공가 철거를 통한 그린인프라의 열섬 저감 효과 예측

학위논문 (석사)-- 서울대학교 대학원 농업생명과학대학 생태조경·지역시스템공학부, 2017. 8. 이동근.Rapid urbanization and decaying downtown areas have caused mass gains in vacant houses in large cities, such as Seoul, and mid-sized cities, such as Incheon and Daejeon. Vacant land and houses lower land prices and can trigger crime, causing negative externalities to adversely affect their surroundings. More cities have been gradually introducing green spaces in vacant land as a means of redevelopment to improve the city and reduce negative externalities. In addition to this societal value, the physical evaporation and shadow effects of green spaces can mitigate the urban heat island effect, which is a serious problem due to the artificial heat of the city. In Korea, quantitative figures for the mitigation of the urban heat island phenomena are derived only for individual sites, and there has been insufficient research on the effects of introducing green spaces into vacant land and housing sites. In particular, it is important to evaluate the potential temperature reduction effect in the planning stage before implementing greening in the vacancies. This is important data that provides baseline data at the decision-making stage. Therefore, it is necessary to quantitatively study the effect of greening vacant land and houses. The purpose of this study is to derive the quantitative effects of urban infrastructure mitigation using meta-analysis to predict the regional effects of green infrastructure on vacant land. First, quantitative figures are derived from the meta- analysis on the impact of a Green Infrastructure Strategy on reducing urban decay. Second, based on the results of the meta-analysis, we quantitatively derive the green infrastructure effect obtained in two selected high-density areas in Sungui-dong, Nam-gu, Incheon. Nam-gu is the second largest city in Incheon and its residential area is the target of urban regeneration. Third, we examine the environmental benefits and opportunity costs of greening. The study was conducted as follows. To understand the quantitative effect of green infrastructure, we derived a regression equation and used meta-analysis to determine the effect of temperature reduction when green space was introduced. Then, the extent of urban decay was evaluated using a previous study and sites A and C, with available ground surface temperature data, were selected in Nam-gu, Incheon. The appropriate type of greening for Sites A and C were selected and the effect of temperature reduction was estimated using meta-analysis results. The results of the study indicate that Sites A and C should be transformed into a Neighborhood Park and pocket park, respectively. These changes would result in a temperature reduction up to 2.751 °C within the park at Site A, and a temperature reduction of ~1.507 °C within a 62-m radius outside the park. The projected performance at Site C was similar, a temperature reduction of up to 2.269 °C internally and ~0.92 °C outside the park. In deriving the results, we considered that various previous studies obtained results from different situations, including climate zones and geography. In addition, the opportunity cost due to greening and the added value to the surrounding area are discussed. Green infrastructure is an effective environmental practice tool to add social, economic, and cultural value. Furthermore, it facilitates the adoption of environment-friendly policies, such as the introduction of green spaces rather developing additional buildings to public places.Chapter 1. Introduction 1 Chapter 2. Literature Review 5 2.1 Greening strategies case study 5 2.2 Case studies of greening vacant land 9 Chapter 3. Methods 12 3.1 Scope of the Study 12 3.1.1 Contents 12 3.1.2 Spatial Context 12 3.2 Methods 15 3.2.1 Study flow 15 3.2.2 Estimation of green infrastructure effect using meta-analysis 17 3.2.3 Selecting the study site and greening type 21 Chapter 4. Results and discussion 26 4.1 Estimation of green infrastructure effect using meta-analysis 26 4.1.1 Results from the search and selection of related documents 26 4.1.2 Derivation of Heat Island Reduction Effect and Trend Equation 28 4.1.3 Equation accuracy 34 4.2 Search and select target sites 40 4.2.1 'Dong' selection for green infrastructure 40 4.2.2 Vacant land for green infrastructure effect 43 4.3 Estimation of green infrastructure effect 51 4.4 Impacts on the surrounding area 52 4.5 The opportunity cost of greening 53 Chapter 5. Conclusions 57 Bibliography 60 Appendix 67 Abstract in Korean 77Maste

Clinical Features and Prognostic Factors of Anaerobic Infections: A 7-Year Retrospective Study

BACKGROUND/AIMS: Risk factors for mortality resulting from anaerobic infection are incompletely defined. The clinical significance of a broad range of pathogenic obligate anaerobic organisms was examined, and factors independently associated with mortality were identified in patients with clinically significant anaerobic infections.0aMETHODS: The medical records of 1,050 patients with anaerobic infections were retrospectively reviewed at Severance Hospital in Seoul, Korea.0aRESULTS: The mean age of the patients was 54.1cally significant cases were polymicrobial anaerobic infections. The mean number of pathogens, including aerobic and anaerobic bacteria, was 3.7athogens by rank were the Bacteroides fragilis group, which accounted for 41.8% of anaerobic infections, followed by Clostridium spp. (11.8%), Prevotella spp. (9.4%), and Peptostreptococcus spp. (8.4%). Escherichia coli (17.5%), Staphylococcus aureus (7.5%), and Klebsiella pneumoniae (7.5%) were common concomitant aerobic organisms. The overall crude mortality rate resulting from anaerobic infection was 29.7%. Among the determining factors associated with mortality, liver disease (p005) were significant in multivariate analysis.0aCONCLUSIONS: Anaerobic infection is polymicrobial and has a significant role in morbidity and mortality. Underlying liver disease was associated with poor prognosis in anaerobic infection.ope

Epidemiology of HIV/AIDS in East Asia

Background:Recent predictions of catastrophic epidemic surge of HIV infection in East Asia concern experts and governmental organizations. As in many other areas, countries in East Asia show diversities in their HIV epidemics, both geographically and temporally. However, they have similar regional, cultural and racial characteristics which allow them to have certain common factors. Having a clear picture of the current extent and feature of HIV/AIDS in this region is a very difficult task largely due to the fast pacing of expending epidemic and difficulty in data-sharing among countries in the region. Hence, we decided to study the epidemiologic feature of HIV/AIDS in East Asia through East Asia Network on HIV (EAN-HIV). Materials and Methods:The epidemiological patterns of HIV/AIDS in East Asian countries were investigated by collecting data through EAN-HIV. Results:The HIV/AIDS epidemic in East Asia started relatively late at mid 1980s. Since then, the number of newly infected HIV/AIDS cases has been steadily increasing with stiffer escalation in recent years. In China and Taiwan, IDU plays an important part in the swiftly growing HIV epidemics; however, in other regions like Korea, Japan, and Hong Kong, MSM (men who have sex with men) seems to be more of a problem. The major subtypes of HIV in East Asia are subtype B, C, and CRF01_AE, and rapidly evolving circulating recombinant forms (CRF) between subtypes such as CRF07_BC give dynamic change to the current status. Conclusion:The incidence of HIV/AIDS is rapidly increasing in East Asia. The epidemic pattern has undergone dynamic changes over time. China seems to be the leading source of HIV/AIDS epidemic in East Asia due to its large population and rapidly growing epidemics.ope

Changing trends of infective endocarditis according to the change in health care system in Korea

Background: In July 2000, there was a dramatic change in Korean health care system with the medical reform, the separation system of pharmacies and prescriptions. Before then, patients could easily get antibiotics without doctors’ prescriptions. Since the symptoms and signs of infective endocarditis are very nonspecific, prior self treatment with antibiotics before admission was common. This study was performed to determine the changing trends of infective endocarditis according to the change in health care system. Methods: One hundred eighty eight patients from 8 different medical institutions were included. Medical records were reviewed retrospectively for each patient who was diagnosed as infective endocarditis by Modified Duke criteria. Patients were separated into two different groups (Group I : patients diagnosed before July 2000, Group II : patients diagnosed after November 2000). Clinical characteristics, blood culture positivity, and in-hospital mortality were compared. Results: There was no difference in clinical manifestation between two groups other than malaise. Blood culture positivity was 57.4% in group I and 71.1% in group II. Blood culture positivity was significantly higher in group II (p=0.038). In-hospital mortality tends to be lower in group II, which was 22.3% in group I and 12.9% in group II (p=0.066). The relationship between higher blood culture positivity and lower in-hospital mortality couldn’t be clarified. Conclusion: There was an increase in blood culture positivity and a tendency to decrease in in-hospital mortality after July, 2000, possibly due to health care reform. This, to my knowledge, is the first effort to investigate the changing trends of an actual clinical disease according to the change in health care system.ope

A Case of Brucellar Spondylitis with Multiple Spine Involvement

Brucellosis, a zoonosis with world wide distribution, is a systemic infection that affects several organs and has protean presentation. Although spondylitis is universally the most common complication of brucellosis and difficult to treat, there is no consensus on the preferred combination of antibiotics use. The authors report a case of a 58-year-old male patient with brucellar spondylitis involving several vertebrae. Diagnosis was made by positive blood culture and magnetic resonance imaging. The authors use a combination method of doxycycline, ciprofloxacin and streptomycin for a period of 3 months. The systemic symptoms were improved after treatment.ope

Prognosis Factors of Clostridium difficile Associated Diarrhea

Background:Clostridium difficile associated diarrhea (CDAD) has a wide range of clinical manifestations. The prognostic factors of CDAD are not fully understood. Materialsand Methods:A retrospective cohort study of 115 patients with CDAD from Aug. 2002 to Dec. 2003 was conducted to evaluate prognostic factors of CDAD. Bacteriologic factors were determined by detecting the binary toxin gene, tcd A, tcd A rep and tcd B gene. Poor prognosis was defined as diarrhea more than 10 days even with classic treatment, recurrence, death, and moribund discharge. Results:Approximately 79% of isolated strains were toxin A+/B+ strains and 21% were toxin A-/B+ strains. There was no difference in prognosis between toxin A+ and toxin A- strains. 39 (33.9%) cases showed poor prognosis and 76 (66.1%) cases showed good prognosis. Univariate analyses revealed that the poor prognostic factors were old age over 70 years old, male, the number of antibiotics used after onset of symptom, the administration of carbapenems, aminoglycosides, glycopeptides after onset of symptom, history of DM and stroke, and high Charlson comorbidity index. Multiple logistic regression analysis identified old age over 70 years old (odds ratio=3.378, P=0.009) and the administration of carbapenems after onset of symptom (odds ratio 7.210, P<0.001) as the independent poor prognostic factors. Conclusion:Old age over 70 and the administration of carbapenems after onset of symptom were the poor prognostic factors for CDAD caused by none-binary toxin producing strains.ope

Sur l&amp;apos;analyse des types d&amp;apos;exercices dans les manuels de français pour les lycées coréens selon les Instructions Officielles du septième plan

Le manuel de français est le seul support fiable dans la classe de français en Corée. Le premier manuel de français date de 1968, il a donc trente-sept ans d&amp;apos;histoire au cours desquels les Instructions Officielles ont changé six fois selon les méthodes. Les Instructions Officielles du septième plan se sont appliquées en 2002 au lycée. Les méthodologistes ont élaboré les manuels à partir de celles-là, en prenant en compte l&amp;apos;approche communicative, selon la consigne du Ministère de l&amp;apos;Education Nationale. Bien que les Instructions Officielles leur offrent des informations (objectifs, contenu à délimiter, méthodologies à mettre en œuvre, etc) pour leur élaboration, et qu&amp;apos;on possède des grilles d&amp;apos;évaluation ou d&amp;apos;élaboration des ensembles didactiques par rapport à l&amp;apos;approche communicative, il n&amp;apos;est point toujours facile de les adapter à l&amp;apos;élaboration des manuels de français. La section d&amp;apos;exercice des manuels de français est habituellement située à la fin de chaque unité. Les exercices des manuels de français sont directement et intrinsèquement liés à un objectif d&amp;apos;apprentissage. Ils ont pour but de faire revoir des règles apprises dans les leçons et d&amp;apos;évaluer le niveau des apprenants. Dans l&amp;apos;enseignement des langues étrangères, l&amp;apos;évaluation n&amp;apos;est pas une fin en soi, c&amp;apos;est-à-dire elle fait partie intégrante de l&amp;apos;enseignement/apprentissage. Donc l&amp;apos;évaluation et l&amp;apos;enseignement/apprentissage sont en rapport solidaire. Dans cette étude, nous avons essayé d&amp;apos;analyser des types d&amp;apos;exercices apparus dans les manuels de français pour les lycées coréens sur la base des fonctions linguistiques(écouter, lire, parler, écrire), des contenus et des types(d&amp;apos;exercice mécanique, d&amp;apos;exercice significatif, d&amp;apos;exercice de communication) pour développer la compétence de communication. Et par là, nous avons obtenu les résultats comme les suivants: 1) Il n&amp;apos;y a pas beaucoup de différences dans les aspects de parler dans les exercices apparus dans les manuels de français. On ne peut pas négliger les éléments linguistiques(grammaire, vocabulaire, prononciation) en début d&amp;apos;apprentissage dans la realité de la classe de langue. 2) Aujourd&amp;apos;hui l&amp;apos;enseignement des langues étrangères souligne l&amp;apos;importance de la compétence communicative. Donc deux formes d&amp;apos;exercices ont été recherchées dans le contenu des exercices: les exercices de question-réponse et les micro-conversations. Malgré tout, les exercices des manuels de français ne sont pas directement liés à un objectif d&amp;apos;apprentissage pour développer la compétence de communication. 3) Il y avait pourtant une différence pour cent dans les trois types d&amp;apos;exercices. Autrement dit, les exercices ont été concentrés sur le type d&amp;apos;exercice mécanique et d&amp;apos;exercice significatif plutôt que le type d&amp;apos;exercice de communication. Mais ce type d&amp;apos;exercice est loin de développer la compétence de communication. Donc le type d&amp;apos;exercice de communication doit s&amp;apos;appliquer à la phase d&amp;apos;exploitation. 4) De plus, on peut trouver le type d&amp;apos;exercice de communication dans les manuels de français selon les Instructions Officielles du septième plan. Nous espérons que les méthodologistes élaboreront les manuels de français selon les Instructions Officielles du huitième plan.;시대적 요청에 따라 외국어 교수법이 다양하게 변천되어 왔다. 따라서 우리나라의 교육과정도 여러 차례 걸쳐 변화해 왔다. 본 연구는 외국어 교수법의 번쳔과 교욱과정의 변천에 따라 보다 더 나은 교육방향과 제시를 위해 제5차, 제6차 그리고 제7차 교육과정에 따른 고등학교 프랑스어 교과서 연습문제를 통시적으로 살펴보면서 제7차 고등학교 프랑스어과 교육과정에 근거하여, 현재 사용하고 있는 고등학교 프랑스어 교과서 연습문제를 언어기능, 내용과 유형별로 분석하여 교과서 연습문제가 다루고 있는 &amp;apos;언어기능&amp;apos;과 &amp;apos;내용&amp;apos;을 균형 있게 측정하고 있는지, 그리고 의사소통 능력을 신장시킬 수 있는 &amp;apos;유형&amp;apos;으로 나타나고 있는지를 검토하고자 한다. 본 연구를 위해 우리가 살펴볼 연구문제는 다음과 같다. (1) 현행 고등학교 프랑스어 교과서 연습문제의 문항이 언어기능별로 교과서간에 어떠한 차이가 있는가? (2) 연습문제에 제시된 듣기 문항의 내용(소리구별, 듣고 행동, 질문/대답 이해, 대화내용 이해, 간단한 말 이해, 대의파악)이 교과서간에 어떠한 차이가 있는가? (3) 연습문제에 제시된 말하기 문항의 내용(말의 반복, 동작/상태 설명, 질문/대답. 인사/묘사 표현, 간단한 표현)이 교과서간에 어떠한 차이가 있는가? (4) 연습문제에 제시된 읽기 문항의 내용(문자이해, 간단한 글 읽기, 간단한 대화글 이해, 의도/목적/배경 파악)이 교과서간에 어떠한 차이가 있는가? (5) 연습문제에 제시된 쓰기 문항의 내용(철자법, 구두법, 학습한 내용, 질문/답, 실물/그림 묘사, 일상생활)이 교과서간에 어떠한 차이가 있는가? (6) 현행 고등학교 프랑스어 교과서 연습문제의 문항이 유형별(기계적 연습, 유의적 연습, 의사소통 활동)로 교과서간에 어떠한 차이가 있는가? 따라서 본 연구자는 위의 여섯 가지 연구문제를 염두 해 두고, 분석 대상은 고등학교 프랑스어 교과서Ⅰ 6종 6권을 선정하였고, 각 교과서의 &amp;apos;연습문제&amp;apos;를 분석하였다. 분석 도구는 선행 연구와 제7차 고등학교 교욱과정 프랑스어과 평가내용을 준거로 제작되고, 사전검사에 의하여 수정된 분석표에 의하여 현재 사용하고 있는 고등학교 프랑스어 교과서 연습문제를 언어기능, 내용과 유형별고 분석해 보았다. 자료, 처리 과정은 각 교과서마다 단원의 수와 문항이 일치하지 않으므로, 모든 빈도는 백분율로 환산되었다. 분석의 결과를 종합해 볼 때, 교과서간 연습문제가 기능측면에서는 말하기 기능이 고르게 반영되었으며 전 교과서에서 가장 큰 비중을 차지한 것은 기초과정에서 중요시되는 언어영역이었다. 표면적으로는 의사소통 중심의 교육을 지향하고 있는 것처럼 보였지만, 실제로 그것을 반복/심화 시키고 평가하는 과정에서 의사소통 활동으로 제대로 이어지지 못하여 의사소통 활동의 비중이 상대적으로 굉장히 적은 비율을 나타내었다. 이와 같이 평가가 교수/학습의 내용과 방법을 제한한다는 선환효과의 측면에서 볼 때, 연습문제가 기계적인 연습 유형에 너무 치우쳐 있다는 것은 의사소통중심의 교육이란 측면에서 바람직하지 않다고 본다. 특히 &amp;quot;암기 위주의 평가를 지양하고 의사소통 기능의 이해/적용 능력 및 유창도에 중점을 두어 평가한다&amp;apos;는 평가 지침에도 맞지 않는다고 본다. 본 연구 결과를 통하여 교사, 교과서 제작자 및 교육 행정가들에게 중요한 교육적 시사점을 제공하고자 한다. 첫째, 본 연구 결과가 교사들과 학습자들에게 연습문제의 중요성을 재인식시킨다는 점이다. 교사와 학습자가 연습문제 풀이 활동을 통하여 교사가 학습자의 부족한 부분을 알고, 개인별 능력별로 보충해 줄 수 있다. 학습자는 자신의 학습곤란을 알고 교사의 도움으로 개선하므로 교사와 학습자간의 상호작용을 이끄는 학습활동이 될 수 있다. 둘째, 교사들에게는 자신이 가르치는 교과서 연습문제 문항 분석의 결과를 보고 언어기능, 내용, 유형별로 부족한 문항을 개발하거나 별도의 보충자료를 활용하여 부족하다고 생각한 부분을 보완할 수 있다. 셋째, 교과서 제작자들에게는 교과서 연습문제 문항의 분석 결과가 교과서 제작의 방향과 기준을 제시해 줄 수 있다고 본다. 다시 말하면 교과서 제작자들 나름대로의 교육과정에 대한 해석은 자의적인 해석으로 자신들이 만든 교과서 연습문제 문항의 분석 결과와 다른 교과서 연습문제 문항의 분석 결과를 비교해 봄으로써 다음 교과서 제작시에 도움을 받을 수 있다고 본다. 넷째, 교과서 연습문제 문항의 분석 결과가 교육부의 교과서 심의 기준에 대한 방향을 제시해 줄 있을 것이다. 본 연구를 통하여 교육부가 좀 더 확실한 심의 기준 하에서 교과서를 검인정하게 된다면, 교육과정에 충실한 교과서들이 제작될 것이다. 그러면 교과서간의 차이가 두드러지게 나타나지 않을 것이라고 본다.논문개요 = vi Ⅰ. 서론 = 1 A. 연구의 필요성 = 1 B. 연구의 목적 = 3 C. 연구의 의의 = 4 D. 연구의 제한점 = 6 Ⅱ. 이론적 배경 = 8 A. 평가와 연습문제 = 8 1. 평가의 의미 = 8 2. 평가와 교수/학습과의 관계 = 10 3. 교과서 연습문제의 기본 성격 = 13 a. 연습의 개념 = 14 b. 연습문제의 역할 = 15 B. 외국어 교수법 발달에 따른 연습문제 = 17 1. 전통교수법과 연습문제 = 18 2. 직접교수법과 연습문제 = 20 3. 청각구두교수법과 연습문제 = 23 4. 시청각교수법과 연습문제 = 27 5. 의사소통교수법과 연습문제 = 30 C. 우리나라 교육과정의 변천에 따른 연습문제 = 38 1. 제5차 교육과정과 연습문제 = 41 2. 제6차 교육과정과 연습문제 = 43 3. 제7차 교육과정과 연습문제 = 46 Ⅲ. 교과서 연습문제 분석 = 50 A. 분석 방법 = 50 1. 분석 대상 = 50 2. 분석 도구 = 51 3. 사전 검사 = 58 B. 분석 및 논의 = 58 1. 제7차 교과서간 연습문제의 문항 분석 및 논의 = 59 2. 제7차 교과서간 연습문제의 언어 기능, 내용 및 유형 = 81 Ⅳ. 결론 및 제언 = 89 참고문헌 = 92 부록 = 96 Re&amp;apos;sume&amp;apos; = 10

Regulation of VEGF receptor 2 signaling by peroxiredoxin Ⅱ in human aortic endothelial cell

혈관재협착증이란 혈관성형술로 인한 혈관의 손상에 의해 혈관이 좁아지게 되는 현상으로 혈관성형술 이후에는 혈관의 재협착증이 빈번하게 일어나는 것으로 알려져 있다. 재협착증이 일어나는 과정에는 혈관의 내피세포와 평활근세포가 중요한 역할을 한다. 혈관재협착증의 주된 요인은 혈관주변의 평활근세포의 증식과 이동 및 세포외 기질의 축적이며 평활근 세포의 증식을 막는것과 함께 시술과정에서 손상된 혈관내피세포가 회복되는 과정이 재협착증을 방지하는데 중요한 역할을 한다. 지금까지는 재협착증을 치료하는데 있어서 평활근세포의 성장을 줄이거나 억제하는 방법만 연구되어 왔다. 그러나 평활근세포의 증식을 억제하는 것만큼 중요한 것은 시술과정에서 손상된 내피세포층의 회복이다. 따라서 새로운 약을 개발함에 있어 평활근세포의 성장은 선택적으로 억제하면서 혈관의 내피세포층은 회복할 수 있게 하는 방법을 생각해야 한다. 최근의 연구결과에 의하면 PeroxiredoxinII(PrxII)가 혈관평활근세포의 성장과 이동을 억제하며 혈관재협착 설치류 모델에서 경동맥 풍선 손상 후 신생혈관내막의 성장을 억제한다는 것이 밝혀졌다. PrxII는 평활근세포의 성장을 조절한다고 잘 알려진PDGFR에 의해 생성된 H2O2를 제거함으로써 이러한 역할을 수행하는것으로 알려져 있다. 그러나 이러한 주목할만한 PrxII의 역할에도 불구하고 혈관내피세포에서의 PrxII 의 역할은 알려지지 않았다. 따라서 이번 실험에서는 PrxII 가 혈관내피세포에서 어떠한 역할을 하는지 알아보고자 하였다. 실험 결과, PrxII 는 혈관 내피세포의 활성을 촉진하는 것으로 나타났다. PrxII 가 없는 경우, 혈관내피세포의 성장 및 활성을 조절한다고 알려진VEGFR2 의 활성이 줄어들어있음을 확인할수 있었다. 우선, VEGFR2의 인산화된 티로신 잔기들이 줄어들어있음을 확인할 수 있었으며 downstream signaling molecule의 활성도 변화가 있었다. 또한 놀랍게도PrxII 가 없음으로 인해 내피세포의 성장이 줄어들었음을 확인할수 있었다. 반면 PrxII와 같은 기능을 한다고 알려진 gliotoxin을 처리했을 경우, VEGFR2의 활성이 증가했음을 알 수 있었다. 이러한 결과들은 평활근세포에서의 결과와 정반대의 결과로, PrxII 를 이용한 약물을 개발하는 것이 혈관재협착증을 치료할수 있는 새로운 방법이 될 수 있음을 밝히는 의미있는 결과라고 할 수 있다.;Restenosis is a maladaptive response of the coronary artery to trauma induced during angioplasty that leads to postprocedural lumen loss. In the development of restenosis, vascular cells, smooth muscle cells (SMCs) and endothelial cells (ECs), play an important role. The characteristic feature of restenosis is smooth muscle cell accumulation within the neointima, and accelerated re-endothelization limits the neointima formation. Therefore stimulating endothelial cell regeneration can be an important therapeutic approach for treating restenosis along with inhibition of smooth muscle cell accumulation in the neointima. PrxII negatively regulates SMCs by regulating PDGFR induced ROS and avtivation of the platelet derived growth factor receptor (PDGFR) in SMCs. Even thought its specific and significant role in regulating SMCs, the role of PrxII in ECs has not been investigated yet. Therefore I investigated the role of PrxII in regulating EC activation using RNAi approach. As a result, PrxII positively regulates the activation of human aortic endothelial cells (HAECs). Depletion of PrxII attenuated VEGFR2 activation in response to VEGF. Phosphorylation of tyrosine residues in the receptor was decreased. Furthermore, PrxII ablation inhibited HAEC proliferation. Additionally, treatment of Gliotoxin(GT), a 2-Cys Prx mimetic, increased VEGFR2 activaiton. Collectively, these results propose that targeting PrxII may prove to be an effective therapeutic strategy for treatment of restenosis.1. INTRODUCTION = 1 2. MATERIALS AND METHODS = 8 2.1. Antibodies and reagents = 8 2.2. Cell culture and transfection = 8 2.3. RT-PCR = 9 2.4. Immunoblotting = 10 2.5. Proliferation Assay = 11 2.6. siRNAs = 12 2.7. Measurement of ROS = 12 2.8. Data analysis = 12 3. RESULTS = 13 3.1. PrxII, but not PrxI, downregulates VEGF-induced VEGFR2 activation in HAEC = 13 3.2. PrxII, but not PrxI, downregulates VEGF-induced H2O2 production in HAEC = 16 3.3. PrxII regulates phosphorylation of tyrosine residues in VEGFR2 = 19 3.4. RT PCR analysis for VEGFR1, 2 in PrxII depleted HAEC = 21 3.5. Consequence of PrxII depletion on VEGFR2 downstream signal transduction molecules in HAEC = 24 3.6. PrxII decreases VEGF induced HAEC proliferation = 26 3.7. Gliotoxin, PrxII mimetic chemical, increases VEGF induced H2O2 production and VEGFR2 signaling in HAEC = 28 4. DISCUSSION = 31 5. REFERENCES = 34 6. 국문초록 = 3

한국인 HIV 감염자에서 약물 대사 효소와 약물 수송단백의

Dept. of Medicine/박사[한글]항에이즈 치료로서 HAART(highly active antiretroviral therapy)가 도입된 이후 HIV 에 대한 치료는 발전을 거듭하고 있다. Efavirenz는 NNRTI(nonnucleoside reverse transcriptase inhibitor) 중 대표적인 제제로서 주로 CYP2B6에 의해, 일부는 CYP2D6에 대사되며, MDR1유전자에 의해 발현되는 P-glycoprotein이 약물수송단백으로서 역할을 하게 된다. 본 연구에서는 CYP2B6 등의 산화대사효소와 MDR1 genes의 변이에 따른 치료 효과 분석 및 약물이상반응과의 관련성을 살펴보고자 한다 총 82명의 HIV 감염자를 치료 반응 유무와 이상반응, 약물 농도의 적절성에 따라 두 군으로 분류하였고 CYP2B6, CYP2D6 및 MDR1에서 11가지 유전자를 선별하여 분석하였다. C1236T의 변이를 가진 환자에서 치료 후 24주에 좀 더 나은 면역학적 치료 반응을 관찰할 수 있었고 CD4+ T 림프구의 증가량 정도가 높았다. 그러나 바이러스적 치료 반응과 대상 유전자의 변이와의 연관성을 증명할 수는 없었다. 약물이상반응 중 두통, 현기증, 악몽, 자살 충동 등의 중추신경계의 이상반응을 경험한 24명과 그렇지 않은 58명을 비교한 결과는 MDR1 A893S (r.2677G>T) 변이가 관련성이 있음을 보여 주었고(p = 0.007), 적절한 혈중 efavirenz 농도를 유지하고 있는 환자군에서는 MDR1 A893S(d.2677G>T) 변이에서 연관성을 관찰하였다. 위와 같은 결과는 에이즈 치료에서 해당 유전자의 단일 염기 다형성이 efavirenz 가 표함된 치료제에 대한 치료 반응이나 이상반응을 예측하는데 중요한 유전적 표지자 역할을 할 것으로 기대된다. [영문]The use of highly active antiretroviral therapy (HAART) has proven efficacy in controlling viral replication in HIV (human immunodeficiency virus) infected patients. Efavirenz, recommended NNRTI (nonnucleoside reverse transcriptase inhibitor) by DHHS (department of health and human service) guideline, is known to be metabolized by CYP2B6 mainly and by CYP2D6 partially and is a substrate for P-glycoprotein, which is encoded by MDR1. The aims of this study were to evaluate the influence of CYP2B6, CYP2D6 and MDR1 protein polymorphism on the virological /immunological response and neuropsychiatric adverse effects of efavirenz using a population genetics approach. Total 82 Korean HIV infected patients were divided into two groups, those who had good immunologic or virologic responses with efavirenz based regimens and or not. And, it was considered to have neuropsychiatric adverse effects of efavirenz or not. Eleven single nucleotide polymorphisms in the CYP2B6, CYP2D6 and MDR1 genes were analyzed. Patients with SNP C1236T tended to have better immunologic response at week 24 and much CD4+ T cells increment. There were no correlation between SNPs of CYP450, MDR1 and virologic response to HAART. Among patient who experienced neuropsychiatric adverse effects (n = 24) and those who did not (n=58), MDR1 A893S (r.2677G>T) variant showed a strong association with the neuropsychiatric adverse effects caused by efavirenz (p = 0.007). These data strongly suggest that A893S polymorphism in the human MDR1 gene is associated with altered drug responses of efavirenz. The adequate trough concentration of efavirenz group more likely had TT genotype than inadequate group in G2677T. It was anticipated that MDR1 polymorphism may play an important role as a genetic marker for predicting responsiveness of efavirenz prior to and after initiation of therapy by these association results in HIV infected patients.ope