위 아전절제술 후 십이지장 위 역류성 위염에서 p53 및 Ki-67 단백 발현 양상

최석채 ( Suck Chei Choi ),김용성 ( Yong Sung Kim ),김기훈 ( Ki Hoon Kim ),김헌수 ( Hun Soo Kim ),윤기중 ( Ki Jung Yun ) 대한소화기기능성질환·운동학회 2007 Journal of Neurogastroenterology and Motility (JNM Vol.13 No.2

목적 : 십이지장 위 역류성 위염은 위절제 등에 의해서 발생하는 것으로 후에 암종이 발생할 가능성이 높은 것으로 알려져 왔다. 그러나 사람에서 십이지장 내용물의 역류와 암종 발생 사이의 병인론적 연구가 흔하지 않다. 이에 십이지장 위 역류성 위염을 보이는 환자의 조직과 대조군 환자의 조직을 대상으로 Ki-67 및 p53 단백 발현 정도를 측정하여 상피 세포증식 유도 및 암억제 유전자의 발현 정도를 비교 연구하였다. 대상 및 방법 : 위암종으로 위아전절제술을 받은 총 57예 중 내시경 및 조직학적으로 십이지장 위 역류성 위염으로 진단된 16예의 내시경 조직과 대조군 16예의 내시경 조직을 대상으로 하여 Ki-67 및 p53 단백 발현을 면역조직화학적 염색을 하였고 그 강도를 점수화하였다. 결과 : 십이지장 위 역류성 위염 소견을 보인 환자의 내시경적 추적 기간은 평균 607일, 대조군 556일 그리고 57예의 평균은 471일로 유의한 차이는 없었다. 십이지장 위 역류성 위염 환자의 Ki-67 발현 강도의 중간값은 3.0로 대조군 중간값 2.0보다 의미있게 높았으며, p53 단백의 발현 강도 중간값도 2.0으로 대조군 중간값 1.0 보다 의미있게 높았다. 결론 : 십이지장 위 역류성 위염은 담즙 등이 점막의 상피세포 증식을 유도하고 유전자 이상을 초래할 가능성이 높아 시간 경과 후 암종이 발생할 가능성이 대조군에 비해서 높을 수 있음을 알 수 있었다. Background/Aims: Duodenogastric reflux of bile and other contents of duodenum is one of the main etiologic fators in chronic gastritis, and chronic inflammation has been recognized as a risk factor of human cancer. The aim of this study was therefore to evaluate the expression of p53 and Ki-67 protein in duodenogastric reflux gastritis. Methods: To evaluate the proliferation activity and tumor suppressor gene expression, 16 cases of duodenogastric reflux gastritis and 16 cases of control gastric tissue after subtotal gastrectomy were examined immunohistochemically using the monoclonal antibodies to Ki-67 and p53 protein. Results: The mean duration of follow-up endoscopic biopsy after subtotal gastrectomy was 607 days in duodenogastric reflux gastritis and 556 days in control groups. The mean intensity of Ki-67 in duodenogastric reflux gastritis was significantly higher than that of control tissues (3.0 vs 2.0). The mean intensity of p53 protein in duodenogastric reflux gastritis was significantly higher than that of control tissues (2.0 vs 1.0). Conclusions: The high expressions of Ki-67 and p53 protein in duodenogastric reflux gastritis may be one of the main mechanisms in the development of gastric stump carcinoma. (Kor J Neurogastroenterol Motil 2007;13:118-122)

수종의 피부종양에서 Proliferating Cell Nuclear Antigen과 Ki - 67 의 표현에 관한 비교 연구

황선욱(Sun Wook Hwang),원영호(Young Ho Won),전인기(Inn Ki Chun),박창수(Chang Soo Park) 대한피부과학회 1995 大韓皮膚科學會誌 Vol.33 No.3

Background : Both PCNA and Ki-67 have been used as marker for cellular proliferation. The drawback of Ki-67 antibody in immunohistochemistry was that it can be labelled only on fresh tissue, however, MIB1 is a newly developed Ki-67 antiboc which can be labelled on formalin-fixed tissue. Objective : The purpase of the present study is to compir the stainability of the Ki-67 antibody with that of the ICNA antibody on formalin-fixed, para fin embedded tissues. Methods : Using MIE1, the newly developed Ki-67 antibody and PC10(PCNA antibody), speci mens of squamous cell carcinoma(SCC), Bowens disease(BL), actinic keratosis(AK) and basal cell epithelioma(BCE) were stained by one hour immunocytial, mistry using a Microprobe immuno/DNA stainer. Results : The labelling indices (LI) of MIB1 were 82.6%, 37.4%, 38.3% & 81.1% respectively in SCC, BD, AK & BC, while the LI of PC10 were 77.69%, 26.6% & 64.4%. The labelled cells of both antibodies differed in distribution patterns on turmor tissues. Conclusion : MIBI cain be used to be an alternative m.rl r for proliferating cells. MIBI PC10, when used together, will be mutually compensatory the study of proliferating cell kinetics. (Kor J Dermatol 1995;33(3): 453-458)

광선각화증, 보웬병, 편평상피세포암에서 Ki-67, Cyclin A, p53, p16의 발현 양상

이효진 ( Hyo Jin Lee ),신동훈 ( Dong Hoon Shin ),최종수 ( Jong Soo Choi ),김기홍 ( Ki Hong Kim ) 대한피부과학회 2012 대한피부과학회지 Vol.50 No.4

Background: Actinic keratosis (AK) and bowen`s disease (BD) are pre-cancerous diseases, and are regarded as an early squamous cell carcinoma (SCC). AK and BD can be progressed into SCC. In this process, tumor suppressor and cell proliferative proteins may play important roles. Objective: To investigate the differences of expression patterns of the immunohistochemical (IHC) staining and useful markers for differential diagnosis in AK, BD and SCC. Methods: Biopsy had proven 17 cases of AK, 20 cases of BD and 17 cases of SCC, which were all selected. IHC staining for Ki-67 and cyclin-A, as cell proliferative markers, p53 and p16 as tumor suppressor markers, were performed. Labeling index (LI) and distribution pattern of IHC expressions were measured. Results: LI of Ki-67 in AK, BD and SCC were 30.6%, 60.2% and 54.8%, respectively. LI of cyclin-A in AK, BD and SCC were 9.2%, 24.4% and 24.1%, respectively. LI of p53 in AK, BD and SCC were 20.7%, 37.9%, and 39.9%, respectively. LI of p16 in AK, BD and SCC were 10.6%, 38.3% and 39.9%, respectively. Lower 1/3 was the most frequent distribution pattern in AK in all IHC stains, full thickness lower 2/3 were the most frequent distribution pattern in BD and SCC in all IHC stains. Conclusion: LI and distribution pattern of Ki-67, cyclin-A, and p16, as well as the distribution pattern of p53 may be useful markers to differentiate AK from BD and SCC. Higher degree and full-thickness distribution pattern IHC expressions in all stains may be helpful in the diagnosis of BD, rather than AK. (Korean J Dermatol 2012;50(4):290∼298)

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

식도의 원주상피 피복 점막에서 점액유전자 발현 및 세포증식능에 대한 연구

최석채 ( Suck Chei Choi ),김용성 ( Yong Sung Kim ),김기훈 ( Ki Hoon Kim ),김헌수 ( Hun Soo Kim ),조향정 ( Hyang Jeong Jo ),윤기중 ( Ki Jung Yun ) 대한소화기기능성질환·운동학회 2007 Journal of Neurogastroenterology and Motility (JNM Vol.13 No.1

목적 : 바렛식도는 지속적인 위식도역류 등으로 원위부 식도에 정상적으로 존재하는 편평상피세포 대신에 배상세포를 포함하는 장형 원주세포로 식도 점막이 피복되는 것을 말한다. 그리고 이형성을 거쳐 선암종으로 진행할 수 있기 때문에 이형성 이전 단계인 바렛식도의 발암과정에 대한 연구가 필요하다. 이에 바렛식도와 배상세포를 포함하지 않은 원주세포만 있는 식도를 대조군으로 하여 점액유전자 및 세포증식능에 대해 비교 연구하였다. 대상 및 방법 : 임상 및 내시경적으로 바렛식도가 의심되어 원위부 식도에서 생검한 환자들 중에서 배상세포가 있어 조직학적으로 바렛식도로 증명된 25명의 환자와 배상세포가 없었던 환자들 중에서 무작위로 선택한 30예를 대조군으로 하였다. 생검 당시의 나이와 성별 그리고 MUC1, MUC2, Ki-67에 대한 면역조직화학적 염색을 시행하였다. 결과 : 바렛식도의 평균 나이 및 남자 비율은 각각 65.3±10.1세, 76.0%이였고, 대조군의 평균 나이 및 남자 비율은 각각 53.0±14.8세, 60.0%로 바렛식도의 나이가 대조군식도보다 의의있게 높았다. MUC1은 바렛식도 및 대조군 모두에서 100% 발현되었고, MUC2 발현율은 바렛식도 및 대조군에서 각각 92%, 20%이었다. Ki-67 발현율은 바렛식도 및 대조군에서 각각 80.0%, 70.0%이였고, Ki-67 발현 강도의 평균은 바렛식도 1.20±0.76, 대조군 0.77±0.57로 발현 강도에서 바렛식도가 의의있게 높았다. 결론 : 바렛식도는 원주세포만 있는 식도에서 보다 좀더 지속적인 위식도역류 등의 자극으로 생긴다. 그리고 MUC2는 주로 바렛식도에서 발현되고 세포증식능은 바렛식도에서 좀더 높으며 이는 MUC2 발현과 관련될 수 있다고 생각된다. Background/Aims: Barrett`s esophagus is characterized by the presence of metaplastic columnar epithelium with goblet cells in the distal esophagus. Barrett`s esophagus progresses through low grade dysplasia and high grade dysplasia to adenocarcinoma. We studied the patient age, the mucin gene and the proliferation activity of biopsy-proven Barrett`s esophagus and simple columnar epithelium-lined esophagus. Methods: To evaluate the mucin gene expression and proliferation activity, twenty five cases of Barrett`s esophagus and thirty cases of control esophagus were examined immunohistochemically with using the monoclonal antibodies to MUC1, MUC2 and Ki-67. Results: The Barrett`s esophagus patients were older (mean: 65.3±10.1 years) than the control patients (mean: 53.0±14.8 years). The MUC1 expression was 100% in both Barrett`s esophagus and the control esophagus. An MUC2 expression was observed in 92.0% of the Barrett`s esophagus and 20.0% of the control esophagus. The rate and intensity of the Ki-67 expression was higher in the Barrett`s esophagus (80.0%, 1.20±0.76) than that in the control esophagus (70.0%, 0.77±0.57). Conclusions: Barrett`s esophagus is a metaplastic lesion due to the more long-standing gastroesophageal reflux than that in a simple columnar epithelium-lined esophagus. The cause of increased proliferation activity in Barrett`s esophagus may be related to the MUC2 expression. (Kor J Neurogastroenterol Motil 2007;13:21-25)

漸進的·急進的 運動負荷가 血液의 pH, Sugar 및 Lactate에 미치는 影響

姜炯基,辛元太,白永守,殷熙寬,宋基成,河哲秀 漢陽大學校 體育科學硏究所 1986 體育科學 Vol.6 No.6

The purpose of this study is to in-vestigate the effects of gradual and radical exercise load on the treadmill for PH, Sugar and Lactate in Blood by selecting 14 subjects in H university, All subjects began exercise by 6mPH for 4 minutes at start and increased exercise speed up to HR 140 by increasing every minute as gradual load. And subjects began exercise by 9mPH at first and increased load up to HR 140 as radical exercise load. The results are as follows: (1) In PH in Blood, gradual exercise load is lower than radical training in all subjects. (p<0.05) (2) In Sugar in Blood, radical exercise load is higher than gradual exercise load in all subjects. (p<0.05) (3) In Lactic Acid in Blood, gradual training is higher than radical exercise load in all subjects. (p<0.01) (4) In Lactic Acid, all subjects showed high value and its is also in Sugar, than the method of exercise load is according to anaerobic energy metabolism.

족부백선의 치료에서 터비나핀과 이트라코나졸의 이중맹검 비교연구

김기홍,최종수,박의수,김상원,김수찬,안성구,서무규,서순봉 대한화학요법학회 1994 대한화학요법학회지 Vol.12 No.2

터비니핀(terbinafine)의 족부백선에 대한 치료효과를 판정하기 위해 6개 병원의 피부과에서 공동연구로 족부백선환자90명에 대하여 치료완료하였으며 2군으로 나누어 터비나핀 1일 250㎎씩 2주간 경구치료와 이트라코나졸 1일 100㎎씩 4주간 치료를 이중맹검으로 실시하여 임상적 및 진균학적인 검사로 치료효과와 약제의 내약성을 평가하였다. 완치율은 터비나핀군은 치료 1주후 6.5%, 2주후 23.9%, 4주후 69.6%, 6주후 89.1%였으며, 이트라코나졸군은 치료 1주후 0%, 2주후 22.7%4주후 59.1%, 6주후 77.3%이었다. 부작용과 내약성은 양군에서 비슷한 성적을 나타내었다. 이상의 결과로 보아 터비나핀 1일 250㎎씩 2주간의 경구투여는 치료율, 안정성 및 부작용에서 이트라코나졸 1일 100㎎씩 4주간 치료효과와 유사하였다. In this randomized double-blind trial on multicenter study, the efficacy of the new antifungal agent, terbinafine was compared with the triazole antifungal agent, itraconazole, in the treatment of patients with various forms of tinea pedis. One hundred and ten patients(55 terbinafine, 55 itraconazole) with tinea pedis were enrolled. Eleven patients were lost to follow-up(5 terbinafine, 8 itraconazole) and 9 reported adverse reaction with premature discontinuation of therapy. And 90 patients were eligible for follow-up until 6 weeks after starting the treatment. Forty six patients received terbinafine 250㎎ daily for two weeks and 44 received intraconazole 100㎎ daily for 4 weeks. They were checked clinical symptoms and mycological improvement with KOH wet mount and culture during the study. Clinical and mycological cure rate of the terbinafine group was 6.5% at 1 week after intialtreatment, 23.9% at 2 weeks, 69.6% at 4 weeks and 89.1% at 6 weeks and that of the itraconazole group was 0% at 1 week after intial treatment, 22.7% at 2 weeks, 59.1% at 4 weeks, and 77.3% at 6 weeks. Adverse reactions and tolerability of both drugs were not different significantly. All these findings suggest that the effects of terbinafine 250㎎ daily for 2 weeks in the treatment of tinea pedeis was similar to that of intraconazole 100㎎ daily for 4 weeks.

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.

주의력결핍-과잉행동장애를 동반한 알코올 의존환자들의 특성 : 임상적/유전학적 자료분석

김붕년,손기현,전지현,곽욱환,유희정,조수철,박철수 大韓神經精神醫學會 2003 신경정신의학 Vol.42 No.3

Objectives : This study was conducted to estimate the comorbidity rate of ADHD in a group of patients with alcohol dependency and to find out the characteristics of alcoholic patients with ADHD using the diverse clinical and genetic variables. Methods : Eighty five patients with alcohol dependency were recruited from 4 mental hospitals in Kyoung-Nam and Kyoung-Ki province. For the evaluation of ADHD symptoms in both childhood and adulthood, the highly structured Diagnostic Interview Schedule for Children-IV (DISC-FV)-ADHD module was used. The various standardized scales and questionnaires were also applied to evaluate the comorbid conditions and psychopathological status. All the subjects' blood was collected and genetic study for the polymorphism of DRD2, TH, 5-HTTLPR, COMT, ALDH2 was performed. Results : 1) The comorbid rate of definite ADHD in alcoholic patients was 38% (28/85). 2) The frequency of unmarried status was significantly higher in ADHD group compared non-ADHD group. 3) The onset of pathologic drinking and auditory hallucination was significantly earlier in ADHD group than non-ADHD alcholic group. 4) In ADHD alcoholic group, antisocial behavior was more frequently reported, and the score of co-dependency scale, depression/anxiety, aggression and obsessive compulsive drinking scales were significantly higher compared to non-ADHD alcoholic group. 5) No signficant difference was found in the frequency of polymorphic alleles in COMT, DRD2, 5-HTTLPR, ALDH2, TH between ADHD and non-ADHD alcoholic group. Conclusion : In alcoholic patients, the rate of adult type ADHD was higher than expected rate in general population. The alcoholic patients with ADHD suffered from more sever degree of alcohol dependency and earlier alcohol related problems. ADHD-alcoholic group showed higher diverse comorbid psychopathology and lower marital status compared to non-ADHD-alcoholic group. No difference, however, was found in genetic data between two groups.

Therapeutic Effects of Recombinant Human Epidermal Growth Factor (rhEGF) in a Murine Model of Concurrent Chemo- and Radiotherapy-Induced Oral Mucositis

RYU, Seung-Hee,KANG, Ki Mun,MOON, Soo Young,CHAI, Gyu Young,HONG, Joon Pio,CHO, Kyoung-Oh,KANG, Mun-Il,CHOI, Eun Kyung,LEE, Sang-wook Journal of Radiation Research Editorial Committee 2010 JOURNAL OF RADIATION RESEARCH Vol.51 No.5

<P>Concurrent chemotherapy with radiotherapy (CCRT) has been applied for the treatment of advanced stage of head and neck cancer patients. However CCRT is associated with several complications including mucositis, dermatitis, stomatitis, etc. This study was conducted to evaluate the therapeutic effect of systemically administrated recombinant human epidermal growth factor (rhEGF) in CCRT-induced oral mucositis in a mouse model. Oral mucositis was induced in male BALB/c mice through combination treatment with cisplatin (11 mg/kg, i.p.) and irradiation (17 Gy) of the head and neck area. rhEGF (1.0 mg/kg/day for consecutive 3 days) was administered systemically, and the therapeutic effect was determined by histological evaluation of the oral mucosa. To elucidate optimal dose of rhEGF on CCRT-induced mucositis, various concentrations (0.04–3 mg/kg) of rhEGF were injected for 3 days. Systemic rhEGF administration accelerated the recovery of body weight. Histologically, rhEGF-treated mice showed significantly increased epithelial cell layer thickness, basal cell number, and expression of Ki-67 compared to control mice. Most effective dose was 1 mg/kg among other doses tested. Systemic administration of 1 mg/kg of rhEGF reduces the severity of oral mucositis induced by CCRT in a mouse model, suggesting that rhEGF can be used for treating CCRT-induced mucositis during the cancer treatment.</P>