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      • Histone deacetylase 3 is selectively involved in L3MBTL2-mediated transcriptional repression

        Yoo, Jung-Yoon,Choi, Kyung-Chul,Kang, HeeBum,Kim, Young Jun,Lee, Jeongmin,Jun, Woo Jin,Kim, Mi-Jeong,Lee, Yoo-Hyun,Lee, Ok-Hee,Yoon, Ho-Geun Elsevier 2010 FEBS letters Vol.584 No.11

        <P><B>Abstract</B></P><P>This is the first report that L(3)mbt-like 2 (L3MBTL2) specifically interacts with the histone deacetylase domain of histone deacetylase 3 (HDAC3) via its MBT domain. Here, we show that L3MBTL2 selectively interacts with HDAC3, but not other class I HDACs. An in vitro peptide-binding assay demonstrated the specific association of HDAC3 with methylated histone-K20 tail and L3MBTL2. Furthermore, depletion of HDAC3 resulted in a decrease of methylated K20-H4, as well as an increase in acetylated histone H3. Consequently, HDAC3 knock-down selectively suppressed L3MBTL2-mediated transcriptional repression. Taken together, our results reveal the concerted action of both HDAC3 and L3MBTL2 in histone deacetylation and methylation-dependent transcriptional repression.</P><P><B>Structured summary</B></P><P>MINT-7719975: <I>L3MBTL2</I> (uniprotkb:Q969R5) and <I>HDAC3</I> (uniprotkb:O15379) <I>colocalize</I> (MI:0403) by <I>fluorescence microscopy</I> (MI:0416)</P><P>MINT-7719941, MINT-7719921: <I>L3MBTL2</I> (uniprotkb:Q969R5) <I>binds</I> (MI:0407) to <I>HDAC3</I> (uniprotkb:O15379) by <I>pull down</I> (MI:0096)</P><P>MINT-7719991: <I>HDAC3</I> (uniprotkb:O15379) <I>physically interacts</I> (MI:0915) with <I>L3MBTL2</I> (uniprotkb:Q969R5) by <I>anti bait coimmunoprecipitation</I> (MI:0006)</P><P>MINT-7719958: <I>L3MBTL2</I> (uniprotkb:Q969R5) <I>physically interacts</I> (MI:0915) with <I>HDAC3</I> (uniprotkb:O15379) by <I>anti tag coimmunoprecipitation</I> (MI:0007)</P><P>MINT-7719897: <I>HDAC3</I> (uniprotkb:O15379) <I>physically interacts</I> (MI:0915) with <I>L3MBTL2</I> (uniprotkb:Q969R5) by <I>two hybrid</I> (MI:0018)</P>

      • 새로운 Acetylcholinesterase inhibitors의 합성

        최순규,김형민,조승환,최학기,박유미,이용균,정대일,김인식,한정태 동아대학교 부설 기초과학연구소 2004 基礎科學硏究論文集 Vol.21 No.1

        노인성 치매의 일종인 alzheimer's disease의 효과적인 억제제를 합성하기 위해 우리는 분자 모델링에 의한 가장 적합한 물질인 m-[(N,N,N-trimethylammonio)phenyl]boronic acid를 합성하였다. 출발물질인 3-aminophenylboronic acid monohydrate의 경우 boronic acid의 작용기인 hydroxyl group을 protecting시킴으로써 반응의 안정성을 기하였다. Quarternary ammonium salt는 과량의 methyliodide와 염기 촉매인 potassium hydrogen carbonate를 사용하여 용매인 methanol에서 반응시켜 상당히 높은 수율을 얻을 수 있었다. 또한 과량의 methyliodide와 염기촉매인 potassium hydrogen carbonate를 사용하여 용매인 methanol에서 반응시킨 결과 boronic acid의 protection없이도 안정하게 반응이 진행되어짐을 확인할 수 있었다. In order to syntheisize a effective inhibotor for alzheimer's disease, we synthesized m-[(N,N,N-trimethylammonio)phenyl]boronic acid 4 which is designed by molecular modeling form. We protected the hydroxyl group of 3-aminophenylboronic acid monohydrate 1 with ethlyne glycol to remove the reactivity if hydroxyl group. To synthesize m-[(N,N,N-trimethylammonio)phenyl]boronic acid 4, we reacted 3-aminophenylboronic acid monohydrate 1 with ezcess methyl iodide and potassium hydrogen carbonate as a base-catalyst in methanol. but On executed reaction without protection on hydroxyl group, we found out the result that the hydroxyl group of boronic acid group at 3-aminophenylboronic acid monohydrate 1 didn't react with excess methyliodide. Synthesized m-[(N,N,N-trimethylammonio)phenyl]boronic acid 4 is in progress about biological tests as a plausible acetylcholinesterase inhibitor.

      • KCI등재
      • 농촌지역 노인들의 우울증상에 관련된 요인들의 특성

        송미숙,전기홍,송현종,김정은,박승구,신상건,이동훈,정성현,최연주,최완철,최민규,황재철,홍지만 아주대학교 1997 아주의학 Vol.2 No.2

        This study was performed to identify risk factors for depression among the elderly in a rural area. A survey was done for the elderly living in Gosam-myenn, Ansung-kun during the period of July 28, 1997 and July 30, 1997. Demographic and sodoeconornic characteristics, and functional and health Status were assessed using a structured questionnaire, and the level of depression was measured by GDS score. The data obtained were analyzed by frequencies, percentage, t-test, ANOVA, and multiple regression, and the results were as follows: 1. The total sample consisted of 133 elderly. Of them, 47 elderly (35.4%) showed significant depressive Symptoms. 2. The GDS score was the highest for the group over 85 years of age (p < 0.05). Those living alone or widowed showed lower GDS score than those living with someone or married (p < 0.05). 3. The GDS score was the highest in the absolutely dependent group, followed by the partially dependent group, and the independent group (p < 0.01). The elderly who perceived their health Status as excellent showed the lowest GDS score. In contrast, those who had more than five chronic diseases showed the highest GDS score. 4. The elderly receiving financial and emotional support from their family or friends showed lower GDS score compared to those without any support. 5. The economically dependent group showed higher GDS score than that of independent group. 6. The elderly who involved in leisure activities showed lower GDS score than those without any involvement. 7. In terms of risk factors for depression, we found that perceived health Status, subjective economic Status, leisure activities, living arrangement and financial support were inversely associated with GDS score, whereas labor support was positively associated with GDS score. Based upon the above findings, this study suggests that these risk factors for depression in the elderly should be taken into consideration for a comprehensive mental health program for the elderly living in the rural area.

      • KCI등재후보

        우리나라 일부 석면사업장의 석면폐 유병률

        백도명,백남원,최정근,손미아,임정기,이원진,문영한,박정선,최병순 大韓産業醫學會 1995 대한직업환경의학회지 Vol.7 No.1

        Asbestos industry has been in operation over 60 years in Korea. However, the prevalence of asbestosis has not been yet reported. With rapid turn-over of workers, previous cross-sectional studies of current workers on the job could not find cases with exposures long enough for the development of asbestosis. This study was done to evaluate asbestosis prevalence of those worksites with operation history of more than 20 years. In total, 139 workers from 5 worksites were examined. Asbestos industries covered in the study include 2 asbestos textile, 1 brake lining, and 2 ship repairing worksites. Chest x-ray was taken from all workers and read by two experts familiar with pneumoconiosis classification according to 1980 ILO guidelines. Those with findings compatible with asbestosis were further ckecked with high resolution computerized tomography (HRCT). Pulmonary function tests were done according to ATS guidelines, and occupational and previous medical history was taken through a standardized interview. Air-borne asbestos was measured according to NIOSH method 7400. The air-borne asbestos concentrations ranged from 0.2-1.3 f/cc for asbestos textile, from 0.7-1.0 f/cc for brake lining, and from 6.3-7.8 f/cc during asbestos removal at ship repairing worksite. Of the 139 workers 25 had abnormal chest radiographic findings, and 10 of them had findings compatible with pneumoconiosis. When work history and current asbestos measurements were accounted, 9 workers who had more than 10 years of asbestos exposure history showed chest radiographic findings of pneumoconiosis with Finally, 4 workers showed finding of pulmonary fibrosis and/or pleural thickening at HRCT, and 2 of them had restrictive lung function changes. The study results showed that, among 139 subjects, there were 4(3%) definite asbestosis cases confirmed with HRCT. The prevalence of probable asbestosis was 7% for 10-14 years of exposure, 13% for 15-19 years of exposure, and 23% for 20 or more years of exposure. The prevalence of compensable asbestosis with abnormal lung function was 4-6% for those with 15 or more years of exposure.

      • 1,2-Benzisothiazol-3-one-1,1-Dioxide 유도체의 합성

        정대일,정희철,변석인,이용균,박유미,최순규,한정태 東亞大學校附設基礎科學硏究所 2002 基礎科學硏究論文集 Vol.19 No.1

        사카린 유도체는 제초제, 항독성, 살균제 등에 광범위하게 연구되어져 오고 있다. 새로운 농략 활성을 가진 물질을 합성하기 위해 먼저 선도물질로 사카린 1을 산화, 염소화 시킨 3-chloro-1,2-benzisothiazol-1,1-dioxide(BID-CI) 2와2cholromethy-1,2-benzisohizol-3-one1,1-dioxide 4를 합성하였다. 선도물질, amines, imidazoles, trones등과 반응시켜 다음과 같은 물질들을 얻었다. ; 3-cyclohexylamino-1,2-benzisothiazol-1,1-dioxide 6, 3-furylamino-1,2-benzisothiazol-1,1-dioxide 8, 3-(3-imidazol)-1,2-benzisothiazol-1,1-dioxide 10, 3-(2-methy-3-imidazol)-1,2-benzisothaizol-1,1-dioxide 12, 2-(3-imidazol)methy-1-1,2-benzisothiazol-3-one-1,1-dioxide 13, and 2-(-3-imidazol)methyl- 1,2-benzisothiazol-1,1-dioxide 14.

      • 社會經濟水準에 따른 都市 未就學兒童의 營養 및 健康狀態에 관한 調査硏究

        崔美茶,李中姬 카톨릭대학교 생활과학연구소 1985 생활과학연구논집 Vol.5 No.1

        The purpose of this study was to investigate the difference of nutritional and growth status for two preschool children with different socio-economic status. This study was conducted from June 10, 1984 to July 12, 1984. The information about general socio-economic status was obtained by survey questionnarre. Three day food recording method was utilized to assess food consumption and measured to estimate the difference of growth rate between the two groups. Hemoglobin and Hematocrit levels were also measured to assess the prevalence of anemia. According to these results. 1. Higher Educatonal status of mother and monthly income of each household were observed in Y, but higher Engel's coefficient was obtained in M. 2. Eventhough average nutrient intake was adequate compared to RDA for most of the preschool children in Y, inadquate intake of Ca, Fe, and Vit B2 were observed for 11.9%, 1.7%, and 2% of the preschool children, respectively. All the nutrients in take were observed below RDA in M expect Vit A, Vit B1 and Niacin. 42%, 18.7% and 10.4% of preschool children exhibited inadquate intake of Ca, Fe and Vit B2, respectively. 3. The proportion of preschool children with weight, height and skinfold thickness below standard in Y was significantly lower than those of preschool children in M(P<0.01). 4. Hemoglobin and hematocrit levels were positively correlated to the Calorie, protein, Fe and Vit. C intake in both area. It is suggestion nutritional education program in two areas.

      • KCI등재

        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.

      • KCI등재후보

        조혈모세포이식 환자에서 침습성 진균 감염에 대한 이트라코나졸 액과 플루코나졸 시럽의 예방 효과 : 전향적, 무작위, 비교 임상시험

        최수미,이동건,최정현,박선희,엄기성,김유진,김희제,민창기,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2005 감염과 화학요법 Vol.37 No.2

        목적 : 조혈모세포이식 환자에서 호중구 감소 기간 동안 이트라코나졸 액(ITZS)과 플루코나졸 시럽(FCZS)의 진균 감염에 대한 예방 효과를 전향적으로 비교해 보고자 하였다. 재료 및 방법 : 2001년 8월부터 2002년 6월까지 가톨릭 조혈모세포이식센터에 입원하여 동종 조혈모세포이식을 받은 만 18세 이상의 환자들을 각각 ITZS와 FCZS군으로 무작위 배정하여 침습성 진균 감염 발생과 약제 관련 부작용을 전향적으로 조사하였다. 결과 : ITZS군에 40명, FCZS군에 38명이 배정되었고, FCZS군 환자의 평균 나이가 더 많았다. 시험 약제 평균투여기간은 ITZS군 16.4일, FCZS군 21.9일로 ITZS군이 더 짧았다. 이는 ITZS군에서 소화기 부작용으로 인한 약제 중단이 더 많았기 때문으로 보인다. 시험 약제 투여 후 총 빌리루빈 수치의 유의한 증가가 관찰되었으나, 약제 관련 부작용은 모든 환자에서 가역적이었다. 호중구감소 기간동안 표재성 진균 감염은 두 군에서 모두 발생하지 않았고, 침습성 진균 감염은 ITZS군 5명(12.5%), FCZS군 8명(21.1%)으로 FCZS군에서 많았으나, 통계학적으로 유의하지 않았고, 사망률에도 유의한 차이는 없었다. 결론 : 침습성 진균 감염에 대한 이트라코나졸 액과플루코라졸 시럽의 예방 효과에 유의한 차이는 없었으나, 앞으로 더 많은 환자를 대상으로 잘 짝지어진 대조군 연구가 필요할 것으로 보인다. 부작용 중 간독성과 관련하여 이식시 투여되는 여러 약제들과의 상호작용에 대한 연구도 필요할 것이다. Background : Though fluconazole is widely used for antifungal prophylaxis, it is ineffective against mould infections including Aspergillus species. Itraconazole has a broader spectrum than fluconazole but the capsule form shows erratic bioavailability in neutropenic patients. In this study, we compared itraconazole oral solution (ITZS) with fluconazole syrup (FCZS) for the prevention of invasive fungal infection (IFI) in allogeneic hematopoietic stem cell transplant recipients. Materials and Methods : Adults receiving allogeneic hematopoietic stem cell transplantation (HSCT) from september 2001 to June 2002, were randomly allocated to either the ITZS group or the FCZS group. We prospectively evaluated the safety and efficacy of each drug. Results : Out of 78 patients (40 patients in the ITZS group and 38 patients in the FCZS group) who were eligible for this study, 37 patients completed the course of prophylaxis without any evidence of IFI. The mean duration of prophylaxis was 16.4 days for the ITZS group and 21.9 days for the FCZS group (P<0.006). Drug-related adverse events occurred in 28 patients (70.0%) and 19 patients (50.0%) in the ITZS group and the FCZS group, respectively. Common adverse events of ITZS were nausea, vomiting, and diarrhea. Drug-related reversible hepatotoxicity occurred in 4 patients in the ITZS group. There was a significant elevation of total bilirubin level in the ITZS group. The incidence of suspected IFI occurred in 5 patients (12.5%) who received ITZS, compared with 8 (21.1%) who received FCZS (P=0.372). There were no proven IFIs or superficial (oral/vaginal) fungal infections in both groups. Overall mortality was not different between the two groups (2.5% in the ITZS group versus 5.3% in the FCZS group, P=0.610). Conclusion : ITZS and FCZS showed similar protection against IFI during pre-engraftment period. Poor tolerability due to gastrointestinal troubles of ITZS might limit its success as prophylactic therapy. Well matched controlled study with large number of patients will be required in the future.

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