SCI 발표논문

1. 2122013

   제1저자 조선욱 · 교신저자 신찬수

   Cho SW, An JH, Park H, Yang JY, Choi HJ, Kim SW, Park YJ, Kim SY, Yim M, Baek WY, Kim JE, Shin CS

   Positive regulation of osteogenesis by bile acid through FXR.

   J Bone Miner Res. 2013;28(10):2109-21.

   Abstract

   Farnesoid X receptor (FXR) is a nuclear receptor that functions as a bile acid sensor controlling bile acid homeostasis. We investigated the role of FXR in regulating bone metabolism. We identified the expression of FXR in calvaria and bone marrow cells, which gradually increased during osteoblastic differentiation in vitro. In male mice, deletion of FXR (FXR(-/-) ) in vivo resulted in a significant reduction in bone mineral density by 4.3% to 6.6% in mice 8 to 20 weeks of age compared with FXR(+/+) mice. Histological analysis of the lumbar spine showed that FXR deficiency reduced the bone formation rate as well as the trabecular bone volume and thickness. Moreover, tartrate-resistant acid phosphatase (TRACP) staining of the femurs revealed that both the osteoclast number and osteoclast surface were significantly increased in FXR(-/-) mice compared with FXR(+/+) mice. At the cellular level, induction of alkaline phosphatase (ALP) activities was blunted in primary calvarial cells in FXR(-/-) mice compared with FXR(+/+) mice in concert with a significant reduction in type I collagen a1(Col1a1), ALP, and runt-related transcription factor 2 (Runx2) gene expressions. Cultures of bone marrow-derived macrophages from FXR(-/-) mice exhibited an increased number of osteoclast formations and protein expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). In female FXR(-/-) mice, although bone mineral density (BMD) was not significantly different from that in FXR(+/+) mice, bone loss was accelerated after an ovariectomy compared with FXR(+/+) mice. In vitro, activation of FXR by bile acids (chenodeoxycholic acid [CDCA] or 6-ECDCA) or FXR agonists (GW4064 or Fexaramine) significantly enhanced osteoblastic differentiation through the upregulation of Runx2 and enhanced extracellular signal-regulated kinase (ERK) and β-catenin signaling. FXR agonists also suppressed osteoclast differentiation from bone marrow macrophages. Finally, administration of a farnesol (FOH 1%) diet marginally prevented ovariectomy (OVX)-induced bone loss and enhanced bone mass gain in growing C57BL/6J mice. Taken together, these results suggest that FXR positively regulates bone metabolism through both arms of the bone remodeling pathways; ie, bone formation and resorption.

   PubMed IF 6.5 내분비대사내과
2. 2112013

   제1저자 이창현 · 교신저자 양종인

   Lee C, Yang JI, Byun HJ, Kang JM, Choi S, Yim JY

   Status of primary liver cancer found through routine health check-up.

   J Korean Med Sci. 2013;28(10):1449-53.

   Abstract

   This study aimed to investigate the status of primary liver cancers found through a routine health check-up. The data of subjects who were diagnosed with primary liver cancer for the first time through a routine health check-up during a period of 8-yr were analyzed. Primary liver cancers were detected for the first time in 34 subjects among 91,219 routine health check-up subjects. Only 11.8% of primary liver cancer subjects had been under previous surveillance. Of them, 55.8% were positive for HBsAg, 17.7% were positive for anti-HCV, and 8.8% were heavy alcohol comsumers. However, 17.7% of the subjects were neither heavy alcohol consumers nor positive for both HBsAg and anti-HCV. Of the subjects, 50.0% had a single nodular tumor, 23.5% had multi-nodular tumors, and 26.5% had an infiltrative tumor. A routine health check-up may provide beneficial opportunities to detect a liver cancer in a very early stage. It is beneficial to start surveillance in high-risk subjects for liver cancer or to detect any liver cancer in subjects without risk factors of chronic viral hepatitis or heavy alcohol consumption.

   PubMed IF 3.2 소화기내과
3. 2102013

   교신저자 윤성수

   Kim H, Lee KH, Sohn SK, Jung CW, Joo YD, Kim SH, Kim BS, Choi JH, Kwak JY, Kim MK, Bae SH, Shin HJ, Won JH, Oh S, Lee WS, Park JH, Yoon SS

   Hepatic sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation in adult patients with idiopathic aplastic anemia.

   Leuk Res. 2013;37(10):1241-7.

   Abstract

   We retrospectively investigated the incidence, risk factors, and outcomes of SOS (sinusoidal obstruction syndrome; previously veno-occlusive disease [VOD]) after allogeneic hematopoietic stem cell transplantation (alloHSCT) in aplastic anemia. Two hundred and sixty patients were included in the analysis. SOS developed in 7.3% (n=19/260) of patients. Classical Cy (200 mg/m(2))-ATG was the most common conditioning regimen (84.2%) in the SOS group. The SOS mortality rate was 4/19 (21.1%). Univariate analyses revealed that Cy 200 mg/m(2) conditioning (p=0.035), classical Cy-ATG conditioning (p=0.007), and horse ATG conditioning (p<0.001) were significant risk factors for developing SOS. Multivariate analysis revealed that only horse ATG conditioning was a poor prognostic factor (HR=3.484; 95% CI 1.226-9.904; p=0.002). Rabbit ATG (HR 12.719; 95% CI 2.332-69.373; p=0.003) and weight gain>10% (HR 35.655; 95% CI 2.208-575.805; p=0.012) were risk factors in the overall SOS group. Both rabbit ATG conditioning and weight gain of more than 10% were associated with poor overall survival with a median of 1.2 months (5Y survival rate, any risk factor vs. none: 74.6% vs. 0.0%; p<0.001; Fig. 2) in the SOS group. In conclusion, SOS is a relatively rare (7.3%) but highly fatal (21.1%) acute complication of alloHSCT in AA, and the horse ATG conditioning regimen was a significant risk factor for developing SOS.

   PubMed IF 2.4 혈액종양내과
4. 2092013

   제1저자 이창훈 · 교신저자 임재준

   Lee CH, Jang EJ, Hyun MK, Lee NR, Kim K, Yim JJ

   Risk of hospital admission or emergency room visit for pneumonia in patients using respiratory inhalers: a case-crossover study.

   Respirology. 2013;18(7):1116-27.

   Abstract

   BACKGROUND AND OBJECTIVE The impact of inhaled corticosteroid (ICS) use on the development of pneumonia has been heavily debated. The aim of this study was to elucidate the association between the use of inhalers, including ICS, and a hospital admission or an emergency room (ER) visit for pneumonia.

   METHODS A case-crossover study was conducted based on the Korean national claims database. We identified users of respiratory inhalers admitted to the hospital or having visited the ER for pneumonia between 1 January 2008 and 31 December 2010. The case period was defined as 0-30 days before the event. Control periods of 30-60, 90-120, 180-210 and 360-390 days before the event were used.

   RESULTS A total of 186 018 inhaler users were admitted to the hospital or visited the ER for pneumonia during the study period. With the period 30-60 days before the event as a control, the use of an ICS without a long-acting β2 agonist (LABA) was associated with an increased risk of hospital admission or ER visit for pneumonia (adjusted odds ratio (aOR), 1.73; 95% confidence interval (CI): 1.64-1.83). In contrast, the use of an ICS and a LABA was associated with a decreased risk for pneumonia-related hospital admission or ER visit (aOR, 0.63; 95% CI: 0.61-0.66).

   CONCLUSIONS We suggest that the use of ICS with LABA decreases the risk of hospital admission or ER visit for pneumonia, whereas the use of ICS alone may increase that risk.

   PubMed IF 7.2 호흡기내과
5. 2082013

   제1저자 강은하 · 교신저자 송영욱

   Kang EH, Park JW, Park C, Yu HG, Lee EB, Park MH, Song YW

   Genetic and non-genetic factors affecting the visual outcome of ocular Behcet's disease.

   Hum Immunol. 2013;74(10):1363-7.

   Abstract

   OBJECTIVE To examine the prognostic factors for visual outcome in Korean BD patients with uveitis.

   METHODS Seventy-seven Korean BD patients with uveitis were enrolled. HLA-B and HLA-A genotypes were determined by PCR-based method. Visual acuity was measured by Snellen chart. Vision loss was graded into visual impairment (VI) defined as VA<20/40 for more than 6 months, loss of useful vision (LUV) as VA < 20/200, and near total blindness (NTB) as VA of light perception or worse.

   RESULTS VI was associated with a longer duration of uveitis, posterior uveitis, and cataract, LUV with male gender, a longer duration of uveitis, posterior uveitis, and cataract, and NTB with a longer duration of uveitis, cataract, and glaucoma. HLA-B*51 and HLA-A*26:01 did not show any association with VI, LUV, or NTB. However, HLA-B*51 carriers had earlier onset of uveitis and HLA-A*26:01 was strongly associated with posterior uveitis. In patients with posterior uveitis, VI was associated with a longer duration of uveitis and cataract, LUV with a longer duration, and NTB with HLA-B*51.

   CONCLUSION Longer duration of uveitis, posterior uveitis, male gender, cataract, and glaucoma were found to be associated with poor visual outcome in BD-related uveitis. HLA-B*51 was associated with NTB in patients with posterior uveitis. HLA-A*26:01 showed no association with VI, LUV, or NTB, however, was strongly associated with posterior uveitis.

   PubMed IF 2.1 류마티스내과
6. 2072013

   제1저자 성문혁 · 교신저자 정숙향

   Seong MH, Kil H, Kim YS, Bae SH, Lee YJ, Lee HC, Kang BH, Jeong SH

   Clinical and epidemiological features of hepatitis C virus infection in South Korea: a prospective, multicenter cohort study.

   J Med Virol. 2013;85(10):1724-33.

   Abstract

   The epidemiological and clinical features of hepatitis C virus (HCV) infection in South Korea were examined in a prospective, multicenter cohort study that included 1,173 adult patients with positive results for anti-HCV antibody who completed a questionnaire survey on the risk factors for HCV infection from January 2007 to December 2011 at five university hospitals. The HCV cohort had a mean age of 55.4 years with 48.3% men, and diagnostic categories of acute hepatitis (n = 63, 5.3%), past infection (n = 37, 3.2%), chronic hepatitis (n = 777, 66.2%), cirrhosis of the liver (n = 179, 15.3%), and hepatocellular carcinoma (n = 117, 10.0%). The major HCV genotypes were genotype 1 (52.7%) and genotype 2 (45.3%). Liver biopsy was performed in 301 patients (25.7%), and 42.8% of the subjects received antiviral therapy against HCV. The behavioral risk factors possibly related to HCV infection were intravenous drug use (5%), needle stick injury (7%), blood transfusion before 1995 (19%), sexual relationship with more than three partners (28%), piercings (35%), tattoos (36%), surgery (43%), acupuncture (83%), diagnostic endoscopy (85%), and dental procedures (93%). Age, intravenous drug use, needle stick injury, transfusion before 1995, and tattoos were the independent risk factors of HCV infection.

   PubMed IF 3.7 소화기내과
7. 2062013

   제1저자 김범석 · 교신저자 김동완

   Keam B, Kim DW, Park JH, Lee JO, Kim TM, Lee SH, Chung DH, Heo DS

   How Molecular Understanding Affects to Prescribing Patterns and Clinical Outcome of Gefitinib in Non-small Cell Lung Cancer? 10 Year Experience of Single Institution.

   Cancer Res Treat. 2013;45(3):178-85.

   Abstract

   PURPOSE Gefitinib was introduced in 2002 for treatment of non-small cell lung cancer (NSCLC); however, it is not clear whether its use in daily practice has changed the outcome of patients. The purpose of this study is to evaluate the question of how molecular understanding regarding gefitinib and epidermal growth factor receptor (EGFR) mutation affect the prescribing patterns and clinical outcomes of treatment with gefitinib in NSCLC, in a real practical field.

   MATERIALS AND METHODS We conducted a retrospective analysis of the consecutive database of NSCLC patients who were treated with gefitinib at Seoul National University Hospital between January 2002 and December 2011. Prescribing patterns and clinical outcomes were analyzed by year.

   RESULTS A total of 1,115 NSCLC patients, who received gefitinib at recurred or metastatic setting, were included in this study. Proportion of patients receiving gefitinib, for the first line, showed a gradual increase, from 5.2% in 2002-2003 to 30.6% in 2010-2011. Proportion of patients who underwent EGFR mutation testing showed a rapid increase, from 0.6% in 2004-2005 to 73.5% in 2010-2011. The response rate also showed a gradual increase, from 17.2% in 2002-2003 to 57.1% in 2010-2011 (p<0.001). The median progression-free survival of gefitinib was increased with statistical significance from 2.8 months in 2002-2003 to 9.1 months in 2010-2011 (p<0.001).

   CONCLUSION We demonstrated that molecular understanding and practical use of EGFR mutation testing have resulted in a change in the prescription patterns of gefitinib. Use of an enrichment strategy can lead to improvement in the efficacy of gefitinib in real practice.

   PubMed IF 4.2 혈액종양내과
8. 2052013

   제1저자 김효진 · 교신저자 이정표

   Kim HJ, Kim H, Cho HS, Hwang JH, Jung IM, Ahn C, Ha J, Oh YK, Lim CS, Chae DW, Kim YS, Lee JP

   Outcomes of kidney allograft in recipients with kidney disease of unknown etiology.

   Clin Transplant. 2013;27(6):866-74.

   Abstract

   The etiology of renal disease is important because the primary renal pathology may affect the outcomes of kidney allograft with respect to recurrence, rejection, and survival. However, for a significant number of patients who undergo kidney transplantation, the disease etiology is unknown. Here, allograft outcomes for patients with kidney disease of unknown etiology (UEK) at three affiliated Korean hospitals were identified. The incidence of biopsy-proven acute rejection (BPAR) for UEK was 22.9%, which was similar to the rates for diabetic nephropathy (DN, 24.4%) and IgA nephropathy (IgAN, 20.0%; p = 0.345). The cumulative incidence of post-transplant glomerulonephritis (PTGN) among patients with UEK was significantly lower than that among patients with IgAN (p < 0.001). Overall graft survival of the UEK group was superior to that of the DN group (hazards ratio 0.39, 95% confidence interval 0.17-0.92, p = 0.030). Preemptive transplantation for UEK significantly reduced the incidence of BPAR (preemptive vs. non-preemptive 9.6% vs. 30.3%, p = 0.001), but graft survival and recurrence were not affected by preemptive transplantation. The outcomes of kidney transplantation for patients with UEK were not inferior to those for patients with IgAN or DN. Preemptive kidney transplantation may be encouraged for UEK patients.

   PubMed IF 1.8 신장내과
9. 2042013

   제1저자 박경우 · 교신저자 김효수

   Park KW, Kang J, Park JJ, Yang HM, Kwon YW, Lee HY, Kang HJ, Koo BK, Oh BH, Park YB, Kim HS

   Thiazolidinedione usage is associated with decreased response to clopidogrel in DM patients.

   Int J Cardiol. 2013;168(1):608-10.

   PubMed IF 3.3 순환기내과
10. 2032013

    제1저자 김민수 · 교신저자 김나영

    Kim MS, Kim N, Kim SE, Jo HJ, Shin CM, Park YS, Lee DH

    Long-term follow up Helicobacter Pylori reinfection rate after second-line treatment: bismuth-containing quadruple therapy versus moxifloxacin-based triple therapy.

    BMC Gastroenterol. 2013;13:138.

    Abstract

    BACKGROUND The increasing trend of antibiotic resistance requires effective second-line Helicobacter pylori (H. pylori) treatment in high prevalence area of H. pylori. The aim of our study was to evaluate the reinfection rate of H. pylori after second-line treatment that would determine the long-term follow up effect of the rescue therapy.

    METHODS A total of 648 patients who had failed previous H. pylori eradication on standard triple therapy were randomized into two regimens: 1, esomeprazole (20 mg b.i.d), tripotassium dicitrate bismuthate (300 mg q.i.d), metronidazole (500 mg t.i.d), and tetracycline (500 mg q.i.d) (EBMT) or 2, moxifloxacin (400 mg q.d.), esomeprazole (20 mg b.i.d), and amoxicillin (1000 mg b.i.d.) (MEA). At four weeks after completion of eradication therapy, H. pylori tests were performed with 13C urea breath test or invasive tests. In patients who maintained continuous H. pylori negativity for the first year after eradication therapy, H. pylori status was assessed every year. For the evaluation of risk factors of reinfection, gender, age, clinical diagnosis, histological atrophic gastritis or intestinal metaplasia were analyzed.

    RESULTS The recrudescence rate of the EBMT was 1.7% and of the MEA group 3.3% (p = 0.67). The annual reinfection rate of H. pylori of EBMT was found to be 4.45% and the MEA group 6.46%. Univariate analysis (Log-rank test) showed no association with any clinical risk factor for reinfection.

    CONCLUSIONS The long-term reinfection rate of H. pylori stayed low in both of bismuth-containing quadruple therapy and moxifloxacin-based triple therapy; thus reinfection cannot affect the choice of second-line treatment.

    TRIAL REGISTRATION Clinical Trial Registration Number NCT01792700.

    PubMed IF 3.2 소화기내과
11. 2022013

    제1저자 박경우 · 교신저자 김효수

    Park KW, Kang J, Kang SH, Ahn HS, Lee HY, Kang HJ, Koo BK, Chae IH, Youn TJ, Oh BH, Park YB, Kandzari DE, Kim HS

    Usefulness of the SYNTAX and clinical SYNTAX scores in predicting clinical outcome after unrestricted use of sirolimus- and everolimus-eluting Stents.

    Circ J. 2013;77(12):2912-21.

    Abstract

    BACKGROUND The SYNTAX score (SS) and clinical SS (cSS) can assess coronary lesion complexity and are useful indices in predicting outcomes after percutaneous coronary intervention. However, their validity has not been fully investigated in daily practice where "limus"-eluting stents are used.

    METHODS AND RESULTS The SS and cSS were independently assessed from the Efficacy of Xience/Promus vs. Cypher in rEducing Late Loss after stENTing (EXCELLENT) registry, together with the 1-year patient-oriented composite endpoint (POCE; all-cause death, any myocardial infarction (MI), and any revascularization) and target-lesion failure (TLF; cardiac death, target-vessel MI, and target-lesion revascularization). Among 5,102 patients, tertiles for SS were defined as low-SS <8, 8≤mid-SS≤16, high-SS >16. Both POCE (4.2% vs. 7.7% vs. 12.2%, P<0.001) and TLF (1.6% vs. 2.4% vs. 4.5%, P<0.001) increased significantly with increasing SS tertile, and SS was an independent predictor of POCE (P<0.001 for trend) and TLF (P=0.023 for trend) in multivariate analysis. The predictability of SS and cSS was similar for POCE (area under the curve (AUC): 0.635 vs. 0.629, P=0.599), whereas SS was superior in predicting restenosis-related outcomes such as revascularization (AUC: 0.624 vs. 0.577, P<0.001) and cSS was superior in other components such as death (AUC: 0.654 vs. 0.795, P<0.001).

    CONCLUSIONS Both SS and cSS were applicable to unrestricted use of "limus"-eluting stents in predicting the risk of 1-year clinical outcomes.

    PubMed IF 5.8 순환기내과
12. 2012013

    제1저자 조현진 · 교신저자 김나영

    Jo HJ, Kim N, Nam RH, Chang H, Kim JH, Park JH, Kang JM, Lee DH, Jung HC

    The Effect of Cochinchina momordica Seed Extract on Gastric Acid Secretion and Morphologic Change in Aged Rat Stomach.

    Gut Liver. 2013;7(5):560-8.

    Abstract

    BACKGROUND/AIMS Cochinchina momordica seed extract (SK-MS10) has a gastric protective effect. We aimed to assess the effect of SK-MS10 on gastric acid secretion with morphologic changes in the aged rat.

    METHODS Acid secretions were evaluated in the male F344 rats of four different ages (6-, 31-, 74-week, and 2-year). The 31-week-old rats were divided to three groups and continuously administered chow containing vehicle, SK-MS10 and lansoprazole, respectively. At the age of 74 weeks and 2 years, basal and stimulated acid was measured and the expression of mRNA and protein of H(+)-K(+)-ATPase were determined. The area of connective tissue of lamina propria was measured.

    RESULTS Basal and stimulated gastric acid significantly decreased and connective tissue of lamina propria increased with age. The expression of mRNA and protein of H(+)-K(+)-ATPase significantly decreased with age. However, 74-week-old rats in the SK-MS10 group had higher stimulated gastric acid secretion than those in the vehicle and lansoprazole groups. In 2-year-old rats of SK-MS10 group, there was no increase of connective tissue.

    CONCLUSIONS As SK-MS10 kept the capacity of acid secretion as well as connective tissue area to comparable to young rats, it might valuable to perform further research regarding mechanism of SK-MS10 as an antiaging agent in the stomach.

    PubMed IF 4.1 소화기내과
13. 2002013

    제1저자 이윤석 · 교신저자 이상협

    Lee YS, Lee SH, Lee MG, Lee SJ, Hwang JH, Shin E, Lee YJ

    Immunoglobulin g4-related disease mimicking unresectable gallbladder cancer.

    Gut Liver. 2013;7(5):616-20.

    Abstract

    Immunoglobulin G4 (IgG4)-related disease is a novel disease entity that can involve diverse organs, causing specific diseases, including autoimmune pancreatitis, sclerosing cholangitis, cholecystitis, inflammatory aortic aneurysm, and inflammatory pseudotumor. IgG4-related disease is characterized by elevated serum IgG4 concentrations, abundant IgG4 lymphoplasmacytic infiltration, and dramatic steroid responses. It is clinically important to differentiate this rare disease from primary sclerosing cholangitis and cholangiocarcinoma, because the treatment and prognosis of these two diseases are completely different. However, the preoperative diagnosis is challenging, and the disease is frequently misdiagnosed. If the serum level of IgG4 is within the normal range, the diagnosis of IgG4-related disease is more difficult. This article reports on a 59-year-old man with IgG4-related disease mimicking unresectable gallbladder cancer with normal serum IgG4 concentrations.

    PubMed IF 4.1 소화기내과
14. 1992013

    제1저자 이주명 · 교신저자 연태진

    Lee JM, Youn TJ, Park JJ, Oh IY, Yoon CH, Suh JW, Cho YS, Cho GY, Chae IH, Choi DJ

    Comparison of 9-month angiographic outcomes of Resolute zotarolimus-eluting and everolimus-eluting stents in a real world setting of coronary intervention in Korea.

    BMC Cardiovasc Disord. 2013;13:65.

    Abstract

    BACKGROUND Clinical outcomes of new-generation drug-eluting stents (DES), Everolimus-eluting stent (EES) or Resolute zotarolimus-eluting stent (R-ZES), have been reported. However, angiographic follow-up data of new-generation DES are limited, especially in Asians. We investigated the angiographic and clinical outcomes of EES and R-ZES in a real-world setting of Korean patients.

    METHODS Angiographic and clinical outcomes of 679 patients (866 lesions) who had been treated with EES or R-ZES from Jun 2008 to May 2010 were evaluated. The primary analysis was to compare in-segment late loss at 9 months and the secondary analyses were to compare the clinical outcomes.

    RESULTS In-segment late loss at 9-month follow-up angiography was 0.23 ± 0.52 mm for EES and 0.29 ± 0.64 mm for R-ZES (p = 0.248). In addition, the rate of binary restenosis did not show between-group differences (5.8% vs. 6.8% for EES and R-ZES, respectively, p = 0.716). During a median follow-up of 33 months, there were no significant differences in Kaplan-Meier estimates of target lesion failure (TLF) (7.5% vs. 7.9% for EES and R-ZES, respectively, p = 0.578) and patient-oriented composite outcomes (POCO including all-cause death, any myocardial infarction, and any revascularization, 22.8% vs. 20.1%, p = 0.888). The adjusted hazard ratios for TLF and POCO were 0.875 (95% CI 0.427 - 1.793; p = 0.715) and 1.029 (95% CI 0.642 - 1.650; p = 0.904), respectively, for EES over R-ZES in the propensity score matched group analysis.

    CONCLUSIONS In Korean patients undergoing new-generation DES implantation for coronary artery disease, EES and R-ZES showed similar angiographic outcomes at 9 months and comparable clinical outcomes during 2.8 years of median follow-up.

    PubMed IF 3.1 순환기내과
15. 1982013

    제1저자 나기영 · 교신저자 임춘수

    Na KY, Kim DK, Kim SG, Lee YK, Lim CS

    Effect of beraprost sodium on arterial stiffness in patients with type 2 diabetic nephropathy.

    Trials. 2013;14:275.

    Abstract

    BACKGROUND Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD). Cardiovascular (CV) complications are the most common cause of death among ESRD patients. Beraprost sodium (BPS) is a prostacyclin analog with vasodilatory and antiplatelet effects.

    METHODS This is a multicenter prospective, randomized, double-blind, placebo-controlled trial to determine whether treatment with BPS improves arterial stiffness in patients with type 2 diabetic nephropathy. A total of 102 participants with type 2 diabetic nephropathy will be screened, enrolled, and randomly assigned to receive either 80 μg BPS or placebo daily for 12 weeks. The primary outcome is the change in brachial-ankle pulse wave velocity between baseline and after 12 weeks of medication use. The secondary outcomes will include changes in the ankle-brachial index, the urine albumin to creatinine ratio, the estimated glomerular filtration rate, lipid profiles, and blood pressure from baseline to after treatment.

    DISCUSSION This clinical trial is the first to investigate the effects of BPS on changes in CV biomarkers, albuminuria, renal function, and lipid profiles in patients with diabetic nephropathy.

    TRIAL REGISTRATION ClinicalTrials.gov number NCT01796418.

    PubMed IF 2.1 신장내과
16. 1972013

    제1저자 Huang D, 김동완 · 교신저자 Park K, Mao M

    Huang D, Kim DW, Kotsakis A, Deng S, Lira P, Ho SN, Lee NV, Vizcarra P, Cao JQ, Christensen JG, Kim TM, Sun JM, Ahn JS, Ahn MJ, Park K, Mao M

    Multiplexed deep sequencing analysis of ALK kinase domain identifies resistance mutations in relapsed patients following crizotinib treatment.

    Genomics. 2013;102(3):157-62.

    Abstract

    The recently approved ALK kinase inhibitor crizotinib has demonstrated successful treatment of metastatic and late stage ALK fusion positive non-small cell lung cancer (NSCLC). However, the median duration of clinical benefit is ~10-11months due to the emergence of multiple and simultaneous resistance mechanisms in these tumors. Mutations in the ALK kinase domain confer resistance to crizotinib in about one-third of these patients. We developed a multiplex deep sequencing method using semiconductor sequencing technology to quickly detect resistance mutations within the ALK kinase domain from tumor biopsies. By applying a base-pair specific error-weighted mutation calling algorithm (BASCA) that we developed for this assay, genomic DNA analysis from thirteen relapsed patients revealed three known crizotinib resistance mutations, C1156Y, L1196M and G1269A. Our assay demonstrates robust and sensitive detection of ALK kinase mutations in NSCLC tumor samples and aids in the elucidation of resistance mechanisms pertinent to the clinical setting.

    PubMed IF 3.6 혈액종양내과
17. 1962013

    제1저자 최종경/류지곤 · 교신저자 이상협

    Choi J, Ryu JK, Lee SH, Hwang JH, Ahn DW, Kim YT, Yoon YB, Yoon CJ, Kang SG, Chung JW

    Palliative treatment of unresectable hepatocellular carcinoma with obstructive jaundice using biliary drainage with subsequent transarterial chemoembolization.

    J Palliat Med. 2013;16(9):1026-33.

    Abstract

    BACKGROUND Nonsurgical biliary drainage is considered as a priority for obstructive jaundice associated with unresectable hepatocellular carcinoma (HCC). Successful drainage allows the patient to receive antitumor therapy, such as transarterial chemoembolization (TACE). However, only limited data are available on clinical outcomes in patients who treated biliary drainage with subsequent TACE.

    OBJECTIVE This study evaluated the clinical outcome of biliary drainage with subsequent TACE in unresectable HCC patients with obstructive jaundice.

    DESIGN This was a retrospective study.

    SETTING/SUBJECTS A total of 60 patients received endoscopic biliary drainage (ERBD) or percutaneous transhepatic biliary drainage (PTBD) in two tertiary care referral centers.

    MEASUREMENTS Successful drainage and survival were measured.

    RESULTS Successful drainage was achieved in 39 (65%) patients. The median survival of 39 patients in whom successful drainage was achieved, regardless of which procedure was performed, was much longer than that of 21 patients without successful drainage (147 days versus 38 days, respectively, P<.001). In particular, the median survival was longer in 17 patients who underwent TACE after achieving successful drainage than in 22 patients who were treated conservatively after achieving successful drainage (410 days versus 77 days, respectively, P<.001). Multivariable analysis in 39 patients in the successful drainage group showed that TACE (hazard ratio 0.15; 95% confidence interval 0.05-0.45, P=.001) was an independent predictive factor of a favorable outcome.

    CONCLUSIONS Effective palliation by successful biliary drainage with subsequent TACE might prolong the survival in patients with obstructive jaundice caused by unresectable HCC.

    PubMed IF 1.8 소화기내과
18. 1952013

    제1저자 오도연 · 교신저자 방영주

    Oh DY, Bang YJ

    Adjuvant and neoadjuvant therapy for gastric cancer.

    Curr Treat Options Oncol. 2013;14(3):311-20.

    Abstract

    To improve outcome of resectable gastric cancer, several treatment strategies have been evaluated. These include adjuvant chemotherapy, adjuvant chemoradiotherapy, and perioperative chemotherapy. The US Intergroup 0116 trial reported the benefit of postoperative chemoradiotherapy using 5-FU/leucovorin in a U.S. population. In this study, only 10 % of patients received D2 resection. For Korean patients after D2 resection, the ARTIST trial failed to show any benefit from adding radiotherapy to adjuvant chemotherapy in terms of 3-year disease-free survival. The MAGIC trial compared perioperative chemotherapy with surgery alone and reported a prolonged 5-year overall survival in the perioperative chemotherapy arm. In resectable gastric cancer, the benefit of adjuvant chemotherapy compared with surgery alone has been clearly demonstrated. After D2 dissection, S-1 adjuvant chemotherapy improved the overall survival (ACTS-GC trial) and capecitabine/oxaliplatin combination chemotherapy improved 3-year disease-free survival (CLASSIC trial). To date, for resectable gastric cancer, the use of chemotherapy in addition to surgery is beneficial for the reduction of recurrence and to improve overall survival. The optimal sequence of chemotherapy and surgery, as well as optimal chemotherapeutic agents, should be further studied. In D2-resected gastric cancer, the addition of radiotherapy to chemotherapy does not appear to provide any additional benefit.].

    PubMed IF 5.8 혈액종양내과
19. 1942013

    제1저자 임수 · 교신저자 고광곤

    Lim S, Sakuma I, Quon MJ, Koh KK

    Potentially important considerations in choosing specific statin treatments to reduce overall morbidity and mortality.

    Int J Cardiol. 2013;167(5):1696-702.

    Abstract

    Hypercholesterolemia and dyslipidemia are independent risk factors for cardiovascular disease and death. Statins are the drugs of choice to decrease plasma cholesterol and have other beneficial actions beyond lipid-lowering leading to substantial improvements in cardiovascular morbidity and mortality. However, evaluation of the effects of statins to reduce overall morbidity and mortality must integrate metabolic consequences of statin therapy with its lipid-lowering effect. Indeed, reduction in LDL-cholesterol to target level achieved by statins does not completely eliminate risk of cardiovascular disease and may elevate metabolic risk factors that contribute to dysregulation of metabolic homeostasis. This may lead to increased incidence of diabetes and its cardiovascular complications that are explained, in part, by reciprocal relationships between insulin resistance and endothelial dysfunction. Genetic factors may determine 40-60% of total cholesterol levels and 70% of the efficacy of statin treatments. Metabolic and cardiovascular phenotypes that are either genetically determined or environmentally acquired are also important determinants of responses to specific statins. Moreover, differences between biological outcomes of specific statins or increasing dosages of statins result in differential metabolic actions due to off-target or unknown mechanism that have important implications for the use of statins to reduce overall morbidity and mortality. In this review, we discuss differential cardiovascular and metabolic pleiotropic actions of specific statins that interact in a context-dependent manner with patient phenotypes and genotypes. These important considerations may influence progression of atherosclerosis, risk of diabetes, and modulation of insulin resistance that help determine overall morbidity and mortality in patients undergoing statin therapy.

    PubMed IF 3.3 내분비대사내과
20. 1932013

    제1저자 윤창환 · 교신저자 최동주

    Yoon CH, Chung WY, Suh JW, Cho YS, Youn TJ, Chun EJ, Choi SI, Chae IH, Choi DJ

    Distal protection device aggravated microvascular obstruction evaluated by cardiac MR after primary percutaneous intervention for ST-elevation myocardial infarction.

    Int J Cardiol. 2013;167(5):2002-7.

    Abstract

    BACKGROUND Protection of distal embolization by balloon occlusion and thrombus aspiration has not improved microvascular circulation nor decreased myocardial injury during primary percutaneous intervention (PCI) for ST-elevation myocardial infarction (STEMI) in randomized trials. In a prospective randomized trial, we investigated the mechanism of the poor effect of distal protection and thrombus aspiration (DP-TA) in 126 patients with STEMI.

    METHODS Patients with first-diagnosed STEMI were randomly assigned to DP-TA pretreatment or conventional PCI (c-PCI). Primary endpoint was reduced left ventricular end-diastolic volume (LVEDV) measured by MRI at post-PCI and 6 months after PCI. Secondary end points were infarct ratio (infarct size to entire LV size) by delayed enhancement (DE), area at risk (AAR) ratio (AAR to entire LV size) by T2 high signal, microvascular occlusion index (MVO) ratio (MVO to entire LV size) by DE, and myocardial salvage index (MSI: (AAR--infarct size)*100/AAR) using cardiac magnetic resonance imaging (MRI) within 3 days after PCI.

    RESULTS Baseline characteristics of the patients including cardiovascular risk factors and lesion characteristics were similar between the two groups. DT-PA failed to improve LV remodeling at 6 months (LVEDV 140 ± 39 vs 133 ± 37 in c-PCI group, p=0.418). Infarct ratio, AAR ratio and MSI were not statistically different between DP-TA group and c-PCI group. However, MVO ratio was significantly larger in DP-TA group than in c-PCI group (2.4 ± 2.7 vs 1.1 ± 1.9, p=0.045).

    CONCLUSION DP-TA was potentially hazardous in primary PCI for STEMI by increasing MVO. DP-TA should not be used in STEMI.

    PubMed IF 3.3 순환기내과
21. 1922013

    제1저자 민주원 · 교신저자 임재준

    Min JW, Lee HY, Lee JS, Lee J, Chung JH, Han SK, Yim JJ

    Effect of prolonged incubation time on results of the QuantiFERON TB gold in-tube assay for diagnosis of latent tuberculosis infection.

    Clin Vaccine Immunol. 2013;20(9):1377-80.

    Abstract

    Previous reports have shown that the sensitivity of the 6-day lymphocyte stimulation test is much higher than those of commercially available gamma interferon release assays (IGRAs). The aim of this study was to elucidate the effect of prolonged incubation on the results of the QuantiFERON TB Gold in-tube (QFT-GIT) assay. Patients aged >20 years with suspected tuberculosis (TB) were recruited prospectively from 1 May 2009 to 31 December 2010. In addition, healthy volunteers with no history of TB treatment were included as controls. For each participant, three sets of the QFT-GIT assay were performed using 24-, 48-, and 72-h incubation tests, and the results were compared. Thirty-seven patients with suspected pulmonary TB and 33 healthy controls were enrolled in the study. Of the 37 patients with suspected TB, the QFT-GIT assay results were positive for 28 (75.7%) after a 24-h incubation period. After prolonged incubation, the results differed in four (10.8%) of the 37 patients suspected of having TB. Among 27 patients with culture-confirmed TB, the sensitivities of the QFT-GIT assay after the 24-, 48-, and 72-h incubation tests were 85.2%, 81.5%, and 81.5%, respectively. Among the 33 healthy controls, the QFT-GIT assay results were positive in two (6.1%) after a 24-h incubation period. The results changed for two (6.1%) of the 33 healthy controls after prolonged incubation. The specificities of the QFT-GIT assay after 24, 48, and 72 h of incubation were 93.9%, 87.9%, and 90.9%, respectively. Prolonging the incubation time did not increase the sensitivity of the QFT-GIT assay. The manufacturer-recommended incubation time of 16 to 24 h should be respected because prolonged incubation can cause indeterminate or false-positive results.

    PubMed IF 2.598 호흡기내과
22. 1912013

    제1저자 이세원, 원주윤 · 교신저자 김효수

    Lee SW, Won JY, Kim WJ, Lee J, Kim KH, Youn SW, Kim JY, Lee EJ, Kim YJ, Kim KW, Kim HS

    Snail as a potential target molecule in cardiac fibrosis: paracrine action of endothelial cells on fibroblasts through snail and CTGF axis.

    Mol Ther. 2013;21(9):1767-77.

    Abstract

    Ischemia/reperfusion (I/R) injury to myocardium induces death of cardiomyocytes and destroys the vasculature, leading to cardiac fibrosis that is mainly mediated by the transdifferentiation of fibroblasts to myofibroblasts and the collagen deposition. Snail involvement in fibrosis is well known; however, the contribution of Snail to cardiac fibrosis during I/R injury and its underlying mechanisms have not been defined. We showed that I/R injury to mouse hearts significantly increases the expression of Snail. An in vitro hypoxia/reoxygenation (Hy/Reoxy) experiment showed that the cell source of Snail induction is endothelial cells rather than cardiac fibroblasts (cFibroblasts) or cardiomyoblasts. When Snail was overexpressed in endothelial cells, they underwent endothelial-to-mesenchymal transition (EndMT) but showed very poor capacity for collagen synthesis. Instead, reoxygenation- or Snail overexpression-mediated EndMT-like cells noticeably stimulated transdifferentiation of fibroblasts to myofibroblasts via secretion of connective tissue growth factor (CTGF). The injection of a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, a selective Snail inhibitor, remarkably suppressed collagen deposition and cardiac fibrosis in mouse I/R injury, and significantly improved cardiac function and reduced Snail and CTGF expression in vivo. Our findings suggested a new mechanism of cell-to-cell communication between EndMT-like cells and fibroblasts for fibrosis induction and implicated Snail as a potential target molecule in cardiac fibrosis after I/R injury.

    PubMed IF 11.4 순환기내과
23. 1902013

    제1저자 김혜원 · 교신저자 송영욱

    Kim HW, Kim JW, Im CH, Shin KC, Lee EY, Lee EB, Song YW

    The clinicopathologic characteristics of granulomatosis with polyangiitis (Wegener's): a retrospective study of 45 patients in Korea.

    Mod Rheumatol. 2013;23(5):864-71.

    Abstract

    OBJECTIVES The aim of this study was to determine the clinicopathologic characteristics of granulomatosis with polyangiitis (Wegener's) (GPA) in Korean patients.

    METHODS The medical records of 45 patients with GPA treated in a single tertiary referral hospital were retrospectively analyzed with respect to clinical manifestations, including histology, ANCA positivity, disease stage, and disease activity. Patients were categorized into granulomatous, vasculitic, or mixed form based on an immunopathologic scoring system of granulomatous-vasculitic activity.

    RESULTS Thirty-one patients (68.9 %) showed ANCA positivity (C-ANCA/P-ANCA, 42.2 %/20.0 %, proteinase-3 (PR3) ANCA/myeloperoxidase (MPO) ANCA, 44.1 %/16.1 %), and these patients (female 48.4 %) were found to be associated with a higher frequency of renal involvement (51.6 vs. 7.1 %, p = 0.004), elevated serum creatinine (29.0 vs. 0 %, p = 0.018), and higher mortality (29 vs. 7.1 %, p = 0.041) than ANCA-negative patients. Thirty-three patients (73.3 %, female 60.6 %) had the granulomatous form, whereas 8.9 and 17.8 % had the vasculitic and mixed forms, respectively. Patients with the granulomatous form were diagnosed earlier in their lives (mean age 51.2 vs. 62.3, p = 0.002) and had a lower frequency of renal involvement (21.2 vs. 100 %, p = 0.005) compared with those with the vasculitic form. Initial remission (69.7 vs. 25.0 %) and relapse (60.8 vs. 0 %) rates were higher for the granulomatous than for the vasculitic form.

    CONCLUSIONS Taken together, in Korean patients with GPA, the granulomatous form was predominant and associated with a younger age at diagnosis and a lower frequency of renal involvement than the vasculitic form. ANCA positivity was found in 68.9 % and associated with renal involvement and higher mortality.

    PubMed IF 2.1 류마티스내과
24. 1892013

    제1저자 문재훈 · 교신저자 차봉수

    Moon JH, Kim HJ, Kim HM, Choi SH, Lim S, Park YJ, Jang HC, Cha BS

    Decreased expression of hepatic low-density lipoprotein receptor-related protein 1 in hypothyroidism: a novel mechanism of atherogenic dyslipidemia in hypothyroidism.

    Thyroid. 2013;23(9):1057-65.

    Abstract

    BACKGROUND The atherogenic effects of hypothyroidism on lipid metabolism could result, in part, from the reduced clearance of remnant lipoproteins. In this study, we investigated the expression of hepatic low-density lipoprotein receptor-related protein 1 (LRP1), a receptor for remnant lipoproteins, in hypothyroidism and the effect of 3,3',5-triiodo-L-thyronine (T3) treatment on hepatic LRP1 expression.

    METHODS C57BL/6 mice were fed a normal diet (control group) or a low-iodine diet supplemented with 0.15% propylthiouracil (PTU/LI group) for 4 weeks. Mice in the PTU/LI group were injected intraperitoneally with T3 (0, 30, and 150 μg/kg of body weight) for 7 days. HepG2 cells were incubated in fetal bovine serum or charcoal-stripped fetal bovine serum with various concentrations of T3. The expression and function of LRP1 in liver samples and cells were analyzed.

    RESULTS Hypothyroidism was successfully induced in PTU/LI mice. Hepatic LRP1 protein expression was lower in the PTU/LI group than in the control group. T3 treatment upregulated hepatic LRP1 protein expression in PTU/LI mice. LRP1 expression in HepG2 cells was reduced after incubation in the medium containing charcoal-stripped fetal bovine serum, which mimics hypothyroidism in vitro, and was recovered by T3 treatment. The protein expression of LRP1 in HepG2 cells was increased by T3 treatment in a dose-dependent manner up to 2.0 nM T3. However, LRP1 mRNA transcription was not affected by hypothyroidism conditions or T3 treatment, either in liver samples or in HepG2 cells. T3 treatment on HepG2 cells increased cellular uptake of lipid-conjugated apolipoprotein E through LRP1.

    CONCLUSIONS Our data demonstrate that hepatic LRP1 expression and function decrease in hypothyroidism and are regulated by the thyroid hormone. These results suggest that in hypothyroidism, decreased expression of hepatic LRP1 may be associated with reduced clearance of circulating remnant lipoproteins.

    PubMed IF 6.6 내분비대사내과
25. 1882013

    제1저자 이윤석 · 교신저자 황진혁

    Lee YS, Jang SE, Lee BS, Lee SJ, Lee MG, Park JK, Lee SH, Ryu JK, Kim YT, Yoon YB, Hwang JH

    Presence of coronary artery disease increases the risk of biliary events in patients with asymptomatic gallstones.

    J Gastroenterol Hepatol. 2013;28(9):1578-83.

    Abstract

    BACKGROUND AND AIM Propensity score indicates a probability of having a confounding factor. It is used to match each patient with the closest propensity score between two groups, which is known as propensity score matching. This study aimed to evaluate the gallstone-related biliary events, defined as biliary colic and acute cholecystitis between coronary artery disease (CAD) and non-CAD patients using propensity score matching.

    METHODS This retrospective cohort study evaluated 267 asymptomatic gallstone patients with CAD and 459 asymptomatic gallstone patients without CAD from March 2003 to December 2009 at two tertiary teaching hospitals in the Republic of Korea. After propensity score matching, total 378 patients, including 126 in study group (with CAD) and 252 in control group (without CAD), were evaluated.

    RESULTS During a median follow-up of 47 months, overall gallstone-related biliary event rate was 33.5% in the study group and 27.5% in the control group. The 5-year cumulative rates were 25.3% versus 17.7% in gallstone-related biliary event and 10.9% versus 1.6% in acute cholecystitis (study versus control group). After propensity score adjustment, the risk of gallstone-related biliary events in the CAD patients significantly increased (hazard ratio 2.11, 95% confidence interval 1.14-3.90, P = 0.017 in matched patients).

    CONCLUSION In patients with asymptomatic gallstones, the coexistence of CAD can increase the risk of gallstone-related biliary events, particularly acute cholecystitis. Therefore, gallstone patients with CAD should be carefully monitored, even if they are asymptomatic.

    PubMed IF 3.5 소화기내과
26. 1872013

    제1저자 박경우 · 교신저자 김효수

    Park KW, Kang SH, Park JJ, Yang HM, Kang HJ, Koo BK, Park BE, Cha KS, Rhew JY, Jeon HK, Shin ES, Oh JH, Jeong MH, Kim S, Hwang KK, Yoon JH, Lee SY, Park TH, Moon KW, Kwon HM, Chae IH, Kim HS

    Adjunctive cilostazol versus double-dose clopidogrel after drug-eluting stent implantation: the HOST-ASSURE randomized trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Safety & Effectiveness of Drug-Eluting Stents & Anti-platelet Regimen).

    JACC Cardiovasc Interv. 2013;6(9):932-42.

    Abstract

    OBJECTIVES This study sought to test the noninferiority of triple antiplatelet therapy (TAT) versus double-dose clopidogrel dual antiplatelet therapy (DDAT) in patients undergoing percutaneous coronary intervention (PCI).

    BACKGROUND Antiplatelet regimen is an integral component of medical therapy after PCI. A 1-week duration of doubling the dose of clopidogrel was shown to improve outcome at 1 month compared with the conventional dose in patients with acute coronary syndrome undergoing PCI. Yet in Asia, the addition of cilostazol is used more commonly than DDAT in high-risk patients.

    METHODS We randomly assigned 3,755 all-comers undergoing PCI to either TAT or DDAT, which was continued for 1 month, to test the noninferiority of TAT versus DDAT. The primary outcome was the cumulative incidence of net clinical outcome at 1 month post-PCI defined as the composite of cardiac death, nonfatal myocardial infarction, stent thrombosis, stroke, and PLATO (Platelet Inhibition and Patient Outcomes) major bleeding.

    RESULTS TAT was noninferior to DDAT with respect to the primary outcome, which occurred in 1.2% and 1.4% of patients, respectively (-0.22% absolute difference, 0.34% 1-sided 97.5% confidence interval, p = 0.0007 for noninferiority; hazard ratio: 0.85; 95% confidence interval: 0.49 to 1.48; p = 0.558 for superiority). The individual risks of cardiac death, nonfatal myocardial infarction, stent thrombosis, stroke, and PLATO major bleeding did not differ significantly between the 2 groups. There were no significant between-group differences in the treatment effect with regard to the rate of the primary outcome.

    CONCLUSIONS The adjunctive use of cilostazol was noninferior to doubling the dose of clopidogrel for 1 month in all-comers undergoing PCI with exclusively drug-eluting stents. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-SAfety & EffectiveneSS of Drug-ElUting Stents & Anti-platelet REgimen [HOST-ASSURE]; NCT01267734).

    PubMed IF 12.7 순환기내과
27. 1862013

    제1저자 박흥우 · 교신저자 조상헌

    Park HW, Kim TW, Song WJ, Kim SH, Park HK, Kim SH, Kwon YE, Kim TB, Lee BJ, Jee YK, Choi BW, Cho SH

    Prediction of asthma exacerbations in elderly adults: results of a 1-year prospective study.

    J Am Geriatr Soc. 2013;61(9):1631-2.

    PubMed IF 4.6 알레르기내과
28. 1852013

    제1저자 김재영 · 교신저자 김나영

    Kim J, Kim N, Park JH, Chang H, Kim JY, Lee DH, Kim JM, Kim JS, Jung HC

    The Effect of Helicobacter pylori on Epidermal Growth Factor Receptor-Induced Signal Transduction and the Preventive Effect of Celecoxib in Gastric Cancer Cells.

    Gut Liver. 2013;7(5):552-9.

    Abstract

    BACKGROUND/AIMS Helicobacter pylori infection induces cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) overexpression, and these factors may engage in cross-talk. The aim of the present study was to evaluate the effect of H. pylori on EGFR signaling pathways and to determine whether celecoxib has an inhibitory effect on this pathway.

    METHODS The AGS cell line was cocultured with H. pylori G27 and the isogenic cagE- mutant. The expression of COX-2, EGFR, heparin binding-epidermal growth factor (HB-EGF), and transforming growth factor-β (TGF-β) was measured by real time-polymerase chain reaction (RT-PCR). Next, Western blot analyses of COX-2, EGFR, total Akt, phosphorylated Akt (pAkt), and phosphorylated glycogen synthase kinase-3β (pGSK3β) were performed after incubating H. pylori-treated AGS cells for 24 hours with various concentrations of celecoxib (0, 10, 20, and 30 µmol/L).

    RESULTS H. pylori infection upregulated the mRNA levels of COX-2, EGFR, HB-EGF, and TGF-β, as detected by RT-PCR. However, AGS cells treated with cagE- mutants, which have a defective type IV secretion system, did not exhibit EGFR upregulation. Celecoxib had inhibitory effects on the H. pylori-induced overexpression of COX-2 (p=0.015), EGFR (p=0.025), pAkt (p=0.025), and pGSK3β (p=0.029) by Western blot analysis.

    CONCLUSIONS H. pylori with an intact type IV secretion system activated the COX-2 and EGFR-Akt pathways in the AGS cell line. As celecoxib exhibited inhibitory effects on the EGFR signaling pathway, the cross-talk of COX-2 and EGFR likely mediates H. pylori-induced gastric cancer.

    PubMed IF 4.1 소화기내과
29. 1842013

    제1저자 이윤종 · 교신저자 이은봉

    Lee YJ, Horie Y, Wallace GR, Choi YS, Park JA, Choi JY, Song R, Kang YM, Kang SW, Baek HJ, Kitaichi N, Meguro A, Mizuki N, Namba K, Ishida S, Kim J, Niemczyk E, Lee EY, Song YW, Ohno S, Lee EB

    Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease.

    Ann Rheum Dis. 2013;72(9):1510-6.

    Abstract

    OBJECTIVES To identify non-major histocompatibility complex susceptible genes that might contribute to Behçet's disease (BD).

    METHODS We performed a genome-wide association study using DNA samples from a Korean population consisting of 379 BD patients and 800 controls. A replication study was performed in a Japanese population (363 BD patients and 272 controls). To evaluate the functional implication of the target single nucleotide polymorphisms (SNP), gene expression levels in peripheral T cells, allele-specific modulation of promoter activity and biological effect of mRNA knockdown were investigated.

    RESULTS We found a novel association of BD to the GIMAP locus, mapped to chromosome 7q36.1 (rs1608157, p=6.01×10(-8) in a minor allele dominant model; rs11769828, allele based p=1.60×10(-6)). A fine mapping study identified an association with four additional SNP: rs1522596 (OR=1.45, p=7.70×10(-6)) in GIMAP4; rs10266069 (OR=1.32, p=2.67×10(-4)) and rs10256482 (OR=1.27, p=5.27×10(-4)) in GIMAP2; and rs2286900 (OR=1.61, p=3.53×10(-5)) in GIMAP1 areas. Replication study using DNA samples from the Japanese population validated the significant association between BD and the GIMAP locus. The GIMAP4 promoter construct plasmid with the minor allele of rs1608157 displayed significantly lower activity than one with the major allele. Moreover, CD4 T cells from BD patients showed a lower level of GIMAP4 mRNA, and GIMAP4 knockdown was protective against Fas-mediated apoptosis.

    CONCLUSIONS These results suggest that a GIMAP cluster is a novel susceptibility locus for BD, which is involved in T-cell survival, and T-cell aberration can contribute to the development of BD.

    PubMed IF 24 류마티스내과
30. 1832013

    제1저자 이승표 · 교신저자 박성지, 김용진

    Lee SP, Park SJ, Kim YJ, Chang SA, Park EA, Kim HK, Lee W, Lee SC, Park SW, Sohn DW, Choe YH

    Early detection of subclinical ventricular deterioration in aortic stenosis with cardiovascular magnetic resonance and echocardiography.

    J Cardiovasc Magn Reson. 2013;15(1):72.

    Abstract

    BACKGROUND Severe aortic stenosis (AS) patients with late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) or left ventricular (LV) systolic dysfunction are known to have worse outcome. We aimed to investigate whether LGE on CMR would be useful in early detection of subclinical LV structural and functional derangements in AS patients.

    METHODS 118 patients with moderate to severe AS were prospectively enrolled. Echocardiography and CMR images were taken and the patients were divided into groups according to the presence/absence of LGE and of LV systolic dysfunction (LV ejection fraction (EF) <50%). The stiffness of LV was calculated based on Doppler and CMR measurements.

    RESULTS Patients were grouped into either group 1, no LGE and normal LVEF, group 2, LGE but normal LVEF and group 3, LGE with depressed LVEF. There was a significant trend towards increasing LV volumes, worsening of LV diastolic function (E/e', diastolic elastance), systolic function (end-systolic elastance) and LV hypertrophy between the three groups, which coincided with worsening functional capacity (all p-value < 0.001 for trend). Also, significant differences in the above parameters were noted between group 1 and 2 (E/e', 14.6 ± 4.3 (mean ± standard deviation) in group 1 vs. 18.2 ± 9.4 in group 2; end-systolic elastance, 3.24 ± 2.31 in group 1 vs. 2.38 ± 1.16 in group 2, all p-value < 0.05). The amount of myocardial fibrosis on CMR correlated with parameters of diastolic (diastolic elastance, Spearman's ρ = 0.256, p-value = 0.005) and systolic function (end-systolic elastance, Spearman's ρ = -0.359, p-value < 0.001).

    CONCLUSIONS These findings demonstrate the usefulness of CMR for early detection of subclinical LV structural and functional deterioration in AS patients.

    PubMed IF 5 순환기내과

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