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.

Protease 생산성이 향상된 Bacillus natto 돌연변이주의 개발

윤기홍 우송대학교 2000 우송대학교 논문집 Vol.5 No.-

청국장 발효균인 Bacillus natto의 protease 생산성이 향상된 변이주를 개발하기 위해 N-methyl-N'-nitro-N-nitrosoguanidine (NTG)를 사용하여 돌연변이를 유발하였다. 돌연변이는 B. natto의 사멸률이 90%가 되도록 중기대수기의 B. natto 배양액에 NTG를 100㎍/㎖ 첨가하여 10 분간 수행하였다. Protease 생산성이 우수한 변이주는 2% skim milk와 2% tween 20을 첨가한 LB 평판배지에서 형성된 콜로니 주변의 skim milk 분해환의 크기와 선명도를 관찰함으로써 선발하였다. 이로써 변이주 M8을 최종적으로 선발하였는데 M8은 모균주에 비해 액체배지에서 최대 성장정도가 약간 저하되었지만, protease 생산성은 8.3 배 증가한 것으로 나타났으며 최대 효소생산성은 46.4 U/㎖ 이었다. 또한 protease는 중기대수기를 지나면서 다량 생성되기 시작하였으며 정지기에 도달하여 그 생산성이 최대에 이르는 것으로 나타났다. 본 실험을 통해 개발된 변이주 M8은 protease 생산성이 향상되었으므로 콩 발효시 단백질의 분해력이 우수할 것으로 예상되며 청국장 발효균으로서의 가치가 높다고 판단된다. Bacillus natto cells, natto-fermenting food microorganism, were mutagenized by N-methly-N'-nitro-N-nitrosoguanidine (NTG) for increasing its protease productivity. Mutagenesis was performed by treating the B. natto cells with 100㎍/㎖ of NTG for 10 min, which caused approx. ninety percent of the cells to die. Mutant strains were isolated by scoring the size and transparency of halo formed around the colonies grown on LB a gar plates containing skim milk (2%) and tweeny 20 (2%). A mutant strain of protease hyper-producer, designated as M8, was finally obtained, and its growth and protease production were investigated. In flask cultures, growth pattern of M8 was similar to that of parent strain, though maximum growth level of M8 decreased little less. Nevertheless, the maximum protease production of mutant M8 was 46.4 U/㎖ corresponding to 8.3-fold increase over the parent strain. It was additionally found that the protease production of mutant M8 was done after mid-logarismic growth phase and reached maximum level at stationary phase. Increasement of its protease productivity is useful for the efficient hydrolysis of soybean protein, expecting that mutant M8 is a promising strain for natto.

Trigonopsis variabilis의 D-amino acid oxidase 정제

윤기홍 우송대학교 1999 우송대학교 논문집 Vol.4 No.-

배지에 methionine을 0.2% 이상 첨가하였을 때 Trigonopsis variabilis 배양균체내 D-amino acid oxidase (D-AAO)의 비활성도는 증가하였으나 균의 성장도는 매우 갑소되었다. 배양 후 배지의 pH가 급격히 감소하였으며 이에 따라 균의 성장이 억제되는 것으로 확인 되었는데 배양액의 pH를 유지할 경우 D-AAO의 생산성을 높일 수 있을 것으로 판단된다. T. variabilis 균체파쇄액으로 부터 DEAE-Sepharose와 Mone Q column을 사용항여 D-AAO의 비활성이 7.23 U/mg protein이 되도록 정제하였는데 정제과정 중 균체파쇄액에 미약하게 존재하는 catalase가 제거되었다. 정제된 D-AAO를 이용하여 cephalosporin C (CPC)의 탈아미노 반응을 수행한 결과 반응액 중에 catalase를 첨가하였을 때는 CPC가 ketoadipyl 7-aminocephalosporanic acid (7-ACA)로 전환되었으나 catalase를 첨가하지 않았을 때는 반응산물의 대부분이 glutaryl 7-ACA로 전환되고 미량의 ketoadipyl 7-ACA와 미지의 물질이 생겨나는 것으로 확인되었다. Specific activity of D-amino acid oxidase (D-AAO) was estimated to be increased in Trigonopsis variabilis cells grown on the broth supplemented with methionine over the concentration of 0.2%, but the cell growth was severely inhibited by the methionine, Final pH of the medium was found to decrease dramatically after the cell growth, suggesting that the dectrased pH caused to inhibit the growth of T. variabilis cell. In order to imprpve the D-AAO productivity of T. variabilis it is required to maintain the medium pH during cell growth. D-AAO was purified from cell-free extract of T. variabilis by DEAE-Sepharose and Mono Q culumn chromatography with specitic acitivity of 7.23 U/mg protein. Catalase activity was not detected in the purified enzyme. When the T. variabilis D-AAO reacted cephalosporin C (CPC) as a substrate with catalase or not, CPC was mainly converted to ketoadipyl 7-aminocephalosporanic acid (7-ACA) in the presence of catalse. In the absence of catalase, the reactants were, however, identified to be glutaryl 7-ACA with trace amount of ketoadipyl 7-ACA and unkwon compounds.

부가 탄소원이 Bacillus sp. 79-23의 변이주에서 셀룰라제의 생산성에 미치는 영향

윤기홍,신인경 우송대학교 부설 산업연구원 1999 산업연구 Vol.1 No.2

Bacillus sp. 79-23의 포자를 감마선으로 조사하여 얻은 7개 변이주의 CMCase 생산성에 미치는 탄소원의 영향을 모균주와 비교 분석하였다. LB 배지에 부가탄소원으로 glucose, xylose, maltose, lactose, CMC, starch, 볏짚, 밀기울을 첨가하여 배양한 후 배양상등액에 존재하는 CMCase의 활성을 측정한 결과 변이주의 효소생산성은 탄소원에 의해 모균주와 유사한 영향을 받는 것으로 나타났으나 변이주에 따라 약간의 차이는 존재하였다. 특히 xylose와 볏짚에 의한 변이주들의 효소생산량간에 차이가 나타났다. 대부분 변이주의 성장정도도 모 균주와 유사한 것으로 확인되었으며 효서는 성장과 연계되어 생산되었다. 그러나 변이주 48에 잇어서 탄소원에 의한 효소 생산성의 영향은 유사하지만 모균주나 다른 변이주에 비해 성장정도가 매우 낮으며 효소 생산량도 다른 균주에 비해 낮은 것으로 밝혀졌다. 이로보아 변이주에서의 유전자 변이는 서로 다른 지역에서 일어난 것으로 생각된다. 한편 CMCase를 코드하는 유전자를 포함한 부위가 모든 변이주와 모균주의 총 유전체 DNA로부터 동일한 primers로 증폭되었으며 그 크기가 전기영동상에서 동일한 것으로 확인되었다. 그러므로 감마선 조사에 의해 얻어진 변이주는 CMCase 유전자 부위에 삽입이나 결손등의 변이가 일어나지 않은 것으로 판단된다. In seven mutant strains which were derived from Bacillus sp. 79-23 by gamma-irradiation of the parental spores, effects of carbon sources were investigated on carboxymethylcellulase (CMCase) production. By measuring the CMCase activity in the supernatants of bacterial cultures which were grown in LB medium containing glucose, xylose, maltose, lactose, carboxymethylcellulose, strach, rice straw, and wheat bran as additional carbon sources, it was identified that seven mutants were comparable to the parent strain. Among the additional carbon sources, xylose and reice straw affected differently the CMCase production according to the mutant stains. It was found that the enzyme production was in association with the growth of parent and mutant strains. Growth of mutant strains reached the level of parent strains. Growth of mutant strains reached the level of parent strain except mutant 47. Mutant strain 48 was poorly grown and produced CMCase less than other mutant strains. As the results of them, it was suggested that mutagenesis of the mutant strains occurred in different positions of their chromosomal DNAs, respectively. DNA fragments with an identical molecular size of 1.6 kb corresponding to the gene encording a Bacillus sp. 79-23 CMCase were amplified from genomic DNAs of all mutants and parent strain using same primers by polymerase chain reaction, proposing that mutations did not be cuased by the insertion and deletion in the structural CMcase genes of the seven mutants.

대두 및 대두발효식품의 항돌연변이성

윤기도,권동진,홍석산,김수일,정건섭 한국미생물생명공학회 ( 구 한국산업미생물학회 ) 1996 한국미생물·생명공학회지 Vol.24 No.4

To investigate the inhibitory effect of soybean and Korean traditional fermented soybean products on the chemically induced mutagenesis, we extracted soybean, Kanjang, Doenjang, Kochujang, and Chonkukjang with water, methanol and hexane. Inhibitory effect of extracts was assayed by the SOS chromotest using Escherichia coli PQ37 as a test strain. 4-nitroquinoline-1-oxide(4NQO), N-methyl-N'-nitro-N-nitrosoguanidine(MNNG), and aflatoxin B_1(AFB_1) were used as mutagens. Methanol extracts showed relatively higher inhibitory effect than water and hexane extracts. Methanol extracts of soybea, Doenjang, Kochujang, and Chongkukjang showed inhibitory effect of 68.4, 96.3, 17.5, and 100.9%, against MNNG, and 28.6, 109.1, 41.3, and 101.8% against AFB_1., respectively. Doenjang methanol extract showed inhibitory effect of 51.0, 96.3, and 109.1% against 4NQO, MNNG, and AFB_1. Inhibitory effect of heat-treated Doenjang and Chongkukjang methanol extracts on the mutagenicity of MNNG and AFB_1 was remained over 95% of the inhibitory effect of heat-untreated extracts, demonstrating the heat stability of the potent antimutagenic activity.

消癌去痰益氣湯의 cyclophosphamide 부작용 형성 억제효과

홍종희,류기원,류봉하,윤상협,김진성 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2002 東西醫學硏究所 論文集 Vol.2002 No.-

Object : It is well known that modern chemotherapy against cancer has side effcts to a living body, especially hemopoietic and immunologial disfunctions. However, there are no effctive ways to reduce them.Recently, traditonal Korean herb medicine has been repoted to have some biological modifying responses. Therefore, we hypothesized that additional application of herb medicine during chemotherapy is more effective to reduce its side effects. While we were studying the effects, we have observed the inhibitory effect of Soamgudamikgitang on formation of side effects derived from Cyclophosphamide, it has been used in clinical practice at Kyung Hee Medicd Center.Methods : We injected 200㎎/㎏ of Cyclophosphamide, one time, to an experimental group, consisting of ten mice. We divided them into eight groups: normal, CPX, SAKT 2㎎, SAKT 10㎎, SAKT 50㎎, SAKI 2㎎+CPX, SAKT 10㎎+CPX, SAKT 50㎎+CPX. We injeted Soamgudamikgitang seven days, five days, three days, and one day before we injected CPX. One day, three days, and five days after CPX injection, we injected Soamgudamikgitang again and then killed all the mice.The parameters determined in this experiment were daily body weight liver and spleen weight, RBC, WBC, and platelet for hemopoietic dysfunction and AST, ALT for hepatotoxicity, BUN, creatine for renal toxcity, Iymphocyte proliferation activity and lymphocyte subsets for immunological toxvity.Results : We have found that Soamgdamikgitang has inhibitory effects on the formation of Cyclophosphamide 's side effects. Significant differences between the group, which contained Cyclophosphamide, and the other group, which contains Cyclophosphamide and 2, 10, 50㎎ of Soamgudamikgitang respectively were observed. Platelets(2㎎ of Soamgudamikgitang, p<O.05 ;10㎎, p<0.Ol ;50㎎, p<0.001), liver weight(SOw p.001), spieen weight(10mg, p<0.05), AST(all groups, p<0.01), ALT(2㎎, p<001 ;10㎎, p<O.05 ;50㎎, p<0.01), BUN(2㎎, p<0.01 ;50㎎, p<0.05). Althought immunological in both lymphocyte proliferation and its subsets were not observed, which shows that Soamgudamikgilang has a strong effect on T cell activities Conclusions : From the above results, we can expect that the combined therapy of Soamgudamikgitang and Cyclophosphamide is more effective for treating cancer Patients.

당뇨병환자에서 게이트심장혈액풀신티그라피를 이용한 심기능 평가

윤상임,송치운,이진홍,안미애,성기양,송민호,이강욱,신영태,김영건,노흥규 충남대학교 의과대학 지역사회의학연구소 1993 충남의대잡지 Vol.20 No.2

Major cardiovascular complications of diabetes are coronary atherosclerosis, diabetic dilated cardiomyopathy, autonomic neuropathy and those are major causes of morbidity and mortality in diabetic patients. Gated blood pool heart scan is noninvasive and useful method for evaluation of functional status of heart in diabetics. We evaluated 52 patients with diabetes and divided 3 groups. Group 1 were 11 patients without proteinuria or with proteinuria less than 550mng during 24 hours. Group 2 were 9 patients with proteinuria more than 550mg during 24 hours and group 3 were 32 patients with endstage renal diasese due to diabetes. We performed 99mTc-HSA cardiac gated blood pool scan and used left ventricular ejection fraction(LVEF), peak ejection rate(PEF) to indices of LV systolic function and peak filling rate(PER) to index of LV diastolic function. The results were follows : 1) LVEF, PER were significantly lower in diabetics with ESRD than diabetics without ESRD, but there were no significant difference between normal controls and diabetics without ESRD 2) PFR was significantly lower in diabetics than normal controls, but there were no significant differences in diabetics with or without nephropathy. 3) There were negative correlation between PER, PFR and duration of diabetes. On the basis of results, PFR is a LV functional index of GBPS which can disclose early change of LV dysfunction in patients with diabetes.

室內디자인의 新構成主義的 傾向에 關한 硏究

尹道根,金洪基 弘益大學校 1990 弘大論叢 Vol.22 No.2

Recently, the interior design, closely related to architectural trends, has been identified its speciality as a prefession, and increasingly extended into scopes. Therefore, those circumstances make us redefine it's essential points and theories of interior design. It accordance with those contexts, for redefining principles of spatial composition in contemporary interior design, and proposing the direction of it's development, this paper examined how the designs of neo-constructivism, the most prevailing since post-modernism in terms of formation of architectural spaces, apply to the interior space. Probably, after these examinations, we would make through a part of new techniques of spatial configurations and try new directions of the scope in interior design and architectural design. Therefore, the main points of the examinations in this paper, based on the essence of interior design and the trend of contemporary architectural design, underlined in the scopes of development, design elements, compositional techniques, and the case study and analysis of neo-constructivism.

황정(黃精) 추출물의 화학구조결정에 관한 연구 (Ⅰ)

윤중호,박주희,김정주,권기락,안철진,주우홍,강진호,신동수 Institute of Genetic Engineering Changwon National 1998 Gene and Protein Vol.2 No.1

본 연구에서는 황정 속에 포함되어 있는 생리활성 물질을 hexane, CHCl₃과 n-butanol층에서 각각의 성분들을 추출하였고, hexane층에서 분리된 화합물 I과 H 중에서, 화합물 I의 봐학구조를 ¹H-nmr, ??, DEPT135, COSY, HMQC, HMBC 스펙트럼 및 MS 스펙트럼 등의 분광학적인 방법에 의해 결정하였다. 화합물 I의 구조는 9,12-(9E, 12E)-octadecadienoic acid 임을 확인하였다. In this Paper, biologically active compounds were extracted using organic solvents as hexane. CHC1₃, n-butanol to give each component. Chemical structure of compound I was characterized using ¹H-nmr, ??, DEPT135, COSY, HMQC, HMBC spectrum and MS-spectrum, in separated compound I and Ⅱ from hexane layer. Finally, chemical structure of compound I was determined as 9,12-(9E,12E)-octadecadienoic acid.

고온성 Bacillus sp.의 Xylanases 특성 비교

윤기홍 우송대학교 1997 우송대학교 논문집 Vol.2 No.-

토양에서 분리된 cellulase-free xylanase 생산균인 고온성 Bacillus sp. KK-1의 배양상등액으로 부터 내열성 xylanase S를 정제하였다. Bacillus sp. KK-1의 xylanase 유전자를 확보하기 위해 총 염색체 DNA를 이용하여 xylanase 유전자를 대장균에 크로닝한 결과 xylanase 활성을 보이는 30개 대장균 형질전환주를 얻어 이들이 생산하는 xylanases의 열안정성을 조사한 결과 모두 xylanase S보다 낮았다. 또한 형질전환주에서 분리된 plasmids를 여러가지 제한효소로 절단하여 분석한 결과 동일한 부분의 DNA조각을 공유하고 있었다. 이로써 이들 형질전환주는 동일한 xylanase를 생산하고 있다고 판단되며 이를 xylanase Y라 명명하고 대장균 형질전환주 균체로 부터 xylanase Y를 정제하였다. 정제된 xylanase S와 xylanase Y의 성질을 비교 분석하였는데 이들은 전혀 다른 성질을 보였으므로 Bacillus sp. KK-1이 최소한 두 종류의 xylanases를 생산하는 것을 알 수 있다. 특히 xylanase S는 열안정성이 매우 높아 65C에서도 약 10시간 방치하여도 효소 활성이 75% 이상 유지 되었으나 xylanase Y는 50C에서 30분간 방치하여도 활성을 약 25% 정도 상실하였다. Xylanase Y가 열안정성이 xylanase S에 비해 매우 낮으므로 Bacillus sp. KK-1를 50C에서 약 16시간 동안 배양하여 얻은 배양상등액에서는 xylanase S와는 달리 xylanase Y의 활성이 거의 상실되어 정제될 수 없었던 것으로 여겨진다. A thermostable xylanase, designated xylanase S, was purified from the culture supernatant of Bacillus sp. KK-1 which was isolated from natural soil. In order to obtain Bacillus sp. KK-1 xylanase gene. xylanase gene was cloned in Escherichia coli from Bacillus sp. KK-1. From approximately 20,000 transformants. 30 E, coli colonies showing xylanase activity was obtained. It was found that almost all xylanases from the E, coil clones was less stable than xylanase S at 60℃. Issert DNAs of recombinant plasmids, isolated from E. coil clones, shared the common DNA fragment of Bacillus sp. KK-1, suggesting that E coli clones produced an identical xylanase. Xylanase, named xylanse Y, was therefore purified from cell free extract of Em coli, The physical and chemical properties fo purified xylanase Y were identified to be different from those of xylanase S, resulting that Bacillus sp. KK-1 produced at least two xylanses. Especcially ,xylanase S retained over 75% io its maximum activity at 65℃ for 10 h. But , xylanase Y lost 25% of its activity at 50℃ within 30 min. From this result. it was supposed that xylanase Y could not purified from the culture supernatant of Banillus sp. KK-1 growing for 16 h at 50℃ because of inactivation of the xylanase Y unlike xylanase S.