정신분열병 환자의 KCNN3 유전자에서 나타나는 삼핵산 반복서열

김도관,임신원,고효정,서민영,손성은,이소영,황혜진,진동규,김병로 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.5

연구목적 : 연구자들은 NMDA 수용체의 channel protein 합성에 관여하는 KCNN3 유전자에서 나타나는 삼핵산 반복서열(triple nucleotide repeat, TNR) 확장이 과연 정신분열병의 발병에 기여하는지를 최근 개발된 TNR copy 수를 정량화 함으로써 알아보고자 하였다. 방 법 : 연구대상은 정신과 외래 및 입원 환자 중 정신분열병 환자 245명과 건강 의학센타를 방문한 정상 성인 116명을 각각 선발하였다. 정신분열병 환자들이 정상인에 비하여 불특정 CAG 삼핵산 반복 서열 확장에 차이가 나는지 repeat expansion detection(RED) 방법을 확인한 다음, 그것이 KCNN3이나 CTG18.1 유전자의 CAG 반복서열 증가에 의한 영향인지 분석하였다. 그리고 untranslated region에서 TNR 증가를 불특정하게 일으킬 수 있는 ERDA1의 CAG 삼핵산 반복서열의 영향을 검증함으로써 KCNN3나 CTG18.1 유전자가 정신분열병의 발병에 기여하는 바를 평가하였다. 결 과 : 정신분열병 환자는 정상인에 비하여 KCNN3 유전자 부위에서 TNR 확장이 현저한 longer allele이 빈번하게 관찰되었다. 즉, KCNN3 유전자 부위에서 CAG 삼핵산 반복이 19번 이상 확장되는 염색체가 신분열병 환자군에서는 73.3% 발견되는 데 비해서 정상인군에서는 65.1% 발견되어 유의한 차이가 있었다(p=0.029, Fisher's exact test). 이러한 차이는 가족력이 있는 정신분열병 환자군(79.7%)에서 가족력이 없는 환자군(70.8%)보다 더욱 현저하게 관찰되었다(p=0.003, Fisher's exact test). 음성형과 양성형 정신분열병 환자군 간에서의 차이는 관찰되지 않았다. CTG18.1 유전자 부위의 TNR 확장이나 불특정 부위 염색체 전체에서의 TNR 확장은 환자군과 정상 대조군 간에 차이가 없었다. 환자군과 대조군 모두에서 불특정 TNR 확장은 ERDA1의 전사와 유의하게 관련성이 있었다(각각 r=0.45, p<0.001 ; r=0.44, p<0.001). 하지만 KCNN3 유전자 부위에서 TNR 확장은 ERDA1 score와 유의한 관련성을 보이지 않았다. 결 론 : 이상의 결과는 KCNN3 유전자가 한국인 정신분열병의, 특히 가족력이 있는 정신분열병의, 발병에 관여할 수 있음을 시사한다. 또한 ERDA1 전사는 불특정 TNR 확장의 원인으로 작용한다는 가설을 뒷받침한다. Objects : We investigated a possible association between the polymophic trinucleotide repeat(TNR) expansion in neuronal potassium channel gene KCNN3 and schizophrenia. Methods : CAG/CTG repeat distribution in KCNN3, CTG8.1 and ERDA1 was examined and the copy number of ligation product in repeat expansion detection(RED) was measured in Korean patients with schizophrenia(n=245) and ethnically matched healthy controls(n=116). Results : Longer alleles in the KCNN3 gene were over-represented in patients. The frequency of alleles with CAG repeats longer than 19 copy in the KCNN3 gene was higher in the patients with schizophrenia as compared to controls(73.3% vs 65.1% ; p=0.029, Fisher's exact test). And this difference was more prominent in schizophrenic patients with familial background(p=0.03, Fisher's exact test). We found no difference in the frequency of longer alleles between negative and positive subtypes of schizophrenia. Ligation product size in RED and alleles with CAG repeat number in the CTG18.1 gene was not increased in the patients. The copy number of ligation product in RED was highly correlated with CAG/CTG copies if ERDA1 in the patient group(r=0.45, p<0.001) as well as in the control group(r=0.44, p=<0.001). However, CAG repeat length in the KCNN3 gene was not correlated with ERDA1 score. Conclusions : Our results support the hypothesis that the longer allele of KCNN3 may be considered as a candidate gene for schizophrenia, especially in the case with familial background. And the RED assay results was affected by the CAG copy number of ERDA1.

기분 장애 환자에서 나타나는 불특정 CAG 삼핵산 반복서열의 확장

손성은,임신원,이소영,황혜진,진동규,박정의,김도관,김이영 대한신경정신의학회 2000 신경정신의학 Vol.39 No.2

연구목적: 기분장애는 그 원인과 발생기전은 아직 밝혀져 있지 않고 있지만, 과거부터 유전적 요인이 질병의 발생과 중요한 연관성을 가지고 있다고 알려져 있다. 특히 양극성 정동장애는 가족력이 있는 경우에 발병될 가능성이 높고, 같은 가족 내에서 발생했을 때 세대가 내려감에 따라서 발병시기가 점차 빨라지며 증세가 심해지는 경향이 있어서 그 유전적 배경에 대해 많은 의문이 있어 왔다. 연구자들은 다양한 증상의 기분장애 환자들의 DNA에서 불특정 CAG 삼핵산 반복(trinucleotide repeat. TNR) 정도를 분석함으로써 TNR 확장이 기분장애의 유전과 관련되는지 살펴보았다. 방법: 환자 군은 DSM-Ⅲ-R 진단기준에 의거하여 양극성 정동장애(N=55), 주요우울장애(N=67) 환자들을 선발하였다. 정상인(N=89)은 정신과적 병력이 없고 다면성 인성검사상 정상의 profile을 나타내는 병원 종사자, 학생 및 건강의학센타 방문자들 중 선발하였다. TNR의 확장은 genomic DNA를 순수분리한 후, (CTG)₁□의 oligonucleotide를 □-□□P-ATP로 방사선 표지하여 반복서열 확장 탐지법(repeat expansion detection)으로 측정하였다. 집단간의 비교를 위해 Mann-Whitney U 검증을 실시하였다. 결과: DNA에서 관찰되는 불특정 CAG 삼핵산 반복 길이의 평균은 양극성 정동장애에서 169.8bp(S.D=58.6), 주요우울장애에서 167.5bp(S.D=63.9)로서 대조군 178.7bp(S.D=56.5)과 비교하였을 때 유의미한 차이는 관찰되지 않았다. 각각의 환자군을 가족력이 있는 군과 없는 환자군으로 나누어 대조군과 비교하였을 때도 유의미한 차이는 관찰되지 않았다. 결론: 불특정 CAG 삼핵산 반복서열 확장이 양극성 정동장애 환자와 주요우울장애 환자들의 유전 양식에 영향을 미친다는 가설을 뒷받침하지 않는다. Objectives: The genetic facotrs have been suggested for the etiology of mood disorders but the mode of inheritance is complex. Increased severity and an earlier onset of the bipolar and major depressive disorder over generations within families(Anticipation) were reported. In order to test the hypothesis that trinucleotide repeat expansions underlie the genetic basis of Bipolar and major depressive disorders, we have analyzed the extent of CAG reapeats in genomic DNA from mood disorder patients. Methods: 55 bipolar disorder, 67 major depressive disorder patients were recruited accord-ing to the DSM-Ⅲ-R criteria. 89 normal controls were recruited from the medical personnel, students and the visitors to the health services center who had no history of psychiatric illness and show normal profile of MMPI. The genomic DNA of patients and controls was analyzed by use of the (CTG)□ oligonucleotide and the repeat expansion detection(RED) method. The Mann-Whitney U test was used to compare the distribution of the number of CAG repeats among the groups. Results: when the bipolar disorder, major depressive disorder patients were compared with the control group, no significant differences were observed. Conclusions: Our results do not support the hypothesis that expanding CAG repeats are causing the observed genetic anticipation in bipolar disorders and major depressive disorders.

Functional Electrical Stimulation to Ankle Dorsiflexor and Plantarflexor Using Single Foot Switch in Patients With Hemiplegia From Hemorrhagic Stroke

Lee, Young-Hee,Yong, Sang Yeol,Kim, Sung Hoon,Kim, Ji Hyun,Shinn, Jong Mock,Kim, Youngho,Kim, Seunghyeon,Hwang, Seonhong Korean Academy of Rehabilitation Medicine 2014 Annals of Rehabilitation Medicine Vol.38 No.3

<P><B>Objective</B></P><P>To evaluate the effects of functional electrical stimulation (FES) to ankle dorsiflexor (DF) and ankle plantarflexor (PF) on kinematic and kinetic parameters of hemiplegic gait.</P><P><B>Methods</B></P><P>Fourteen post-stroke hemiplegic patients were considered in this study. Electrical stimulation was delivered to ankle DF during the swing phase and ankle PF during the stance phase via single foot switch. Kinematic and kinetic data were collected using a computerized motion analysis system with force plate. Data of no stimulation (NS), DF stimulation only (DS), DF and PF stimulation (DPS) group were compared among each other.</P><P><B>Results</B></P><P>Peak ankle dorsiflexion angle during swing phase is significantly greater in DS group (-1.55°±9.10°) and DPS group (-2.23°±9.64°), compared with NS group (-6.71°±11.73°) (p<0.05), although there was no statistically significant difference between DS and DPS groups. Ankle plantarflexion angle at toe-off did not show significant differences among NS, DS, and DPS groups. Peak knee flexion in DPS group (34.12°±13.77°) during swing phase was significantly greater than that of NS group (30.78°±13.64°), or DS group (32.83°±13.07°) (p<0.05).</P><P><B>Conclusion</B></P><P>In addition to the usual FES application stimulating ankle DF during the swing phase, stimulation of ankle PF during stance phase can help to increase peak knee flexion during the swing phase. This study shows the advantages of stimulating the ankle DF and PF using single foot switch for post-stroke gait.</P>

위 임파종과 십이지장 선암이 병발한 중복암

김영수(Young Soo Kim),장세경(Sae Kyung Chang),박기룡(Ki Ryong Park),김호정(Ho Jeong Kim),신순현(Sun Hyun Shinn),김종숙(Jong Suk Kim),박용욱(Yong Ook Park) 대한소화기학회 1987 대한소화기학회지 Vol.19 No.2

Double prirnary cancer is defined as the case of primary malignant tumors of different site origins, which are different histologically in each other. The absolute number of reported cases of double primary malignant tumors has increased in recent years by means of more developed diagnostic procedure. But the occurrence of multiple primary malignant tumors is relatively rare. We have experienced a case with double primary malignant tumors of different site origins such as gastric lymphoma and duodenal adenocarcinoma, which were diagnosed by biopsies with gastric fiberoptic endoscopy. For its great rarity, we report this case with review of literatures.

Carbon dioxide storage in a conglomerate formation

Kue-Young Kim,Junho Oh,Kwon Gyu Park,Young-Jae Shinn,Weon Shik Han,Eungyu Park 대한지질학회 2017 대한지질학회 학술대회 Vol.2017 No.10

Preliminary results of numerical simulation in a small-scale CO₂ injection pilot site : 1. Prediction of CO₂ plume migration

최병영(Byoung-Young Choi),박용찬(Yong-Chan Park),신영재(Young-Jae Shinn),김구영(Kue-Young Kim),채기탁(Gi-Tak Chae),김정찬(Jeong-Chan Kim) 대한지질학회 2015 지질학회지 Vol.51 No.5

Simulation of CO₂ injection in a small-scale pilot site in the Pohang Basin, Korea: Effect of dissolution rate of chlorite on mineral trapping

Choi, Byoung-Young,Shinn, Young-Jae,Park, Yong-Chan,Park, Jinyoung,Kwon, Yi-Kyun,Kim, Kue-Young Elsevier 2017 International journal of greenhouse gas control Vol.59 No.-

<P><B>Abstract</B></P> <P>In Korea, a small-scale pilot project for CO<SUB>2</SUB> injection was launched to target an offshore reservoir within the Pohang Basin. The objectives of this study are to present the effects of CO<SUB>2</SUB> injection in a sloping aquifer on the evolution of the CO<SUB>2</SUB> plume and its impact on mineral trapping using TOUGHREACT. The results show that the CO<SUB>2</SUB> plume is asymmetrical and rapidly migrates along the slope in the up-dip direction from the injection well. With the migration of the CO<SUB>2</SUB> plume, the increased acidity accelerates the water-rock interactions. As the CO<SUB>2</SUB>-water-rock interactions start quickly due to the rapid spreading of the CO<SUB>2</SUB> plume, the amount of mineral trapping slightly increases due to the precipitation of siderite by chlorite dissolution. However, the stability of siderite is sensitive to the dissolution rate of chlorite. At low chlorite dissolution rates, siderite is more stable than ankerite in an undersaturated state. At high chlorite dissolution rates, ankerite is more stable because of the higher pH. In addition, the amount of mineral trapping increases considerably up to 3.7kg/m<SUP>3</SUP>, which is about 90 times that at the initial rate (0.04kg/m<SUP>3</SUP>). This simulation indicates that the uncertainty in the dissolution rate of chlorite must be considered when estimating the capacity of mineral trapping in situations in which iron-containing carbonate minerals significantly influence the mineral trapping.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The CO<SUB>2</SUB> injection in a small-scale pilot site is simulated to assess mineral trapping by TOUGHREACT. </LI> <LI> The dissolution rate of chlorite affects on the stability of ankerite and siderite, and consequently the amount of mineral trapping. </LI> <LI> The uncertainty in the chlorite dissolution rate must be considered in situations in which iron-containing carbonate minerals. </LI> </UL> </P>

Active Warming during Preanesthetic Period Reduces Hypothermia without Delay of Anesthesia in Cardiac Surgery

Helen Ki Shinn,Young Lan Kwak,Young Jun Oh,Seung Ho Kim,Ji Young Kim,Mi Hyeon Lee 대한마취과학회 2005 Korean Journal of Anesthesiology Vol.48 No.6

Serotonin transporter genotype and function in relation to antidepressant response in Koreans.

Myung, Woojae,Lim, Shinn-Won,Kim, Seonwoo,Kim, Hyeran,Chung, Jae Won,Seo, Min Young,Kim, Jong-Won,Carroll, Bernard J,Kim, Doh Kwan Springer-Verlag 2013 Psychophamacology Vol.225 No.2

<P>Serotonin transporter (5-HTT) gene polymorphisms are linked with antidepressant response to selective serotonin reuptake inhibitor drugs (SSRIs), though the favorable allelic variant differs by ethnic group (Caucasian versus Korean or Japanese). In Caucasian patients, response also is linked to measures of platelet 5-HTT function. Here, we study both 5-HTT gene polymorphisms and 5-HTT function as determinants of antidepressant response to SSRIs in Korean patients. We enrolled 99 patients with major depression and 48 control subjects. For statistical power, both samples were enriched with the l/l 5-HTTLPR polymorphism, which is uncommon in Koreans. Patients were treated with fluoxetine or sertraline. Response was assessed at 6 weeks. Subjects were genotyped for s/l polymorphism in the 5-HTT promoter region (5-HTTLPR). Platelet 5-HTT activity was determined as maximal uptake rate (Vmax) and affinity constant (Km). Response was differentially associated with the s allele of 5-HTTLPR, which also was significantly associated with Vmax. These associations are opposite to those reported in Caucasian populations. Responders had significantly higher Vmax and Km than nonresponders. In Koreans as well as Caucasians, high Vmax is related to antidepressant response to SSRIs, though the 5-HTTLPR polymorphism associations with both response and function differ by ethnicity. Both ethnicity and function must be considered in evaluating candidate gene biomarkers of response to SSRIs in depression.</P>

국내 이산화탄소 지중격리저장 실증실험 후보부지의 역학적 안정성 평가 기초해석

김아람(A-Ram Kim),김형목(Hyung-Mok Kim),김현우(Hyun-Woo Kim),신영재(Young-Jae Shinn) 한국암반공학회 2017 터널과지하공간 Vol.27 No.2

이산화탄소 지중저장 사업의 성공적인 수행을 위해서는 저장시스템의 안정성을 확보할 수 있는 대상지층을 선정하고 현장 지질조건에 최적화된 주입 조건을 설계해야 한다. 본 연구에서는 국내 실증실험 대상 예상후보지의 하나인 장기분지의 지질구조를 바탕으로 2차원 간략해석모델을 구축하고 TOUGH-FLAC 연계해 기법을 사용하여 초기응력조건과 주입량이 이산화탄소 격리저장시스템에 미치는 영향을 분석하였다. 기초해석 결과, 수직응력이 수평응력보다 우세한 정단층 응력조건에서 전단미끄러짐 가능성이 가장 높은 결과를 보였으며, 단위시간당 주입량을 달리하는 주입량 시나리오 해석에서는 주입량을 단계적으로 증가시켜 주입하는 경우가 공극압의 증가폭이 가장 크고 활동마찰계수를 이용한 전단미끄러짐 가능성 평가 결과에서도 가장 불리한 것으로 평가되었다. For a successful performance of Carbon Capture Sequestration (CCS) projects, appropriate injection conditions should be designed to be optimized for site specific geological conditions. In this study, we built a simple 2-dimensional analysis model, based on the geology of Jang-gi basin which is one of the potential sites of domestic CCS projects. We evaluated the impact of initial stress conditions and injection rate through coupled TOUGH-FLAC simulator. From the preliminary analysis, we constructed risk scenarios with the higher potential of shear slip and performed scenario analysis. Our analysis showed that normal stress regime produced the highest potential of shear slip and stepwise increasing injection rate scenario resulted in much larger pore pressure build up and consequent higher potential of the shear slip, which was evaluated using a mobilized friction coefficient.