항암제 처리한 백혈병 세포주에서의 Apoptosis 발현

김삼용,윤소현,김현수,김종숙,윤환중,김진경,조덕연 충남대학교 암연구소 1998 癌共同硏究所 硏究誌 Vol.2 No.1

The bcl-2 proto-oncogene encodes a 26 kD protein that promotes cell survival by blocking apoptosis. The bax protein is a member of the bcl-2 familly, now known to form heterodimers with the bcl-2 protein. The ratio of bax to bcl-2 is be critical in determining the fate of the cell in response to stimuli that can induce apoptosis. Extract of Pulsatilla Koreana (SB-31) showed promising antitumor activity in vitro with Topo I inhibitory action. In the present study, the relationship between apoptosis and the apoptosis related proteins, bcl-2 and bax were investigated in human leukemic cell lines HL-60, U-937 and CEM-CM3. All anticancer drugs(adriamycin, etoposide, camptothecin, SB-31) induced extensive apoptosis in HL-60, U-937 cells and CEM-CM3 cells. The expression of bcl-2 and bax protein were determined in cell lines by western blotting before and after incubation with anticancer drugs at different time points. 1) In HL-60 or U-937 cell lines, down regulation of bcl-2 and up-regulation of bax were found after incubation with ADR, VP-16 or camptothecin. 2) In HL-60 or U-937 cell lines, no significant change in bcl-2 or bax protein expression resulted after incubation with SB-31. 3) In CEM-CM3 cells, virtually no change was noted in bcl-2/bax expression after incubation with ADR, VP-16, camptothecin or SB-31. It is suggested that different leukemic cell lines use different pathways of apoptosis activation and a given cell may utilize different pathways of apoptosis activation in response to different cytotoxic agents.

냉동 제대혈 세포의 체외 증폭

김삼용,김철희,배광봉,김현수,박상준,김종숙,윤환중,조덕연 충남대학교 암연구소 1998 癌共同硏究所 硏究誌 Vol.2 No.1

Background : Cord blood(CB), which has no HLA restriction, is an alternative to bone marrow for hematopoietic stem cell transplantation. The use of cord blood, however, is limited by the number of progenitor/stem cells necessary to reconstitute the older child or adult. Therefore, ex vivo expansion of CB could have tremendous impact on diverse clinical settings. We studied the ex vivo expansion of isolated population of CD34_(+) cells from cryopreserved CB cells. Methods : CD34 cells were isolated from cryopreserved CB mononuclear cells. Purified cells were cultured with various combinations of hematopoietic growth factors including erythropoietin(EPO), stem cell factor(SCF), granulocyte-colony-stimulating factor(G-CSF), gra-nulocyte, macrophage-colony-stimulating factor(GM-CSF), interleukin-1β(IL-1β), 1L-3, and IL-6. After 7, 10 or 14 days of culture, the fold increases of colony-forming unit- granu-locyte, macrophage(CFU-GM), burst-forming unit-erythroid(BFU-E), colony-forming unit-mix (CFU-Mix), and high proliferative potential colony-forming cell(HPP-CFC) were evaluated. Results : Ten-day culture with the combination of EPO, SCF, G-CSF, IL-1β, and IL-3 resulted in a median of 60-fold increase of CFU-GM, which was greater than those with the combinations of less than 5 growth factors. The addition of IL-6 or GM-CSF to this combination did not enhance CFU-GM expansion. Ten-day culture was significantly superior to 7-day culture for CFU-GM expansion. Prolongation of culture to 14 days, however, revealed decreased expansion of CFU-GM compared to 10 days. BFU-E and CFU-Mix were expanded to 2~5 folds in 7-day culture with the combination of EPO, SCF, and G-CSF. Further expansion was not achieved in 10-day culture and colonies disappeared in 14-day culture. HPP-CFC was expanded to a median of 7.5 folds in 7-day culture with the combination of EPO, SCF, G-CSF, IL-1β, IL-3, and IL-6. Neither 10-day or 14 day-culture enhanced expansion of HPP-CFU. Conclusion : Cryopreserved cord blood cells maintain ex vivo expansion potential. In our system, 10-day culture with the combination consisting of EPO, SCF, G-CSF, IL-1β, and IL-3 seems to be adequate for hematopoietic progenitor/stem cell expansion from cryopreserved cord blood cells.

이하선관 절단의 임상적 고찰

김한용,김병삼,김환익,이삼용,조백현 大韓成形外科學會 1991 Archives of Plastic Surgery Vol.18 No.2

본 병원에 내원한 절단된 이하선관 환자 총 20명(남자:10명 여자 10명)중 4명을 제외한 16명에서 추적조사가 가능하였으며 이 중 14명에서 이하선관의 원활한 관통이 이루어졌고 1명에서 관의 폐세기 생겨 2차 수술이 필료 했으며 다른 1명의 경우 농의 배출이 있었으나 항생제 투여와 구강위생등으로 별 다른 문제 없이 치료 되었고 또 1례의 이하선 타석을 치험하여 보고하는 바이다. Due to increasing trend of traffic accident, number of patient has been gradually increased. Facial injury, for its anatomical vulnerability, is most common site of injury and greatly exceeding injuries of other body region in trauma patient. There are occasional report of Stensen`s duct damage accompanying facial injury and much problem can arise when first aid is performed without knowledge of anatomy or concern for patient. Generally, Stensen`s duct located at mid 1/3 portion of line passing through tragus of ear and subnasale, another word, above the masseter muscle. Once deep lacerated wound has occurred in this region, one must suspect damage of Stensen`s duct. Among the 20 patients (Male: 10, Female:10) who have beeb treated at Chonnam National University Hospital for severed Srensen`s duct, 14 cases have obtained favorable result, not counting 4 patients with whom follow-up study was not possible. In unsuccessful cases of two, 1 case required secondary operation due to occurance of ductal stricture. In another case, leakage of pus has been observed but with proper oral care and antibiotic administration, it has been treated withiut any difficulty. Facial nerve injury accompanying Stensen`s duct been frequently observed, buccal branch being the most common site of involvement. Time interval from severance of duct to repairing the duct was 7 to 21 hours on average and time delay of this level has not impose much limit to obtain successful result. Suture material for Dowel, no matter what kind used, has achieved favorable result and time interval of 9 to 21 days given before the removal was long enough to obtain successful operative result without any development of complication. It is generally accepted view that salivary stone is most common disease entity among the salivery glands and ducts, and stone mostly occur in submandibular duct and rarely in Stensen`s duct. We have performed end-to-end anatomosis using a 23 guage polyethylene catheter as a Dowel in severed duct in 20 patients who have been admitted our hospital for cut repair and obtained satisfiable result. In 1 case, we have experienced stone on the Stensen`s duct, therby reporting this case with through reviews of literature.

유도 '되치기 본'의 개선 방안에 관한 연구

김의환,김도준,김규수,김관현,김종달,최종삼,조용철,박순진,윤익선,안병근,정 훈,김미정,한성철 龍仁大學校 武道硏究所 1999 武道硏究所誌 Vol.10 No.1

The purpose of this study was to reform practically a Korean Judo's Doechigi-Bon(Forms of Counterattack, judo's Gaeshi no Kata, Judo's Uradori no Kata, Judo's Gonosen no Kata) that was established in 1955 Korea, according to changing of techniques by Judo's modernization, in order to have Judo's carefulness and systematic diffusion. Reform procedure of Judo's Doechigi-Bon was 1st stage, Questionnaire survey 303 judokas, 2nd stage, Technical seminar by judo experts(12 judo professor) 4 times, 3rd stage, wording report for reform, 4rd stage, Discussion and judgement of Teaching and Judgement commission of Korean judo Association(KJA), 5th stage, Public hearing for reform in KJA, 6th stage, Report and decision of board of directors in KJA, 7th stage, public publication of Judo News(No.53) in KJA. Basic principle of reform of Judo's Doechigi-Bon were as table 1. Table 1. Basic principle of reform of Judo's Doechigi-Bon ------------------------------------------------------------------------------- Items Reformed Key Points of Judo's Doechigi-Bon ------------------------------------------------------------------------------- 1. Structure 1) Grand classification : Classified by 3 parts(1,2,3Gyo) 2)Medium classification : Te waza, Goshi waza, Ashi waza devided per each part(Gyo) 3)Sub-classification : Classified five techniques per each part(Gyo) 2. Contents 1) Selected established techniques as possible 2) Considered rationalty and overlapping of counterattack techniques 3. Decision of Conterattack techniques 1) Refered to results of Basic Questionnaire survey 2) Priority to decisions of Judo expert technical seminar -------------------------------------------------------------------------------- Reformed Korean Judo's Doechigi-Bon(Forms of Counterattack techniques-KJA, 1999) are as follows: 1. Gyo; ① Uki otoshi -> Uchi mata ② Harai goshi -> Harai goshi gaeshi ③ O soto gari -> O soto gake ④ Ko uchi gari -> Sasae tsurikomi ashi ⑤ O uchi gari -> Ko soto gari 2. Gyo; ① Ippon seoi nage -> Okuri eri jime ② Tsuri domi goshi -> Uki waza ③ Okuri ashi harai -> Okuri ashi harai ④ Ko soto gari -> Tai otoshi ⑤ Hiza guruma -> Hiza guruma 3. Gyo; ① Kata guruma -> Sumi gaeshi ② Tai otoshi -> Ko soto gari ③ Hane goshi -> Harai tsurikomi ashi ④ Uchi mata -> Tai otoshi ⑤ Tomoe nage -> O uchi gari

韓國經濟開發計劃과 財政의 經濟的役割(Ⅱ) : 1972~'81

金蓮起,李龍三 大邱大學校 社會科學硏究所 1998 社會科學硏究 Vol.5 No.3

韓國은 1960年 1人當 GNP가 $79에 불과한 빈곤한 國家였으며 그때의 輸出은 $3,290만인데 輸入은 그 10培인 $35,400만이었기 때문에 外國의 資本이 없으면 經濟 活動을 제대로 할 수 없었다. 이와 같이 美國을 비롯한 외국의 援助가 감소됨에 따라 政府는 外國의 資本을 도입하는 經濟開發5個年計劃을 세워 自立經濟의 確立을 목표로 하였으며 이러한 經濟開發計訓을 성공시키기 위해서는 무엇보다 財政運營의 役割이 중요하였다. 특히 經濟開發에 중점을 둔 貯政役融資의 活動은 경제성장에 지대한 영향을 미쳤다 고 할 수 있다. 따라서 본 論文에서는 1972~'81년의 韓國經濟開發計刻에 있어서 중요한 기능을 한 財政의 經濟的 役割을 살펴보고자 하는 것이 목적이다.

TPA로 야기된 HL-60 세포의 기질부착 저해작용을 이용한 Protein Kinase C 저해 생약의 탐색

김선희,안종석,김삼용,유관희,안병준 충남대학교 약학대학 의약품개발연구소 1993 藥學論文集 Vol.9 No.-

Thirty-five kinds of herbal drugs, believed to be active for treatment of tumors, were selected as the experimental materials for observing their effects on TPA-induced adherence of HL-60 cell and activity of protein kinase C. They were extracted with ethyl ether(E) and ethyl acetate(EA), methanol(M) in sequence. Among the extracts, Sophorae Flos(EA), Paeoniae Radix(EA), Equisetum hiemale(EA), Phellodendri Cortex(E, EA), Mori Cortex radicis(EA), Ferula assafoetida(E, EA), Sophora subprostrata(EA, M) and Cnidium monnieri(E) inhibited the TPA-in-duced adherence of HL-60 cell more than 50% and Sophorae Flos(E, EA, M), Paeoniae Radix(E, EA, M), Eguisetum hiemale(E), Phellodenri Cortex(E,H), Mori Cortex radicis(M), Ferula assafoetida(M), Sophora subprostrata(EA, M), Cnidium monnieri(M) and Artemisia argyi(M) showed inhibiting effects on the activity of protein kinase C more than 50%. The extracts showing good inhibiting effects on the adherence and enzyme activity were Sophorae Flos(EA), Paeoniae Radix(EA), Phellodendri Cortex(E), Sophora subsprostrate(EA) and Equisetum hiemale(EA).

성인 급성 백혈병의 치료에 관한 연구

김종완,장준,신승훈,윤일국,박철신,김삼용 충남대학교 의과대학 지역사회의학연구소 1989 충남의대잡지 Vol.16 No.2

19 adult ALL patients were treated with follwing regimens; VP regimen to 5 patients, VPA regimen to 4 patients, multi-drug combined intensive therapy of Hoelzer regimen to 10 patients. The results of therapy are as follows: 1. Complete remission occured in 3 patients on VP regimen(60%), 4 patients on VPA regimen (100%), 8 patients on Hoelzer regimen (80%), respectively, and overall complete remission rate was 78.9%. 2. Mean survival time of total patients was 13.8 months, and in complete remission group, it was 16.2 month, but in non-complete remission group, it was 1.8 month. 3. Factors favorable for complete remission were absence of organomegaly(P<0.05) and initial leukocyte count under 30,000/㎟(P<0.01), factors favorable for the survival duration were initial leukocyte count under 30,000/㎟(P<0.05) and remission within 4 weeks of treatment.(P<0.01). 4. Recurrence rate were 40% in VP regimen, 50% in VPA regimen, and 20% in Hoelzer regimen. 5. During the remission induction period, common side effects of chemotherapy were alopecia, nausea, vomiting, mucositis, and general weakness and it was severe in VPA regimen and Hoelzer reimen than in VP regimen. But no significant difference was noted between VPA regimen and Hoelzer regimen. From the above results, we could confirm the importance of multiple drug combined intensive chemotherapy of remission regimen and periodic reinduction chemotherapy.

2000년 시드니 올림픽 유도경기 대비 세계 우수선수들의 개인별 기술 및 패턴에 관한 연구 : 남자선수를 중심으로

김종달,김규수,한성철,최종삼,윤익선,조용철,김의환 용인대학교 무도연구소 2000 武道硏究所誌 Vol.11 No.1

The purpose of this study was to analyze international contest levels and the competition techniques traits of each category, individual scoring - losing techniques of world elite judokas who were awarded in the international judo tournaments (I.J.T.) (part 1: ~O.G '96, part 2 :from O.G '96 to July, 2000), and who are expected to participate in the 27th Olympic Games(O.G.) Sydney 2000 to prepare the 27th O.G. which will be held from 16. to 22. September 2000 at Exhibition (Center, Darling Harbour, in Sydney, Australia The records of the results and contents of competition were obtained out of (115 for man,) I.J.T., world elite judokas. To decide individual contest levels, groups were derided into 3(A,B,C)groups and points were graded by 3 ways. The I.J.T. that were derided into 3 groups are shown in the table 1.

진행위암에 대한 병합화학요법

김삼용,조덕연 충남대학교 의과대학 지역사회의학연구소 1987 충남의대잡지 Vol.14 No.2

Twenty-three patients with advanced stage metastatic or unresectable gastric cancer were given combination chemotherapy consisting of Fluorouracil, Doxorubicin, and Cisplatin(FAC) or Mitomycin(FAM). 5 patients receiving FAC and 6 patients receiving FAM were evaluable. 3 patients receiving FAC and 3 patients receiving FAM achieved partial response. So, overal response rate was 60% for FAC and 50% for FAM. Median duration of response was 13 weeks for FAC and 20 weeks for FAM. 1 patient receiving FAC and 2 patients receiving FAM who achieved partial response are alive. Median survival was 8 months for FAC and 7 months for FAM. Responders had a longer survival than nonresponder in both regimens. There was no difference in response and median survival between 2 regimens. Toxicities were mainly gastrointesinal and hematologic, but were moderate and well tolerated in both groups. In conclusion, these regimens have substantial effects on advanced or unresectable gastric cancer without severe toxicities.

미만성 대형 B-세포 림프종에서의 예후인자에 관한 연구

김삼용,곽승근,박상은,윤환중,조덕연,김진만 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

미만성 대형 B-세포 림프종은 가장 흔한 악성 림프종의 한 종류로서 우리나라에서는 전체 비호지킨 림프종의 50%를 차지한다. 비호지킨 림프종에서 병기는 호지킨병과는 달리 예후 인자로서의 유용성이 적다. 따라서 병기만을 예후 인자로서 평가하는 한계를 극복하기 위해 국제예후지표(International Prognostic Index)가 도입되었다. 특정 환자에서 IPI 점수와 함께 그 환자의 림프종의 생물학적 특성을 분석한다면 예후 예측에서 정확도가 높아질 것이다. 본 연구에서는 미만성 대형 B-세포 림프종에서 국제예후지표의 유용성을 확인하고자 하였으며, 각종 생물학적 지표의 면역화학염색을 통하여 이들을 배세포 중심 아형(germinal center subgroup : 이하 GC양 아형으로 약함)과 활성화 B-세포 아형(post-germinal center subgroup; 이후 pGC양 아형으로 약함)으로 분류하고 이들의 예후 예측에 대한 적절성을 평가하였다. 결과는 다음과 같다. 1. 연령분포는 37세에서 69세로 중앙치는 56세이었으며, 남자는 17예(65.4%), 여자가 9예(34.6%)였다. 병기는 Ⅰ, Ⅱ, Ⅲ, Ⅳ기가 각각 2예(7.7%), 11예 (42.3%), 5예(19.2%), 8예(30.8%)였다. 'B'증상은 5예(19.2%)에서 양성이었다. 진단 당시 혈청 LDH치가 상승한 경우가 11예(42.3%)였고, 거대종양(직경이 10㎝이상)을 갖는 경우가 5예(19.2%)이었다. ECOG 수행등급은 0이 2예(7.7%), 1이 18예(69.2%), 2가 5예(19.2%), 3이 1예(3.8%)이었다. 2. 면역조직화학염색 상 bcl-2의 양성은 17예(65.4%), bcl-6의 양성이 20예(76.9%)이었다. CD10이 양성인 경우가 5예(19.2%)이었다. IRF-4가 양성인 경우는 8예(30.8%)였다. 26명의 환자에서 bcl-6, CD10과 IRF-4를 이용하여 GC양 아형과 pGC양 아형으로 분류 하였는데, GC양 아형은 14예(53.8%)이었고, pGC양 아형은 7예(26.9%), 분류가 되지 않는 경우가 5예(19.3%)이었다. 3. 평균 48개월 동안 추적한 결과 중앙생존기간은 44개월이었고 생존기간은 1~100+개월에 분포하였다. Kaplan-Meier법에 의한 5년 누적 생존률은 32%이었다. 4. 병기, 'B' 증상, 혈청 LDH 농도, ECOG 수행등급, 거대종양유무가 통계학적으로 의미있는 임상적 예후 인자였다. 5. 면연조직화학염색에서는 bcl-2만이 통계학적으로 유의한 예후인자였다. 6. GC양 아형은 pGC양 아형에 비해 생존기간은 좋았으나, 통계학적 유의성은 없었다. 7. 다변량 분석결과 bcl-2 발현과 혈청 LDH치만이 예후에 영향을 미쳤다. Clinical Significanceof Expression of Biomarkers in Patients with Diffuse Large B-cell Lymphoma Diffuse large B-cell lymphoma(DLBL) is the most common type of lymphoma in Korea, representing about 50% of non-Hodgkin's Lymphomas. Although DLBL is usually considered as a specific category, the diversity in clinical presentation, morphology, genetic and molecular alterations strongly suggest that these tumors represent a heterogeneous group of neoplasia rather than a single clinicopathological entity. Clinical prognostic systems, including the International Prognostic Index (IPI), although useful to assess overall prognosis, embraces patients with heterogeneous prognoses. It is likely that the prognostic assessment of patients with DLBL might be improved by using biological features. During the last decade, most studies dealing with the heterogeneity of DLBL have focused on individual protein expression and molecular alterations. The expression of individual antigens related to different stages of B-cell differentiation, including CD10, bcl-6, and IRF-4, may help to define groups of tumors with different clinical and pathological characteristics. To determine the clinical significance and prognostic value of individual biomarker expression and the biomarker expression patterns according to germinal center subgroup or post-germinal center subgroup of DLBL as defined by a relatively small number of single antigens, we studied 26 patients with de novo DLBL, whose archival pathology specimen were available for immunohistochemistry studies, atChungnam National University Hospital from September 1992 to December 2000. Archival specimens from each patient were immunostained with respective antibodies for CD10, bcl-6, IRF-4, bcl-2 antigens. Two immunophenotyping profiles were distinguished according to the pattern of differentiation; germinal center(GC;CD10/Bcl-6+/IRF-4-) subgroup or postgerminal center (pGC ; CD10/bcl-6/IRF4+) subgroup. The results are as follows; 1) Baseline characteristics of patients were ; median age of patients was 56(range ; 37-69). 17 patients(65.4%) were male. 5 patients(l9.2%) had 'B' symptoms. Stages were as follows ; stage Ⅰ2 patients(7.7%), stage Ⅱ 11 patients(42.3%), stage Ⅲ 5 patients(l9.2%), stage Ⅳ 8 patients(30.8%). 11 patients (42.3%) had elevated LDH levels. 25 patients(96.2%) had ECOG performance grade 0-Ⅱ and 1 patient had grade Ⅲ. 5 patients(l9.2%) bad bulky disease. 2) The results of immunohistochemical study were as follows ; positive bcl-2 staining in 17 patients(65.4%), positive bcl-6 in 20 patients(76.1%), positive CD10 in 5 patients(l9.2%), positive IRF-4 staining in 8 patients (30.8%). 3) After a median follow up duration of 48 months, the median survival duration was 44 months with a range of survival of 1-100+ months. 5-year overall survival rate was 32% by Kaplan-Meier method. 4) The clinical factors affecting survival were elevated serum LDH level, B symptoms, bulky disease, stage at diagnosis and ECOG performance status 5) Among the biomarkers, only bcl-2 expression affected survival of DLBL patients 6) The germinal center like subgroup had superior survival than post-germinal center like subgroup but had no statistical significance. 7) Multivariate analysis showed that bcl-2 and serum LDH level had siginificance on survival Conclusion In addition to the known clinical prognostic factors, immunohistochemically defined characteristics such as bcl-2 expressionin DLBL is important and subgroups(germinal center or post-germinal center subgroup) of DLBL may have importance in predicting prognosis of DLBL patients