SCI 발표논문

1. 1932014

   제1저자 박정환 · 교신저자 진호준

   Park JH, Kim YC, Koo HS, Oh SW, Kim S, Chin HJ

   Estimated amount of 24-hour urine sodium excretion is positively correlated with stomach and breast cancer prevalence in Korea.

   J Korean Med Sci. 2014;29 Suppl 2(Suppl 2):S131-8.

   Abstract

   Stomach cancer is one of the most common cancers in Korea. The aim of this study was to identify the association between the prevalence of cancer, particularly stomach cancer, and the amount of 24-hr urine sodium excretion estimated from spot urine specimens. The study included 19,083 subjects who took part in the Korean National Health and Nutritional Examination Survey between 2009 and 2011. The total amount of urine sodium excreted in a 24-hr period was estimated by using two equations based on the values for spot urine sodium and creatinine. In subjects who had an estimated 24-hr urine sodium excretion of more than two standard deviations above the mean (group 2), the prevalence of stomach cancer was higher than in subjects with lower 24-hr sodium excretion (group 1). By using the Tanaka equation to estimate it, the prevalence of stomach cancer was 0.6% (114/18,331) in group 1, whereas it was 1.6% (9/568) in group 2 (P=0.006). By using the Korean equation, the prevalence was 0.6% (115/18,392) in group 1, and 1.6% in group 2 (8/507) (P=0.010). By using the Tanaka equation, breast cancer in women is more prevalent in group 2 (1.9%, 6/324) than group 1 (0.8%, 78/9,985, P=0.039). Higher salt intake, as defined by the estimated amount of 24-hr urine sodium excretion, is positively correlated with a higher prevalence of stomach or breast cancer in the Korean population.

   PubMed IF 3.2 신장내과
2. 1922014

   제1저자 안신영 · 교신저자 진호준

   Ahn SY, Kim S, Kim DK, Park JH, Shin SJ, Lee SH, Choi BS, Lim CS, Kim S, Chin HJ

   Urinary sodium excretion has positive correlation with activation of urinary renin angiotensin system and reactive oxygen species in hypertensive chronic kidney disease.

   J Korean Med Sci. 2014;29 Suppl 2(Suppl 2):S123-30.

   Abstract

   It is not well described the pathophysiology of renal injuries caused by a high salt intake in humans. The authors analyzed the relationship between the 24-hr urine sodium-to-creatinine ratio (24HUna/cr) and renal injury parameters such as urine angiotensinogen (uAGT/cr), monocyte chemoattractant peptide-1 (uMCP1/cr), and malondialdehyde-to-creatinine ratio (uMDA/cr) by using the data derived from 226 hypertensive chronic kidney disease patients. At baseline, the 24HUna/cr group or levels had a positive correlation with uAGT/cr and uMDA/cr adjusted for related factors (P<0.001 for each analysis). When we estimated uAGT/cr in the 24HUna/cr groups by ANCOVA, the uAGT/cr in patients with ≥200 mEq/g cr was higher than in patients with <100 mEq/g cr (708 [95% CI, 448-967] vs. 334 [95% CI, 184-483] pg/mg cr, P=0.014). Similarly, uMDA/cr was estimated as 0.17 (95% CI, 0.14-0.21) pM/mg cr in patients with <100 mEq/g cr and 0.27 (95% CI, 0.20-0.33) pM/mg cr in patients with ≥200 mEq/g cr (P=0.016). During the 16-week follow-up period, an increase in urinary sodium excretion predicted an increase in urinary angiotensinogen excretion. In conclusion, high salt intake increases renal renin-angiotensin-system (RAS) activation, primarily, and directly or indirectly affects the production of reactive oxygen species through renal RAS activation.

   PubMed IF 3.2 신장내과
3. 1912014

   제1저자 구호석 · 교신저자 진호준

   Koo HS, Kim YC, Ahn SY, Oh SW, Kim S, Chin HJ

   Analysis of correlation between 24-hour urinary sodium and the degree of blood pressure control in patients with chronic kidney disease and non-chronic kidney disease.

   J Korean Med Sci. 2014;29 Suppl 2(Suppl 2):S117-22.

   Abstract

   We investigated the association between 24-hr urinary sodium (24UNA) and adequacy of blood pressure (BP) control in patients with chronic kidney disease (CKD) and nonCKD. All data were collected retrospectively by accessing the electrical medical records in patients with 24-hr urine collection and serum creatinine. Enrolled 400 subjects were subgrouped by the amount of 24UNA, or CKD stage. The appropriate BP was defined as BP < 130/80 mmHg for subjects with proteinuria, and BP < 140/90 mmHg for subjects without proteinuria. The mean level of 24UNA was 166±76 mEq/day. The 24UNA group was an independently related factor to diastolic BP as a continuous variable. The rate of appropriate BP control in patients with proteinuria was highest in 24UNA <100 mEq/L (P=0.012). The odds to fail achievement of BP target in subjects with 24UNA≥90 mEq/day was 2.441 (1.249-4.772, P=0.009) higher than that of 24UNA <90 mEq/day among participants with proteinuria. There was difference in the amount of 24UNA between CKD and non-CKD except each stage of CKD group. In conclusion, salt intake estimated by 24-hr urine sodium excretion is a risk factor to achieve appropriate BP control.

   PubMed IF 3.2 신장내과
4. 1902014

   제1저자 오지은 · 교신저자 진호준

   Oh J, Lee J, Koo HS, Kim S, Chin HJ

   Estimated 24-hour urine sodium excretion is correlated with blood pressure in Korean population: 2009-2011 Korean National Health and Nutritional Examination Survey.

   J Korean Med Sci. 2014;29 Suppl 2(Suppl 2):S109-16.

   Abstract

   No large-scale studies have investigated the association between salt intake and hypertension in Korean population. To investigate the relationship of blood pressure to salt consumption, we analyzed data from 19,476 participants in the 2009-2011 Korean National Health and Nutritional Examination Survey (KNHANES). Urinary sodium excretion over 24-hr (24HUNa) was estimated from spot urine tests using Tanaka's equation. The study subjects were stratified into hypertensive and normotensive groups. Hypertensive participants (n=6,552, 33.6%) had higher estimated 24HUNa, 150.4±38.8 mEq/day, than normotensive participants, 140.5±34.6 mEq/day (P<0.001). The association between 24HUNa and blood pressure outcomes was not affected by adjustment for other risk factors for hypertension (odds ratio 0.001; 95% confidence interval 0.001-0.003; P<0.001). Increases in 24HUNa of 100 mEq/day were associated with a 6.1±0.3/2.9±0.2 mmHg increase in systolic/diastolic blood pressure in all participants. This effect was stronger in hypertensive participants (increase of 8.1±0.5/3.4±0.3 mmHg per 100 mEq/day) and smaller in normotensive participants (2.9±0.3/1.3±0.2 mmHg). These results support recommendations for low salt intake in Korean population to prevent and control adverse blood pressure levels.

   PubMed IF 3.2 신장내과
5. 1892014

   제1저자 이하정 · 교신저자 진호준

   Lee H, Cho HJ, Bae E, Kim YC, Kim S, Chin HJ

   Not salt taste perception but self-reported salt eating habit predicts actual salt intake.

   J Korean Med Sci. 2014;29 Suppl 2(Suppl 2):S91-6.

   Abstract

   Excessive dietary salt intake is related to cardiovascular morbidity and mortality. Although dietary salt restriction is essential, it is difficult to achieve because of salt palatability. However, the association between salt perception or salt eating habit and actual salt intake remains uncertain. In this study, we recruited 74 healthy young individuals. We investigated their salt-eating habits by questionnaire and salt taste threshold through a rating scale that used serial dilution of a sodium chloride solution. Predicted 24-hr urinary salt excretions using Kawasaki's and Tanaka's equations estimated dietary salt intake. Participants' mean age was 35 yr, and 59.5% were male. Salt sense threshold did not show any relationship with actual salt intake and a salt-eating habit. However, those eating "salty" foods showed higher blood pressure (P for trend=0.048) and higher body mass index (BMI; P for trend=0.043). Moreover, a salty eating habit was a significant predictor for actual salt intake (regression coefficient [β] for Kawasaki's equation 1.35, 95% confidence interval [CI] 10-2.69, P=0.048; β for Tanaka's equation 0.66, 95% CI 0.01-1.31, P=0.047). In conclusion, a self-reported salt-eating habit, not salt taste threshold predicts actual salt intake.

   PubMed IF 3.2 신장내과
6. 1882014

   제1저자 김용철 · 교신저자 진호준

   Kim YC, Koo HS, Kim S, Chin HJ

   Estimation of daily salt intake through a 24-hour urine collection in Pohang, Korea.

   J Korean Med Sci. 2014;29 Suppl 2(Suppl 2):S87-90.

   Abstract

   There is an established relationship between a high salt diet and public health problems, especially hypertension and cardiovascular disease. We estimated daily salt intake in a group of adults and assessed its association with related variables in Pohang, Korea. We conducted a cross-sectional survey in 2013 with 242 adults. Urine was collected for 24 hr to estimate daily salt intake, and questionnaires about salt preference were administered. The mean daily salt intake was 9.9±4.6 g. There was no difference in salt intake between high systolic blood pressure (SBP) participants and normal SBP participants (10.5±4.7 g/d vs. 9.6±4.3 g/d, P=0.339), but high diastolic blood pressure (DBP) participants reported more salt intake than normal DBP participants (10.4±4.9 g/d vs. 9.7±4.1 g/d, P=0.049). Salt intake and body mass index demonstrated a positive correlation (P=0.001). A preference for Korean soup or stew was associated with high salt intake (P=0.038). Dietary salt intake in Korean adults is still higher than the recommendation from the World Health Organization. More efforts should be made to reduce the salt consumption of Korean adults.

   PubMed IF 3.2 신장내과
7. 1872014

   제1저자 오세원 · 교신저자 나기영

   Oh SW, Lee YM, Kim S, Chin HJ, Chae DW, Na KY

   Cobalt chloride attenuates oxidative stress and inflammation through NF-κB inhibition in human renal proximal tubular epithelial cells.

   J Korean Med Sci. 2014;29 Suppl 2(Suppl 2):S139-45.

   Abstract

   We evaluated the effect of cobalt chloride (CoCl2) on TNF-α and IFN-γ-induced-inflammation and reactive oxygen species (ROS) in renal tubular epithelial cells (HK-2 cells). We treated HK-2 cells with CoCl2 before the administration of TNF-α/IFN-γ. To regulate hemeoxygenase-1 (HO-1) expression, the cells were treated CoCl2 or HO-1 siRNA. CoCl2 reduced the generation of ROS induced by TNF-α/IFN-γ. TNF-α/IFN-γ-treated-cells showed an increase in the nuclear translocation of phosphorylated NF-κBp65 protein, the DNA-binding activity of NF-κBp50 and NF-κB transcriptional activity and a decrease in IκBα protein expression. These changes were restored by CoCl2. We noted an intense increase in monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normal T cell expressed and secreted (RANTES) production in TNF-α/IFN-γ-treated cells. We demonstrated that this effect was mediated through NF-κB signaling because an NF-κB inhibitor significantly reduced MCP-1 and RANTES production. CoCl2 effectively reduced MCP-1 and RANTES production. The expression of HO-1 was increased by CoCl2 and decreased by HO-1 siRNA. However, knockdown of HO-1 by RNA interference did not affect MCP-1 or RANTES production. We suggest that CoCl2 has a protective effect on TNF-α/IFN-γ-induced inflammation through the inhibition of NF-κB and ROS in HK-2 cells. However, CoCl2 appears to act in an HO-1-independent manner.

   PubMed IF 3.2 신장내과
8. 1862014

   제1저자 정승민, 변영상 · 교신저자 정숙향

   Chung SM, Byoun YS, Kim HS, Jang ES, Kim JW, Jeong SH

   The feasibility of discontinuing lamivudine in lamivudine-resistant chronic hepatitis B patients on lamivudine and adefovir combination therapy.

   Intervirology. 2014;57(6):337-43.

   Abstract

   OBJECTIVES This study investigated the antiviral efficacy of adefovir (ADV) rescue therapy and the feasibility of lamivudine (LAM) discontinuation in LAM-resistant chronic hepatitis B (CH-B) patients who had attained a virological response (VR) with LAM + ADV combination therapy.

   METHODS The VR and virological breakthrough (VBT) were analyzed in 106 consecutively enrolled LAM-resistant CH-B patients who received ADV rescue therapy during a mean follow-up period of 55.2 months. Seventy-four patients achieved VR, and were divided into the LAM-discontinuation group (n = 39) and the LAM-continuation group (n = 35). The VR and VBT between the 2 groups were compared.

   RESULTS For all 106 LAM-resistant CH-B patients, the overall cumulative probabilities of VR at 1, 2, 3 and 5 years of ADV rescue therapy were 40.6, 55.7, 64.6 and 81.3%, respectively. The cumulative probabilities of VBT at 1, 2, 3 and 5 years were 0, 2.9, 8.8 and 13.9%, respectively. Whether they discontinued or continued LAM after achieving VR on LAM + ADV therapy, VR and VBT were not significantly different during a mean follow-up period of 40.4 months.

   CONCLUSIONS There was a good long-term VR with ADV rescue therapy for LAM-resistant CH-B patients. Moreover, discontinuing LAM was found to be feasible for patients who attained VR during ADV + LAM therapy.

   PubMed IF 1.8 소화기내과
9. 1852014

   제1저자 김세훈 · 교신저자 강혜련, 조상헌

   Kim SH, Park DE, Lee HS, Kang HR, Cho SH

   Chronic low dose chlorine exposure aggravates allergic inflammation and airway hyperresponsiveness and activates inflammasome pathway.

   PLoS One. 2014;9(9):e106861.

   Abstract

   BACKGROUND Epidemiologic clinical studies suggested that chronic exposure to chlorine products is associated with development of asthma and aggravation of asthmatic symptoms. However, its underlying mechanism was not clearly understood. Studies were undertaken to define the effects and mechanisms of chronic low-dose chlorine exposure in the pathogenesis of airway inflammation and airway hyperresponsiveness (AHR).

   METHODS Six week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low dose chlorine exposure of naturally vaporized gas of 5% sodium hypochlorite solution. Airway inflammation and AHR were evaluated by bronchoalveolar lavage (BAL) cell recovery and non-invasive phlethysmography, respectively. Real-time qPCR, Western blot assay, and ELISA were used to evaluate the mRNA and protein expressions of cytokines and other inflammatory mediators. Human A549 and murine epithelial (A549 and MLE12) and macrophage (AMJ2-C11) cells were used to define the responses to low dose chlorine exposure in vitro.

   RESULTS Chronic low dose chlorine exposure significantly augmented airway inflammation and AHR in OVA-sensitized and challenged mice. The expression of Th2 cytokines IL-4 and IL-5 and proinflammatory cytokine IL-1β and IL-33 were significantly increased in OVA/Cl group compared with OVA group. The chlorine exposure also activates the major molecules associated with inflammasome pathway in the macrophages with increased expression of epithelial alarmins IL-33 and TSLP in vitro.

   CONCLUSION Chronic low dose exposure of chlorine aggravates allergic Th2 inflammation and AHR potentially through activation of inflammasome danger signaling pathways.

   PubMed IF 2.8 알레르기내과
10. 1842014

    제1저자 박진균 · 교신저자 박은아

    Park JK, Park EA, Lee W, Kim YK, Lee EY, Song YW, Lee EB

    Baseline MRA predicts the treatment response to vasodilator udenafil in patients with secondary Raynaud's phenomenon.

    Clin Exp Rheumatol. 2014;32(6 Suppl 86):S-167-70.

    Abstract

    OBJECTIVES High-resolution MR angiography (HR-MRA) demonstrates blood flow in the digital arteries, which correlates with the severity of Raynaud's phenomenon (RP). This study investigates whether baseline HR-MRA of the hand can predict the treatment response to udenafil, a new PDE5-inhibitor, in patients with secondary RP.

    METHODS Baseline MRA and Doppler ultrasound were obtained in 12 patients with secondary RP. The patients were treated with udenafil 100 mg/day for 4 weeks and changes in blood flow were measured. Blood flow on MRA was scored on a 4-point scale: 0, no visible flow; 1, visible flow to the proximal phalanx; 2, to the middle phalanx; and 3, to the distal phalanx. Peak systolic velocity (PSV) was measured to determine blood flow. Paired t-test and ANOVA were used to determine the treatment response of the different MRA scores.

    RESULTS On baseline MRA, 53.3% of digital arteries had an MRA score of 0, 25.8% MRA score of 1, 9.2% MRA score of 2, and 11.6% MRA score of 3. Overall, 4-week udenafil treatment improved digital flow (p<0.05) in all MRA scores. Digital arteries with MRA score 2 showed the best response with improvement in PSV by 14.5 mm/sec (p<0.01), whereas improvement in arteries of MRA scores 1 and 3 were not better than an MRA score of 0 (all, p>0.05).

    CONCLUSIONS Digital arteries with moderate blood flow observed on MRA respond best to treatment with udenalfil. Therefore, baseline MRA may help predict treatment response in patients with secondary RP.

    PubMed IF 3.2 류마티스내과
11. 1832014

    제1저자 이세훈 · 교신저자 이세훈

    Lee SH, Bang YJ, Mainwaring P, Ng C, Chang JW, Kwong P, Li RK, Sriuranpong V, Toh CK, Yuan J, Pitman Lowenthal S, Chung HC

    Sunitinib in metastatic renal cell carcinoma: an ethnic Asian subpopulation analysis for safety and efficacy.

    Asia Pac J Clin Oncol. 2014;10(3):237-45.

    Abstract

    AIMS We evaluated and compared the safety and efficacy of sunitinib in Asian and non-Asian patients with metastatic renal cell carcinoma enrolled in a previously reported global expanded access program.

    METHODS Previously treated and treatment-naïve patients received open-label sunitinib at a starting dose of 50 mg/day for 4 weeks, followed by 2 weeks off treatment, in repeated 6-week cycles. Safety was assessed regularly, tumor measurements were performed per local practice, and survival data collected where possible.

    RESULTS Data were available for 212 Asian patients from Asian sites (Asian-A), 113 Asian patients from non-Asian sites (Asian-O) and 4046 non-Asian patients. The most common grade 3/4 treatment-related adverse events were neutropenia, thrombocytopenia, hand-foot syndrome, diarrhea, asthenia and fatigue. The incidence of many adverse events was greater in Asian-A than in Asian-O or non-Asian patients. Sunitinib efficacy was comparable between Asian and non-Asian patients, with an objective response rate of 18% versus 14%; median progression-free survival of 8.7 versus 10.9 months; and overall survival of 18.9 versus 18.4 months, respectively.

    CONCLUSIONS Sunitinib demonstrated tolerable safety and similar efficacy in Asian and non-Asian patients. Geographic differences in the reported frequency of specific adverse events were noted across Asian patients.

    PubMed IF 2.1 혈액종양내과
12. 1822014

    제1저자 김유정 · 교신저자 허대석

    Kim YJ, Kim SJ, Lee JK, Choi WS, Park JH, Kim HJ, Sim SH, Lee KW, Lee SH, Kim JH, Kim DW, Lee JS, Bang YJ, Heo DS

    Prediction of survival in terminally ill cancer patients at the time of terminal cancer diagnosis.

    J Cancer Res Clin Oncol. 2014;140(9):1567-74.

    Abstract

    PURPOSE We aimed to investigate the prognostic factors that can predict terminal stage survival (TSS) at the time of terminal cancer diagnosis.

    METHODS We prospectively evaluated 141 patients immediately after the diagnosis of terminal cancer by their attending oncologists. A total of 32 factors, including performance status, clinical prediction of survival, time to terminal cancer (TTC), clinical symptoms, signs, and laboratory tests including the neutrophil-lymphocyte ratio (NLR), were analyzed. TSS was defined as the time from the diagnosis of terminal cancer to death.

    RESULTS The mean age of the 141 patients studied was 58.7 years, and 53 were female (38 %). The median TSS was 1.7 months (95 % confidence interval [CI] 1.43-1.97). In the univariate analyses, the TSS was significantly associated with 16 of the 32 factors tested. In the multivariate analysis, a lower Karnofsky performance status (KPS), a shorter TTC (<24 months), a high NLR (≥5), and a high C-reactive protein (CRP) level (≥10 mg/dL) were independently associated with a poorer prognosis. A scoring system (scale, 0-6) developed based on the multivariate analysis could be used to classify terminal cancer patients into better (0-2 points; TSS 3.9 months), intermediate (3-4 points; TSS 1.7 months), or worse (5-6 points; TSS 0.9 month, P < 0.001) prognosis.

    CONCLUSION The median TSS after the diagnosis of terminal cancer in advanced cancer patients was 1.7 months. The scoring system using KPS, TTC, NLR, and CRP could predict TSS in these patients.

    PubMed IF 3.3 혈액종양내과
13. 1812014

    제1저자 박준원 · 교신저자 이은봉

    Park JW, Moon SY, Lee JH, Park JK, Lee DS, Jung KC, Song YW, Lee EB

    Bone marrow analysis of immune cells and apoptosis in patients with systemic lupus erythematosus.

    Lupus. 2014;23(10):975-85.

    Abstract

    OBJECTIVES To examine the immune cell profile in the bone marrow of systemic lupus erythematosus (SLE) patients and to assess its clinical relevance.

    METHODS Sixteen bone marrow samples from 14 SLE patients were compared with seven healthy control samples. The numbers of immune cells and apoptotic cells in the bone marrow were examined by immunohistochemistry. The association between immune cell subsets and clinical features was investigated.

    RESULTS CD4+ T cells, macrophages and plasma cells were more common in the bone marrow of SLE patients than in healthy controls (p=0.001, p=0.004 and p<0.001, respectively). Greater numbers of CD4+ T cells and macrophages were associated with high-grade bone marrow damage. The percentage of apoptotic cells in bone marrow of SLE patients was significantly higher than that in controls (p<0.001) and was positively correlated with the number of plasmacytoid dendritic cells (p=0.013). Increased number of plasma cells along with high interleukin-6 expression was correlated with anti-double stranded DNA antibody levels and the SLE disease activity index (p=0.031 and 0.013, respectively).

    CONCLUSION Bone marrow from SLE patients showed a distinct immune cell profile and increased apoptosis. This, coupled with a correlation with disease activity, suggests that the bone marrow may play a critical role in the pathogenesis of SLE.

    PubMed IF 1.8 류마티스내과
14. 1802014

    제1저자 정현섭 · 교신저자 윤성수

    Cheong HS, Koh Y, Ahn KS, Lee C, Shin HD, Yoon SS

    NT5C3 polymorphisms and outcome of first induction chemotherapy in acute myeloid leukemia.

    Pharmacogenet Genomics. 2014;24(9):436-41.

    Abstract

    AIMS The cytosolic 5'-nucleotidase-III (NT5C3) is involved in the metabolism of the nucleoside analog, cytosine arabinose (AraC), and the expression level of NT5C3 is correlated with sensitivity to AraC in acute myeloid leukemia (AML) patients. The current study examined whether the NT5C3 polymorphisms could affect chemotherapy outcomes in 103 Korean AML patients.

    METHODS Forty-seven single nucleotide polymorphisms in NT5C3 were genotyped using the Illumina GoldenGate genotyping assay. The genetic effects of the polymorphisms on the outcome of chemotherapy were analyzed using χ and logistic regression models.

    RESULTS Although none of the NT5C3 polymorphisms was associated with a complete remission rate, a common single nucleotide polymorphism, rs3750117, showed a significant association with induction rate after the first course of chemotherapy (Pcorr=0.004 and odds ratio=11.28) in AML patients. In addition, NT5C3 expression levels were significantly increased in patients with risk allele homozygote.

    CONCLUSIONS The data suggest that genotyping the NT5C3 polymorphism may have the potential to identify patients more likely to respond to AraC-based chemotherapy.

    PubMed IF 1.6 혈액종양내과
15. 1792014

    제1저자 최지민 · 교신저자 임종필

    Choi JM, Lee C, Han YM, Lee M, Choi YH, Jang DK, Im JP, Kim SG, Kim JS, Jung HC

    Long-term oncologic outcomes of endoscopic stenting as a bridge to surgery for malignant colonic obstruction: comparison with emergency surgery.

    Surg Endosc. 2014;28(9):2649-55.

    Abstract

    BACKGROUND Self-expandable metallic stents (SEMS) are now regarded as an effective and safe intervention for malignant colorectal obstruction (MCO). However, manipulation of the tumor might lead to the spillage of tumor cells and result in distant metastases. We aimed to compare the long-term oncologic outcomes of SEMS as a bridge to surgery with those of emergency surgery for MCO.

    METHODS Between June 2005 and December 2011, 60 patients who underwent elective curative resection after endoscopic SEMS insertion were included in the "SEMS group". The SEMS group was matched to 180 patients who underwent emergency curative surgery for MCO during the same period ["Emergency surgery (ES) group"]. The clinicopathologic characteristics, recurrence-free survival (RFS), and overall survival (OS) were compared between the two groups.

    RESULTS There were no significant differences in demographics, tumor stage, location, and histology between the SEMS group and the ES group. The median follow-up times were 41.4 months (IQR, 22.2-60.0 months) for the SEMS group and 45.0 months (IQR, 20.9-68.1 months) for the ES group. The proportions of patients who received postoperative adjuvant chemotherapy were comparable (SEMS group vs. ES group, 68.3 % vs. 77.8 %; P = 0.210). The long-term prognosis did not significantly differ between two groups in either the 5-year RFS rate (79.6 % vs. 70.2 %; P = 0.218) or the 5-year OS rate (97.8 % vs. 94.3 %; P = 0.469).

    CONCLUSIONS Long-term oncologic outcomes of SEMS insertion as a bridge to surgery were comparable to those of primary curative surgery.

    PubMed IF 3.3 소화기내과
16. 1782014

    제1저자 김혜원 · 교신저자 이은봉

    Kim HW, Park JK, Yang JA, Yoon YI, Lee EY, Song YW, Kim HR, Lee EB

    Comparison of tuberculosis incidence in ankylosing spondylitis and rheumatoid arthritis during tumor necrosis factor inhibitor treatment in an intermediate burden area.

    Clin Rheumatol. 2014;33(9):1307-12.

    Abstract

    Clinical characteristics of antitumor necrosis factor (TNF) agents-related tuberculosis (TB) in ankylosing spondylitis (AS) are not well described. The aim was to compare the incidences and the characteristics of TB in AS and rheumatoid arthritis (RA) during TNF inhibitor treatment. AS (n = 1,322) and RA (n = 3,154) patients who received medical care between January 2001 and August 2011 were enrolled. The incidence of TB in patients treated, or not, with TNF inhibitors and the clinical features associated with TB were explored. Seven patients with AS and seven with RA developed TB while receiving TNF inhibitor therapy, resulting in an incidence rate of 600.2/100,000 person-years (PYs) (95 % confidence interval (CI), 241.3-1236.3) for those with AS and 771.6/100,000 PYs (95 % CI, 310.2-1589.9) for those with RA. Incidence rate ratios for TNF inhibitor-treated vs. untreated patients were 4.87 for AS (95 % CI, 1.50-15.39; p < 0.001) and 3.61 for RA (95 % CI, 1.38-8.07; p < 0.001). Low body mass index was identified as a significant risk factor for TB in the AS group (odds ratio (OR), 13.0; p = 0.002). Extrapulmonary TB was predominant at 85.7 % during TNF inhibitor treatment. Three (42.8 %) of the AS patients, but none of the RA patients, developed TB with concomitant isoniazid. All AS patients recovered from TB whereas two of seven RA patients died. Treatment with TNF inhibitors significantly increases the risk of extrapulmonary TB in AS. Symptoms of infection should warrant clinicians to evaluate for TB during TNF inhibitor therapy in AS patients.

    PubMed IF 2.7 류마티스내과
17. 1772014

    제1저자 임수 · 교신저자 Meigs JB

    Lim S, Meigs JB

    Links between ectopic fat and vascular disease in humans.

    Arterioscler Thromb Vasc Biol. 2014;34(9):1820-6.

    Abstract

    The average of overweight individual can have differential fat depots in target organs or specific compartments of the body. This ectopic fat distribution may be more of a predictive factor for cardiovascular risk than obesity. Abdominal visceral obesity, a representative ectopic fat, is robustly associated with insulin resistance and cardiovascular risk. Fat depots in the liver and muscle tissue cause adverse cardiometabolic risk by affecting glucose and lipid metabolism. Pericardial fat and perivascular fat affect coronary atherosclerosis, cardiac function, and hemodynamics. Fat around the neck is associated with systemic vascular resistance. Fat around the kidney may increase blood pressure and induce albuminuria. Fat accumulation in or around the pancreas alters glucose metabolism, conferring cardiovascular risk. Ectopic fat may act as an active endocrine and paracrine organ that releases various bioactive mediators that influence insulin resistance, glucose and lipid metabolism, coagulation, and inflammation, which all contribute to cardiovascular risk. Because both obese and apparently lean individuals can have ectopic fat, regional fat distribution may play an important role in the development of cardiovascular diseases in both nonobese and obese people.

    PubMed IF 8.8 내분비대사내과
18. 1762014

    제1저자 임수 · 교신저자 장학철

    Lim S, Choi SH, Kim KM, Choi SI, Chun EJ, Kim MJ, Park KS, Jang HC, Sattar N

    The association of rate of weight gain during early adulthood with the prevalence of subclinical coronary artery disease in recently diagnosed type 2 diabetes: the MAXWEL-CAD study.

    Diabetes Care. 2014;37(9):2491-9.

    Abstract

    OBJECTIVE To investigate the association of the rate of weight gain (Ratemax_wt) between the age of 20 years and the age of maximum lifetime weight gain with indicators of subclinical coronary artery disease (CAD) at the time of diagnosis of type 2 diabetes (T2D).

    RESEARCH DESIGN AND METHODS We studied 1,724 consecutive Korean subjects aged ≥30 years with recently diagnosed (within 3 months) T2D and one or more cardiovascular risk factors to investigate the association of Ratemax_wt with subclinical CAD. We used 64-slice cardiac computed tomography angiography to evaluate the degree of coronary artery stenosis, multivessel involvement, plaque characteristics, and coronary artery calcium score (CACS). Body weight at age 20 years (Wt20y) was obtained from participant records. Participants recalled their maximum weight (Wtmax) before T2D diagnosis and age at maximum weight (Agemax_wt). The Ratemax_wt was calculated as (Wtmax - Wt20y) / (Agemax_wt - 20 years).

    RESULTS The prevalence of coronary artery stenosis (≥50%), multivessel involvement (two or more vessels), plaque characteristics, and CACS ≥100 were 11.4%, 6.6%, 19.7%, and 12.8%, respectively. Mean Wt20y and Wtmax were 60.1 ± 10.5 and 73.0 ± 11.5 kg, respectively. Mean Agemax_wt was 41.3 ± 10.7 years, and Ratemax_wt was 0.59 ± 0.56 kg/year. After adjusting for cardiovascular risk factors, including current BMI, the highest quarter of prior weight gain was significantly associated with coronary artery stenosis, multivessel involvement, and plaque characteristics, particularly mixed and noncalcified plaque.

    CONCLUSIONS The findings suggest that a greater rate of prior weight gain may accelerate the development of subclinical vascular complications in patients with newly diagnosed T2D.

    PubMed IF 22.6 내분비대사내과
19. 1752014

    제1저자 이정원 · 교신저자 김나영

    Lee JW, Kim N, Nam RH, Park JH, Choi YJ, Kim JM, Kim JS, Jung HC

    GenoType HelicoDR test in the determination of antimicrobial resistance of Helicobacter pylori in Korea.

    Scand J Gastroenterol. 2014;49(9):1058-67.

    Abstract

    OBJECTIVE Antimicrobial resistance of Helicobacter pylori is most important factor in eradication success. GenoType HelicoDR test has been developed for rapid detection of antimicrobial resistance. The present study evaluated the clinical usefulness of GenoType HelicoDR test in Korea.

    MATERIALS AND METHODS To detect 23S rRNA for clarithromycin resistance and gyrA mutations for fluoroquinolone resistance, both DNA sequencing after minimal inhibitory test (MIC) and GenoType HelicoDR test were performed in H. pylori isolates from the gastric mucosa of 101 patients. The eradication results of clarithromycin and moxifloxacin-containing triple therapy were evaluated by the 23S rRNA and gyrA mutations.

    RESULTS For 42 isolates with A2143G mutation by GenoType HelicoDR, 83.3% (35/42) of concordance rate was estimated with DNA sequencing method and 85.7% (36/42) for MIC test. For 43 isolates with N87K mutation by GenoType HelicoDR, 71.1% (31/43) of concordance rate was estimated with DNA sequencing and 88.4% (38/43) for MIC test. The sensitivity and specificity of GenoType HelicoDR test in determination of 23S rRNA mutation were 94.9% and 87.1%, and those of gyrA 98.2% and 80.0%. The sensitivity and specificity of GenoType HelicoDR test in determination of clarithromycin resistance based on MIC test were 55.0% and 80.0%, for fluoroquinolone 74.4% and 70.0%.

    CONCLUSION GenoType HelicoDR test is useful to determine mutations responsible for clarithromycin or fluoroquinolone-containing eradication failure but has a limitation for the clinical applicability in determination of resistance.

    PubMed IF 1.8 소화기내과
20. 1742014

    제1저자 최영훈, 고성준 · 교신저자 김병관

    Choi YH, Koh SJ, Kim JW, Kim BG, Lee KL, Im JP, Kim JS, Jung HC

    Do we need colonoscopy following acute diverticulitis detected on computed tomography to exclude colorectal malignancy?

    Dig Dis Sci. 2014;59(9):2236-42.

    Abstract

    BACKGROUND Although colonoscopy verification is warranted after an acute event of diverticulitis to exclude underlying malignancy, little evidence is available to support the recommendations.

    AIM The aim of this study was to examine whether subsequent colonoscopy is warranted in patients with diverticulitis on computed tomography (CT).

    METHODS The study was composed of patients diagnosed with acute diverticulitis on CT scan from January 2001 to March 2013. Patients who had subsequent colonoscopy within a year from the date of CT were included. For each diverticulitis case, two age- (± 5 years) and sex-matched controls were identified from healthy individuals who had received screening colonoscopy. We evaluated the diagnostic yield of advanced colonic neoplasia in colonoscopy.

    RESULTS One hundred and forty-nine patients underwent subsequent colonoscopy within a year from the date of CT. Among the patients, 11 (7.4 %) had colon cancer and 5 (3.4 %) had advanced adenoma. A case-control study revealed that the odds of detecting an advanced neoplasia among patients with diverticulitis on CT were approximately 8.8 times greater than in the age- and sex-matched controls [OR 8.84; 95 % CI 2.90-26.96; p < 0.001]. On analysis of the diverticulitis group, age (≥ 50 years) is an independent risk factor for detecting advanced colonic neoplasia.

    CONCLUSIONS The yield of advanced colonic neoplasia was substantially higher in patients with acute diverticulitis than in asymptomatic, average-risk individuals. Colonoscopy verification is warranted in patients with diverticulitis detected on CT, especially in those aged 50 years or older.

    PubMed IF 2.8 소화기내과
21. 1732014

    제1저자 송우정 · 교신저자 조상헌

    Song WJ, Kim JY, Jo EJ, Lee SE, Kim MH, Yang MS, Kang HR, Park HW, Chang YS, Min KU, Cho SH

    Capsaicin cough sensitivity is related to the older female predominant feature in chronic cough patients.

    Allergy Asthma Immunol Res. 2014;6(5):401-8.

    Abstract

    PURPOSE The present study aimed to examine the age and gender distributions among chronic cough patients referred to a tertiary cough clinic in Korea, and to investigate clinical factors related to the demographic findings.

    METHODS Study participants were unselectively recruited from adult chronic cough patients who attended the cough clinic for the first time during one year. To validate their representativeness, their age and gender distributions were compared to the entire chronic cough population, or with those presenting with other chronic disease. Data from the baseline investigations were analyzed to identify clinical factors related to the demographic findings.

    RESULTS A total of 272 chronic cough patients were included. They had a middle-aged female predominant feature (mean age: 52.8±15.7 years and female 69.1%). Their age and gender distributions were almost identical to the entire chronic cough population, but were distinct from patients with hypertension. Among clinical factors, the older female predominance was associated with enhanced capsaicin cough sensitivity, and also with the presence of 'cough by cold air' symptom. Allotussia and laryngeal paresthesia were highly common in chronic cough patients, affecting 94.8% and 86.8% of them, respectively.

    CONCLUSIONS The present study demonstrated older female predominance among adult chronic cough patients attending a referral cough clinic in Korea. The demographic features were significantly associated with the capsaicin cough responses and also potentially with allotussia (particularly cold air as the trigger). These findings suggest a role of cough reflex sensitization in the pathophysiology of chronic cough in adults.

    PubMed IF 4.3 알레르기내과
22. 1722014

    제1저자 구보경 · 교신저자 박경수

    Koo BK, Chae S, Kim KM, Kang MJ, Kim EG, Kwak SH, Jung HS, Cho YM, Choi SH, Park YJ, Shin CH, Jang HC, Shin CS, Hwang D, Yi EC, Park KS

    Identification of novel autoantibodies in type 1 diabetic patients using a high-density protein microarray.

    Diabetes. 2014;63(9):3022-32.

    Abstract

    Autoantibodies can facilitate diagnostic and therapeutic means for type 1 diabetes (T1DM). We profiled autoantibodies from serum samples of 16 T1DM patients, 16 type 2 diabetic (T2DM) patients, and 27 healthy control subjects with normal glucose tolerance (NGT) by using protein microarrays containing 9,480 proteins. Two novel autoantibodies, anti-EEF1A1 and anti-UBE2L3, were selected from microarrays followed by immunofluorescence staining of pancreas. We then tested the validity of the candidates by ELISA in two independent test cohorts: 1) 95 adults with T1DM, 49 with T2DM, 11 with latent autoimmune diabetes in adults (LADA), 20 with Graves disease, and 66 with NGT and 2) 33 children with T1DM and 34 healthy children. Concentrations of these autoantibodies were significantly higher in T1DM patients than in NGT and T2DM subjects (P < 0.01), which was also confirmed in the test cohort of children (P < 0.05). Prevalence of anti-EEF1A1 and anti-UBE2L3 antibodies was 29.5% and 35.8% in T1DM, respectively. Of note, 40.9% of T1DM patients who lack anti-GAD antibodies (GADA) had anti-EEF1A1 and/or anti-UBE2L3 antibodies. These were also detected in patients with fulminant T1DM but not LADA. Our approach identified autoantibodies that can provide a new dimension of information indicative of T1DM independent of GADA and new insights into diagnosis and classification of T1DM.

    PubMed IF 9.3 내분비대사내과
23. 1712014

    제1저자 조선욱/김영아 · 교신저자 박영주

    Cho SW, Kim YA, Sun HJ, Ahn HY, Lee EK, Yi KH, Oh BC, Park DJ, Cho BY, Park YJ

    Therapeutic potential of Dickkopf-1 in wild-type BRAF papillary thyroid cancer via regulation of β-catenin/E-cadherin signaling.

    J Clin Endocrinol Metab. 2014;99(9):E1641-9.

    Abstract

    BACKGROUND Aberrant activation of the Wnt/β-catenin pathway is a common pathogenesis of various human cancers. We investigated the role of the Wnt inhibitor, Dkk-1, in papillary thyroid cancer (PTC).

    METHODS Immunohistochemical β-catenin staining was performed in tissue microarray containing 148 PTCs and five normal thyroid tissues. In vivo effects of Dkk-1 were explored using ectopic tumors with BHP10-3SC cells.

    RESULTS In 27 PTC patients, 60% of patients showed β-catenin up-regulation and Dkk-1 down-regulation in tumor vs normal tissues. Tissue microarray analysis showed that 14 of 148 PTC samples exhibited cytoplasmic-dominant β-catenin expression compared to membranous-dominant expression in normal tissues. Aberrant β-catenin expression was significantly correlated with higher rates of the loss of membranous E-cadherin expression and poor disease-free survival than that in the normal membranous expression group over a median follow-up period of 14 years. Implantation of Dkk-1-overexpressing BHP10-3SC cells revealed delayed tumor growth, resulting from the rescue of membranous β-catenin and E-cadherin expressions. Furthermore, tissue microarray analysis demonstrated that BRAF(WT) patients had higher rates of aberrant expressions of β-catenin and E-cadherin than BRAF(V600E) patients. Indeed, the inhibitory effects of Dkk-1 on cell survival were more sensitive in BRAF(WT) (BHP10-3SC and TPC-1) than in BRAF(V600E) (SNU-790 and BCPAP) cells. Overexpression of BRAF(V600E) in normal thyroid epithelial (H tori) cells also reduced the effects of Dkk-1 on cell survival.

    CONCLUSION A subset of PTC patients showed aberrant expression of β-catenin/E-cadherin signaling and poor disease-free survival. Dkk-1 might have a therapeutic role, particularly in BRAF(WT) patients.

    PubMed IF 5.4 내분비대사내과
24. 1702014

    제1저자 장성혜, 박진균 · 교신저자 이은봉

    Chang SH, Park JK, Lee YJ, Yang JA, Lee EY, Song YW, Lee EB

    Comparison of cancer incidence among patients with rheumatic disease: a retrospective cohort study.

    Arthritis Res Ther. 2014;16(4):428.

    Abstract

    INTRODUCTION Rheumatic diseases (RDs) are associated with different cancers; however, it is unclear whether particular cancers are more prevalent in certain RDs. In the present study, we examined the relative incidence of several cancers in a single homogeneous cohort of patients with different RDs.

    METHODS Patients (N = 3,586) diagnosed with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM) or polymyositis were included. Cancer diagnosis was based on histopathology. The 2008 Korean National Cancer Registry served as the reference for calculating standardized incidence ratios (SIRs).

    RESULTS During the follow-up period of 31,064 person-years, 187 patients developed cancer. RA and SLE patients showed an increased risk of non-Hodgkin's lymphoma (SIR for RA patients = 3.387, 95% confidence interval (CI) = 1.462 to 6.673; SIR for SLE patients = 7.408, 95% CI = 2.405 to 17.287). SLE patients also had a higher risk of cervical cancer (SIR = 4.282, 95% CI = 1.722 to 8.824). SSc patients showed a higher risk of lung cancer (SIR = 4.917, 95% CI = 1.977 to 10.131). Endometrial cancer was increased only in patients with DM (SIR = 30.529, 95% CI = 3.697 to 110.283). RA patients had a lower risk for gastric cancer (SIR = 0.663, 95% CI = 0.327 to 0.998). The mean time between the RD and cancer diagnoses ranged from 0.1 to 16.6 years, with the shortest time observed in patients with DM (2.0 ± 2.1 years).

    CONCLUSIONS Different RDs are associated with particular cancers. Thus, cancer surveillance tailored to specific RDs might be beneficial.

    PubMed IF 5.4 류마티스내과
25. 1692014

    제1저자 조유리 · 교신저자 김윤준

    Cho Y, Lee DH, Lee YB, Lee M, Yoo JJ, Choi WM, Cho YY, Paeng JC, Kang KW, Chung JK, Yu SJ, Lee JH, Yoon JH, Lee HS, Kim YJ

    Does 18F-FDG positron emission tomography-computed tomography have a role in initial staging of hepatocellular carcinoma?

    PLoS One. 2014;9(8):e105679.

    Abstract

    BACKGROUND AND AIM The utility of fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET/CT) in initial staging of hepatocellular carcinoma (HCC) has yet to be fully explored. We assessed the usefulness of (18)F-FDG PET/CT in initial staging of HCC.

    METHODS A total of 457 consecutive patients initially diagnosed with HCC at Seoul National University Hospital between 2006 and 2012 were evaluated retrospectively to assess the impact of (18)F-FDG PET/CT on staging and compliancy with Milan criteria, relative to dynamic CT of liver and chest x-ray.

    RESULTS Seven among the 457 patients studied showed a shift in Barcelona Clinic Liver Cancer [BCLC] stage (A → C: 6 patients; B → C: 1 patient) and 5 patients who had originally met Milan criteria no longer qualified. (18)F-FDG PET/CT had value in initial staging of early (stage A) or intermediate (stage B) HCC, as determined by dynamic CT of liver and BCLC or AJCC classifications, whereas BCLC stage 0 and stage C tumors were unchanged (P<0.001). (18)F-FDG PET/CT disclosed additional metastases in patients with American Joint Committee on Cancer [AJCC] T2 (2.7%), T3a (5.3%), and T3b (4.8%) classifications.

    CONCLUSIONS In initial staging of HCC, (18)F-FDG PET/CT provided additional information, impacting the patients with BCLC (stages A and B) and AJCC (T2 and T3) classifications. Its use might be thus appropriate for these patient subsets, especially if hepatic resection or liver transplantation is planned.

    PubMed IF 2.8 소화기내과
26. 1682014

    제1저자 김수환 · 교신저자 김지원

    Kim SH, Jeong JB, Kim JW, Koh SJ, Kim BG, Lee KL, Chang MS, Im JP, Kang HW, Shin CM

    Clinical and endoscopic characteristics of drug-induced esophagitis.

    World J Gastroenterol. 2014;20(31):10994-9.

    Abstract

    AIM To investigate clinical, endoscopic and pathological characteristics of drug-induced esophagitis.

    METHODS Data for patients diagnosed with drug-induced esophagitis from April 2002 to May 2013 was reviewed. Patients diagnosed with malignancy, viral or fungal esophagitis were excluded. Clinical, endoscopic and pathological characteristics of patients diagnosed with drug-induced esophagitis were analyzed.

    RESULTS Seventy-eight patients were diagnosed with drug-induced esophagitis. Their mean age was 43.9 ± 18.9 years and 35.9% were male. Common symptoms were chest pain (71.8%), odynophagia (38.5%) and dysphagia (29.5%). The endoscopic location was in the middle third of esophagus in 78.2%. Endoscopic findings were ulcer (82.1%), erosion (17.9%), ulcer with bleeding (24.4%), coating with drug material (5.1%), impacted pill fragments (3.8%) and stricture (2.6%). Kissing ulcers were observed in 43.6%. The main causative agents were antibiotics and non-steroidal anti-inflammatory drugs. All the patients were treated with proton pump inhibitors (PPIs) or sucralfate, and the causative drugs were discontinued. Nineteen patients with drug-induced esophagitis were followed up with endoscopy and revealed normal findings, scars or healing ulcers.

    CONCLUSION Drug-induced esophagitis mainly presents as chest pain, odynophagia and dysphagia, and may be successfully treated with PPIs and discontinuation of the causative drug. Kissing ulcers were observed in 43.6%.

    PubMed IF 7.7 소화기내과
27. 1672014

    제1저자 이정환 · 교신저자 이정표

    Lee J, An JN, Hwang JH, Kim YL, Kang SW, Yang CW, Kim NH, Oh YK, Lim CS, Kim YS, Lee JP

    Effect of dialysis initiation timing on clinical outcomes: a propensity-matched analysis of a prospective cohort study in Korea.

    PLoS One. 2014;9(8):e105532.

    Abstract

    BACKGROUND Controversy persists regarding the appropriate initiation timing of renal replacement therapy for patients with end-stage renal disease. We evaluated the effect of dialysis initiation timing on clinical outcomes. Initiation times were classified according to glomerular filtration rate (GFR).

    METHODS We enrolled a total of 1691 adult patients who started dialysis between August 2008 and March 2013 in a multi-center, prospective cohort study at the Clinical Research Center for End Stage Renal Disease in the Republic of Korea. The patients were classified into the early-start group or the late-start group according to the mean estimated GFR value, which was 7.37 ml/min/1.73 m2. The primary outcome was patient survival, and the secondary outcomes were hospitalization, cardiovascular events, vascular access complications, change of dialysis modality, and peritonitis. The two groups were compared before and after matching with propensity scores.

    RESULTS Before propensity score matching, the early-start group had a poor survival rate (P<0.001). Hospitalization, cardiovascular events, vascular access complications, changes in dialysis modality, and peritonitis were not different between the groups. A total of 854 patients (427 in each group) were selected by propensity score matching. After matching, neither patient survival nor any of the other outcomes differed between groups.

    CONCLUSIONS There was no clinical benefit after adjustment by propensity scores comparing early versus late initiation of dialysis.

    PubMed IF 2.8 신장내과
28. 1662014

    제1저자 임수 · 교신저자 임수

    Lim S, Barter P

    Antioxidant effects of statins in the management of cardiometabolic disorders.

    J Atheroscler Thromb. 2014;21(10):997-1010.

    Abstract

    Redox systems are key players in vascular health. A shift in redox homeostasis-that results in an imbalance between reactive oxygen species (ROS) generation and endogenous antioxidant defenses has the potential to create a state of oxidative stress that subsequently plays a role in the pathogenesis of a number of diseases, including those of the cardiovascular and metabolic system. Statins, which are primarily used to reduce the concentration of low-density lipoprotein cholesterol, have also been shown to reduce oxidative stress by modulating redox systems. Studies conducted both in vitro and in vivo support the role of oxidative stress in the development of atherosclerosis and cardiovascular diseases. Oxidative stress may also be responsible for various diabetic complications and the development of fatty liver. Statins reduce oxidative stress by blocking the generation of ROS and reducing the NAD+/NADH ratio. These drugs also have effects on nitric oxide synthase, lipid peroxidation and the adiponectin levels. It is possible that the antioxidant properties of statins contribute to their protective cardiovascular effects, independent of the lipid-lowering actions of these agents. However, possible adverse effects of statins on glucose homeostasis may be related to the redox system. Therefore, studies investigating the modulation of redox signaling by statins are warranted.

    PubMed IF 3.4 내분비대사내과
29. 1652014

    제1저자 곽수헌/박영주/고민지 · 교신저자 조남한

    Kwak SH, Park YJ, Go MJ, Lee KE, Kim SJ, Choi HS, Kim TH, Choi SH, Lim S, Kim KW, Park DJ, Kim SS, Lee JY, Park KS, Jang HC, Cho NH

    A genome-wide association study on thyroid function and anti-thyroid peroxidase antibodies in Koreans.

    Hum Mol Genet. 2014;23(16):4433-42.

    Abstract

    Genetic factors are thought to be an important determinant of thyroid function and autoimmunity. However, there are limited data on genetic variants in Asians. In this study, we performed a genome-wide association study on plasma thyroid-stimulating hormone (TSH) and free thyroxine (fT4) concentration and anti-thyroid peroxidase (anti-TPO) antibody positivity in 4238 Korean subjects. In the Stage 1 genome scan, 3396 participants from the Ansung cohort were investigated using 1.42 million genotyped or imputed markers. In the Stage 2 follow-up, 10 markers were genotyped in 842 participants from the Korean Longitudinal Study on Health and Aging cohort. An intronic variant in VAV3, rs12126655, which has been reported in Europeans, was significantly associated with plasma TSH concentration in the joint Stages 1 and 2 analyses (P = 2.2 × 10(-8)). We observed that a novel variant, rs2071403, located 75 bp proximal to the translational start site of TPO was significantly associated with plasma anti-TPO antibody positivity in the joint Stages 1 and 2 analyses (P = 1.3 × 10(-10)). This variant had a marginal sex-specific effect, and its association was more significant in females. Subjects possessing the rs2071403A allele, associated with an absence of the anti-TPO antibody, had decreased TPO mRNA expression in their thyroid tissue. Another intronic variant of HLA-DPB2, rs733208, had a suggestive association with anti-TPO antibody positivity (P = 4.2 × 10(-7)). In conclusion, we have identified genetic variants that are strongly associated with TSH level and anti-TPO antibody positivity in Koreans. Further replications and meta-analysis are required to confirm these findings.

    PubMed IF 3.1 내분비대사내과
30. 1642014

    제1저자 고영일 · 교신저자 윤성수

    Koh Y, Jung WJ, Ahn KS, Yoon SS

    Establishment of cell lines from both myeloma bone marrow and plasmacytoma: SNU_MM1393_BM and SNU_MM1393_SC from a single patient.

    Biomed Res Int. 2014;2014:510408.

    Abstract

    PURPOSE We tried to establish clinically relevant human myeloma cell lines that can contribute to the understanding of multiple myeloma (MM).

    MATERIALS AND METHODS Mononuclear cells obtained from MM patient's bone marrow were injected via tail vein in an NRG/SCID mouse. Fourteen weeks after the injection, tumor developed at subcutis of the mouse. The engraftment of MM cells into mouse bone marrow (BM) was also observed. We separated and cultured cells from subcutis and BM.

    RESULTS After the separation and culture of cells from subcutis and BM, we established two cell lines originating from a single patient (SNU_MM1393_BM and SNU_MM1393_SC). Karyotype of the two newly established MM cell lines showed tetraploidy which is different from the karyotype of the patient (diploidy) indicating clonal evolution. In contrast to SNU_MM1393_BM, cell proliferation of SNU_MM1393_SC was IL-6 independent. SNU_MM1393_BM and SNU_MM1393_SC showed high degree of resistance against bortezomib compared to U266 cell line. SNU_MM1393_BM had the greater lethality compared to SNU_MM1393_SC.

    CONCLUSION Two cell lines harboring different site tropisms established from a single patient showed differences in cytokine response and lethality. Our newly established cell lines could be used as a tool to understand the biology of multiple myeloma.

    PubMed IF 2.9 혈액종양내과

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