HMG-CoA 환원효소 억제제에 의한 ICAM-1 유전자의 발현조절

김현진,정효균,홍우정,김군순,조영석,김도희,채수흥,구본정,송민호,노흥규,김영건 충남대학교 의과대학 지역사회의학연구소 2001 충남의대잡지 Vol.28 No.1

Background : ICAM-1 act as one of major adhesion molecules in the atherosclerotic lesion. ICAM-1 expression is mainly regulated at the level of transcription and depend on IFN-γ signal transduction pathway in which the STAT1 transcrption factor is a critical intermediate. IFN-γreceptor not only initiates tyrosine 701 phosphorylation of STAT1 by Jak1 and Jak2, but also phosphorylates serine 727 through the activation of Raf-1/MAP kinases. HMG-CoA reductase inhibitors have anti-atherosclertic effects, beyond normalization of hypercholesterolemia, by directly acting on endothelial cells, macrophages and vascular smooth muscle cells. HMG-CoA reductase inhibitors suppress the synthesis of isoprenoid intermediates such as geranylgeranyl-pyrophosphate or farnesylpyrophosphate. These effects results inhibitors suppress the synthesis of isoprenoid intermediates such as geranylgeranyl-pyrophosphate or farnesylpyrophosphate. These effects results inhibition posttranslational farnesylation and geranyl-geranylation processing of small GTP-binding preoteins and inhibition of normal signaling activities. Method : We made several 5'-deletion constructs of rat ICAM-1 promoter and analyzed the promoter activities by measuring the luciferase activity after transfection into ECV304 cells and smooth muscle cells. We checked the level of total and phosphorylated STAT1 protein by immunoblot analysis using specific antibodies. Results : Lovastatin inhibits IFN-γ-induced ICAM-1 gene expression in the ECV304cell. The cells pretreated with PD98059, MEKK inhibitor showed significantly low ICAM-1 RNA induction with IFN-γ stimulatio. IFN-γ induced phosphorylation of tyrosine 701 was not significantly changed by the pretreatment of lovastatin. But lovastatin suppresses IFN-γ-induced phosphorylation of ERK1/ERK2 which are responsible for the seine 727 phosphorylation in STAT1. Conclusion : We showed that HMG-CoA reductase inhibitors, lovastatin, suppresses IFN-γ mediated ICAM-1 gene expression through the inhibition of transcription. HMG-CoA reductase inhibitor suppresses IFN-γ-induced phosphorylation of serine 727 in STAT1 through the modulation of MAP kinases.

갑상선 세포에서 전사보조활성인자인 CBP와 CIITA의 인터페론-감마 활성 부위에 대한 조절 : CBP and CIITA on GAS(Interferon- γ Activated Site)-Mediated Transcription in Thyroid Cells

채수흥,홍우정,김군순,조영석,김도희,김현진,구본정,송민호,김영건,노흥규 충남대학교 의과대학 지역사회의학연구소 2001 충남의대잡지 Vol.28 No.1

Background : In the previous stuides, we identified that the interferon-r activated sequence (GAS) in the 5-flanking region of rat ICAM-1 gene is major element for interferon-r-inducible expression of the gene in rat thyroid cells, FRTL-5. We here, investigated the role of transcriptional coactivators, CBP(CREB binding protein) and CⅡTA (class Ⅱ transactivator) in the modulation of the activity of GAS which could interacts with signal transducers and activators of transcription-1 and 3 (STAT1 and STAT3). Methods : The expression of CBP RNA and protein were quantitated in FRTL-5 after stimulation with interferon-r (IFN-r), thyroid stimulating hormone (TSH), forskolin and methimazole. Direct association of CBP with STAT were analyzed by immunoprecipitation. The transcriptional roles of CBP and CⅡTA in the regulation of GAS were assessed by the cotransfection with their expression vectors with reporters; 5-deletion constructs of rat ICAM-1 promoter or 8xGAS-luc constructs, into FRTL-5 thyroid cells. Results : The level of CBP RNA and protein were not changed by the treatment with TSH, IFN-r, forskolin and methimazole in FRTL-5, FRT and BRL liver cells. The CBP could be directly associated with STAT1. Furthermore, the overexpression of CBP significantly increases the both promoter activities; rat ICAM-1 gene promoter which has GAS element and 8xGAS-luc cassette constructs. However, the cotransfection of CⅡTA decreased the constitutive and CBP-mediated transactivation of rat ICAM-1 promoter and 8xGAS-luc cassette constructs. Conclusion : We identified that the two tanscriptional coactivators; CBP and CⅡTA has differential roles in the regulation of transcriptional activity of GAS drived promoter. CBP increases the GAS activity through the direct binding with STAT1, but CⅡTA inhibited the CBP-mediated transactivation of GAS activity.

고령자를 위한 주거시설 치수 표준화 연구

김석준,권순정,오은진,김노석,김상길,이특구 한국의료복지시설학회 2008 의료·복지 건축 Vol.14 No.3

As the elderly population is growing rapidly, guidelines for planning and designing of the elderly housing are required for improving housing environment of the elderly. The purpose of this study is making the basic dimensional standardization of residential spaces for the elderly. The dimensional standard of spaces suggested in this guideline considers characteristics of both aged and the general users. The spaces studied in this research include bedroom, living room, bathroom, kitchen and other circulation spaces in the elderly housing. The design guidelines of furniture, equipment for the aged with sizing of the areas are provided. Finally, applicability of the output is reexamined by implementing this guidelines to the sample planning and design of the elderly housing

양성 갑상선 결절에서의 무수 알코올 치료 효과

김도희,나소영,이효진,홍우정,김군순,조영석,구본정,송민호,김영건,노흥규 충남대학교 의과대학 의학연구소 2002 충남의대잡지 Vol.29 No.1

목적 : 양성 갑상선 결절 환자에서의 PEI의 치료효과 및 부작용을 알아보고자 하였다. 방법 : 양성 갑상선 결절 환자 88명을 대상으로 초음파 소견에 따라 낭종성 결절, 복합성 결절, 고형성 결절 등 세 그룹으로 분류후 전체 및 각각에 대한 PEI의 치료효과 및 부작용을 조사하였다. 결과 : 양성 갑상선 결절 환자 88명을 PEI로 치료후 결절의 크기가 50%이상 감소한 경우는 전체 환자중 77.2%이었고 각 결절별로 살펴보면 고형성 결절에서 52.6%, 복합성 결절에서 72.4%, 낭종성 결절은 92.5%이었다. 부작용은 동통, 결절내 출혈, 감염, 결절의 누출등이 있었으나 대부분 무증상이었다. 결론 : PEI는 양성 갑상선 결절 환자증 적응증을 잘 살펴 고려해 볼 수 있는 치료법이라 생각되며 특히 낭종성 결절 환자에서 주사기에 의한 흡인후에 재발한 경우 일차적인 치료로 PEI를 고려해 볼 수 있겠다. Ultrasonography(US)-guided percutaneous ethanol injection (PEI) has been performed for the treatment of autonomous functioning thyroid nodules, thyroid cysts, & cold thyroid nodules. The author studied the efficacy of PEI in the treatment of benign cold thyroid nodules both solid and cystic (complex & pure). Eighty-eight euthyroid outpatients (age:44.2±13.9years, 75 women and 13 men) with benign cold thyroid nodules or simple thyroid cysts (69 with a single nodule and 19 with a prominent nodule within multinodular goiter) were includied in this study. After PEI, each subtype of thyroid nodules was divided into three groups in according to volume reduction complete response (90% or more of volume reduction), partial response (50% or more of reducton but below 90%), and failure (below 50% or increase in size) group. Overall response rates of PEI for benign thyroid nodules were complete 45(51.1%), partial 23(26.1%), failure 20(22.7%). In 20 cold solid nodules, complete response was observed in 6(30.0%), partial response in 5(25.0%), and failure in 9(45.0%). In 28 complex cysts, complete response was observed in 8(28.6%), partial response in 12 (42.9%), and failure in 8(28.6%). In 40 pure cysts, complete response was observed in 31(77.5%), partial response in 6 (15.0%), and failure in 3 (7.5%). Side effects comprised pain 8 (9.2%), intranodular bleeding 13 (14.6%), extracapsular leakage 1(1.1%), infection 1 (1.1%), increased size l(1.1%), and none 64(72.7%). PEI may prove a safe & effective tool for the therapy of cold thyroid nodules in selected cases and may be the treatment of choice of recurrent thyroid cysts. However, further investigation involving a larger number of patients and a longer follow-up is needed.

노인요양시설의 적정 침실 면적에 관한 연구

권순정,한정한,오은진,김석준,김노석,이특구 한국의료복지시설학회 2008 의료·복지 건축 Vol.14 No.3

The purpose of this study is to suggest optimum size of residents' bedrooms in nursing homes. Bedroom is an essential part of nursing homes because nursing home residents spend most of their times in bedrooms and occupy the largest part of facility area. Therefore it is necessary to set an adequate standard related to resident room area in nursing facilities, which have a great effect on planning longterm care facilities for the elderly. The body dimensions of elderly people and care givers have been collected from the previous study. Based on the body dimensions data, the behaviors of elderly as well as care givers have been analysed. The minimum areas-exclusive of toilets, closets, vestibules and so on - have been proposed from the results of the behavior analysis.

발작과 의식저하를 동반한 급성 Methyl Bronmide 중독 2예

조광덕,임수빈,이순금,최성훈,김태훈,한군희,송경일 대한간질학회 2003 대한간질학회지 Vol.7 No.2

폐경후 골다공증 환자에서 체질량지수에 따른 Alendronate의 효과

조영석,나소영,이효진,홍우정,김군순,김도희,구본정,송민호,김영건,노흥규 충남대학교 의과대학 의학연구소 2002 충남의대잡지 Vol.29 No.2

배경 : 폐경후 골다공증은 심각한 문제로 대두되고 있다. 현재 Alendronate는 폐경후 골다공증의 치료제로서 널리 쓰이고 있다. 저자는 Alendronate의 골밀도에 효과를 알아보고 골다공증의 위험인자에 따른 Alendronate의 반응 정도를 평가하기 위하여 본 연구를 수행하였다. 방법 : Alendronate를 평균 12개월간 복용한 35명의 폐경후 골다공증환자에서 체질량지수와 폐경후 기간에 따른 치료효과를 조사하였다. 결과 : 전체 대상군에서 Alendronate 10㎎을 12개월간 투여한후 골밀도의 평균 변화율은 요추와 대퇴골 경부에서 각각 7.83±7.39%와 2.99±9.22%이었다. 과체중군에서 평균변화율은 요추와 대퇴골 경부에서 각각 7.15±4.5%와 3.05±2.86%였다. 양군간에 통계적 유의성이 있는 차이는 없었다. 폐경후 7년이 경과되지 않은 군에서의 평균변화율은 요추와 대퇴골 경부에서 각각 6.9±5.3%와 5.71±0.08%였다. 양군간에 통계적인 유의성이 있는 차이는 없었다. 결론 : 마른체형이 골다공증의 발병에는 영향이 있으나, Alendronate 치료효과의 차이는 없는 것을 확인할 수 있었다. 더불어 폐경이 있고 7년이 초과된 군과 년이 경과되지 않은 군에서의 Alendronate 치료효과의 차이는 없는 것을 확인할수 있었다. 이는 골흡수가 상당히 진행된 상태에서도 Alendronate가 치료효과를 가지고 있음을 반영한다고 할 수 있겠다. Postmenopausal osteoporosis is a serious health problem. The aminophosphonate Alendronate is widely used for treatment of postmenopausal osteoporosis. We studied the effect of l0㎎ of alendronate given daily for mean 12 months on bone mineral density in 35 women(mean age 61yrs. mean BMI 23.24㎏/m^(2)) with osteoporosis. An over weight group is defined such that BMI was above 23㎏/m^(2). All the women received 1500㎎ calcium carbonate daily. The bone mineral density of L-spine and femoral neck was measured by dual-energy X-ray absorptiometry. Alendronate increased BMD at mean 12 months at the L-spine (7.15±4.5%) and femoral neck(3.05±2.86%) in normal women. Alendronate increased bone mineral density at 12 months at the L-spine(6.00±5.3%) and femoral neck(4.17±4.87%) in overweight women. There was no difference between two groups. In the less than 7 years group of postmenopausal duration. alendronate increased bone mineral density at 12 months at the L-spine(6.9±4.9%) and femoral neck(3.18±7.1%). In the more than 7 years group of postmenopausal duration, alendronate increased hone mineral density at 1% months at the L-spine(6.5±5.3%) and femoral neck(5.71±0.08%). There was no difference between two groups. In postmenopausal women with osteoporosis, therapy with alendronate produced significant increases in BMD of the L-spine and femoral neck in both group. There was no difference between normal and over-weight groups. and between less than 7 years group and more than 7 years group of postmenopausal duration.

그레이브스병에서 방사성 요오드 치료에 따른 갑상선 자극 호르몬 수용체 결합억제 면역글로불린(Thyrotropin Binding Inhibitory Immunoglobulin, TBII)의 변화

조영석,권기현,이준철,나소영,이효진,홍우정,이유선,김군순,송민호,김영건,노흥규 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

Prediction of thrapeutic response to radioiodine in Graves' disease is poorly understood. Although thyrotropin binding inhibitor immunoglobulin(TBII) level is a strong index for relapse after antithyroid drug medication, conflicting results are reported regarding its prognostic significance in Graves' disease treated with RAI. This study is dengned to evaluate possible relationship between post-treatment hypothyroidism and TBII in Graves' disease treated with RAI. Fourty two patient with Graves' disease after radioiodine treatment were studied retrospectively. The subject were divided into hypothyroid group and euthyroid or hyperthyroid group. We evaluated the association of hypothyroidism and TBII with radioiodine treatment dose. The mean age of hypothyroid group was 48±11 years and euthyroid or hyperthyroid group was 47±12 years. There was no difference in two groups. And there was no significant difference in post- treatment TBII between two groups(49.9±28.5%, 29.9±14.3%, p-value >0.05). The treatment-dose had no influence on post-treatment thyroid state. Euthyroid or hyperthyroid group was done with 13.6±6.9mCi and hypothyroid group was 17.0±10.4mCi(p-value > 0.05). TBII had no prognostic significance on long-term hypothyrodism in Graves' disease treated with radioiodine. And, treatment-dose had no influence on post-treatment thyroid state.

Disruption of CR6-interacting factor-1 (CRIF1) in mouse islet beta cells leads to mitochondrial diabetes with progressive beta cell failure.

Kim, Yong Kyung,Joung, Kyong Hye,Ryu, Min Jeong,Kim, Soung Jung,Kim, Hyeongseok,Chung, Hyo Kyun,Lee, Min Hee,Lee, Seong Eun,Choi, Min Jeong,Chang, Joon Young,Hong, Hyun Jung,Kim, Koon Soon,Lee, Sang-H Springer Verlag 2015 Diabetologia Vol.58 No.4

<P>Although mitochondrial oxidative phosphorylation (OxPhos) dysfunction is believed to be responsible for beta cell dysfunction in insulin resistance and mitochondrial diabetes, the mechanisms underlying progressive beta cell failure caused by defective mitochondrial OxPhos are largely unknown.</P>

A Procedure for Statistical Thermal Margin Analysis Using Response Surface Method and Monte Carlo Technique

Hyun Koon Kim,Young Whan Lee,Tae Woon Kim,Soon Heung Chang Korean Nuclear Society 1986 Nuclear Engineering and Technology Vol.18 No.1

경수로심의 열 여유도를 분석하기 위하여 반응표면 및 Monte Carlo 방법을 이용하는 통계적 분석 방법이 제시되었다. 통계적인 열 여유도 분석 방법은 입력변수들의 불확실도를 확률론적으로 처리함으로써 열 여유도의 최적 평가를 수행한다. 이 방법은 원자력 1호기 정상상태의 원자로심 분석에 응용되었으며 또한 종래의 결정론적 방법 및 웨스팅하우스의 개선된 열설계 방법과도 비교되었다. 본 연구를 통하여 반응표면 분석 방법은 통계적인 열 여유도 분석에 유용함을 알 수 있었으며, 이 방법을 통한 열 여유도의 증가도 확인되었다. A statistical procedure, which uses response surface method and Monte Carlo simulation technique, is proposed for analyzing the thermal margin of light water reactor core. The statistical thermal margin analysis method performs the best.estimate thermal margin evaluation by the probabilistic treatment of uncertainties of input parameters. This methodology is applied to KNU-1 core thermal margin analysis under the steady state nominal operating condition. Also discussed are the comparisons with conventional deterministic method and Improved Thermal Design Procedure of Westinghouse. It is deduced from this study that the response surface method is useful for performing the statistical thermal margin analysis and that thermal margin improvement is assured through this procedure.