한국의 C형간염바이러스 RNA 양성인 간질환자 및 건강 공혈자에서의 C형간염바이러스 유전자형의 분포양상

이진경,홍석일,황유성,이선호,민원기,성영철,이동순 대한임상병리학회 1996 대한임상병리학회지 Vol.16 No.4

장내의 탄수화물과 지방 흡수 억제를 통한 체지방 및 비만 개선 효과에 관한 연구

정은희,윤승원,이홍석,윤유식,유경미,황인경 한국조리과학회 2003 한국식품조리과학회지 Vol.19 No.1

In a previous study, a dietary supplement was developed in our lab using natural herbal extracts against digest enzyme activity in GI tract for weight control. This natural herbal extracts could regulate absorption of glucose and lipid by the inhibition of digest enzyme activity. In this study, we screened the natural herbs that inhibit glucoamylase activity and developed an water extract of cinnamon. The cinnamon extract delayed and decreased the increment of carbohydrate degradation through the inhibition of glucoamylase activity in vitro. Fifty volunteers were subjected to the intake of the herbal extracts by taking twice a day for 60 days. As a result, the treated subjects lost 3kg of body weight and 3.5kg of body fat mass after the treatment. Furthermore, the body mass index and waist size were significantly decreased during the experimental period. Above results suggested that the administration of the dietary additives composed of cinnamon and natural herbal extract improves the obesity by the decrement of body weight and body fat mass.

The Smurf ubiquitin ligases regulate tissue separation via antagonistic interactions with ephrinB1

Hwang, Yoo-Seok,Lee, Hyun-Shik,Kamata, Teddy,Mood, Kathleen,Cho, Hee Jun,Winterbottom, Emily,Ji, Yon Ju,Singh, Arvinder,Daar, Ira O. Cold Spring Harbor Laboratory Press 2013 Genes & development Vol.27 No.5

<P>Smad ubiquitin regulatory factors (Smurfs) play important roles in cell growth and differentiation. Hwang et al. present a new mechanism of Smurf regulation in <I>Xenopus</I> with evidence that Smurf1 and Smurf2 essentially compete for association with ephrin B1 (Smurf2 triggers ephrinB1 degradation, and Smurf1 counteracts it) and so regulate its expression. This unique mechanism for ubiquitin ligases is responsible for regulating the tissue boundaries at the mesoderm/ectoderm border during embryogenesis.</P>

Antimorphic PV.1 Causes Secondary Axis by Inducing Ectopic Organizer

Hwang, Yoo-Seok,Seo, Jeong-Jae,Cha, Sang-Wook,Lee, Hyun-Shik,Lee, Sung-Young,Roh, Dong-Hyun,Kung, Hsiang-fu,Kim, Jaebong,Park, Mae Ja 경북대학교 병원 2002 경북대학교병원의학연구소논문집 Vol.6 No.1

Xenopus homeobox gene, PV.1 ventralizes activininduceddorsal mesoderm and inhibits neuralization of ectoderm in animal cap when overexpressed. Here we generated PV.1/engrailed fusion construct (N-PV1-EnR) to perform loss-of-function study for this transcription factor.N-PV1-EnR showed an extremely antimorphic effect, causing a partial secondary embryonic axis when expressed at ventral marginal zone of blastula. In ventral marginal zone cells, this chimeric protein induced organizer genes and suppressed ventral markers mimicking those effects reported for dominant negative BMP-4 receptor (DNBR).Moreover, N-PV1-EnR rescued the ventralized embryos caused by the ectopic dorsal expression of PV.1 but not by that of Xvent-2. These results suggested that PV.1 functions at downstream of BMP-4 as a ventralizing effector which acts separately from Xvent-2 and the dominant negative effect gained by this specific mutant is applicable for the further studiesof BMP-4 downstream pathway.

BMP 신호 하부 인자인 PV.1 단백질의 결합 단백질 동정

황유석(Yoo-Seok Hwang),채정필(Jeong-Pil Chae),김동선(Dong-Sun Kim),박권무(Kwon Moo Park),배용철(Yong Chul Bae),박매자(Mae Ja Park) 대한해부학회 2007 Anatomy & Cell Biology Vol.40 No.3

척추동물에서 BMP의 배(ventral)쪽 신호 전달 경로의 하위에 있는 전사조절인자들은 등배(dorsalventral)쪽 축을 따라 형성되는 중배엽에 있어서도 그 기능을 공유 한다는 것이 보고 되었다. 본 연구에서는 BMP 신호 물질의 하위 유전자인 PV.1 단백질이 배쪽과 등쪽에서의 신호전달에 있어서 차별적 기능을 알기 위하여 PV.1과 상호 결합하는 단백질을 검색하였다. 효모 이중 접합법을 이용하여 24개의 PV.1 결합 단백질을 검색하였고, 이중 결합하는 Xvent-2와 Xclaudin-6에 대한 PV.1 단백질의 도메인(domain) 연구를 하였다. PV.1 단백질의 C-terminus인 197-241 지역이 Xclaudin-6와 결합하는 반면에 Xvent-2는 PV.1 단백질의 C-terminus 전반에서 결합한다는 것을 확인하였다. 또한 PV.1과 결합하는 Xvent-2는 동형 이중 결합(Homodimerization)뿐만 아니라 PV.1과 결합하는 Xclaudin-6과도 이형 이중 결합(Heteodimerization)을 한다는 것을 확인하였다. Homeodomain transcription factors functioning downstream of BMP ventral pathway have been reported to share similar domain of roles in mesoderm patterning along the dorsal-ventral axis. To elucidate the differential role of PV.1 in the aspect of relationship between dorsal and ventral region, we tried to screen PV.1- interacting proteins. Twenty-four PV.1-interacting proteins were identified by yeast two-hybrid screening. Xvent-2 and Xclaudin-6 among these, went under domain study. The C-terminus of PV.1, more specifically 197-241 region was found to interact with Xclaudin-6. Meanwhile Xvent-2 has mild affinity to overall C-terminal region of PV.1. At the same time it was found that Xvent-2 homodimerizes and also binds to Xclaudin-6.

Reverse J-Curve Relationship Between On-Treatment Blood Pressure and Mortality in Patients With Heart Failure

Lee, Sang Eun,Lee, Hae-Young,Cho, Hyun-Jai,Choe, Won-Seok,Kim, Hokon,Choi, Jin-Oh,Jeon, Eun-Seok,Kim, Min-Seok,Hwang, Kyung-Kuk,Chae, Shung Chull,Baek, Sang Hong,Kang, Seok-Min,Choi, Dong-Ju,Yoo, Byun American College of Cardiology 2017 JACC. Heart failure Vol.5 No.11

<P><B>Graphical abstract</B></P><P>[Figure]</P><P><B>Abstract</B></P><P><B>Objectives</B></P><P>This study aimed to assess the relationship between on-treatment blood pressure (BP) and clinical outcomes of patients with heart failure (HF).</P><P><B>Background</B></P><P>Lower BP has been reported to be related to increased mortality in various cardiovascular diseases. The optimal BP level for patients already experiencing HF is contentious.</P><P><B>Methods</B></P><P>The Korean Acute Heart Failure registry prospectively enrolled a total of 5,625 consecutive patients hospitalized for acute HF in 10 tertiary university hospitals in Korea between March 2011 and February 2014. Clinical profiles including BP were collected at admission, discharge, and during outpatient follow-up. Mean on-treatment BP was calculated from BP at discharge and at each follow-up visit. We evaluated the effects of mean on-treatment BP on the clinical outcomes of patients.</P><P><B>Results</B></P><P>Patients were followed up for a median 2.2 years. One-year mortality after discharge was 18.2%. The relationship between on-treatment BP and all-cause mortality followed a reversed J-curve relationship. A nonlinear, multivariable Cox proportional hazard model identified a nadir of systolic and diastolic BPs of 132.4/74.2 mm Hg in patients, for whom the mortality rate was lowest (p < 0.0001). The relationship with increased mortality above and below the reference BP was more definitive for diastolic BP and for HF with a preserved ejection fraction.</P><P><B>Conclusions</B></P><P>Systolic and diastolic BPs <130/70 mm Hg at discharge and during follow-up was associated with worse survival in HF patients. These data suggest that the lowest BP possible might not be an optimal target for HF patients. Further studies should establish a proper BP goal in HF patients. (Registry [Prospective Cohort] for Heart Failure in Korea [KorAHF]; NCT01389843)</P>

Predictive factors of mortality within 30 days in patients with nonvariceal upper gastrointestinal bleeding

( Yoo Jin Lee ),( Bo Ram Min ),( Eun Soo Kim ),( Kyung Sik Park ),( Kwang Bum Cho ),( Byoung Kuk Jang ),( Woo Jin Chung ),( Jae Seok Hwang ),( Seong Woo Jeon ) 대한내과학회 2016 The Korean Journal of Internal Medicine Vol.31 No.1

Background/Aims: Nonvariceal upper gastrointestinal bleeding (NVUGIB) is a common medical emergency that can be life threatening. This study evaluated predictive factors of 30-day mortality in patients with this condition. Methods: A prospective observational study was conducted at a single hospital between April 2010 and November 2012, and 336 patients with symptoms and signs of gastrointestinal bleeding were consecutively enrolled. Clinical characteristics and endoscopic findings were reviewed to identify potential factors associated with 30-day mortality. Results: Overall, 184 patients were included in the study (men, 79.3%; mean age, 59.81 years), and 16 patients died within 30 days (8.7%). Multivariate analyses revealed that comorbidity of diabetes mellitus (DM) or metastatic malignancy, age ≥ 65 years, and hypotension (systolic pressure < 90 mmHg) during hospitalization were significant predictive factors of 30-day mortality. Conclusions: Comorbidity of DM or metastatic malignancy, age ≥ 65 years, and hemodynamic instability during hospitalization were predictors of 30-day mortality in patients with NVUGIB. These results will help guide the management of patients with this condition.

LC, Acute : O-063 ; Efficacy and safety of Transjugular intrahepatic portosystemic shunt and Balloon Occluded Retrograde Transvenous Obliteration for gastric variceal bleeding

( Yoo Jin Lee ),( Woo Jin Chung ),( Yu Jin Hah ),( Hyung Ki Lee ),( Ho Young Lee ),( Jae Seok Hwang ),( Byung Kuk Jang ),( Kyung Sik Park ),( Kwang Bum Cho ),( Eun Soo Kim ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background/Aim: Transjugular Intrahepatic Portosystemic Shunt (TIPS) has been undergone for control of gastric variceal bleeding. But, TIPS has some limitations as hepatic encephalopathy or shunt occlusion, etc. Balloon Occluded Retrograde Transvenous Obliteration (BRTO) also has been undergone for these patients. So, we compared the effectiveness and safety of TIPS and BRTO for control of gastric variceal bleeding. Methods: Between January 2003 and February 2012, TIPS or BRTO have been undergone for gastric variceal bleeding. All patients had patent portal veins on preprocedural computed tomography. The patient who failed BRTO underwent TIPS for rescue therapy. Data regarding technical success, rebleeding, hepatic encephalopathy and survival were analyzed by Chisquare test and Kaplan-Meier method with Log-rank test. Results: 1. Among 100 patients, 32 patients underwent TIPS and 68 underwent BRTO. Technical success was achieved in 96.9% (31/32) in TIPS group and 86.8% (59/68) in BRTO group. There was no statistical difference of age, sex distribution, and Child-Pugh class in each group. 2. Early rebleeding within 5 days after procedure were 18.8% (6/32), 4.4%(3/68) (p=0.019) and late rebleeding after 5 days were 18.8% (6/32), 1.5% (1/68) in each group (p=0.002). 3. Hepatic encephalopathy was developed or aggravated in 53.1% (17/32), 4.4%(3/68) (p<0.001). 4. After procedure, Child-Pugh class was aggravated in 50% (16/32) and 19.1% (13/68) (p=0.004). 5. The survival time were 45.4 in TIPS and 62.3 months in BRTO group (p=0.04). 6. Procedure related complications did not have statistical difference in each group. Conclusion: BRTO can more effectively control of gastric variceal bleeding with less worsening of Child-Pugh class, hepatic encephalopathy, relatively decreased rebleeding rate and longer survival period than TIPS. So, if the patients who have ceased gastric variceal bleeding in the presence of gastrorenal shunt, BRTO may be considered as initial therapeutic procedure for control of gastric variceal bleeding.

수술로 절제된 간의 국소 결절성 증식의 임상적 특징

황남철,최문석,이준혁,고광철,백승운,유병철,이종철,이광웅,조재원,박철근 대한간학회 2004 Clinical and Molecular Hepatology(대한간학회지) Vol.10 No.2

목적: 간의 국소 결정성 과형성은 일반적으로 특별한 치료가 필요 없는 양성 종양이다. 그러나 드물지만 합병증이 발생한 경우와 진단이 불확실한 경우에는 수술을 시행하게 된다. 이에 저자들은 간절제술을 시행한 국소 결절성 과형성의 임상적, 영상학적 특징들을 알아보고자 하였다. 대상과 방법: 1995년부터 2003년까지 수술을 시행하여 조직을 확인한 국소 결절성 과형성 환자 10명을 대상으로 연령, 성별, 실험실 검사 및 영상 소견과 조직 소견을 분석하였다. 결과: 연령의 중앙값은 37.5세, 남녀 비는 1.5:1이었다. 5예에서는 간세포선종이나 간세포암종을 감별할 수 없어서 수술을 시행하였으며, 수술 후 우연히 진단된 예는 4예이었다. 간세포암종의 위험 인자를 가지고 있었던 예는 4예(B형 간염 바이러스 보유자 3예, 간경변 2예)이었다. CT검사가 시행되었던 6예 중 5예는 동맥기에서 조영 증강을 보였고 문맥기 및 지연기로 감에 따라 주변과 동일(4예)한 또는 감소(2예)되는 양상을 보여 간세포암종과의 감별이 어려웠다. 크기는 3.2±2.2㎝이었으며 위치는 간우엽의 후하구역(S6)에 가장 많았다(30.0%). 4예에서 수술 전 침생검을 시행하였으나 고분화 간세포암종이나 간세포선종과의 감별이 어려웠다. 결론: 임상상, 영상검사 및 간침생검으로도 간세포암종이나 간세포선종과의 감별이 어려운 경우 수술을 시행하였으며 수술 전에는 발견하지 못하였지만 다른 질환으로 인한 수술시 우연히 발견된 경우도 있어 국소 결절성 과형성의 수술 전 진단이 어려운 경우가 적지 않음을 알 수 있었다. Background/Aims: Focal nodular hyperplasia (FNH) is a benign hepatic tumor with few serious complications and no malignant transformation. However, differential diagnosis between FNH and other liver tumors, especially hepatocellular carcinoma, is often difficult. Methods: Clinical features of surgically resected FNH were reviewed. From January, 1995 to February, 2003, 10 patients with surgically resected FNH were enrolled. Their age, sex, results of laboratory examination, imaging studies and pathologic findings were evaluated. Results: Median age was 37.5 years and sex ratio (male:female) was 1.5:1. In 5 cases, resection to exclude hepatic adenoma or HCC was performed. Four cases were diagnosed incidentally after surgery. Four patients had risk factors for HCC, such as hepatitis B virus infection, liver cirrhosis or both. The size of FNH was 3.2 2.2 cm. The most common site of the tumor was segment 6 (30.0%). Differential diagnosis with HCC was difficult in 5 of six cases in whom CT was performed. Although needle biopsies were performed preoperatively in 4 cases, it was difficult to distinguish FNH from hepatic adenoma or HCC. Conclusions: FNH was resected due to uncertainty of diagnosis, or incidentally during hepatectomy in patients with other liver disease. In the former, differential diagnosis with hepatic adenoma or HCC was a major problem despite extensive work-up including dynamic CT or biopsy. (Korean J Hepatol 2004;10:135-141)

Basic, Research : Autophagy-related Marker LC3 can Predict Survival in Patient with Hepatocellular Carcinoma after Hepatic Resection

( Yoo Jin Lee ),( Yu Jin Ha ),( Yu Na Kang ),( Koo Jeong Kang ),( Woo Jin Chung ),( Jae Seok Hwang ),( Byoung Kuk Jang ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Patients and methods: Expression of autophagy related markers (LC3 and Beclin 1) and ER stress related markers (GRP78 and CHOP) were analyzed by immunohistochemistry on tissues from completely resected specimens of 190 HCC patients. Their influence on clinicopathologic features and prognosis were evaluated using Chi-square test and Kaplan-Meier analysis. Correlations of each proteins were determined by Spearman`s correlation analysis. Results: Expression of LC3 was not correlated with TNM, BCLC stage or Edmonson-Steiner grading, whereas, had correlation with longer overall survival (OS) (P=0.039) and longer disease free survival (DFS) (P=0.068) by Kaplan-Meier analysis. Multivariate analysis indicated that LC3 expression was significantly independent prognostic factors of OS (OR, 0.379; 95% CI, 0.192-0.748; P-value=0.005) and DFS (OR, 0.520; 95% CI, 0.299-0.843; P-value=0.009). Positive correlation was not observed in the expression of autophagy related markers with ER stress related markers. Conclusions: Our study showed that expression of LC3 was correlated with overall survival and disease free survival regardless of tumor staging or liver function state. These results suggest that expression and extent of LC3 might be a strong prognostic factor of HCC.