Assessment of Hepatic Steatosis Improvement Using Controlled Attenuation Parameter in Patients with Non-Alcoholic Fatty Liver Disease under Regular Follow Up

( Kyu Sik Jung ),( Jun Yong Park ),( Mi Na Kim ),( Hana Park ),( Yun Bin Lee ),( Joo Ho Lee ),( Yeonjung Ha ),( Beom Kyung Kim ),( Seung Up Kim ),( Sang Hoon Ahn ),( Do Young Kim ),( Hana Park ),( Kyu 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: The change of hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) patients under regular follow up has not been widely investigated. We investigated the serial changes of hepatic steatosis assessed by controlled attenuation parameter (CAP) and the predictors for improvement of hepatic steatosis in NAFLD patients. Methods: Among 513 NAFLD patients diagnosed upon ultrasound and CAP > 250 dB/m at baseline, 304 patients underwent repeated CAP measurement at baseline and at follow up. The improvement of hepatic steatosis was defined as a >10% decline of CAP value from the baseline. Results: Mean age of 304 patients was 58.8 ± 11.4 years and 80.1% were male. The mean CAP value significantly decreased from baseline to follow up (292.3 dB/m to 277.1 dB/m, P<0.001). During the median follow up of 15.3 (9.5-20.3) months, 34.5% patients showed improvement of hepatic steatosis. In a univariate analysis, low body mass index (BMI), low weight, low liver stiffness value, low triglyceride level, and low ALT at follow up were predictors for improvement of hepatic steatosis. In multivariate analyses, low weight (P=0.004; hazard ratio [HR],0.965; confidence interval [CI], 0.941-0.988) and low ALT (P=0.004; HR,0.971;CI, 0.951-0.990) at follow up, or low BMI (P=0.006; HR,0.881; CI, 0.805-0.964) and low ALT (P=0.004; HR,0.971; CI, 0.951-0.990) at follow up were the independent predictors. In patients with weight reduction more than 10% (n=22), CAP value significantly decreased (from 288.0 dB/m to 228.9dB/m, P<0.001). Conclusions: Weight reduction, and ALT decrease were independent predictors for improvement of hepatic steatosis. Long term effect of weight reduction on improvement of hepatic steatosis and fibrosis should be investigated further.

Dkk-1 Promotes Angiogenesis through Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma

( Sang Hyun Seo ),( Hye Jung Park ),( Kyungjoo Cho ),( Hye Won Lee ),( Beom Kyung Kim ),( Jun Yong Park ),( Do Young Kim ),( Sang Hoon Ahn ),( Seung Up Kim ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Dickkopf-1(DKK1), a negative regulator of the Wnt/ ß-catenin pathway, has been recently found to be up-regulated in hepatocellular carcinoma (HCC). However, the biological function of DKK1 in HCC has not yet been well documented. Our previous in vitro data suggest that DKK1 can enhance angiogenesis by endothelial cell, independent of the Wnt signaling pathway. This study aimed to investigate the tumorigenic potential and angiogenic role of DKK1 in mouse model. Methods: We assessed tumorigenic functions of DKK1 in Hep3B cells expressing endogenous DKK-1 and in DKK1-deficient Hep3B cells created using CRISPR/Cas9 technology. These edited cells were injected subcutaneously in immunosuppressed mice and tumor growth was followed for 6 weeks. With the evidence of tumorigenic potential in DKK1, transgenic mouse models expressing DKK-1 or luciferase were developed using hydrodynamic transfection. Transposons encoding an activated form of human H-RAS were mixed with transposons encoding either DKK1 or luciferase. All mice were monitored at least twice per week and sacrificed when moribund. Subcutaneous tumors and tumor-bearing livers were formalin fixed for hematoxylin- eosin and immunofluoroscence staining. Results: DKK1-deficient Hep3B xenografts exhibited significantly less growth compared to control Hep3B cells expressing DKK1. In addition, the forced expression of DKK1 with H-RAS through the hydrodynamic transfection formed many tumors in the liver, compared to luciferase liver. We investigated the expression of angiogenesis markers, including CD31, VEGFR2 and mesenchymal markers, including vimentin, fibronectin in the subcutaneous tumors and tumor-bearing livers. Quantity of angiogenic and mesenchymal cells were found to be reduced in the established DKK1 homozygous knockout mice (all P<0.05). Taken together, it was confirmed that the expression of CD31 (P<0.0001), VEGFR2 (P<0.0001), vimentin, and fibronectin (P<0.0001) were up-regulated with DKK1 in the mouse liver. Conclusions: Our findings indicate that DKK1 appears to facilitate angiogenesis, and the progression of HCC through inducing the EMT.

Uncoupling Protein 3의 골격근 세포내 과발현이 OLETF 백서 및 배양된 골격근 세포에서 포도당대사에 미치는 영향

한정희,박혜선,고정민,김하영,강호경,이인규,박중열,홍성관,이재담,이기업 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.6

연구배경:Uncoupling protein(UCP)는 미토콘드리아의 내막에 위치하는 단백질로 세포내의 과다한 에너지를 열로 발산시키는 기능을 가진다. 최근 동물의 갈색지방조직에만 존재하는 UCP와 유사성을 가진 아형들(UCP2,3)이 사람에게도 존재함이 알려져 큰 관심을 끌도 있는데 이중 UCP3는 그 발현이 골격근세포와 갈색지방조직에만 국한된다. 본 연구에서는 UCP3가 체내 인슐린 감수성을 결정하는데 가장 중요한 조직인 골격근에 국한되어 발현되는 점에 착안하여 UCP3를 골격근세포에 과발현시켰을 때 포도당 대사에 어떠한 영향이 나타나는 지를 조사하였다. 방법:25주령의 8마리의 OLETF 백서를 대상으로 하여 4마리는 골격근에 adenovirus 2mL(1×10¹²pfu/mL)를 주사하여 대조군으로 하였고 4마리는 골격근에 재조합법으로 제작된 adenovirus­UCP3 2mL(1×10¹²pfu/mL)를 주사하였다(UCP3 과발현군). UCP3를 투여한 백서에서 먹이섭취가 증가하는 경향이 있어 그 전날 대조군이 먹은 야의 먹이만큼 투여하였다. 골격근에 adenovirus를 주사한 10일 후에 euglycemic hyperinsulinemic clamp를 시행하였다. Adenovirus­UCP를 C2C12 골격근 세포에 transfection시켜 UCP3를 C2C12 골격근 세포에 transfection시켜 UPS3­C2C12를 만들고 C2C12 골격근 세포와 UPS3­C2C12 골격근 세포에서 포도당 수송 및 당원합성을 측정하였다. 결과:UCP3 과발현 OLETF에서 체중이 감소하는 경향을 보였고 인슐린 감수성이 증가하였다. C2C12세포에서 기저상태 포도당 수송은 1.28±0.17μmol/L/min였고 100nM 인슐린으로 2시간 처리한 후 2.67±0.20 μmol/L/min로 증가하였다. UCP3­C2C12 세포에서는 기저상태 포도당 수송이 3.98±0.13μmol/L/min로 증가되었고 인슐린 처리 후 5.74±0.44μmol/L/min로 증가하였다. 인슐린을 처리한 UCP3­C2C12 세포에 P13K 억제제인 wortmannin을 첨가하였을 때 포도당 수송활성이 3.81±0.20μmol/L/min로 감소하였다. 기저상태 당원합성은 C2C12 세포에서 0.25±0.01μmol/L/min였고 인슐린 처리 후 0.45±0.01μmol/L/min로 증가하였다. UCP3­C2C12 세포에서는 기저상태 당원합성이 0.62±0.01μmol/L/min였고 인슐린 처리 후 1.26±454μmol/L/min로 증가하였다. UCP3­C2C12세포에 wortmannin을 첨가하였을 때 당원합성율이 0.80±0.04μmol/L/min로 감소하였다. 결론:UCP3 과발현이 OLETF 백서에서 인슐린 감수성을 증가시켰고 골격근세포에서 포도당 수송 및 당원합성을 증가시켰다. wortmannin을 첨가하였을 때 포도당 수송 및 당원합성이 감소함으로 보아 이 과정이 인슐린 신호전달체계인 P13K에 일부 의존함을 알 수 있었다. Background : UC P3 is a mitochondrial membrane protein expressed selectively in the skeletal muscle and brown adipose tissue. Since the skeletal muscle is the main organ determining insulin sensitivity in the body, it was hypothesized that UCP3 overexpression in skeletal muscle cells would improve glucose metabolism. Methods : An adenovirus-UCP3 was produced by a recombinant DNA method. OLETF rats were divided into 2 groups. Four rats were injected with the adenovirus-UCP3 (UCP3 group) and others were injected with the adenovirus(control group) in the skeletal muscle. The UCP3 group was provided with the same quantity of food as that consumed by the control group on the previous day. Insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp method. In a separate experiment, glucose transport and glycogen synthesis we evaluated in C2C212 cells transfected with ether an adenovirus or the adenovirus-UCP3. Results : The insulin sensitivity improved significantly and the body weight decreased in the UCP3 group. The glucose transport and glycogen synthesis were higher in the UCP3-C2C12 skeletal muscle cells at the basal state. After insulin treatment, glucose transport and glycogen synthesis were also higher in the UCP3-C2C12 cells but the increments were reduced after treatment with wortmannin, a PI3K inhibitor. Conclusion : Insulin sensitivity was higher in the UCP3-overexpressed OLETF rats in the in vivo study. UCP3 transfection also increased glucose transport and glycogen synthesis in the cultured skeletal muscle cells by a PI3K dependent mechanism(J Kor Diabetes Asso 25 :460~468, 2001).

Comprehensive analysis of time- and dose-dependent patterns of gene expression in a human mesenchymal stem cell line exposed to low-dose ionizing radiation.

Jin, Young-Woo,Na, Young-Ji,Lee, Young-Ju,An, Sungkwan,Lee, Jung Eun,Jung, Meeseon,Kim, Heesun,Nam, Seon Young,Kim, Cha Soon,Yang, Kwang Hee,Kim, Seung Up,Kim, Woo Kyung,Park, Woong-Yang,Yoo, Keun-You National Hellenic Research Foundation 2008 ONCOLOGY REPORTS Vol.19 No.1

<P>We focused on the transcriptional responses induced by low and very low doses of ionizing radiation with time effect. Regardless of their importance only a few limited studies have been done. Here we applied a large-scale gene transcript profile to elucidate the genes and biological pathways. Immortalized human mesenchymal stem cells were irradiated with 0.01, 0.05, 0.2 and 1 Gy of gamma radiation and total RNA was extracted from each cell line at 1, 4, 12 and 48 h after exposure. The essential transcriptional responses were identified according to dose and time. A total of 6,016 genes showed altered expression patterns at more than one time point or dose level among the investigated 10,800 genes. Genes that showed dose-dependent expression responses were involved in signal transduction, regulation of transcription, proteolysis, peptidolysis and metabolism. Those that showed time-dependent responses were divided into two distinct groups: the up-and-down group was associated with 'cellular defense mechanisms' such as apoptosis, cell adhesion, stress response and immune response and the down-and-up group with 'fundamental cellular processes' such as DNA replication, mitosis, RNA splicing, DNA repair and translation initiation. Genes showing both dose-and time-dependent responses exhibited a mixture of both features. A highly non-linear relationship between the IR dose and the transcriptional relative response was obtained from the dose-dependent group. The time-dependent group also exhibited a non-linear relationship as the complex effect group did. Some of the early-reactive-phase (1-4 h) genes showed a differential expression response to 0.01, 0.05 and 0.2 Gy but were unresponsive to 1 Gy. Some of the late-recovery-phase (12-48 h) genes showed a differential expression to 1 Gy but were relatively unresponsive to other doses. We further characterized the gene expression patterns that could be implicated in the molecular mechanism of the cellular responses to low and very low-dose irradiation.</P>

파종시기가 다른 일미찰의 등숙 중 호화 특성 비교

김미정, 박효진, 이유영, 김선림, 김정태, 우관식, 권영업, 정일민 忠北大學校 農業科學硏究所 2014 農業科學硏究 Vol.30 No.2

This study was conducted to investigate the pasting properties of waxy corn ‘Ilmichal’ during ripening with different sowing date. Starch content of Ilmichal was increased as matured (p<0.05). Analysis of pasting properties with waxy corn starch using a rapid visco analyser (RVA) showed linear changes in peak viscosity, trough viscosity, final viscosity, breakdown and consistency according to ripening. There were significantly positive correlation between starch content of Ilmichal and peak viscosity (0.39*), trough viscosity (0.58***), final viscosity (0.58***), and consistency (0.57**). Differential scanning calorimerty (DSC). The enthalpy of gelatinization was increased as ripening. But onset and peak temperature were decreased. There were significantly positive correlation between starch content of Ilmichal and onset temperature (0.44*), peak temperature (0.38*), and completion temperature (0.59***), on the other hand, crude protein content presented significantly negative correlation between completion temperature (-0.41*).

뉴로메드정(옥시라세탐 800㎎)에 대한 뉴라세탐정의 생물학적동등성

최성업,김종석,윤미경,김정일,박석,한상범,이재휘,최영욱 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.3

The purpose of the present study was designed to evaluate the bioequivalence of two oxiracetam tablets, Neuromed tablet (Korea Drug Co., reference drug) and Neuracetam tablet (Sam Jin Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Release of oxiracetam from the tablet in vitro was tested using KP Ⅷ Apparatus Ⅱ method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty-four healthy volunteers, 23.7 ± 2.4 year in age and 68.9 ± 6.2 ㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was performed. After oral administration of a tablet containing 800 ㎎ of oxiracetam, blood samples were taken at predetermined time intervals and concentrations of oxiracetam in plasma were determined using HPLC-MS-MS. The dissolution profiles of two formulations were very similar at all dissolution media. In addition, pharmacokinetic parameters such as AUCt, C_(max) and T_(max) were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed AUC, and C_(max), untransformed T_(max). The results showed that the differences between two formulations based on the reference drug were 0.42%, 0.45% and -12.58% for AUCt, C_(max) and T_(max), respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log0.94 ~ log1.06 and log 0.90 - log 1.07 for AUCt and C_(max), respectively), indicating that Neuracetam tablet is bioequivalent to Neuromed tablet. The major pharmacokinetic parameters, AUCt, and C_(max), met the criteria set by KFDA for bioequivalence indicating that Neuracetam tablet is bioequivalent to Neuromed tablet.

중부지역 옥수수 파종기에 따른 생육단계 및 수량성 변화

서종호, 문중경, 정건호, 서민정, 구자환, 박장환, 배환희, 신성휴, 권영업 忠北大學校 農業科學硏究所 2014 農業科學硏究 Vol.30 No.2

Maize hybrids were planted on April 1, April 25, May 20 and June 15 in 2012, 2013 at the experimental paddy and upland fields in Suwon city , respectively to know changes of growth stage and yield according to different planting time. Maize planting on April 1 was not recommended because total growing days at planting on April 1 was not different with that at planting on April 25 due to many days from planting to emergence over 20 days at planting on April 1. Total growing days were not much different among three planting time after April 25 because days from silking to maturity was lengthened though days from planting to silking was shortened at later planting time. Stalk weight was decreased as planting time was delayed, particularly at planting times after May 20 at paddy field by excess water injury during early growth stage. But, grain yield was not low as in May and June. It is needed to introduce early maturity maize variety as Yanganok at late planting for higher grain yield and enough time for soil preparation for next winter crops

침 시술로 발생한 Non-O1, Non-O139 Vibrio cholerae에 의한 패혈증

임태섭,지아영,이중희,장수연,김인수,김영주,김범경,김승업,박준용,안상훈,한광협,김도영 Ewha Womans University School of Medicine 2013 EMJ (Ewha medical journal) Vol.36 No.S

Vibrio cholerae is mainly known to cause gastrointestinal infection after seawater exposure or raw seafood intake. It is rarely reported to cause cellulitis or sepsis, but threre has been no known case after acupuncture. Herein, We report a 56-year-old cirrhotic patient of non-O1, non-O139 Vibrio cholerae septicemia caused by cellulitis of both lower extremities after acupuncture.

Factors associated with successful adherence to follow-up among adult asthma patients: three year follow-up study from a tertiary hospital (초)

( Woo Jung Song ),( Jae Woo Jung ),( Min Hye Kim ),( Jae Woo Kwon ),( Tae Wan Kim ),( Sae Hoon Kim ),( Hye Ryun Kang ),( Heung Woo Park ),( Yoon Seok Chang ),( Sang Heon Cho ),( Kyung Up Min ),( Yoo Y 대한내과학회 2010 대한내과학회 추계학술대회 Vol.2010 No.-

Survival Rates of Breast Cancer Patients Aged 40 to 49 Years according to Detection Modality in Korea: Screening Ultrasound versus Mammography

Won So Yeon,Park Hyung Seok,Kim Eun-Kyung,Kim Seung Il,Moon Hee Jung,Yoon Jung Hyun,Park Vivian Youngjean,Park Seho,Kim Min Jung,Cho Young Up,Park Byeong-Woo 대한영상의학회 2021 Korean Journal of Radiology Vol.22 No.2

Objective: The aim of this study was to compare the survival rates of Korean females aged 40 to 49 years with breast cancer detected by supplemental screening ultrasound (US) or screening mammography alone. Materials and Methods: This single-institution retrospective study included 240 patients with breast cancer (mean age, 45.1 ± 2.8 years) detected by US or mammography who had undergone breast surgery between 2003 and 2008. Medical records were reviewed for clinicopathologic characteristics and detection methods. Disease-free survival (DFS) and overall survival (OS) were compared between patients with breast cancer in the US and mammography groups using the log-rank test. Multivariable cox regression analysis was used to identify independent variables associated with DFS and OS. Results: Among the 240 cases of breast cancer, 43 were detected by supplemental screening US and 197 by screening mammography (mean follow-up: 7.4 years, 93.3% with dense breasts). There were 19 recurrences and 16 deaths, all occurring in the mammography group. While the US group did not differ from the mammography group in tumor stage, the patients in this group were more likely to undergo breast-conserving surgery and radiation therapy than the mammography group. The US group also showed better DFS (p = 0.016); however, OS did not differ between the two groups (p = 0.058). In the multivariable analysis, the US group showed a lower risk of recurrence (hazard ratio, 0.097; 95% confidence interval, 0.001–0.705) compared to the mammography group. Conclusion: Our study found that Korean females aged 40–49 years with US-detected breast cancer showed better DFS than those with mammography-detected breast cancer. However, there were no statistically significant differences in OS.