group was sustained off therapy, with 3.73 log10 reduction at week 34 and 2.02 log10 reduction at week 48. At week 24, 59.0% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (less than 300 copies/mL). The proportion of patients who achieved normalization of alanine aminotransferase (ALT) levels was 68.2% in the clevudine group and 17.5% in the placebo group at week 24 (P<0.0001). ALT normalization in the clevudine group was well maintained during post-treatment follow-up period. The incidence of adverse events (AEs) was similar between the clevudine group and the placebo group. No resistance to clevudine was detected with 24 weeks of administration of drug.
CONCLUSION A 24-week clevudine therapy was well tolerated and showed potent and sustained antiviral effect without evidence of viral resistance during treatment period in HBeAg-positive chronic hepatitis B.
- 502007
제1저자 이경훈 · 교신저자 김인호
, , , , , , , ,
P2X7 receptor polymorphism and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation.Haematologica. 2007;92(5):651-7.
PubMed IF 8.2 혈액종양내과Abstract
BACKGROUND AND OBJECTIVES The P2X7 receptor (P2X7 R) is a key player in the processing and release of interleukin (IL)-1. To evaluate whether the A1513C polymorphism of the P2X7 R gene is related to allogeneic stem cell transplantation outcome, we performed an association analysis between this polymorphism and clinical outcomes in patients treated with an HLA-matched sibling stem cell transplant.
DESIGN AND METHODS Patients (n=152) with a malignancy or aplastic anemia underwent allogeneic stem cell transplantation at a single institute. Peripheral blood DNA of these 152 patients and their 152 donors was genotyped. Genotypes of 145 recipients and 150 donors were obtained and analyzed for the polymorphism.
RESULTS The frequencies of the A and C alleles in all 295 study subjects were 72% and 28%, respectively. The genotypes in patients were AA in 75, AC in 58, and CC in 12; the genotypes in donors were AA in 74, AC in 70, and CC in 6. Overall survival was significantly shorter for recipients with the CC genotype than for those with the AA or AC genotype (92 days for 1513CC vs. 821 days for 1513AA or 1513AC, p=0.012), and for recipients from donors with the CC genotype than for recipients from donors with the AA or AC genotype (63 days for 1513CC vs. 702 days for 1513AA or 1513AC, p=0.024). Multivariate analyses, which included sex, age, transplant method (reduced intensity conditioning vs. conventional conditioning), stem cell source, risk group, and P2X7R recipient and donor genotypes, as parameters, identified high-risk group (hazard ratio 3.25, 95% confidence interval 1.83~5.77) and a donor 1513CC genotype (hazard ratio 2.66, 95% confidence interval 1.02~6.91) as risk factors for a shorter survival. Microbiologically documented bacteremia occurred in 66.7% of recipients with the CC donor genotype and in 17.6% of recipients of transplants of AA or AC genotype (p=0.014).
INTERPRETATION AND CONCLUSIONS We conclude that the A1513C polymorphism in the P2X7R gene is related to the occurrence of infections and survival after allogeneic stem cell transplantation. Thus, the determination of this polymorphism may be helpful for the optimal selection of patients and donors.
- 492007
제1저자 박완범 · 교신저자 최강원
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Tuberculosis manifested by immune reconstitution inflammatory syndrome during HAART.AIDS. 2007;21(7):875-7.
PubMed IF 2.9 감염내과Abstract
The proportion of tuberculosis manifested by immune reconstitution inflammatory syndrome (IRIS) after HAART has not been established. We describe the incidence and clinical features of tuberculosis manifested by IRIS after HAART in an intermediate tuberculosis burden area. The findings suggest that a significant proportion of the tuberculosis occurring early after starting HAART is manifested by IRIS.
- 482007
제1저자 서정원 · 교신저자 채인호
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Sirolimus-eluting stent showed better one-year outcomes than paclitaxel-eluting stent in a real life setting of coronary intervention in Koreans.Int J Cardiol. 2007;117(1):31-6.
PubMed IF 3.3 순환기내과Abstract
OBJECTIVE The drug-eluting stent (DES) has been proven its efficacy in randomized trials. But the difference of efficacy between sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in unselected patients is in controversy. Therefore, we investigated the clinical and angiographic outcomes of these two types of the DES.
METHODS All consecutive patients treated with DES from March 2003 to March 2004 at two centers were analyzed.
RESULTS We analyzed 440 patients with 519 lesions who were treated with the two types of DES (SES 353 lesions/296 patients, PES 166 lesions/144 patients). PES group had more acute myocardial infarction (AMI) patients. Angiographically, the number of stents per lesion, maximal deployment pressure, stent diameter and the percent residual stenosis after procedure were different between the two groups. Angiographic follow-up was available in 103 patients (71.5%) in the PES group and 208 patients (70.3%) in the SES group. PES showed the higher binary restenosis rate (PES 17.9%, SES 4.5%, p<0.0001) and the larger late loss (PES 0.60x0.83 mm vs. SES 0.16x0.40 mm, p<0.001) than SES. PES was the predictor of binary restenosis at six months (OR 4.67, CI 2.20-9.91). At one year follow-up, PES also had more cardiac events (composites of death of all cause, MI, and target lesion revascularization) than SES (PES 13.9% vs. SES 6.1%, p<0.001). PES was a significant predictor of cardiac events at one year (OR 2.47, CI 1.23-4.95).
CONCLUSION SES showed better clinical and angiographic outcomes compared to PES in a daily routine practice of coronary intervention in Koreans.
- 472007
제1저자 이경훈 · 교신저자 임석아
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Prognostic significance of bcl-2 expression in stage III breast cancer patients who had received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy.BMC Cancer. 2007;7:63.
PubMed IF 4.1 혈액종양내과Abstract
BACKGROUND Bcl-2 is positively regulated by hormonal receptor pathways in breast cancer. A study was conducted to assess the prognostic significances of clinico-pathologic variables and of ER, PR, p53, c-erbB2, bcl-2, or Ki-67 as markers of relapse in breast cancer patients who had received the identical adjuvant therapy at a single institution.
METHODS A cohort of 151 curatively resected stage III breast cancer patients (M:F = 3:148, median age 46 years) who had 4 or more positive lymph nodes and received doxorubicin and cyclophosphamide followed by paclitaxel (AC/T) as adjuvant chemotherapy was analyzed for clinico-pathologic characteristics including disease-free survival (DFS) and overall survival (OS). Patients with positive ER and/or PR expression received 5 years of tamoxifen following AC/T. The protein expressions of biomarkers were assessed immunohistochemically.
RESULTS The median follow-up duration was 36 months, and 37 patients (24.5%) experienced a recurrence. Univariate analyses indicated that the tumor size (P = 0.038) and the number of involved lymph nodes (P < 0.001) significantly affected the recurrences. However, the type of surgery, the histology, histologic grade, the presence of endolymphatic emboli, and a close resection margin did not. Moreover, ER positivity (P = 0.013), bcl-2 positivity (P = 0.002) and low p53 expression (P = 0.032) were found to be significantly associated with a prolonged DFS. Furthermore, multivariate analysis identified 10 or more involved lymph nodes (HR 7.366; P < 0.001), negative bcl-2 expression (HR 2.895; P = 0.030), and c-erbB2 over-expression (HR 3.535; P = 0.001) as independent indicators of poorer DFS. In addition, bcl-2 expression was found to be significantly correlated with the expressions of ER and PR, and inversely correlated with the expressions of p53, c-erbB2 and Ki-67. Patients with bcl-2 expression had a significantly longer DFS than those without, even in the ER (+) subgroup. Moreover, OS was significantly affected by ER, bcl-2 and c-erbB2.
CONCLUSION Bcl-2 is an independent prognostic factor of DFS in curatively resected stage III breast cancer patients and appears to be a useful prognostic factor in combination with c-erbB2 and the number of involved lymph nodes.
- 462007
제1저자 김성학 · 교신저자 김태유
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Zinc-fingers and homeoboxes 1 (ZHX1) binds DNA methyltransferase (DNMT) 3B to enhance DNMT3B-mediated transcriptional repression.Biochem Biophys Res Commun. 2007;355(2):318-23.
PubMed IF 2.5 혈액종양내과Abstract
DNA methyltransferases (DNMT) 3B is a de novo DNMT that represses transcription independent of DNMT activity. In order to gain a better insight into DNMT3B-mediated transcriptional repression, we performed a yeast two-hybrid analysis using DNMT3B as a bait. Of the various binding candidates, ZHX1, a member of zinc-finger and homeobox protein, was found to interact with DNMT3B in vivo and in vitro. N-terminal PWWP domain of DNMT3B was required for its interaction with homeobox motifs of ZHX1. ZHX1 contains nuclear localization signal at C-terminal homeobox motif, and both ZHX1 and DNMT3B were co-localized in nucleus. Furthermore, we found that ZHX1 enhanced the transcriptional repression mediated by DNMT3B when DNMT3B is directly targeted to DNA. These results showed for the first the direct linkage between DNMT and zinc-fingers homeoboxes protein, leading to enhanced gene silencing by DNMT3B.
- 452007
제1저자 양예원 · 교신저자 임재준
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Aetiologies and predictors of pulmonary cavities in South Korea.Int J Tuberc Lung Dis. 2007;11(4):457-62.
PubMed IF 3.6 호흡기내과Abstract
OBJECTIVE To identify the aetiologies of pulmonary cavities and the clinical predictors of cavities of mycobacterial origin.
SETTING A tertiary referral hospital in South Korea, where the prevalence of tuberculosis (TB) is intermediate.
DESIGN A retrospective review of clinical records and radiographic examinations of patients presenting pulmonary cavities on simple chest radiograph between January and December 2005.
RESULTS Of 131 patients enrolled with pulmonary cavities, 66 (50.4%) had cavities of mycobacterial origin. Age <50 years (P = 0.04) and largest cavity located in the upper lobes (P = 0.04) increased the likelihood that the cavities were of mycobacterial origin. Conversely, history of malignancy (P = 0.02), lesions confined to one lobe (P = 0.02) and multiple enlarged mediastinal lymph nodes (P = 0.03) suggested a non-mycobacterial cause.
CONCLUSION Mycobacterial infection accounted for half of the cavitary lesions identified in this study. In older patients with a history of malignancy, non-nodular infiltration, lesions confined to one lobe and with multiple lymphadenopathy, diseases not caused by mycobacteria should be considered.
- 442007
제1저자 김인호 · 교신저자 박선양
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Allogeneic stem cell transplantation for patients with advanced hematological malignancies: comparison of fludarabine-based reduced intensity conditioning versus myeloablative conditioning.J Korean Med Sci. 2007;22(2):227-34.
PubMed IF 3.2 혈액종양내과Abstract
We compared the outcomes of allogeneic hematopoietic stem cell transplantation using reduced intensity and myeloablative conditioning for the treatment of patients with advanced hematological malignancies. A total of 75 adult patients received transplants from human leukocyte antigen-matched donors, coupled with either reduced intensity (n=40; fludarabine/melphalan, 28; fludarabine/cyclophosphamide, 12) or myeloablative conditioning (n=35, busufan/cyclophosphamide). The patients receiving reduced intensity conditioning were elderly, or exhibited contraindications for myeloablative conditioning. Neutrophil and platelet engraftment occurred more rapidly in the reduced intensity group (median, 9 days vs. 18 days in the myeloablative group, p<0.0001; median 12 days vs. 22 days in the myeloablative group, p=0.0001, respectively). Acute graft-versus-host disease (>or=grade II) occurred at comparable frequencies in both groups, while the incidence of hepatic veno-occlusive disease was lower in the reduced intensity group (3% vs. 20% in the myeloablative group, p=0.02). The overall 1-yr survival rates of the reduced intensity and myeloablative group patients were 44% and 15%, respectively (p=0.16). The results of present study indicate that patients with advanced hematological malignancies, even the elderly and those with major organ dysfunctions, might benefit from reduced intensity transplantation.
- 432007
제1저자 신기철 · 교신저자 송영욱
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Radiation synovectomy using 188Re-tin colloid improves knee synovitis as shown by MRI in refractory rheumatoid arthritis.Nucl Med Commun. 2007;28(4):239-44.
PubMed IF 1.4 류마티스내과Abstract
BACKGROUND Radiation synovectomy is a useful local treatment for patients with refractory synovitis. We previously demonstrated the efficacy and safety of Re-tin colloid for treating rheumatoid arthritis patients with refractory knee synovitis. This open-label, prospective controlled study investigates magnetic resonance imaging (MRI) changes as well as clinical response in knees after receiving different radioactivities of intra-articular Re-tin colloid.
METHODS Sixteen patients with rheumatoid arthritis refractory to intra-articular corticosteroid therapy were treated with intra-articular injection of Re-tin colloid (555 MBq in six patients, 740 MBq in five, and 925 MBq in five). Contralateral knees were used as controls. Treatment efficacy and safety were evaluated 1, 3 and 6 months later. We compared the changes of synovial thickening and joint effusion between baseline and 6 months. Synovial thickness was measured by gadolinium-enhanced MRI.
RESULTS Pain intensities on a visual analogue scale were significantly lower (median pain reduction, 78.9%; P=0.0001), joint swelling improved (median, -1.5; P=0.001), range of motion increased (median, 6 degrees , P=0.005), and joint tenderness decreased (median, -1; P=0.005) in treated knees after 6 months. The control knees did not show any significant clinical improvement. At 6 months after therapy, synovial thickening of treated knees improved in 87.5% of patients (P<0.001), and synovial thicknesses were significantly decreased in treated knees (P=0.0067). Furthermore, reduction in synovial thickness was most noticeable in the group treated with 925 MBq (P=0.007). No abnormalities in leukocyte or platelet counts, liver function tests, or urine analysis were observed.
CONCLUSION Radiation synovectomy using Re-tin colloid in refractory rheumatoid arthritis patients improved MRI findings as well as clinical parameters.
- 422007
제1저자 이준규 · 교신저자 김용태
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Risk for post-ERCP pancreatitis after needle knife precut sphincterotomy following repeated cannulation attempts.J Clin Gastroenterol. 2007;41(4):427-31.
PubMed IF 2.7 소화기내과Abstract
GOALS The aim of this study was to determine the risk and identify the factors associated with post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in patients who undergo needle knife precut sphincterotomy (NKS). In addition, we evaluated the effect of gabexate for the prevention of post-ERCP pancreatitis.
BACKGROUND NKS, after repeated cannulation attempts during ERCP, is known to increase the risk of post-ERCP pancreatitis. However, the specific risk factors for post-ERCP pancreatitis have not been identified, and the preventive role of protease inhibitors, such as gabexate, has not yet been established.
STUDY The medical records of 200 patients who underwent NKS, after repeated cannulation attempts during ERCP, were reviewed retrospectively. The potential risk factors for post-ERCP pancreatitis were investigated. The effect of gabexate infused after the ERCP procedure was also evaluated.
RESULTS Thirteen (6.5%) patients out of 200 developed post-ERCP pancreatitis. Sex, age, the presence of pancreatitis at procedure, underlying disease, direction of the sphincterotomy, success or failure of cannulation after NKS, diameter of common bile duct, pancreatic duct status, and the presence of acinar filling were not associated with the risk of pancreatitis. Gabexate infusion after ERCP increased the incidence of ERCP-associated pancreatitis.
CONCLUSIONS We could not identify any risk factors associated with the development of post-ERCP pancreatitis in patients who underwent NKS after repeated cannulation attempts during ERCP. However, gabexate administered after the ERCP procedure was found to increase the incidence of pancreatitis.
- 412007
제1저자 최기돈 · 교신저자 김나영
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Analysis of the 3' variable region of the cagA gene of Helicobacter pylori isolated in Koreans.Dig Dis Sci. 2007;52(4):960-6.
PubMed IF 2.8 소화기내과Abstract
CagA protein of Helicobacter pylori is injected into epithelial cells, and it undergoes tyrosine phosphorylation, resulting in inducing cytoskeletal rearrangements. A few studies have suggested that the number of CagA tyrosine phosphorylation motifs (EPIYA) and subtypes of CagA were associated with gastric cancer. This study was performed to characterize the 3' variable regions of the cagA gene of H. pylori and to investigate whether or not there is any relationship between the diversities of cagA and the disease outcome in Korea. Seventy-nine patients (chronic gastritis, 15; duodenal ulcer, 27; benign gastric ulcer, 18; gastric cancer, 19) were enrolled. Biopsy specimens were taken from the antrum for H. pylori culture, and genomic DNA was extracted. PCR and DNA sequence analysis was carried out for the 3' variable region of the cagA gene. Seventy-eight strains (98.8%) contained three EPIYA motifs and one strain (1.2%) isolated from a patient with duodenal ulcer contained four EPIYA motifs. Seventy-six strains (96.2%) were the East Asian type. In conclusion, there was no significant difference between the number of EPIYA motifs or CagA subtypes and various gastroduodenal diseases in Korea.
- 402007
제1저자 김태영 · 교신저자 방영주
, , , , , ,
DLC-1, a GTPase-activating protein for Rho, is associated with cell proliferation, morphology, and migration in human hepatocellular carcinoma.Biochem Biophys Res Commun. 2007;355(1):72-7.
PubMed IF 2.5 혈액종양내과Abstract
DLC-1 (deleted in liver cancer-1) is a tumor suppressor gene for hepatocellular carcinoma and other cancers. To characterize its functions, we constructed recombinant adenovirus encoding the wild-type DLC-1 and examined its effects on behaviors of a hepatocellular carcinoma cell line (SNU-368), which does not express DLC-1. Here, we found that restoration of DLC-1 expression in the SNU-368 cells caused an inhibition of cell proliferation with an increase of a subG1 population. Furthermore, DLC-1 overexpression induced disassembly of stress fibers and extensive membrane protrusions around cells on laminin-1. DLC-1 overexpression also inhibited cell migration and dephosphorylated focal adhesion proteins such as focal adhesion kinase (FAK), Cas (p130Cas; Crk-associated substrate), and paxillin. These observations suggest that DLC-1 plays important roles in signal transduction pathway regulating cell proliferation, cell morphology, and cell migration by affecting Rho family GTPases and focal adhesion proteins.
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