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Clozapine이 인체내에서 인간조직적합성항원에 미치는 영향
강병조,김문두,곽경필 경북대학교 의학연구소 2000 경북대학교병원의학연구소논문집 Vol.4 No.1
The histocompatibillty antigen (human leukocyte antigen : HLA) has been used for organ transplantation, discrimination of one's real children and transfusion, etc. The objective of this study was to find out how dozapine affects HLA class I and II type in the humanbody when therapeutic doses are applied. The subject consists of 3 persons for lass I and class II They were administered for about 3 months with clozapine 157-250mg/day (mean dally dose 200mg). Analysis of HLA lass I type was the microcytotoxicity test of Terasaki and class II type was PCR method of Erhich. The results were as followings: Two of 3 were changed in HLA-A, B, C type. All three were not chanced in HLA-DR type. In conclusion, the short-term application, about 3 months, of therapeutic dose of clozapine is not considered to bring about changes in DNA level.
곽경필,이양현,강병조 대한생물치료정신의학회 1998 생물치료정신의학 Vol.4 No.1
요 약치료 저항성 정신분열증 환자의 클로자핀반응의 임상적 예측인자를 알아보고자 70명의 환자를 대상으로 개방 연구를 실시하였다. 기존의 항정신병 약물을 중지하고 7일간의 배설기간을 가진 후 기초평가를 실시하였고 최종 12주까지 임상적 평가를 실시하였다.최종평가시 PANSS 전체점수가 기초평가에 비해 20%이상 호전되었을 때를 반응군이라 하였을 때 78.5%가 반 응군에 속하였다. 치료 전 평가한 PANSS 세부항목상 환각행동, 흥분, 적개심, 빈약한 신뢰감, 비협조성, 판단과 병식의 결여, 충동조절장애 등의 소항목들이 반응-비반응군간에 유의한 차이가 있었다. 그리하여 이런 항목들이 있는 환자들이 클로자핀에 의하여 좋은 예후를 가져온다고 볼 수 있다.비록 본 연구가 대조군이 없는 개방연구라는 점을 감안해 볼 때 본 연구의 결과에 대한 추후 보완된 이중맹검 대조군 연구가 필요할 것으로 생각된다. In order to find the clinical predictors of clozapine response in patients with refractory schizophrenia, the clinical responses of 70 schizophrenic inpatients with treatment-refractory illness were examined in open trial. After all previous antipsychotic medications had been withdrawn for 1 week, the patients were treated with clozapine according to a standardized titration and dosage schedule. Patients who tolerated and responded to treatment were maintained on a regimen(100-600mg/day) of clozapine for up to 12 weeks. The psycho- pathologic severity and functioning status of the patients were assessed by PANSS, CGI, GAF at baseline and weeks 4, 12 of treatment. Clinical improvement as defined by a 20% or more reduction in total PANSS score at end point, was shown by 77.1% of the patients. The predictors of response to clozapine were associated with hallucinatory behavior, excitement, hostility, poor rapport, uncooperativeness, lack of judgement and insight, poor impulse control subscale of PANSS. These findings have important implications for the use of clozapine and our understanding of the pathophysiology of treatment-resistant schizophrenia.
임정호,곽경필,김문두,강병조 대한생물치료정신의학회 1997 생물치료정신의학 Vol.3 No.1
최근 난치성 정신분열증 환자에서 가장 효과적인 약으로 알려진 clozapine은 골수에 작용하여 심각한 부작용인 무과립 구증을 일으킬 수 있다. 무과립구증의 원인 및 기전에 대한 연구는 매우 많으나 현재까지 확실한 결론이 나지 않은 상태이다. 저자들은 clozapine의 이러한 골수 독성에 근거하여 clozapine이 인체내에서 염색체에 어떤 변화를 주는지 아닌지를 알아보기 위해 clozapine 단독치료를 시행한 환자에게서 치료전과 치료중에 얻어진 말초혈액 림프구를 배양하여 염색체에 어떤 변화가 생기는지를 조사하였으나, clozapine에 의한 염색체의 자발적인 변이는 관찰되지 않았다. Objective : Many drugs and environmental chemicals can induce aneuploidy or chromosome instability in vivo or in vitro. Modification of the fidelity of cellular division may occur via a variety of mechanisms and chemical interactions. The clozapine is new antipsychotic drug with superior effect than classic antipsychotics. But, it may produce agranulocytosis and seizure in some patients. Agranulocytosis is a serious side effect of this drug but the cause and mechanism of this side effect is not clearly explained. Some study suggested that oxidative stress can induce chromosome aberration and the other study suggested that clozapine produce free radical and it can induce oxidative stress on some kind of cells. Therefore we decided to investigate whether clozapine and its metabolites can induce genotoxic effect in vivo. Method : The patients were chronic schizophrenic patients without a treatment at least one year. Diagnosis was made by DSM-IV criteria and agreed by both of two psychiatrists. Blood sampling was done before the treatment and during the treatment with considerable time interval. We used peripheral blood lymphocyte culture method and we counted the numerical aberrations, sister chromatid exchanges. Results : Chromosome aberration was not detected in all samples. Conclusion : Clozapine did not induce spontaneous chromosome aberration to human lymphocytes in vivo.
( Kyung Phil Kang ),( Jin Wook Kim ),( Sook Hyang Jeong ),( Na Young Kim ),( Dong Ho Lee ),( Taek Man Nam ),( Jae Il Chung ),( Hyun Cheul Choi ),( Jung Hoon Lee ),( Sang Hub Lee ),( Young Soo Park ),( 대한소화기학회 2007 SIDDS Vol.9 No.-
Background/Alms: In east Asia, the prevalence of GERD is less common than in Western countries, but has been increasing recently. However the report about atypical GERD (A-CERD) was rare in east Asia. The aim is to assess the clinical characteristics and therapeutic response of standard or half dose of proton pump inhibitors(PPIs) in A-GERD. Methods: The medical records of 217 A-GERD patients who had been taken 24hr-ambulatory PH monitoring in Seoul National University Bundang Hospital from January 2003 to April 2006 were reviewed. They were requested from gastrointestinal division (106/217), pulmonary division. (101/217), otorhinolaryngologic division (6/217), and others(4/217). Results: (1) 33.2% (72/217) of total A-GERD patients showed abnormal acid reflux disease in 24hr-ambulatory PH monitoring: 22.9% (31/135) of total A-GERD patients showed erosive reflux disease (ERD) in endoscopy. (2) Chief complaint was chronic cough; 45.3% (98/217), globus sensation; 22.6% (49/217), atypical chest pain; 15.2% (33/217), others (hoarseness, halitosis, etc); 17.0% (37/217). (3) 41.0% (89/217) of total A-GERD patients needed medications to relieve A-GERD symptoms. A-GERD patients were treated with standard dose PPIs 75.3% (67/89) of half dose PPIs 24.7% (22/89); there were no statistically significant differences in therapeutic response between standard dose PPIs and half dose PPIs (moderately improved 38.8%, markedly improved 49.3% vs moderately improved 63.6%, markedly improved 36.4%, respectively, p=0.057). Conclusions (1) 33.2% of to total A-GERD patients showed abnormal acid reflux disease in 24hr-ambulatory PH monitoring. (2) 77% of A-GERD patients showed non-erosive reflux disease and only 23% patients showed erosive reflux disease in endoscopy. (3) Even half dose PPIs as well as standard dose PPIs showed satisfactory symptom improvement of A-GERD in Korea. Therefore, standard or even half dose of PPIs could be a excellent therapeutic potion for A-GEFE in Korea; compared to double dose PPIs for A-GERD in Western countries.
Kang, Do Y.,Lee, Hyoun W.,Choi, Phil J.,Lee, Kyung E.,Roh, Mee S. Blackwell Publishing Asia 2009 Pathology international Vol.59 No.2
<P>The aim of the present study was to evaluate the expression of sodium/iodide symporter (NIS) and glucose transporter 1 (Glut1) in 139 primary lung cancers on immunohistochemistry, and to determine the diagnostic utility of NIS as an imaging reporter. Immunoreactivity for NIS and Glut1 was noted in 75 (54.0%) and 72 (51.8%) of the 139 cases, respectively. Analysis of NIS expression on Western blot confirmed the immunohistochemistry. NIS expression was significantly higher in the adenocarcinomas than in the other carcinomas, and Glut1 expression was significantly higher in the squamous cell carcinomas than in the other carcinomas (each <I>P</I> < 0.0001). The frequency of NIS expression in those carcinomas lacking Glut1 expression was significantly higher than in those with Glut1 expression (<I>P</I> = 0.012). Among 64 adenocarcinomas, the frequency of the NIS(+)/Glut1(−) phenotype was 61.0%, which was the most frequent expression pattern. By studying the expression pattern of NIS in lung cancer, the present paper provides a helpful foundation for examining the potential utility of NIS-mediated radioiodide as an alternative diagnostic modality, especially for the management of patients with lung adenocarcinoma lacking Glut1 expression.</P>
Lee Kyung-Eun,Kang Do-Young,Choi Phil-Jo,Hong Young-Seoub,Roh Mee-Sook,Shon Jae-Jeong,Lee Jung-Min,Hwang Soo-Myoung The Korean Society for Biomedical Laboratory Scien 2006 Journal of biomedical laboratory sciences Vol.12 No.3
Sodium iodide symporter (NIS) plays a key role in thyroid hormone production by efficiently accumulating iodide from the circulating blood into the thyocytes, and this is done against an electrochemical gradient. Thyroid transcription factor-l (TTF-l) is a homeodomain-containing protein expressed in embryonic diencephalons, thyroid, and lung and has been found to bind to thyroid specific promoters and to activate their transcriptional activity. TTF-l may be one of the factors capable of activating NIS gene expression in the thyroid gland, thus it accounts for the lower levels of NIS gene expression that are seen in the extrathyroidal tissues. However, a high frequency of TTF-l expression has been observed, especially in primary lung adenocarcinoma. The present study was undertaken in order to elucidate the relationship between the expression of NIS and TTF-l in primary lung adenocarcinoma. Immunohistochemical studies for NIS and TTF-l were performed in 64 primary lung adenocarcinomas. Immunoreactivities for NIS and TTF-l were found in 49 (76.6%) and 45 (70.3%) out of 64 cases, respectively. Forty-one (83.7%) of the 49 cases with positive NIS immunoreactivity showed positive TTF-l expression, whereas 11 (73.3%) of the 15 cases with negative NIS immunoreactivity showed negative TTF-l expression (P<0.05). So the NIS expression was significantly associated with the TTF-l expression. These findings suggest that TTF-l may be one of the factors capable of activating NIS gene expression in primary lung adenocarcinoma. Further studies are needed to define the relation between NIS and TTF-l for examining the mechanisms of tissue-specific NIS expression.