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.

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.

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.

술중 전향적 대장세척술과 대장아전절제술을 이용한 폐쇄성 좌측 대장 및 직장암의 일차절제 및 문합술

윤완희,홍기훈,송인상 충남대학교 의과대학 지역사회의학연구소 1997 충남의대잡지 Vol.24 No.2

The proper surgical management of obstructing left colorectal cancers in an issue of debate. Staged operation including proximal colostomy has generally been accepted as a safe and standard method of management. But staged colonic procedures are associated with significant morbidity and mortality, and many patients, unfit for further surgery, are left with a permanent colostomy. Many other methods such as the use of long intestinal tube, transanastomotic obturation balloon colostomy, intracolonic bypass tube (Coloshield) were developed, but they have failed to gain wide accepance. We have already reported the initial results of intraoperative antegrade colonic irrigation for one-stage operation in obstructing left colorectal cancers. In this investigation, we evaluated the results of prospective trials of primary resection and anastomosis using intraoperative colon irrigation and subtotal colectomy in obstructing loft colon and rectal carcinomas. During recent five years, 19 cases of obstructing left colon and rectal carcinomas which could not received regular colon preparation due to marked abdominal distension were enrolled to this study. There were 12 men and 7 women, and mean age was 61. 14 of the 19 patients which tumors located below mid-descending colon were subjected to primary resection and anastomosis using intraoperative antegrade colonic irrigation, 4 patients which tumors located above the mid-descending colon were treated with subtotal colectomy, and remaining one patient which tumor located upper rectum was performed subtotal coloectomy because of underlying colonic ischemia. There was no mortality and significant postoperative complications such as anastomotic leakage, pelvic abscess of intraabdominal sepsis which seemed to related with anastomotic dehiscence. Therefore, primary resection and anastomosis using intraoperative colonic irrigation of subtotal colectomy depending on tumor locations in cases of obstructing left colon and rectal carcinomas might be useful methods to obtain safe one-stage restorative colorectal resections

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.

토끼 장간막 동맥에서 Ammonium Sulfate에 의한 내피세포 의존성 이완의 특성에 대한 연구

윤상경,홍기환 부산의대 1991 부산의대잡지 - 부산대학교 의과대학 Vol.31 No.2

濟州北方,成德沿岸海域에 있어서 植物플랑크톤 群集의 季節變動 特性

尹良湖,金暎起,盧洪吉 濟州大學校海洋硏究所 1992 해양과환경연구소 연구논문집 Vol.16 No.-

Fieldsurvey for oceanographic conditions and the seasonal succession of phytoplankton were carried out in the Hamdok port from April 1989 to February 1990. Water temperature ranged between 11.4℃ in January and 27.3℃ in August, and salinity fluctuated greatly, with a maximum of 35.6 in August and minimun of 21.8‰ in April. A total of 120 species of phytoplankton belonging to 69 genera were observed in which, at least, 8 genera, Oxyphysis, Amphidinium, Cochlodinium, Torodinium, Nematodinium, Katodinium, Ebria and Streptotheca are first records in the Cheju coastal waters. The predominant species are centric diatoms, Skeletonema costatum, Chaetoceros opp. through the year, while they are unarmoured phytoflagellates, Heterosigma akashiwo, Gymnodinium sp., Gyrodinium sp. in warmer seasons. And phytoplankton cell number fluctuated between 4.1×10³cells/1 in winter and 2.4×10 cells/1 in spring blooms, and it was under the control of centric diatoms for a year. On the other hand, it is occupied by phytoflagellates including some unarmoured dinoflagellates in summer season.

Critical role of bile acid (BA) in the cellular entry and permissiveness of Hepatitis B virus in vitro

Hong‑Jai Lee,Bo‑Young Shin,Jae‑Seung Moon,Ailyn Fadriquela,Selikem Abla Nuwormegbe,Chun‑Chang Ho,Jin‑Su Shin,Jee‑Sang Yoon,Sang‑Kyou Lee,Soo‑Ki Kim 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.3

Background Lack of universal replication system for hepatitis B virus with narrow host range and organ tropism has hampered to uncover the pathogenesis of HBV. Previously, we reported the essentiality of humoral milieu and its components toward HBV and hepatitis C virus survival/viability in vitro. Of these components, the precise role of enterohepatic humoral milieu such as bile acid (BA) on HBV cultivation in vitro and in vivo is unknown. Objective We explored whether BA, specifically taurochenodeoxycholic acid (tCDCA) would directly regulate the viral DNA and surface antigen expression of HBV in vitro, consequently rendering HBV to enter into human or murine immortalized hepatocytes, and non-hepatocytes. Result We found that higher concentration of taurochenodeoxycholic acid (tCDCA) is able to preserve the genomic stability of HBV in cell-free DMEM, showing higher the surface antigenicity than taurocholic acid (tCA). In line, we found that in vitro cell culture condition (100 μmol/L of tCDCA coupled with 1 × 108 g e/mL HBV) would be optimal for HBV entry into target cells. Using this, human (HepG2, Huh7), and rodent (Hepa1c1c7, H4-II-E) hepatoma cell lines were infected by HBV, as evidenced by the presence of HBV biomarkers (HBsAg, and HBV DNA in culture supernatant, as well as HBcAg in cell). Further, cellular entry test revealed that HBV is able to infect 12 different non-hepatic cell lines regardless of species, and organ/tissue, consequently reproducing progeny as confirmed by HBV biomarkers. Last, reinfection test showed that the progenies of HBV from immortalized HepG2, and Hepa1c1c7 cells are able to enter into each or vice versa naïve HepG2, and Hepa1c1c7 cells with or without BA. Conclusion This study demonstrates that enterohepatic humoral milieu such as BA, specifically tCDCA would directly regulate HBV DNA and its surface antigen expression in vitro, consequently rendering HBV to enter into human or murine immortalized hepatocytes, and non-hepatocytes. This is the first note to render HBV permissive to human or rodent hepatic and non-hepatic cells via sole manipulation of humoral milieu, thus establishing the platform for in vitro robust replication system of HBV.

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.