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.

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.

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.

유전자재조합 대장균으로부터 Bacillus sp. 79-23의 Cellulase 정제와 특성분석

윤기홍 우송대학교 부설 산업연구원 1999 산업연구 Vol.1 No.1

Carboxymethyl celluase (CMCase) was purified from cell-free extract of the recombinant Escherichia coli carrying a Bacillus sp. 79-23 CMCase gene (celS) by DEAE-Sepharose and phenyl-Sepharose column chromatography with specific activity of 400 U/mg protein. The molecular mass of the purified enzyme was estimated to be approximately 37.5 daltons by sodium dodecyl sulfatepolycarylamide gel electrophoresis. The viscosity of carboxymethyl celluose was dramatically decreased by the purified enzyme identifying that the purified enzyme is a CMCase, while the enzyme was known to be active on para-nitrophenyl-β-cellobioside. The CMCase activity was markedly inhibited by cellobiose, but was not inhibited by glucose. The enzyme activity was activated by divalent metal ions such as Mn²+ and Cu²+, but was completely inhibited by Hg²+. The enzyme was very stable below 50℃ and retained 80% of its maximum activity after incubation for 3 hours at 55℃, suggesting that few problems are in handing the Bacillus sp. CMCase as industrial enzyme at ambient temperature.

초등 사회과 3학년 지역화 교수·학습자료개발 연구

홍기대,손정선,김언식,김용조,이광성,김경운 光州敎育大學校 初等敎育硏究所 2002 初等敎育硏究 Vol.17 No.-

The purpose of this study is in developing locally-oriented teaching-learning materials to motivate students to effectively take part in activities using map and in improving the field work of social studies to plan a map learning and to give them the ability of practice. It represents the right order involved in teaching the activities using map after doing preceding learning : classroom, playground, and the environs of the school including to some learning methods such as a puzzle map, a correlative of learning. Field trip study planning and lesson-plan are designed in case of Sewage disposal plant, Duknam filtration plant, Bonchon industrial complex relating to field trip study. There are some effects expected which follow through this study. First, teachers are able to draw learner's interest in finding learning sources directly through the community where they live. Second, learners have active participation in class, motivation, drawing their interests through map learning by doing preceding study of learner-centered. Third, teachers can make use of it as useful tools to get high achievement goal with self-direct learning.

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

Mannanase를 생산하는 Bacillus속 균의 RAPD-PCR 분석

윤기홍 우송대학교 2004 우송대학교 논문집 Vol.9 No.-

가정에서 제조된 된장에서 mannanase 생산성이 높은 균으로 분리된 9종의 균주는 모두 포자를 형성하며 그람양성 간균으로 Bacillus속에 속하는 것으로 추정된다. 이들 분리균간에 유전체의 유사성을 조사하기 위해 10 nucleotides로 구성된 oligonucleotides 6 종과 12 nucleotides로 구성된 oligonucleotides 2종을 primer로 사용하여 Random Amplified Polymorphic DNA-중합연쇄반응 (RAPD-PCR)의 조건을 검토한 결과 40℃보다는 30℃와 35℃에서 annealing 반응을 수행하는 것이 효율적이었다. RAPD-PCR에 의해 증폭된 DNA를 agarsoe gel 전기영동으로 분석한 결과 primer에 따라 증폭된 DNA의 양과 그 크기의 다양성이 달랐으며, 분리균에 따라서도 특이한 증폭 DNA가 관찰되었다. 균주에 따라 증폭된 DNA를 비교한 결과 된장에서 분리된 9 종의 균주는 Bacillus licheniformis와는 달랐으며, Bacillus subtilis와 유사하였다. 특히 분리균 중 5 종류는 B. subtilis와 유사도가 매우 높았으며, 분리균간에도 서로 유사도가 높은 균이 있었지만 동일하지는 않은 것으로 확인되었다. 따라서 RAPD-PCR 방법에 의해 균주간 유사성을 비교하는 것은 다양한 미생물 자원을 확보하는데 유용한 방법이라고 여겨진다. Nine bacterial strains producing the extracellular mannanase were isolated from Korean soybean paste. The isolates are regarded as Bacillus on the basis of their morphological properties, which are gram positive and rod in shape with spore. To examine the similarity between genomes of the isolates, Random Amplified Polymorphic DNA - Polymerase Chain Reaction (RAPD-PCR) was performed with 6 kinds of oligonucleotides consisting of 10 nucleotides and 2 kinds of oligonucleotides consisting of 12 nucleotides. As a results of RAPD-PCR at different annealing temperatures such as 30℃, 35℃ and 40℃, many different DNA fragments were generated at 30℃ and 35℃ more than 40℃. Relatedness of the nine isolates from soybean was determined by comparing the amplified DNA fragments between the isolate strains, Bacillus subtilis and B. licheniformis, expecting that the nine isolates are different from B. licheniformis and five of them are very similar to B. subtilis. It was also found that all isolates are different strains. Therefore, RAPD-PCR is regarded as a useful method for preparing the bank of the diverse microorganisms from nature.

판소리의 갈래와 역사적 성격

윤기홍 연세대학교 국어국문학과 1987 연세어문학 Vol.20 No.-

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.