The Korean Academy of Tuberculosis and Respiratory Diseases : Slide Session ; OS-104 : Critical Care ; The Amount of Visceral Adipose Tissue Quantitatively Measured by Abdominal Computed Tomography Is Dose-Dependently Associated with Mortality in Patients

( Sung Jun Ko ),( Sun Mi Choi ),( Jin Woo Lee ),( Young Sik Park ),( Chang Hoon Lee ),( Jae Joon Yim ),( Chul Gyu Yoo ),( Young Whan Kim ),( Sung Koo Han ),( Sang Min Lee ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Adipose tissue is recently recognized as not only energy reservoir but also endocrine organ producing proin ammatory cytokines. Especially the impact o visceral adipose tissue(VAT) in critical illnesses has been proposed, but researches on the association between VAT and sepsis were scarce and quantitative measurement of VAT had not been used. Methods: In this retrospective cohort study, we enrolled patients with sepsis who examined abdominal computed tomography(A-CT) within 1 month of occurrence of sepsis, among the patients admitted to intensive care unit(ICU). Age, sex, anthropometric values, comorbidities and APACHE II score were reviewed. The areas of VAT and total adipose tissue(TAT) on the section of A-CT image of the umbilicus level were measured by calculating pixels presenting fat density. Results: Among 287 patients admitted to ICU due to sepsis, 178 patients were included for this study. Median age was 65 and 59.0% were men. In-hospital mortality rate was 57.9%. Women had higher TAT and subcutaneous adipose tissue, lower VAT/TAT ratio compared to men. The amount of VAT and VAT/TAT ratio were higher in in-hospital mortality group than in survivor group(90.41cm2 vs. 63.83cm2 and 45.88% vs. 32.79%, p=0.001 and <0.001, respectively). After adjusting age, sex, APACHE II score and comorbidities, multivariate logistic regression analysis revealed that the amount of VAT and VAT/TAT ratio were independent prognostic factors of sepsis with obvious dose-dependent relationship(VAT/TAT ratio quartile 3: OR 8.832, p<0.001 and quartile 4: OR 29.477, p<0.001, compared to quartile 1 respectively). Conclusion: The amount of VAT and VAT/TAT ratio quantitatively measured by A-CT were positively correlated with mortality in sepsis, and this association was dose-dependent. Visceral obesity should be considered as the poor prognostic factor of sepsis.

Goodness-of-Fits of the Spirometric Reference Values for Koreans and USA Caucasians to Spirometry Data from Residents of a Region within Chungbuk Province

( Sang Yong Eom ),( Sun In Moon ),( Dong Hyuk Yim ),( Chul Ho Lee ),( Guen Bae Kim ),( Yong Dae Kim ),( Jong Won Kang ),( Kang Hyeon Choe ),( Sung Jin Kim ),( Byung Sun Choi ),( Seung Do Yu ),( Soung 대한결핵 및 호흡기학회 2012 Tuberculosis and Respiratory Diseases Vol.72 No.3

Background: Korean regression models for spirometric reference values are different from those of Americans. Using spirometry results of Korean adults, goodness-of-fits of the Korean and the USA Caucasian regression models for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were compared. Methods: The number of study participants was 2,360 (1,124 males and 1,236 females). Spirometry was performed under the guidelines of the American Thoracic Society and the European Respiratory Society. After excluding unsuitable participants, spirometric data for 729 individuals (105 males and 624 females) was included in the statistical analysis. The estimated FVC and FEV1 values were compared with those measured. Goodness-of-fits for Korean and USA Caucasian models were compared using an F-test. Results: In males, the expected values of FVC and FEV1 using the Korean model were 12.5% and 5.7% greater than those measured, respectively. The corresponding values for the USA Caucasian model were 3.5% and 0.6%. In females, the difference in FVC and FEV1 were 13.5% and 7.7% for the Korean model, and 6.3% and 0.4% for the USA model, respectively. Goodness-of-fit for the Korean model regarding FVC was not good to the study population, but the Korean regression model for FEV1, and the USA Caucasian models for FVC and FEV1 showed good fits to the measured data. Conclusion: These results suggest that the USA Caucasian model correlates better to the measured data than the Korean model. Using reference values derived from the Korean model can lead to an overestimation regarding the prevalence of abnormal lung function.

Isolation of a Potential Anchoring Motif Based on Proteome Analysis of Escherichia coli and Its Use for Cell Surface Display

Yim, Sung Sun,An, Seul Ji,Han, Mee-Jung,Choi, Jae Woong,Jeong, Ki Jun Springer-Verlag 2013 Applied biochemistry and biotechnology Vol.170 No.4

<P>For bacterial cell surface display, the target protein needs to be linked to an anchoring motif, and it is essential to choose an appropriate anchoring motif for efficient and stable display of the protein on the cell surface. To isolate a potential anchoring motif that would allow a stable and enhanced display of target proteins on the surface of an Escherichia coli host, we analyzed the outer membrane proteome of E. coli. On the basis of this proteomic analysis, the outer membrane protein X (OmpX), which has a small, monomeric β-barrel structure and is highly expressed, was selected as a potential anchoring motif. The role of OmpX as an anchoring motif for cell surface display was demonstrated using three important industrial enzymes: endoxylanase, lipase, and alkaline phosphatase. Two different positions (Lys(122), Val(160)) in the extracellular loops of OmpX were examined for C-terminal fusion, and the biological activities and localization of the displayed enzymes were analyzed. All three enzymes examined were efficiently displayed on the E. coli cell surface with high activity. These results reveal that the use of OmpX as an anchoring motif is an efficient method to display functional enzymes on the surface of an E. coli host.</P>

ITGA1 polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population.

Yim, Dong-Hyuk,Zhang, Yan-Wei,Eom, Sang-Yong,Moon, Sun In,Yun, Hyo-Yung,Song, Young-Jin,Youn, Sei-Jin,Hyun, Taisun,Park, Joo-Seung,Kim, Byung Sik,Lee, Jong-Young,Kim, Yong-Dae,Kim, Heon WJG Press 2013 World journal of gastroenterology Vol.19 No.35

<P>To evaluate the association between the genetic polymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer.</P>

Engineering of Corynebacterium glutamicum for production of D-xylonic Acid

Sung Sun YIM,Jae Woong CHOI,Eun Jung JEON,Ki Jun JEONG 한국생물공학회 2016 한국생물공학회 학술대회 Vol.2016 No.10

Consensus Molecular Subtypes Reflecting Distinct Clinical Phenotypes of Hepatocellular Carcinoma: Deciphering Resectable Hepatocellular Carcinoma

( Sung Hwan Lee ),( Sun Young Yim ),( Sang-hee Kang ),( Bo Hwa Sung Hwan Lee ),( Sun Young Yim ),( Sang-hee Kang ),( Bo Hwa ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Hepatocellular carcinoma (HCC) is a heterogeneous disease with therapeutic resistance even in the early stage. Current genomic subtyping systems reflect the heterogeneity of HCC, but its clinical use is hampered by discrepancies among different studies. Methods: By integrating 15 previously established genomic signatures for HCC subtypes, we identified five clinically and molecularly distinct consensus subtypes using transcriptomic data from 8 HCC cohorts with 1754 patients (Discovery set; n=1006, Validation set; n=748). Results: We demonstrated five consensus subtypes of HCC showing distinct molecular and clinical features regarding STM, CIN, IMH, BCM, and DLP subtypes. Briefly, STM (STeM) is characterized by high stem cell features, vascular invasion, and sensitivity to sorafenib. CIN (Chromosome INstable) has moderate stem cell features, but high genomic instability and low immune activity. IMH (IMmune High) is characterized by high immune activity predicting possible responders for immunotherapies. BCM (Beta-Catenin with Male high predominance) is characterized by prominent beta-catenin activation, low miRNA expression, and hypomethylation. DLP (Differentiated and Low Proliferation) is differentiated with high HNF4A activity. Lastly, we developed and validated a robust predictor of integrated consensus subtype with subtype-specific serum biomarkers using integrative genomic and statistical analysis. Conclusions: Consensus subtypes of HCC from the comprehensive genomic analysis showed distinct biological and clinical phenotypes, including different dependency for oncogenic pathways and discriminated therapeutic efficacy. Based on the clinical relevance of consensus subtypes for current available therapeutic options in terms of molecular target therapies and immunotherapies, our findings may provide the foundation for rationalized biomarker-based clinical trials for resectable HCC.

Aldh2 knockout 마우스에서 8주간 에탄올 노출에 따른 뇌조직의 thiobarbituric acid reactive substances 농도

Sun-In Moon(문선인),Sang-Yong Eom(엄상용),Jung-Hyun Kim(김정현),Dong-Hyuk Yim(임동혁),Hyong-Kyu Kim(김형규),Yong-Dae Kim(김용대),Heon Kim(김헌) 한국생명과학회 2011 생명과학회지 Vol.21 No.8

과다한 음주는 알츠하이머 및 파킨슨 질병과 같은 각종 만성 퇴행성 뇌질환의 대표적인 원인 중 하나로 알려져 있다. 체내에 유입된 에탄올은 알코올 탈수소효소(alcohol dehydrogenase, ADH)에 의해 아세트알데히드로 대사된 후 다시 알데히드탈수소효소 2(aldehyde dehydrogenase 2, ALDH2)에 의해 아세트산으로 대사되어 배출된다. 에탄올의 대사과정 중에는 다량의 free radical이 생성되어 체내에서 산화적 스트레스를 유발하는 것으로 알려져 있고, 아세트알데히드는 활성산소를 생산하는 독성물질로 잘 알려져 있다. 본 연구에서는 8주간 에탄올에 노출된 Aldh2 knockout 마우스를 사용하여 ALDH2 효소 활성이 뇌 조직과 소변의 지질과산화에 미치는 영향에 대하여 살펴보았으며, 지질과산화 정도를 측정하기 위해 HPLC를 통한 TBARS 정도를 측정하였다. 연구결과, 마우스에서 만성 에탄올 섭취는 뇌 조직 TBARS 생성에 영향을 주지 않는 것으로 나타났으나, 소변 TBARS는 Aldh2 (-/-) 마우스에서 에탄올을 투여함에 따라 유의한 증가를 보였다(p<0.05). 본 연구 결과로부터 8주간 에탄올을 경구 투여한 마우스에서 ALDH2의 활성은 체내의 전반적인 활성산소 생성에는 중요하게 관여하는 것으로 보이지만 뇌조직에서의 활성산소 생성에는 영향을 주지 않는 것으로 보이며, 이는 에탄올 노출과 이에 따른 활성산소가 다양한 만성 뇌질환을 유발한다는 기존의 가설에서 ALDH2의 활성이 중요하게 관여하지 않을 가능성을 시사한다. Excessive alcohol consumption causes various degenerative brain diseases including Alzheimer’s disease and Parkinson’s disease. Absorbed ethanol is metabolized to acetaldehyde and acetic acid by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Acetaldehyde is well known as a toxicant through generation of reactive oxygen species (ROS). Therefore, ALDH2 activity may play important roles in the pathogenesis of alcohol-induced brain diseases. In this study, we demonstrated the effects of ALDH2 enzyme activity on lipid peroxidation in brain tissues and urine of mice exposed to ethanol for 8 weeks. Five male, 8-week old Aldh2 (+/+) and Aldh2 (-/-) mice (C57BL/6J strain) in each group were exposed to ethanol for 8 weeks (2 g/㎏ wt./day) using gavage, and those in the control group received 0.9% saline alone. Thiobarbituric acid reactive substances (TBARS) level, a marker for lipid peroxidation, was measured in whole brain tissue and urine by high performance liquid chromatography. As a result, chronic ethanol treatment did not show any statistical change on the TBARS level of brain tissue in both Aldh2 (+/+) mice and in Aldh2 (-/-) mice. However, following ethanol exposure for 8 weeks in Aldh2 (-/-) mice, the urinary TBARS levels were significantly increased to more than double compared to the pretreatment group. This result was not observed in Aldh2 (+/+) mice. These results suggest that although ALDH2 enzyme activity plays a role in the generation of ROS in the whole body, it does not seem to be important in the pathogenesis of alcohol induced degenerative brain diseases.

Direct Production of D-Xylonic Acid With Engineered Corynebacterium Glutamicum by Degrading Hemicellulose

Sung Sun YIM,Jae Woong CHOI,Se Hwa LEE,Eun Jung JEon,Ki Jun JEonG 한국생물공학회 2017 한국생물공학회 학술대회 Vol.2017 No.4

Plenary Session 1 : PS-1-6 ; Hepatitis B surface antigen level can predict off-treatment sustained virologic response in chronic hepatitis B patients treated with nucleos(t)ide analogues

( Sang Jun Suh ),( Jong Eun Yeon ),( Sun Jae Lee ),( Hyun Jung Lee ),( Eileen L Yoon ),( Ji Hoon Kim ),( Yeon Seok Seo ),( Hyung Joon Yim ),( Kwan Soo Byun ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

Background: Current guidelines suggest the criteria for discontinuation of nucleos(t)ide analogues (NA) in selected patients. However treatment induced virological response is not permanent. Aim of our study is to evaluate the clinical significance of HBsAg titer in predicting sustained virologic response after NA therapy discontinuation. Methods: From Jun 1998 to Dec 2010, medical record of 81 chronic hepatitis B patients who discontinued NA was analyzed retrospectively. Sustained virologic response (SVR) was arbitrarily defined as undetectable HBV DNA by real-time PCR(with lower limit of detection of 116 copies/mL, 20 IU/mL) persisted more than 12 months after treatment discontinuation. Results: Median age was 51 years, 54 (67%) patients were male, and 50 (62%)patients were HBeAg positive. Median baseline ALT, HBV DNA and HBsAg were 292 IU/mL, 7.1log10 IU/mL and 3.3log10 IU/mL. NA were lamivudine (n=53), adefovir (n=15), lamivudine combined with adefovir (n=4), and entecavir (n=9). Median treatment duration and follow-up period were 26 and 27 months. 11/81 (14%) patients had SVR. The cumulative relapse rates were 37/81 (46%) at 6 months and 42/81 (52%) 12 months after treatment discontinuation. The baseline ALT, HBV DNA and presence of HBeAg were not different between patients with or without SVR. In univariate analysis, age, treatment duration and HBsAg level at treatment discontinuation were different in patients with or without SVR; 51 vs. 43 years, p=0.033; 53 vs. 25 months, p=0.011; 2.1 vs. 3.3log10 IU/mL, p=0.003. In multivariate analysis, only HBsAg level at treatment discontinuation remained as an independent factor associated with SVR (p=0.019). The cutoff value of HBsAg level <2log10 IU/mL was predictive of SVR [(AUROC, 0.991; 95% confidence interval[CI], 0.000-1.000; p<0.05); sensitivity, 100%; specificity, 93%; positive predictive value, 69%; negative predictive value, 100%]. Conclusions: Large proportion of patients treated with oral antivirals relapsed after the treatment discontinuation. In the decision of the treatment discontinuation, HBsAg level <2log10 IU/mL at treatment discontinuation can predict sustained viral suppression in selected patients.

HCC : The Comparison of Hepatic Arterial Infusion Chemotherapy vs. Sorafenib Therapy in Advanced Hepatocellular Carcinoma with Portal Vein Invasion

( Sang Jun Suh ),( Hyung Joon Yim ),( Sun Jae Lee ),( Hyun Jung Lee ),( Eileen L Yoon ),( Sun Young Yim ),( Hae Rim Kim ),( Seoung Hee Kang ),( Keun Hee Kang ),( Ji Hoon Kim ),( Yeon Seok Seo ),( Jong 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background and aims: Sorafenib is the only approved treatment to advanced hepatocellular carcinoma (HCC). However, its efficacy was relatively worse in the Asian-Pacific trial compared with the Global trial and clinical utility is limited by high cost. Several reports suggested survival benefit of hepatic arterial infusion chemotherapy (HAIC) in patients with advanced HCC with main portal vein invasion. This study is aimed to compare the efficacy of HAIC with sorafenib in HCC patients with main portal vein invasion. Methods: Patients of advanced HCC with main portal vein invasion who had received treatment between 2008 and 2012 at Korea University Medical Center were included. Sorafenib was initiated with 400 mg twice daily, and HAIC was performed with infusion of cisplantin 60mg/m2 for 1 day and 5-flurouracil 500mg/m2 for 3 days every 4 weeks. We evaluated overall survival (OS), time-to-progression (TTP), and disease control rate (DCR). Results: Seventy six patients were treated by sorafenib (n=37) or HAIC (n=39). Proportion of patients with Child-Pugh class A liver function (70% vs. 72%, P=1.000), ECOG performance status 0-1 (68% vs. 70%, p=0.431) and lymph node metastasis (41% vs. 36%, P=0.814) was not significantly different. Solid organ metastasis was more common in sorafenib group than HAIC group (46% vs. 7.7%, P<0.001). Median OS was 6.9 months and 11.1 months in sorafenib and HAIC group (P=0.100). TTP was 1.9 months (sorafenib) and 5.3 months (HAIC) (P<0.001). DCR was 34% (sorafenib) and 72% (HAIC) (P=0.006). In patients without solid organ metastasis, OS was 8.8 months (sorafenib) and 11.1 months (HAIC) (P=0.097). TTP was 1.9 months (sorafenib) and 6.0 months (HAIC) (P<0.001). DCR was 29% (sorafenib) and 76% (HAIC) (P=0.031). Conclusions: HAIC can be alternative treatment option for advanced HCC with main portal vein invasion, and could provide favorable disease control rate in those patients without solid organ metastasis.