Clozapine이 불응성 정신분열증 환자의 혈장 단가아민에 미치는 영향

이민수,김승현,유승호,Lee, Min Soo,Kim, Seung Hyun,Ryu, Seung Ho 대한생물정신의학회 1996 생물정신의학 Vol.3 No.2

It has been known that clozapine is more selective mesolimbic dopamin $D_2$ receptor antagonist and related to 5-HT receptor. In this study, we wxamined the plasma homovanillic acid(HVA), serotonin(5-HT), and 5-hydroxyindoleacetic acid(5-HIM) levels in refractory schizophrenics during clozapine treatment. And we assessed the effects of clozapine on these plasma monoamine metabolites and their association with psychopathology and treatment response. Eight refractory schizophrenic patients(DSM-IV) have entered the study for 3 months during clozapine treatment. Patients were admitted to the inpatient sevice and withdrawn from all neuroleptics for 7-14 days but exceptionally occasional doses of lorazepam was given if needed for behavioral control. The dose of clozapine was titrated as tolerated to 800mg/day. The plasma HVA. 5-HIM and 5-HT levels were measured before treatment and following 2nd week, 4th week, 8th week, and 12th during treatment. Psychopathology was assessed with Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Synrome Scale(PANSS) before and during clozapine treatment. During clozapine treatment, no statistically significant changes were found in plasma HVA, 5-HIM, 5-HT levels, and HVA/5-HIM ratio between baseline and following 2nd week, 4th week, 8th week, 12th week. However, the change in plasma 5-HIAA/5-HT ratio from baseline to 4th week was statistically significant. Generally, changes of plasma HVA, 5-HIAA, 5-HT levels and HVA/5-HIAA ratio were not associated with psychopathology but 5-HIAA was associated with in positive symptoms and general psychopathology of PANSS. These results suggest that clozapine has been found to have relatively weak dopaminergic blokade and stronger serotonergic antagonism.

XQuery에서의 XML 데이터 특성을 고려한 group by 지원을 위한 질의 표현 기법에 대한 연구

이민수,조혜영,오정선,김윤미,송수경,Lee Min-Soo,Cho Hye-Young,Oh Jung-Sun,Kim Yun-Mi,Song Soo-Kyung 한국정보처리학회 2006 정보처리학회논문지D Vol.13 No.4

현재 널리 채택되고 있는 XML은 플랫폼에 의존하지 않는 데이터 표현 형식으로 B2B 응용 프로그램이나 워크플로우 상황에서처럼 느슨하게 연결된(loosely coupled) 이기종 시스템 간에 정보를 교환하는 데 매우 유용하게 사용되고 있다. XML의 이러한 장점 때문에 점차 증가하는 XML에 대한 관리 및 검색에 대한 요구 사항에 대처할 수 있도록 강력한 질의 언어인 XQuery가 만들어졌다. 문서의 검색을 위한 질의 언어인 XQuery는 다양한 데이터 소스로부터 가져온 XML 데이터를 고유한 구조를 가진 질의 결과로 구성할 수 있도록 설계되었으며 현재 XML 질의 언어의 표준이다. XQuery는 반복문 등을 포함하는 강력한 검색 기능을 지원하나 데이터를 그룹화 하는 경우에는 질의 표현이 상대적으로 어렵고, 복잡한 형태를 취한다. 따라서 본 논문에서는 XQuery에 그룹화 처리를 위한 명시적인 groupby절을 도입한 질의 표현 기법을 모색함으로써 XML 데이터의 재구성과 집계 함수 처리를 위한 그룹화를 보다 효율적으로 처리할 수 있도록 하였다. 이를 위해서 XQuery에 groupby절을 도입하기 위한 EBNF(Extended Backus-Naur Form)를 제안하고, 네이티브 XML 데이터베이스인 eXist 기반의 XQuery 그룹화 질의 처리 시스템을 구현하였다. XML is the most popular platform-independent data expression which is used to communicate between loosely coupled heterogeneous systems such as B2B Applications or Workflow systems. The powerful query language XQuery has been developed to support diverse needs for querying XML documents. XQuery is designed to configure results from diverse data sources into a uniquely structured query result. Therefore, it became the standard for the XML query language. Although the latest XQuery supports heavy search functions including iterations, the grouping mechanism for data is too primitive and makes the query expression difficult and complex. Therefore, this work is focused on supporting the groupby clause in the query expression to process XQuery grouping. We suggest it to be a more efficient way to process grouping for restructuring and aggregation functions on XML data. We propose an XQuery EBNF that includes the groupby clause and implemented an XQuery processing system with grouping functions based on the eXist Native XML Database.

분자생물학의 정신과적 적용

이민수,Lee, Min-Soo 대한생물정신의학회 1994 생물정신의학 Vol.1 No.1

Advances in molecular biology have renewed hope for the discovery of disease relevant gene. The basic strategy is gene mapping and likely to have on important role in psychiatric research and practice. Recent linkage studies of chromosomal loci to psychiatric diseases shed light on the potential for new genetics in psychiatric science. This article reviews molecular application to psychiatrymethodological issues in genetic linkage, study of gene expression by analysis of mRNA, and current linkage studies in psychiatric diseases.

분자유전학을 통한 정신분열증의 이해

이민수,김표한,Lee, Min-Soo,Kim, Pyo-Han 대한생물정신의학회 1996 생물정신의학 Vol.3 No.1

Molecular genetic approaches contribute to the understanding of the underlying genetic mechanism for schizophrenia. Currently genetic evidence rests on molecular genetic methods. However, the result are contradictory and somewhat confusing due to genetic heterogeneity, incomplete penetrance, misspecification of genetic model. It is expected that molecular genetics could provide key answers to the genetic cause of schizophrenia. The purpose of this article is to call attention of the readers to heterogeneity, linkage, association, basic molecular genetic methods and genetic markers and to the need far further research. It is the author's hope thai continuous research on the molecular genetics con provide clinicians with better understanding of the schizophrenia.

데이터웨어하우스에서 유전자 알고리즘을 이용한 구체화된 뷰 선택 기법

이민수,Lee, Min-Soo 한국정보처리학회 2004 정보처리학회논문지D Vol.11 No.2

데이터 웨어하우스는 복잡한 질의 및 분석을 위해서 다양한 종류의 여러 정보 출처들로부터 정보를 모아서 저장한다. 일반적으로 웨어하우스에는 자주 실행되는 질의들을 미리 계산해서 구체화된 뷰의 형태로 저장한다. 웨어하우스를 설계할 때 가장 중요한 일들 중의 하나는 웨어하우스에서 유지될 구체화된 뷰의 선택이다. 이것은 뷰들의 유지를 위해 제한된 시간이 주어졌을 때, 모든 질의들에 대한 총 질의 응답 시간을 최소화하는 방법으로 일련의 뷰들을 선택하는 것이다(유지-비용 뷰 선택 문제). 본 논문에서는 최적에 가까운 일련의 뷰들을 계산하기 위해 유전자 알고리즘을 사용하여 유지-비용 뷰 선택 문제에 대한 효율적인 해결책을 제안한다. 특히 OR 뷰 그래프들의 관점에서의 유지-비용 뷰 선택 문제를 다룬다. 본 논문의 접근방식은 휴리스틱 방법을 사용한 기존의 탐색-기반 접근 방식들에 비해서, 시간 복잡도에서 큰 향상을 보여준다. 본 논문의 알고리즘은 최적의 질의 비용에 비해 10%이내의 추가비용만을 갖는 해결책을 제시하면서도 실행시간 측면에서는 매우 향상된 선형 증가만을 보인다. 본 논문의 알고리즘에 대한 프로토타입을 구현하였으며 이것을 사용하여 논문에서 제안하는 접근방식의 분석을 수행하였다. A data warehouse stores information that is collected from multiple, heterogeneous information sources for the purpose of complex querying and analysis. Information in the warehouse is typically stored In the form of materialized views, which represent pre-computed portions of frequently asked queries. One of the most important tasks of designing a warehouse is the selection of materialized views to be maintained in the warehouse. The goal is to select a set of views so that the total query response time over all queries can be minimized while a limited amount of time for maintaining the views is given(maintenance-cost view selection problem). In this paper, we propose an efficient solution to the maintenance-cost view selection problem using a genetic algorithm for computing a near-optimal set of views. Specifically, we explore the maintenance-cost view selection problem in the context of OR view graphs. We show that our approach represents a dramatic improvement in terms of time complexity over existing search-based approaches that use heuristics. Our analysis shows that the algorithm consistently yields a solution that only has an additional 10% of query cost of over the optimal query cost while at the same time exhibits an impressive performance of only a linear increase in execution time. We have implemented a prototype version of our algorithm that is used to evaluate our approach.

불응성 정신분열증환자의 Clozapine 치료효과

이민수,정인과,곽동일,Lee, Min-Soo,Jung, In-Kwa,Kwak, Dong-Il 대한생물정신의학회 1995 생물정신의학 Vol.2 No.1

Clozapine은 정형적 항정신병약물에 반응하지 않는 불응성 정신분열증 환자에게 효과적이며, 추체외로부작용이 적은 비정형적 향정신병약물로 보고되고있다. 따라서 저자들은 불응성 정신분열증환자를 대상으로 clozapine의 항정신병효과 및 부좌용에 대해 대표적 전형적 항정신병약물인 haloperidol과 비교연구하였다. 대상환자를 clozapine투여군(17명) 과 haloperidol 투여군 (16명)으로 나누어 12주 동안 각각의 약물을 투여하는 전향적 개방대조연구를 하였다. 두가지 약물의 치료효과와 부작용은 BPRS, PANSS, Simpson-Angus Rating Scale 및 Adverse Events-Somatic Symptoms를 사용하여 평가하였다. 약물투여 12주후 clozapine투여군이 76.5% 에서 치료반응을 보인데 비해 haloperidol투여군은 31.2%의 치료반응을 보임으로써 두약물 투여군간에 유의한 차이가 있었다. BPRS와 PANSS 척도상 clozapine투여군이 haloperidol투여군에 비하여 BPRS, PANSS 양성증상 및 일반증상 척도는 약물투여 8주후부터, PANSS 음성척도는 약물투여 4주후부터 12주까지 일관성있게 지속적으로 의미있는 호전을 보였다. Clozapine투여군에서는 타액분비(70.6%), 졸리움(52.9%), 변비(29.4%) 및 저혈압(23.4%)이, haloperidol투여군은 진전(37.5%), 정좌불능(25.0%), 강직(18.8%) 및 무운동(18.8%)이 흔히 보고되었다. 하지만 두약물 투여군 모두에서 대부분 경미하고 환자가 견딜 정도였다. Clozapine투여군에서 약물투여 전에 비해서 약물투여 12주후 백혈구와 호중구의 유의한 변화는 없었다. 이상의 결과를 종합해볼 때, clozapine은 정형적 항정신병약물에 치료효과가 없거나 추체외로부작용 때문에 약물투여가 어려운 경우의 한국인 불응성 정신분열증환자에게 효과적인 비정형적 항정신병약물이다. Clozapine, on atypical antipsychotic drug, has been estimated to be a major improvement in the treatment-refractory schizophrenic patients. We evaluated the clozapine efficacy in the treatment of schizophrenic patients who are refractory to classic neuroleptics. The patients were assigned in a prospective, open, comparative trial for 12 weeks. Following an dose titration, 33 inpatients with treatment-refractory schizophrenia diagnosed according to DSM-III-R were given a clozapine(N=17, approximate 300-600mg/day) or haloperidol(N=16, approximate 20-30 mg/day) for 12 weeks. The clinical state was assessed before treatment, and 1st, 4th, 8th and 12th week during treatment using Brief Psychiatric Rating Scale(BPRS) and Positive and Negative Syndrome Scale(PANSS). Assessment of side effects were mode weekly using Simpson-Angus Scale for Extrapyramidal Side Effects and Adverse Events-Somatic Symptoms. Clozapine produces significant improvement than haloperidol on the BPRS and PANSS scores. 77% (13/17) of the clozapine-treated patients were categorized as responders, who showed at least 20% decrease in total BPRS scores, compared with 31% (5/16) of haloperidol-treated patients. Extrapyramidal side effects occurred in only one patient in clozapine group, but nine patients in haloperidol group. Salivation, sleepiness, constipation and hypotension were most frequent adverse effects observed in clozapine group. There was no significant changes in total WBC and neutrophil during clozapine treatment. These findings suggest that clozapine is on effective antipsychotic drug for the Korean treatment-refractory schizophrenic patients, who are nonresponsive to or unable to tolerate classcal antipsychotic drugs due to extrapyramidal side effects.

정신분열병과 $5-HT_{2A}$ / T102C 다형성의 관계

이민수,남종원,곽동일,Lee, Min Soo,Nam, Jong Won,Kwak, Dong Il 대한생물정신의학회 1998 생물정신의학 Vol.5 No.2

The $5-HT_{2A}$ receptor is of great interest for research into schizophrenia and psychopharmacology in light of the observation that schizophrenic patients has 5-HT cortical-subcortical imbalance and atypical antipsychotic clozpine has $5-HT_{2A}$ antagonists properties. An significant association between schizophrenia and the T102C polymorphism of the gene for $5-HT_{2A}$receptor has been reported. In this study, we investigated an association between schizophrenia and the T102C polymorphism of the gene for $5-HT_{2A}$ receptor in Korean schizophrenic patients. The subjects consisted of 139 schizophrenic patients and 88 normal controls. Genomic DNA was amplified by PCR and digested with MsPI. The uncutt product identified allele 1(nucleotide sequence TCT) ; digested products of 216bp and 156bp identified allele 2(nucleotide sequence TCC). The allele frequencies and the genotypic distribution of $5-HT_{2A}$ receptor gene were not significantly different between schizophrenic patients and normal controls. Since allele frequencies of the T102C polymorphism may differ between individuals of different ethnic backgrounds, it needs to be conducted in an advanced research.

SSRIs 이후의 항우울제

이민수,남종원,Lee, Min Soo,Nam, Jong Won 대한생물정신의학회 1999 생물정신의학 Vol.6 No.1

New antidepressants have become available for clinical use in the 1990s. Before this decade, the drugs available to treat depression consisted essentially of monoamine oxidase inhibitors, tricyclic antidepressants, and lithium. Following the introduction of SSRIs, the options have expanded and now include SSRIs, nefazodone, venlafaxine, mirtazapine, reboxetine, tianeptine. Newer antidepressants possess a variety of pharmacological characteristics that are relevant to the choice of an antidepressant for clinical use. This review summarizes some of the major pharmacological characteristics among the drugs.

세로토닌 수송체와 기분장애

이민수,Lee, Min Soo 대한생물정신의학회 2001 생물정신의학 Vol.8 No.2

As numbers of serotonin's function are so many, studies of serotonin are numerous nowadays. In the beginning, concentration of metabolites such as 5-HIAA was a key issue, but recent studies have been challenged for serotonin receptor genes and their relation to mood disoder. Serotonin transporter(5-HTT) gene is a strong candidate gene of mood disoder for following reason. Serotonin transporter is a key protein in the serotonin pathway as it regulate the concentration of serotonin in the synaptic clept and essential pathophysiology of depression is dysregulation of 5-HTT so that all antidepressants have effect of 5-HTT antagonist. The decrease of 5-HTT in the platelet and in brain of the depressive patients is much consistent results in the studies of the pathophysiology of mood disorder till now. By this, we will be able to develop simple and easy marker for diagnosis, type, and treatment monitoring of depression. Many psychiatrists have sought the independent genes in relation to depression or schizophrenia. Obviously, the hereditary vulnerability contributes to etiology of mood disorders, but it is difficult to discriminate the independent genes because of many environmental factors. Moreover, in the hereditarily complex diseases such as mood disorder, the only vulnerability of gene can not sufficiently explain the etiology. In the future, to exclude the role of the gene-environmental interaction, the methods such as gene transfer can be considered. In the opposite direction, by using the gene destruction method, the role of target genes can be examined. As yet the concept of the gene expression, neural plasticity, neurogenesis and etc, is the elementary stage. The development of this field will help to establish the treatment strategy of chronic and refractory mood disorders.

세로토닌 재흡수억제제의 약리학과 임상적용

이민수,김표한,Lee, Min-Soo,Kim, Pyo-Han 대한생물정신의학회 1995 생물정신의학 Vol.2 No.2

1) Paroxetine이 5-HT흡수에 가장 강력하고, 선택적이었으며, 그 다음이 fluvoxamine, sertraline, fluoxetine순이었고, sertraline은 다른 SSRIs와는 달리 NE보다 DA억제작용이 더 강했다. 2) Paroxetine이 muscarinic cholinergic 수용체에 대한 친화력이 다소 높았을 뿐, 전반적으로 SSRIs는 histamine $H_1$과 ${\alpha}_1$에 대한 친화력은 약했다. 3) Paroxetine은 ${\beta}$-adrenoceptor와 cyclic AMP에 영향을 미치지 않는 반면, sertraline은 ${\beta}$-adrenoceptor와 cyclic AMP의 감소를 가져왔다. 4) SSRIs의 생체이용율은 대략 50%이었으며, 투약후 2~8시간 사이에 최고혈중농도에 도달하였으며, 특히 sertraline은 음식물과 같이 복용시 혈장의 concentration time curve와 최고 농도를 증가시켰다. 5) Sertraline은 혈중농도가 용량에 비례하였으며, 모든 SSRIs는 비교적 큰 용량분포를 보이고, 높은 비율로 혈장 단백질과 결합되어 있었다. 6) Fluoxetine 대사물의 5-HT 억제 작용이 제일 강했다. 그러나 paroxetine, fluoxetine, sertraline 대사물은 강도는 서로 다르지만 간의 isoenzyme IID6를 억제하며, 그 중에서 paroxetine의 억제작용이 제일 강력하다. 7) Sertraline은 TCAs나 haloperidol과 병합사용시 TCAs나 haloperidol의 혈중농도의 유의한 변화가 없었으며, MAOI A형인 moclobemide와 비교적 안전하게 병용 치료할 수 있다. 8) SSRIs는 TCAs와 비교해볼 때 치료효과는 유사하였으나 fluvoxamine은 자살사고에, paroxetine은 우울중에서 나타나는 불안과 운동성 초조증에 효과적이다. 9) 급성 우울증 삽화시 현저한 효과를 보인 후 적어도 4개월 이상의 유지치료기간이 필요하다. 10) SSRIs는 위장관계통의 부작용이 가장 많았고, 부작용은 일반적으로 분복한 경우가 적었다. In comparison with tricyclic antidepressants(TCAs), one of the most interesting characteristics of selective serotonin reuptake inhibitors(SSRIs) is its structural differences, reveals different pharmacological properties. The applications at the moment are most effective in clinical applications to depression. The limited result of the research to date on the various applications of SSRIs has not revealed the total potential and applicability of SSRIs. Therefore, attending physicians utilizing SSRIs do not know the full capabilities of the drug on patients and what the patients may reap in terms of benefit from its curing elements. Physicians must first try to understand the full potential of SSRIs and its potential applications for it to be effective on patients. recently, it has been determined that SSRIs and other drugs when administered together may be more effective in the healing process because SSRIs complements and aids in the enhancement and effect of the other drugs. This article is written to give attention to the reader of the pharmacological properties and the clinical use of SSRIs. It is the authors's hope that continuous research on the particular aspects of SSRIs can aid the clinicians in the use of this SSRIs.