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.

WLL 기지국용 다운 컨버터 설계

김윤영,문성익,허광삼,양두영 제주대학교 산업기술연구소 2000 尖端技術硏究所論文集 Vol.11 No.1

In this paper, A down converter to convert RF signal into IF signal is designed at the WLL base-station. It consists of low noise amplifier module and down mixer module. The low noise amplifier module is composed of three-stage and a feedback circuit is added in the first-stage low noise amplifier in order to obtain unconditional stability and good flatness. The configuration of the down mixer module is a single-ended type gate mixer. For the good isolation characteristic of each port, a bandpass filter and a lowpass filter are inserted in the input and output port. To design the down converter without the IF power amplifier, it is important to maximize conversion gain. So the down converter of this paper is designed for the purpose of obtaining a high conversion gain. From the results, the IF output power is -12.68dBm when the LO and the RF power level are 7dBm and -80dBm, respectively. Also when the LO power level is 7dBm, P1dB is -0.19dBm, and the RF input power range shows 70dB on wide operating range.

WLL 기지국용 다운 컨버터 설계

김윤영,문성익,허광삼,양두영 濟州大學校 産業技術硏究所 2000 산업기술연구소논문집 Vol.11 No.1

In this paper, A down converter to convert RF signal into IF signal is designed at the WLL basestation. It consists of low noise amplifier module and down mixer module. The low noise amplifier module is composed of threestage and a feedback circuit is added in the first-stage low noise amplifier in order to obtain unconditional stability and good flatness. The configuration of the down mixer module is a single-ended type gate mixer. For the good isolation characteristic of each port, a bandpass filter and a lowpass filter are inserted in the input and output port. To design the down converter without the IF power amplifier. it is important to maximize conversion gain. So the down converter of this paper is designed for the purpose of obtaining a high conversion gain. From the results, the IF output power is -12.68dBm when the LO and the RF power level are 7dBm and -80dBm. respectively. Also when the LO power level is 7dBm. PldB is -0.19dBm. and the RF input power range shows 70dB on wide operating range.

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

대기업의 스포츠 마케팅 전략에 관한 연구 : 스포츠 이벤트 전략을 중심으로

김윤섭,정승삼 경희대학교 체육과학연구소 2000 體育學論文集 Vol.28 No.-

Sponsorship in Sports Marketing not only has the advantage of enhancing brand awareness and boosting sales, but it also enblance differentiated strategy from that of competitors. Enterprise Company has been active in Sports marketing since the 1986 Seoul Asian Games, and has continuously carried out its brand image strategy through Sports marketing. This study conducted a survey on sports marketing activities of large enterprises in the nation. The study also made an investigation into the sports event marketing strategies adopted by the large firms as a more active marketing technique. As a result, the study came to the following conclusion on the applications of sports event marketing of the large companies. First, a sports event marketing strategy should define a specific target market and develop a marketing mix first which will be most suitable for the target market. Second, to ensure an efficiency of sports event marketing, an event strategy should be employed to segment a specific market to which a form will provide goods or services that are suited to the target market. Third, sports event marketing should make use of a communication system in the company to satisfy diverse needs of consumers while taking into consideration limitations to capabilities of the company and competition in the market. Fourth, in case of sports marketing using sports as a communication strategy, the company should develop a product that has a differentiated visual identity highlighting the company's image and product lines.

Silica Gel-MoO₃觸媒에 의한 Methanol의 酸化反應

김재구,정국삼,홍윤명 연세대학교 산업기술연구소 1983 논문집 Vol.15 No.2

The vapor phase oxidation of methanol to formaldehyde over silica gel supported-MoO₃catalyst was studied at atmospheric pressure as a function of reaction temperature, feed rate and concentration. The silica gel supported-MoO₃catalyst was found very selective in formaldehyde formation but conversion was rather poor. The following rate equation was deduced assuming a steady state with two stage irreversible oxidation-reduction process. γ= ? The rate equation matched experimental data reasonably well and activation energies of the steps were calculated to be 8.345Kcal/g-mole and 7.074Kcal/g-mole respectively.

림프절 종창의 임상적 관찰

김삼용,김현수,김종숙,박상준,최지영,윤환중,조덕연 충남대학교 의과대학 지역사회의학연구소 1995 충남의대잡지 Vol.22 No.2

Objectives : Clinical management of patient with lymphadenopathy requires judicious judgement of clinicians. Careful evaluation of lymph node enlargement by various clinical parameters will help to disclose the etiology of lymph node enlargement. This study was conducted to identify the clinical manifestations and etiology of lymphadenopathy in korean patients. Methods : A total 192 patients with lymph node enlargement were studied retrospectively. All patients who underwent excisional lymph node biopsy during the period from January 1992 to July 1994 were included. The lymph node biopsy and clinical records were reviewed and patient characteristics were analyzed by various clinical parameters. Results : A female predominance was noted in lymphadenopathy of tuberculosis (58.5%), Kikuchi's syndrome (70%). In lymphadenopathy of nonspecific, tuberculosis, kikuchi syndrome, per centage of patients younger than 40 years of age were 84.5%, 75.6%, 100%, respectively. In lymphadenopathy of tuberculosis and metastatic cancer, the duration of lymphadenopathy below 30days were 51.2%, 73.9%, respectively. The two most common etiology of cervical lymphadenopathy were nonspecific lymphadenitis (47.7%) and tuberculous (26.8%). The two most frequent etiology of supraclavicular lymphadenopathy were nonspecific lymphadenitis (46.3%) and metastatic lymphadenopathy (26.8%) and the most common etiology of axillary lymphadenopathy was nonspecific lymphadenopathy (34.5%). The most common frequent of lymph node enlargement with size below 1㎠ was nonspecific lymphadenitis, while above 2.25㎠ it was metastatic lymphadenopathy. Conclusion : Careful evaluation regarding patient age, sex, size of lymph node, consistency, location of lymph node, presence or absence of systemic symptoms should be pursued before performing a biopsy and management.

연약지반 성토시 사면의 안정에 미치는 Geotextile의 효과

김수일,조삼덕,우제윤 연세대학교 산업기술연구소 1982 논문집 Vol.14 No.2

Geotextiles have been extensively used in road constructions as effective and economical materials performing several functions such as separation, filtration, drainage, protection against frost break, and as reinforcement to improve the load bearing capacity and stability of road. In this study, a method for the analysis of embankment reinforced with geotextile is studied. Computer program based on the simplified Bishop method is modified in order to investigate quantitively the effect of gotextile on the slope stability of embankment on weak soils. Evaluation of the tensile strength required for the design safety factor is also possible utilizing the computer program in this study.

백혈병 세포주에 대한(±)-ar-Turmerone, 자근 및 황금추출물에 의한 항암제의 세포독성 증강효과

이윤영,유관희,김삼용,안병준 충남대학교 약학대학 의약품개발연구소 1991 藥學論文集 Vol.7 No.-

Using the colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay, we evaluated the chemosensitivity of 8 anticancer drugs{vincristine(VCR), vinblastine(VBL), adriamycin(ADR), cisplatin(CPDD), etoposide(VP-16), cytosine arabinoside(ara-C), bleomycin(Bleo) and cyclophosphamide(CYC)} and the cytotoxicity-enhancing effects of (±)-ar-turmerone and the extracts of the crude drugs {Lithospermum erythrorhizon(LE) and Scutellaria baicalensis (SB)} on the above mentioned anticancer drugs against HL-60 and KG-1 cells among 8 anticancer drugs, VCR, VBL, ADR, and CPDD inhibited the growth of both cell lines by more than 50%, while VP-16, ara-C, Bleo, and CYC were less effective. (±)-ar-Turmerone had significant inhibitory effects against both cell lines, showing the ID_50 values of 11.730 ㎍/㎖ and 0.292 ㎍/㎖ for HL-60 and KG-1 cells. respectively. But the extracts of LE and SB roots showed no significant cytotoxic effects. According to ID_50 values, the cytotoxicities of VCR, VBL and ADR against HL-60 were enhanced two, eight and three times by mixing (±)-ar-turmerone, five, seven and three times by adding the extract of LE root, and twenty, six and three times by mixing the extract of SB root, respectively. The cytotoxicities of the above mentioned drugs against KG-1 cell were enhanced two, seven and three times by mixing (±)-ar-turmerone, two, three and three times by combining with the extract of LB root, and two, five and two times by adding the extract of SB root, respectively. The cytotoxicity-potentiating effects of (±)-ar-turmerone and the extracts of LE and SB roots againg HL-60 cell were greater than KG-1 cell.