PGA2-induced expression of HO-1 is mediated by transcriptional upregulation of Nrf2

Sang-sun Lee,Yun-Jeong Choe,Hyein Lee,Sun-Young Lee,Ho-Shik Kim 대한독성 유전단백체 학회 2019 Molecular & cellular toxicology Vol.15 No.2

Backgrounds: Prostaglandin (PG) A2 reportedly stimulated expression of heme oxygenase (HO)-1 at the level of transcription via the activation of p38MAPK. Details of the mechanism, however, have not been provided, and this includes identification of the transcription factors responsible for PGA2-induced HO-1 expression. Herein is described an analysis of the role of nuclear factor erythroid 2 related factor 2 (Nrf2) and how PGA2 increases the activity of Nrf2 during PGA2-induced HO-1 expression. Methods: Expressions of HO-1 and Nrf2 were analyzed at the levels of both mRNA and protein. Nrf2 siRNA, SB203580, an inhibitor of p38MAPK, and scavengers of reactive oxygen species (ROS) were used to identify the effects of Nrf2, p38MAPK and ROS on PGA2-induced HO-1 expression. Results: Although SB203580 suppressed PGA2-induced HO-1 expression, genetic activation of p38MAPK could not stimulate the transcription of HO-1. Cycloheximide (CHX), an inhibitor of protein translation, almost completely prevented PGA2-induced increase of HO-1 transcription, but it did not prevent the phosphorylation of p38MAPK, which suggests that both de novo protein synthesis and p38MAPK activity are required to induce the transcription of HO-1 in response to PGA2 treatment. In addition, PGA2 increased the level of both Nrf2 mRNA and protein in a dose-dependent manner. Knockdown of Nrf2 using small interfering RNA (siRNA) suppressed PGA2-induced HO-1 expression. The PGA2-induced transcription of Nrf2 was prevented by ROS scavengers such as n-acetyl-l-cysteine and tempol but not CHX. Furthermore, siRNA against p38MAPK did not change the level of nuclear Nrf2 protein. Conclusion: These findings suggest that PGA2 induces HO-1 transcription via an increase in Nrf2 protein, the transcription of which is initiated by an accumulation of ROS that is independent of the p38MAPK activation pathway.

PGA2 induces the expression of HO-1 by activating p53 in HCT116 cells

Hyein Lee,Sang-Sun Lee,Ji-Young Park,Yun-Jeong Choe,이선영,Ho-Shik Kim,H.-S. Kim 대한독성 유전단백체 학회 2017 Molecular & cellular toxicology Vol.13 No.2

Prostaglandin (PG) A2 which is a cytotoxic PG, was reported to induce the expression of heme oxygenase (HO)-1 via activation of p38MAPK to keep U2OS cells from cell cycle arrest in G2M phase. The expression of HO-1 is primarily regulated at the level of transcription. But the transcription factors that are responsible for PGA2-induced HO-1 expression were not clarified yet. Here, we report that PGA2-induced transcription of HO-1 is mediated by p53, a tumor suppressive transcription factor. In HCT116 cells, PGA2 treatment led to the phosphorylation of p53 and an increase of p21WAF1 transcription as well as the activation of HO-1 transcription. Knocking p53 down via RNA interference or inhibiting the p53’s transcriptional activity by pifithrin-α treatment led to suppression of the increase in the level of both HO-1 expression and activity of HO-1 promoter. Pretreatment of NU- 7441, a chemical inhibitor of DNA-activated protein kinase (DNA-PK), prevented both the PGA2-induced phosphorylation of p53 and an increase of HO-1 transcription. In addition, N-acetyl-l-cysteine, a scavenger of reactive oxygen species (ROS), also mimicked the effect of NU-7441 on the PGA2-induced activation of p53 and HO-1 transcription. Collectively, these results suggest that PGA2 induces the expression of HO-1 via activation of p53, which is mediated by the ROSDNA- PK pathway.

전통주 주박의 항혈전 활성 평가

김미선(Mi-Sun Kim),이예슬(Ye-Seul Lee),김종식(Jong Sik Kim),신우창(Woo-Chang Shin),손호용(Ho-Yong Sohn) 한국생명과학회 2014 생명과학회지 Vol.24 No.8

전통주 주박을 이용한 고부가가치 식품소재 개발을 위해, 상업적 시설에서 생산된 3종 약주(J-B, J-S, J-Y) 및 2종 탁주(J-H, J-W) 주박의 ethanol 추출물 및 열수 추출물을 조제하고 이들의 혈액응고 저해활성, 혈소판 응집저해 활성 및 인간 적혈구 용혈활성을 평가하였다. 5종 주박의 pH는 3.90~4.29로 유사하였으나, brix는 5.0~27.0으로 다양하게 나타났으며, 수분 및 알코올 함량에서도 시료에 따라 1.8배의 차이를 나타내었다. 주박의 색차와 성분은 첨가된 부재료 및 사용누룩에 좌우되었으며, J-W 주박의 경우 수분함량이 80.3%, brix 13, 알코올 함량 1.8%를 함유하여 다른 주박에 비해 다양한 식품제조에 용이하게 이용 가능하리라 판단되었다. Ethanol 추출효율은 J-H, J-W, J-B, J-S, J-Y의 순, 열수 추출효율은 J-S, J-B, J-W, J-H, J-Y의 순으로 높았으며, 총폴리페놀 및 총플라보노이드함량은 ethanol 추출물 중에서는 J-H, 열수 추출물 중에서는 J-Y 주박에서 가장 높았다. 5종 주박의 10종 추출물은 모두 5 mg/ml 농도까지 인간 적혈구에 대한 용혈활성이 나타나지 않았으며, J-B, J-S, J-Y의 약주 주박의 ethanol 추출물에서 유의적인 혈액응고저해 활성이 나타났으며, J-W 탁주 주박의 열수 추출물에서 thrombin 저해 활성과 J-B, J-S 및 J-H 주박 열수 추출물에서 혈액 응고인자 저해활성을 확인하였다. 혈소판 응집저해 활성평가의 경우 J-W 탁주 주박의 ethanol 및 열수 추출물에서만 아스피린에 필적하는 우수한 활성이 확인되었다. 본 연구결과는 다양한 약주 및 탁주 주박이 항혈전 활성을 가지고 있으며, 주박으로부터 항혈전제 개발이 가능함을 제시하고 있다. In this study, ethanol and hot water extracts of lees from Korean traditional wine (J-B, J-S, J-Y, J-H, and J-W) were prepared, and their effects on blood coagulation, platelet aggregation, and hemolysis of human red blood cells (hRBCs) were investigated to develop functional food ingredients from lees. The pH and brix of the lees ranged from 3.90 to 4.29 and 5.0 to 27.0o, respectively, and there was a huge difference in the water and ethanol content among the lees. The nuruk and additives used affected the color and physicochemical properties of lees. The J-W takju made from only rice and traditional nuruk, which has 13o brix and 1.8% of alcohol, has potential as functional food ingredient. With regard to the extraction yields of lees, higher yields were obtained from J-H, which contains different medicinal plants, in ethanol, followed by J-W, J-B, J-S, and J-Y. Higher extraction yields of lees were obtained from J-S in hot water, followed by J-B, J-W, J-H, and J-Y, respectively. The ethanol extract of J-H and the hot water extract of J-Y had the highest contents of total polyphenol and total flavonoids among the lees extracts. The 10 lees extracts did not show hemolysis activity against hRBCs up to 5 mg/ml. In an anticoagulation activity assay, the ethanol extracts of three yakju lees (J-B, J-S, and J-Y) and the hot water extract of J-W inhibited thrombin activity, whereas the hot water extract of J-B, J-S, and J-H inhibited blood coagulation factors. In an antiplatelet aggregation activity assay, only the J-W takju lees showed significant inhibition activity. Our results suggest that lees from traditional wine had high potential as a novel antithrombosis agent.

Nutlin-3 induces HO-1 expression by activating JNK in a transcription-independent manner of p53

CHOE, YUN-JEONG,LEE, SUN-YOUNG,KO, KYUNG WON,SHIN, SEOK JOON,KIM, HO-SHIK Spandidos Publications 2014 International journal of oncology Vol.44 No.3

A recent study reported that p53 can induce HO-1 by directly binding to the putative p53 responsive element in the HO-1 promoter. In this study, we report that nutlin-3, a small molecule antagonist of HDM2, induces the transcription of HO-1 in a transcription-independent manner of p53. Nutlin-3 induced HO-1 expression at the level of transcription in human cancer cells such as U2OS and RKO cells. This induction of HO-1 did not occur in SAOS cells in which p53 was mutated and was prevented by knocking down the p53 protein using p53 siRNA transfection, but not by PFT-alpha, an inhibitor of the transcriptional activity of p53. Accompanying HO-1 expression, nutlin-3 stimulated the accumulation of ROS and the phosphorylation of MAPKs such as JNK, p38 MAPK and ERK1/2. Nutlin-3-induced HO-1 expression was suppressed by TEMPO, a ROS scavenger, and chemical inhibitors of JNK and p38 MAPK but not ERK1/2. In addition, nutlin-3-induced phosphorylation of JNK but not p38 MAPK was inhibited by TEMPO. Notably, the levels of nutlin-3-induced ROS were correlated with the mitochondrial translocation of p53 and this induction was prevented by PFT-beta, an inhibitor of the mitochondrial translocation of p53. Consistent with the effect of the ROS scavenger and MAPK inhibitors, PFT-beta reduced HO-1 expression and the phosphorylation of JNK induced by nutlin-3. In the experiments of analyzing cell death, the knockdown of HO-1 augmented nutlin-3-induced apoptosis. Collectively, these results suggest that nutlin-3 induces HO-1 expression via the activation of both JNK which is dependent on ROS generated by p53 translocated to the mitochondria and p38 MAPK which appears to be stimulated by a ROS-independent mechanism, and this HO-1 induction may inhibit nutlin-3-induced apoptosis, constituting a negative feedback loop of p53-induced apoptosis.

Prostaglandin A₂-induced Apoptosis is Not Inhibited by Heme Oygenase-1 in U2OS Cells

Kyoung-Won Ko(고경원),Sun-Young Lee(이선영),Ji-Hyun Ahn(안지현),Jaetaek Kim(김재택),In-Kyung Kim(김인경),Ho-Shik Kim(김호식) 한국생명과학회 2008 생명과학회지 Vol.18 No.11

Prostaglandin A₂ (PGA₂)는 사람 골육종 세포인 U2OS 세포주에서 apoptosis와 heme oxygenase (HO)-1의 발현을 함께 유도하였다. PGA₂에 의한 apoptosis는 HO-1의 과도한 발현이나 HO-1에 대한 small interfering RNA에 의한 발현저하에 의하여 변동되지 않았으나 H₂O₂에 의한 세포사망은 HO-1의 발현 수준에 반비례하여 변동되었다. 또한 thiol antioxidant인 N-acetyl-L-cysteine (NAC)은 PGA₂에 의한 세포사망과 HO-1의 발현 증가를 모두 차단하였지만, non-thiol antioxidant인 butylated hydroxyanisole (BHA)과 ascorbic acid는 세포사망과 HO-1의 발현 유도를 차단하지 않았다. 이와 같은 결과들은 PGA₂는 산화성 손상에 의해서가 아니라 PGA₂의 thiol-reactivity에 의하여 apoptosis와 HO-1의 발현을 유도하며, HO-1의 발현은 PGA₂에 의한 apoptosis와는 독립적인 현상이거나 기능적으로 apoptosis 유도의 하부에 위치하고 apoptosis의 진행에는 기여하지 않을 것이라는 것을 시사해 준다. Prostaglandin A₂ (PGA₂), one of cyclopentenone PGs, induced both apoptosis and heme oxygenase (HO)-1 expression in U2OS cells. PGA₂-induced apoptosis was not perturbed by either over-expression or knock-down of HO-1, whereas H₂O₂-induced cell death was inversely modulated by the expression level of HO-1. In addition, N-acetyl-L-cysteine (NAC), a thiol antioxidant, blocked both apoptosis and HO-1 expression induced by PGA₂. But, non-thiol antioxidants like butylated hydorxyanisole (BHA) and ascorbic acid did not block either apoptosis or HO-1-induction. Taken together, these results suggest that PGA₂ induces both apoptosis and HO-1 expression, which are critically related to the thiol-reactivity of PGA₂, but not oxidative stress, and HO-1 expression may be independent or functionally located downstream of apoptosis by PGA₂ without contribution to apoptosis progression.

한국 로스쿨 체제, 과연 사법시험의 대안인가?

이호선 ( Ho Sun Lee ) 한국법정책학회 2015 법과 정책연구 Vol.15 No.4

법조인 양성을 둘러싼 두 가지 상반된 입장이 사법시험 폐지가 가까워 짐에따라 점점 더 뜨거운 갈등으로 다가오고 있다. 한쪽에서는 사법시험 폐지를 규정하고 있는 변호사시험법 개정을 통해 사법시험을 유지하자고 하고, 다른 쪽에서는 대학원제 로스쿨 일원화를 주장하고 있다. 사법시험을 지지하는 사람들의 핵심 주장들 중 하나는 사법시험이 기회균등을 통해 중산층들에게 법조인이 되는 기회를 줌으로써 사회적 이동의 기능을 수행할 수 있다고 한다. 따라서 이들은 사법시험이 로스쿨 제도와 병존되어야만 한다고 주장한다. 반면 사법시험폐 지론자들은 최저 소득층에게는 법조인이 되는 기회가 장학금을 통해 충분히 보장되고, 사법시험 준비에 들어가는 부담은 로스쿨 비용만큼이나 비싸다고 주장 한다. 사시폐지론자들의 이론적 지지대로서 가장 많이 이용되는 논문이 몇몇 언론에도 보도가 되었던 이재협 교수 등의 “로스쿨 출신 법률가, 그들은 누구인 가? - 사법연수원 출신 법률가와의 비교를 중심으로”이다. 이 교수 등은 사법시 험에 합격한 사람들의 평균 가구당 소득은 오히려 로스쿨 재학생들 가구당 소득 보다 다소 높고, 두 집단 사이에 부모의 직업과 사회적 지위에도 유의미한 차이가 없다는 결론을 내리고 있다. 이들의 논문에서 사법시험 출신에 관한 부분은 2009년 이후 합격자들 중 300명을 상대로 한 설문조사에 터잡고 있다. 그러나 이재협 교수의 연구 대상의 모집단이 3,519명 - 2012년 이후 합격자까지 총원은 4,621명 -이고, 표본집단의 84%가 서울 거주자이며, 그 중 18%가 상위 5대로펌에 소속되어 있음을 감안할 때 필자는 위 연구의 진실성에 의심을 가질 수 밖에 없었다. 이에 저자는 표본집단을 확장함으로써 이재협 교수 등의 연구 결과를 검증하고, 사법시험이 사회적 이동성의 역할을 수행하는지, 특히 중산층의 계층 이동 역할을 하는지 알아보기로 하였다. 필자는 총 4,621명 모집단 중에서 1,286명으로부터 응답을 받았고, 2009-2012 사법시험 합격자들의 경우 총 3,519명 중 1,051명으로부터 응답을 받았다. 그 결과 이 조사와 이재협 등의 연구와 상당한 차이가 있음이 드러났다. 먼저 사법시험합격자들의 가구당 월평균 소득은 이재협 등의 연구의 약 1/3에 불과하였다. 이 수준은 통계청에서 발표하는 전국 가구당 평균 소득과 유사하다. 그리고 가정의 사회적 배경에 관하여 이 조사는 사법시험 합격자 집단의 97%가 예컨대, 법조인, 법학 교수, 판사, 정치인, 고위 관료, 임원, 중견 언론인 등 사회적으로 중요한 지위에 있는 집안과 관 계없음을 보여주었다. 무엇보다 중요한 것은 사법시험 합격자의 69%가 만일로 스쿨 한 체제만 존속하고 있었다면 자신들은 경제적 부담으로 인해 법조인이 되는 것을 포기하였을 것이라고 응답하고 있다는 점이다. 이는 사회적 통합에 불가결한 공정과 투명성 역할은 두말할 나위 없고, 사회적 이동통로로서, 그리고 기회균등의 수단으로서의 사법시험의 역할을 로스쿨 체제가 대체할 수 없음을 말해준다. There are two opposite arguments over the way how to fostering lawyers, and this conflict is getting hotter as the termination of Korea Judicial Exam is being closer than ever. One of these is in maintaining KJE by revising the National Bar Exam Act, which provides the abolishment of KJE, and the other is to insist single system for lawyers through graduate law-schools. One of the core arguments of those who are supporting KJE is that it can fulfill a function for social movement by giving middle class a guarantee to become lawyers with equal opportunities. In particular, they uphold that the merits which cannot be filled by NBEA are in openness to all classes, and it never forces the people to pay demanding cost to become lawyers. Therefore, they are insisting that KJE must coexist with law-school system. Meanwhile, the anti-KJEs claims that the opportunities to become lawyers for the lowest class can sufficiently secured by scholarship, and the burden for preparing KJE is just as costly as law-school expenses. The firm ground for anti-KJEs, which are most frequently quoted, is the article, “Law School Lawyers in Korea, Who Are They? - Focused on comparing with JRTI lawyers” by Lee, Jae-Hyup et al. receiving coverage for some media. In this article, Mr. Lee and his fellows concludes that the average household incomes of those who passed the KJE are rather more than those of law school students and that there is no significant differences in parents’ job and social status between two groups . The part about KJE in their paper was based on questionnaire survey analysis targeting three -hundred successful candidates since 2009. However, considering that the population of Mr. Lee’s research is 3,519 - the total numbers including the successful candidates those who passed beyond 2012 are 4,621 - and 84% of sampling is composed of those who lives in Seoul, and 18% in top five law-firms, the author was forced to have a doubt about the veracity of the study. So the author tried to verify the result of Mr. Lee and his fellows’ research by expanding the sampling size, and whether or not the KJE has been doing a role of social mobility, especially for middle class. The author got answers from 1,286 lawyers among totally 4,621, and from 1,051 among 3,519 lawyers who passed KJE 2009-2012. The results show that there is much difference between this research and Mr. Lee’s. First of all, the average household monthly income of KJE group is only one-third of Mr. Lee’s analysis. This level is equivalent to the national average household income reported by Statistical Office. And in regard to family social background, this survey demonstrates that the 97% of the KJE group is irrelevant to any meaningful social position, e.g. lawyer, law-professor, judge, politician, high-ranking bureaucracy, CEO, and junior executives in the press. More than anything, it should be noted that 69% of the successful candidates of KJE would give up to become lawyer due to the heavy expenses, if there are only one way of law-school system. This research suggest that law-school system cannot replace the role of KJE as the channel for social mobility and the means of equal opportunity, needless to say as the symbol of fairness and transparency indispensible to social integration.

Study of decreased melanin production through p53 by heme oxygenase-1 inhibitor in normal human melanocytes

( Hee Sun Lim ),( Sun A Jin ),( Jee Bum Lee ),( Seong Jin Kim ),( Seung Chul Lee ),( Young Ho Won ),( Sook Jung Yoon ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Heme oxygenase (HO)-1 is induced by oxidative stress and plays important roles in anti-apoptosis and the rapid growth of several solid tumors. p53 has a central role in skin pigmentation and may impact onmelanoma at all stages. However, there has been little study of HO-1 in relation with p53 on melanin production Objectives: To know the effect of HO-1 on melanogenesis through p53 in normal human melanocytes Methods: Human melanocytes (hM) were primarily cultured from foreskin. After incubation, cells were rinsed twice with PBS then transfection with p53 siRNA Results: Melanin content was detected with ELISA and Western blot analysis and RT-PCR of tyrosinase, MITF were performed after ZnPP treatment and p53 transfection. After ZnPP treatment, melanin content was decreased, and tyrosinase and MITF protein levels were decreased. Tyrosinase and MITF mRNA levels were also decreased. However, melanin content and tyrosinase and MITF protein levels were increased after CoPP treatment. After p53 transfection, HO-1 expression was decreased when HO-1 stimulator was treated. In addition, melanin content was decreased, and tyrosinase expression was decreased in Western blot analysis Conclusion: These results suggest that melanogenesis is inhibited by ZnPP by decreased melanin production, tyrosinase and MITF protein and mRNA levels. Furthermore, those inhibitory effects of ZnPP may be dependent on p53 in normal human melanocytes. Therefore, HO-1 may play an important role in melanogensis

한국인에서 일광 노출의 유해성에 대한 인지도와 일광 차단제의 이용 행태에 대한 연구

김상태,김기호,오선진,이승철,강세훈,윤재일,김진준,박석범,김홍용 대한피부과학회 1999 大韓皮膚科學會誌 Vol.37 No.6

Background: Although deleterious effects of sunlight have been increased recently, the surveillance of the attitudes toward sun-exposure and the behavioral aspect of using sunscreens in Koreans has hot been carried out. Objective: Our purpose was to evaluate the attitude toward the harmfulness of sun-exposure and behaviors of using sunscreens in Korea. Method: Five hundred and fifty-two subjects were surveyed to assess the attitude toward sun-exposure, as well as the subjects knowledge about, and the use of sunscreens. Underlying data including demographic data, skin colors, skin types, occupation, and sun-exposure, were obtained. Results: Fifty-four percent of subjects believed that sun-exposure is bad for their skins, but, on the contrary, 12.5% believed it to be beneficial. Fifty-two percent of subjects used sunscreens. Almost all subjects(93.8%) knew why to use sunscreens but 62.7% of subjects did not know the meaning of sun protective factors(SPF). Women, indoor workers, subjects less than 40 years old, with less sun-exposed, fair colored skin, or with skin type I, II, III tended to know the deleterious effects of sunlight and the meaning of SPF and used more sunscreen. Conclusion: High risk population-men, outdoor workers, subjects oider than 40 years old, with more sun-exposed, dark colored skin, or skin type VI, V could be targeted with campaigns that promote attitudinal and behavioral changes.

PGA2-induced expression of HO-1 is mediated by transcriptional upregulation of Nrf2

Lee, Sang-sun,Choe, Yun-Jeong,Lee, Hyein,Lee, Sun-Young,Kim, Ho-Shik THE KOREAN SOCIETY OF TOXICOGENOMICS AND TOXICOPRP 2018 MOLECULAR AND CELLULAR TOXICOLOGY Vol. No.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.