간내 담석과 동반된 간내 담도암에서의 p53과 Ki-ras의 발현

김명환,이성구,서동완,이승규,남승우,박능화,민영일,김연석,심기남,공경엽 대한소화기학회 1997 대한소화기학회지 Vol.30 No.5

Background/Aims: Hepatolithiasis or primary intrahepatic stones may be accompanied later by intrahepatic cholangiocarcinoma. This cancerous lesion is frequently associated with atypical hyperplastic epithelium that was suspected of being precancerous. To investigate the Ki-ras or p53 mutation may play a role in carcinogenesis, and to determine whether atypical hyperplastic epithelium may be precancerous, this study was performed in intrahepatic cholangiocarcinomas associated with hepatolithiasis. Methods: We examined 12 patients with intrahepatic cholangiocarcinomas associated with hepatolithiasis. Ki-ras point mutations were assessed by direct DNA sequencing. Expressions of p53 protein were immunohistochemically assessed. The overexpression of p53 and point mutation of Ki-ras were examined in normal, hyperplastic, atypical hyperplastic, and can- cerous tissues separately. Results: The expressions of p53 protein were detected in 4 (33%) of 12 cholangiocarcinomas and Ki-ras point mutations at codon 12 were found in 2 (17%) of 12 cholangiocarcinomas. In those two carcinoma cases which contained the mutant sequence of Ki-ras, the same point mutation from wild type GGT (glycine) to GAT (aspartic acid) was. found in the associated atypical hyperplastic epithelium. However, none of the normal and hyperplastic epithelium harbored Ki-ras or p53 mutations. Conclusions: The overexpression of p53 may play a part in the carcinogenesis of some intrahepatic cholangiocarcinomas associated with hepatolithiasis, whereas the role of Ki-ras mutations in those cases is dubious. However, Ki-ras point mutation at codon 12 may be responsible for either cancer or atypical hyperplastic epithelium associated with hepatolithiasis in certain cases, suggesting atypical hyperplastic epithelium may give rise to carcinoma.

관동맥질환에서 저밀도 지단백 입자 크기의 분포

임효영,김인숙,승기배,강동헌,전두수,장기육,박준철,이수영,홍순조,최규보 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.8

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.

당뇨병성 합병증을 가진 환자에서 혈중 Erythropoietin 농도

김동규,유기동,허광식,김상용,윤성호,조영신,권용은,김태원,김건영,정종훈,배학연 朝鮮大學校 附設 醫學硏究所 1998 The Medical Journal of Chosun University Vol.23 No.1

연구 배경 : 고혈당성에 의한 산화환원반응 이상(가저산소증)이 조절 되지않는 당뇨병의 특징으로 혈관과 신경 기능에 대한 진성 저산소증의 효과와 유사하며, 당뇨 합병증의 병태생리에 중요한 역할을 한다. 고혈당이 있는 인슐린 비의존형 당뇨병 환자에서 인슐린 수준이 정상이듯이, 빈혈이 있는 당뇨병 환자에서 EPO의 농도는 실제 혈색소 농도의 감소비율과 차이가 있을 것이라 추측된다. Friedman 등은 당뇨병성 합병증 원인 인자로 가저산소증(pseudohypoxia) 또는 저산소증(hypoxia)을 제기하였고 이런 인자들이 EPO의 상대적 또는 절대적 결핍에 의한 것임을 보고하였다. 방법 : EPO-Trac^(TM 125)I RIA kit을 이용하여 방사면역측정법으로 EPO 수준을 검사하였다. 전혈 3㎖을 5-10㎖ 시험관에 정맥 채혈하였으며, 용혈과 장기간의 보존을 위하여 원심분리를 즉시 시행하여 혈청을 영하 200C에서 냉동 보관 후 일괄적으로 검사 결과를 얻었다. 결과 : 1996년 9월부터 1997년 2월까지 조선대학교 부속병원 내과에 입원한 2형 당뇨병 환자 63례를 대상으로 하여 다음과 같은 결과를 얻었다. 1) 당뇨병성 합병증이 없는 군과 있는 군간의 혈색소, 혈중 EPO농도의 차이는 유의한 차이가 있었으며 혈색소의 감소율보다 혈중 EPO의 감소율이 더 높았다. 2) 당뇨병성 망막증의 유무에 따른 혈색소 농도의 차이는 유의한 차이가 없었으나 혈중 EPO농도는 유의한 차이가 있었다. 증식성군에서만 혈중 EPO의 감소비율이 혈색소에 비해 높았다. 3) 당뇨병성 신증의 유무에 따른 혈색소, 혈중 EPO농도는 유의한 차이가 있었고 혈색소 감소율에 비해 EPO농도의 감소율이 높았다. 신증의 중증도에 따른 혈색소, EPO의 차이는 미세알부민뇨군을 제외하고는 유의한 차이를 보였고 혈색소 감소율에 비해 EPO의 감소율이 더높았다. 4) 당뇨병성 신경병증의 유무에 따른 혈색소 농도의 차이는 유의한 차이가 없었으며 EPO농도는 유의한 차이를 보였다. 혈색소와 EPO의 감소비율은 비슷하였다. 신경병증의 중등도에 따른 혈색소와 EPO농도의 변화는 유의한 차이가 없었으나 stage 3에서는 혈색소감소율보다 EPO감소율이 더높았다. 결론 : 당뇨병성 합병증을 가진 환자에서 빈혈의 정도는 대부분 혈청 EPO치의 절대적 감소에 의함을 간접적으로 밝혀낼 수 있었으며 차후 더 많은 대상으로 비교 분석이 필요하리라 사료된다. Background: Hyperglycemic-induced redox(pseudohypoxia) imbalance is a characteristic feature of poorly controlled diabetes that mimics the effects of true hypoxia on vascular and neural functions and plays an important role on the pathogenesis of diabetic complications. As is true for apparently "normal" insulin levels typically found in NIDDM even in the presence of hyperglycemia, a "normal" erythropoietin level in an anemic diabetic subject may be disproportionally low for the actual red cell mass. Therefore, Friedman et al suggested that pseudohypoxia or hypoxia as an etiological factor of diabetic complications are due to absolute or relative erythropoietin deficiency Method: EPO-TracTM 125I RIA kit was used for the quantitative determination of erythropoietin(EPO) in serum by radioimmunoassay. An adequate sample of blood (3ml whole blood) was collected aseptically by venipuncture in a 5~10ml glass tube to yield a minimum of 400 L of serum per assay. The serum was promptly removed from the clot by centrifugation in order to avoid hemolysis. Then to increase its storage time it was frozen at -200C in a nonself defrosting freezer. Finally, tests were undertaken simultaneously Results We studied 63 cases with diabetes mellitus, who were admitted to Chosun University Hospital from September, 1996 to February, 1997 at the Department of Internal Medicine. We defined the control group, as diabetic patients who did not have anemia(<13mg/dl), diabetic complications(retinopathy, nephropathy, neuropathy) and the remainders were defined as the experimental group(we excluded anemic patients, who had secondary causes of anemia and diabetic patients with end stage renal disease)Data were as follow 1) The relationship of Hb and the 24hr urine protein between diabetic patients with and without complications significantly differed(p=0.02, < 0.001 respectively), but the Hb level was poorly related between diabetic patients with and without retinopathy(except in preproliferative, proliferative subgroups) and neuropathy. 2) Subgroups of patients with diabetic complications had higher 24hr urine protein than patients without diabetic complications, except stage I diabetic neuropathy 3) The EPO level was significantly different between diabetic patients with and without complications. 4) The correlation between EPO and Hb was significantly different, especially in diabetic patients with retinopathy and nephropathy according to severity of diabetic complications, compared with patients who did not have diabetic complications such as retinopathy and nephropathy. Conclusion: We know that anemia induced by diabetic complications is due to relative EPO deficiency than absolute EPO deficiency, and further evaluation and studies are needed on many cases in the future

당뇨병성 합병증을 가진 환자에서 혈증 Erythropoietin 농도

김동규,유기동,허광식,김상용,윤성호,조영신,권용은,김태원,김건영,정종훈,배학연 조선의대 1998 The Medical Journal of Chosun University Vol.23 No.1

Effects of <i>Ginkgo biloba</i> Extract on Promotion of Neurogenesis in the Hippocampal Dentate Gyrus in C57BL/6 Mice

YOO, Dae Young,NAM, YoonYi,KIM, Woosuk,YOO, Ki-Yeon,PARK, Jaeil,LEE, Choong Hyun,CHOI, Jung Hoon,YOON, Yeo Sung,KIM, Dong-Woo,WON, Moo-Ho,HWANG, In Koo Japanese Society of Veterinary Science 2011 The Journal of veterinary medical science Vol.73 No.1

<P><I>Ginkgo biloba </I>leaf extract (Gb) has been known to improve blood flow and preclude the tissue from free radical damage. Effects of Gb were examined by using Ki67, a specific proliferative marker for cellular proliferation, and doublecortin (DCX), a marker for immature neurons, indicating degree of neuroblast differentiation in the hippocampal dentate gyrus (DG) of adult C57BL/6 mice. The mice were fed with Gb at 40 and 100 mg/kg once daily for 28 days. The increase of Ki67- and DCX-immunoreactive cells in the DG was increased in a dose-dependent manner. Especially, the group having 100 mg/kg Gb showed a significant increase of DCX-immunoreactive neuroblasts with well-developed tertiary dendrites. Expression of DCX protein in the Gb groups was also significantly increased upon compared with the vehicle group. The results suggested that repeated intake of Gb would enhance cell proliferation and neuroblast differentiation in the mouse DG.</P>

서울의 PPNG 발생 빈도(1991-1992)

김재홍,윤기범,박평원,김영진,전경민,김영태,김중환,곽호,구상완,송민석,유옥,지혜구,김동원,문상은,박영립,정승호,성범진,성순제,엄주용,황정열,이기홍,이주협,전태진 대한화학요법학회 1994 대한화학요법학회지 Vol.12 No.1

The prevalence of PPNG among pretreated gonorrhea cases isolated at the STD clinic of Choong-Ku Public Health Center in Seoul has been studied and reported annually since 1981. In 1991, 123 strains of N.gonorrhoeae were isolated, among which 58(47.1%) were PPNG. In 1992, 98 starains of N.gonorrhoeae were isolated, among which 51(52.0%) were PPNG. In all, 109(49.3%) strains were found to be PPNG among 221 strains isolated between 1991-1992. The prevalence of PPNG in Seoul showed increased tendency till 1989, thereafter, it has been stationary or slightly decreasing.

재발성 류마티즘 환자에서 발작의 유발인자

주유철,이동민,양종태,신병철,임태영,서정균,정기영,최동헌,김원,조영신,고희관 조선대학교 2001 The Medical Journal of Chosun University Vol.26 No.2

Background and Objectives : Palindromic rheumatism (PR) is known to be triggered without any obviously inciting events in most patients, although, in a few cases, attacks have been noted to relate to another events such as weather change, childbirth, ingestion of certain foods, or over-exercise. The aim of this study was to characterize the triggering factors on palindromic attacks. Materials and Methods : We evaluated sixty-four patients with PR for the presence of triggering factors and the relationship between attacks and triggering factors by interview of patients. We considered that there was an probable association between episodes and PR, if episodes within 24 hours prior to PR had triggered at least 50% of all attacks and a definite association between episodes and PR, if episodes within 24 hours prior to PR had triggered 100% of all attacks. Results : In 15 patients (35.9%), there was a possible association between episodes of PR and initiating events. In 8 patients (12.5%), there was a definite association between episodes of PR and initiating events. The triggering factors were physical over-activity including exercise (19/64: 29.7%), foods, such as rawfish, crab, and chicken, including alcohol (19/96: 19.8%). However, there were no difference between the groups with and without the triggering factor in sex ratio, duration and onset of PR, the positive rate of rheumatoid factor and involved sites. Conclusion : Our observations showed that PR was triggered by physical over-activity more than in previous reports and hypersensitivity to foods was a causative factor in some patients with PR. However, patients with triggering factors had a similiar clinical profile to patients without triggering factors.

아리스톨로크산 함유 생약제에 대한 안전성평가연구 : 3개월간 반복투여독성시험을 통한 신장독성평가

황명실,박미선,문지영,이지선,염영나,이효민,신동환,강진석,윤은경,최미나,육미영,장동덕,길광섭,김승희,양기화 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-

본 실험에서는 아리스톨로크산을 함운하고 있는 생약제중 하나인 마두령(.4risfoforfioe JTurruf)의 90일 반복투여독성시헌을 실f,」하였다. 마두령에서 아리스톨로크산을 정량분석한 결과 마두령 단일 건조븐말의 경운 2.112mg/g, 잉상에서 처방되고 있는 마든령복방 (마두령외 9가지 생약제 복합처방) 건조분말꼭 경무에는 0.066m9/5으로 각각 검출되었다. 본 실험에서 용량설정은 마두령 처리군 (저용량 군; 21.3m9/k9/day (임상용량), 중용량군; 2t3mgfg/day, 고용량군; 2430mg딘g b.w./day), 마두령복방 처리군 (427mg/kg b.w./da?; 임상용량) 및 positive control (아리스톨로크산) 처리군 (저용량군;0.05mgag/da17, 중용량군; 0.Smg/kg/day, 고용량군; 5mg./kg/dal·1으료 하여 랫드에게 경구투여하였다. 마두령단방 처궈근 및 마두령복방 처리군에서 저용량군과 중응량군에서는 잉상관찰 및 생화학적 분석에서 패조군과 유의적인 차이가 없었다. 그러나 마두령단방 고용량근에서는 간, 신장의 상대적인 무계가 증가되었고, 신장의 유두이행상피증식 및 암종이 관찰되었으며, 위에서는 편평세포암종이 관찰되었다. 하자만 간손상이나 간암은 유발하지는 않는 것으로 판단되었다. 결론끌으로 본 실험의 결과에서는 아리스톨로크산 함유 생약제인 마두령이 임상용량인 저응량 처리군에서는 독성을 나타내지 않았으나, 고용쏭으로 장기 복용시켰을 깅우 설치류의 전위부위 및 신장에서 독성이 있음을 알 수 있었다. Chines herbs nephropathy (CHN) has been described in young women who had taken a slimming pills containing some chines herbs. Aristolochic acid (AA), suspected substance as the causal factor of CHN, is known a carcinogen. The Aristolochiae fructus (fruit of Aristolochia contorta) was used in Korean Traditional Medicine consists of appropriate amounts of mixed natural products. Subchronic toxicity of A. furctus containing aristolochic acid was investigated in SD rats. The body weight and clinical signs were observed after orally administration of A. futctus at doses of 21.2, 213, and 2130 mg/kg/day; mixture (including 9 other herbs) at dose of 427 mg/kg/day; aristolochic aicd (Ⅰ+Ⅱ) at doses of 0.05, 0.5, and 5 mg/kg/day for 3 months. At the end of the treatment, high dose treated animals revealed a deficit in final body weight about 25% compared with that of control. Organ weights of kidney, liver, testis, or ovary were increased with dose dependent manner. No changes considered to be due to the administration of A. furctus, mixture or aristolochic acid were in hematological and clinical study. However, significant changes at histopathological study of kidney and stomach were boserved in high-dose treated groups. In conclusion, for human health safety it needs appropriate regulatory actions regarding the use of natural herbal medicines known or suspected of containing aristolochic acid.

개에서 발생한 이버멕틴 중독증 1례

여동원,윤기영,박정호,이왕희,송근호,박성준 忠南大學校 獸醫科大學 附設 動物醫科學硏究所 2011 動物醫科學硏究誌 Vol.18 No.1

A 1-year old, intact male Jin-do dog with ataxia, hypersalivation and anorexia was referred to the Veterinary Medical Teaching Hospital of Chungnam National University. Ivermectin toxicosis was diagnosed by the history taking, clinical signs, physical examination and neurological examination. After therapy with intravenous fluid and lipid emulsion administration, the clinical signs were found to have significantly improved.