CD34+ 조혈 모세포 이식 2례

김정아,정현식,김원석,윤성수,이홍기,박찬형,박성규,김동욱,이종욱,한치화,민우성,김춘추,김동집 대한조혈모세포이식학회 1996 대한조혈모세포이식학회지 Vol.1 No.1

Background: In most solid tumors, the CD34 antigen has not been detected, so positive selection of CD34+ cells may reduce tumor cell contamination and the CD34+ cells are capable of reconstituting hematopoiesis. We tried CD34+ cell transplantation in two patients. Method: CD34+ cells from chemotherapy + G-CSF mobilized PBPCs or bone marrow were positively selected with an avidin-biotin immunoadsorption column (CEPRATE SC system). Case 1. One course of chemotherapy using cyclophosphamide(200㎎/㎡) and etoposide (4.2g/㎡), combined with G-CSF(5㎍/㎏) S.C. was used in a relapsed lymphoma patient. This patient responded to the induction chemotherapy. CD34+ cells from harvested bone marrow were selected by the CellPro immunoadsorption column. The total number of mononuclear cells loaded onto the CellPro was 2.4×10^(8)/㎏, with 1.1% CD34+ cells. After column separation, the total number of positively selected cells was 5.16×10^(6)/㎏. The number of CFU-GM was 76.8×10⁴/㎏. This patient was treated with melphalan (140㎎/㎡) and TBI (1200cGy) and the positively selected CD34+ cells were infused. The time to neutrophil recovery greater than 0.5×10^(9)/L was 19 days and the time to platelet recovery greater than 50×10^(9)/L was 21 days. Case 2. Two courses of mobilizing chemotherapy were given 4 weeks apart using taxol(210㎎/m2) and adriamycin(60㎎/m2), combined with G-CSF(5㎍/㎏) S.C. in a breast cancer patients with 7 axillary node metastasis. CD34+ cells from each single leukapheresis product were selected by the CellPro immunoadsorption column. In the first collection, the total number of nucleated cells was 4.4×10^(8)/kg, with 0.42% CD34+ cells. In the second collection, the total number of nucleated cell was 2.8× 10^(8)/㎏ with 0.43% CD34+ cells. After colum separation, the total numbers of collected cells were 4.0×106/kg and 4.8×10^(6)/kg, the total number of CD34+ cells were 1.2×10^(6)/㎏ and 0.82×10^(6)/㎏. Colonogenic assays of positively selected CD34+ cells gave rise to myeloid erythroid, and multilineage colonies, with a median of 190 CFU-GM, 190 BFU-E, and 164 CFU-GEMM per 1×10³ adsorbed cells, respectively. High-dose chemotherapy with cumulative doses of 40mg/㎡ mitoxantrone, 750mg/㎡ thioptepa, and 1000mg/㎡ carboplatin was administered. Positively selected CD34+ cells were rapidly infused 24 hours after the end of high-dose chemotherapy. The time to neutrophil recovery greater than 0.5×10^(9)/L was 16 days and the time to platelet recovery greater than 50×10^(9)/L was 20 days.

G-CSF로 체내 증폭된 골수를 이용한 동종 조혈모세포이식

이종욱,김정아,민창기,김희제,엄현석,박수정,서정곤,김동욱,홍영선,민우성,김춘추,김동집 대한조혈모세포이식학회 1998 대한조혈모세포이식학회지 Vol.3 No.2

연구배경: 이식시 주입되는 골수세포수는 생착 속도 및 생존율과 밀접한 관계가 있으나, 임상적으로 환자의 체중이 공여자에 비해 지나치게 많을 때 단위 체중당 환자에게 주입되는 세포의 양이 적어 문제가 될 수 있다. 방법: 저자들은 가톨릭 조혈모세포이식 센터에서 동종 골수이식을 시행한 환자들 중 환자의 체중이 공여자에 비해 10kg이상 많은 경우 골수 채취 전에 공여자에게 3일간 피하로 G-CSF(10ug/kg/day)를 투여하여 골수를 체내(in vivo) 증폭시킨 후 골수이식을 시행한 25예의 환자를 대상으로 고식적인 방법으로 골수이식을 시행한 위험인자가 일치되는 대조군과 비교하여 이식된 세포수, 혈구의 회복속도 및 이식편대 숙주반응(GVHD)의 발생율, 그리고 생존율 등을 비교 분석하였다. 결과: 단기간의 G-CSF 투여로 증폭된 골수의 총 유핵세포수, 단핵구수는 대조군에 비해 3-5배, CD34 + 세포수는 6배 증폭되었으며, 두 군간에 세포의 면역표현형(CD4, CD5, CD7, CD8, CD20)의 차이는 없었다. 중성 백혈구 수가 0.5×10^(9)/L 이상 회복되는 시기는 두 군간의 차이가 없었으나(15.5일 vs 16일; p=0.131), 혈소판 수가 30×10^(9)/L 이상으로 회복되는 시기는 G-CSF 투여군에서 의의있게 단축되었다(20일 vs 26일; p=0.013). 두 군간 급성 및 만성 GVHD의 발생률과 정도의 차이는 없었으며, 이식 후 재발 및 생존율의 차이도 없었다. 결론: 이식전 공여자에게 단기간 G-CSF를 주사하여 생체내에서 골수 조혈모세포를 증폭시킨 후 이식하는 방법은 공여자와 환자의 심각한 체중 차이로 인해 단위체중당 이식되는 조혈모세포양이 부족한 환자들에게 안전하고 유용한 방법일 뿐만 아니라 GVHD의 증가 없이 빠른 혈구회복을 기대할 수 있는 이식기법이라고 생각한다. 향후 증폭된 골수 조혈모세포의 특성 연구 및 이의 효용성을 확인하기 위한 전향적인 연구가 필요하리라고 생각된다. Background: Sufficient stem cell doses are necessary to overcome engraftment failure in allogeneic bone marrow transplantation(BMT). Cell doses harvested may depend on body weight (BW) difference between donor and recipient. In practice, it is important to achieve large number of stem cells from donor who were lower BW than that of recipient. Methods: We have tried to inject G-CSF(10ug/kg/day) subcutaneously for 3 days to the allogeneic donor with lower BW than recipient before harvest to increase BM inoculum. BM was infused into patients without any manipulation on day 5. A total 25 patients were enrolled; 12 AML, 6 ALL, 5 SAA and 2 CML(expansion group). We compared the expansion group with 25 historical control patients, matched for diagnosis and clinical characteristics, who underwent unprimed BMT. Results: Recipient BW is not different between the expansion and control group. However, allogeneic donors in the control group weigh heavier than those in the expansion group. The yield of TNC, MNC, and CD34^(+) cells from G-CSFprimed BM was significantly higher than that from unprimed BM. There was no difference in immunophenotyping analysis(CD4, CD5, CD7, CD8, CD20) between two groups. The median time reaching to absolute neutrophil count more than 0.5×10^(9)/L was not different(15.5 vs 16 days: p=0.131), but time to platelet recovery more than 30×10^(9)/L was significantly shorter for the patients who received G-CSF-primed BM (20 vs 26 days: p=0.013). There was no difference in the incidence of acute and chronic GVHD, relapse rate and overall survival between the two groups with a median follow-up of 13 months. Conclusion: These data suggest that the short-term administration of G-CSF to an allogeneic donor prior to BM harvest seems to be a feasible method to achieve an adequate number of cell doses for patients who weigh higher than donors. Randomized, prospective study is needed to evaluate the efficacy of allogeneic BMT using in vivo expansion of BM by G-CSF.

C형 간염바이러스항체 검출을 위한3세대 효소면역측정 시약의 비교

이장혁,서순팔,기승정,송정원,신명근,신종희,양동욱,김세종 대한임상병리학회 1997 대한임상병리학회지 Vol.17 No.4

HPLC를 이용한 Alnus속 식물에서의 diarylheptanoids의 정량분석

정동욱,김준식,조수민,이연아,김광호,김세원,이민원 중앙대학교 약학연구소 1999 약학 논총 Vol.13 No.-

Quantitative determination of diarylheptanoids (oregonin and hirsutanonol), which were characteristic components of Alnus spp. has been conducted by High Performance Liquid Chromatography. The HPLC analysis was carried out using an YMC J'sphere ODS-H80 column [150×4.6mm, S-4μm. 80A(particle)] and a combination of acetonitrile and H2O was used as mobile phase in gradient solvent system. The results showed differnce in the species (Alnus japonica, A hirsuta and A. hirsuta var. sibirica)

알쯔하이머병 환자의 뇌혈류 장애 : Statistical Parametric Mapping을 이용한 Tc-99m ECD SPECT 분석 Statistical Parametric Mapping analysis of Tc-99m ECD SPECT

양동원,김범생,손영민,박정욱,정용안,손형선,김상윤 대한치매학회 2002 Dementia and Neurocognitive Disorders Vol.1 No.2

Background and Objectives . Alzheimer's disease (AD) is the most common cause of the dementia Pathologic and functional changes of AD are known to be unevenly distributed in the brain. This study investigates changes of cerebral blood flow (CBF) in patients with AD to determine brain regions with hypoperfusion that reflects progression of disease. Methods. Tc-99m-ECD single photon emission computed tomography (SPECT) was performed to measure regional CBF and statistical parametric mapping (SPM) 99 soft ware was used for the automated and objective approach to analyze SPECT image data. Twenty-five patients with mild to moderate dementia who met NINCDS-ADRDA critena for AD (male 11 female 14) and 17 age-matched normal control subjects were studied. The severity of AD was measured by clinical dementia rating (CDR) scale Results. SPM analysis of SPECT images revealed that CBF in the anterior cingulate gyrus left superior panetal cortex left medial frontal cortex left infenor temporal cortex. right thalamus and left hippocampus was significantly decreased in AD patients compared with normal controls (corrected p<0.05). The reduction of CBF according to CDR was localized in the left hippocampus and infenor temporal cortex right antenor and postenor ciagulate cortex and right superior panetal cortex (uncorrected p<0.01). Conclusions : Our data suggest that the cognitive dysfunction of AD is strongly related with functional abnormality in discrete brain areas 99m-Tc ECD SPECT with SPM analysis could be used as a useful functional imaging tool in AD study.

Toluene(1)-water(2)-2-propanol(3)-ethyl acetate(4) 4성분계의 액-액평형

최성욱,정상훈,김영일,이진우,박동원 동아대학교 공과대학부설 생산기술연구소 1998 生産技術硏究所硏究論文集 Vol.3 No.1

We studied on the phase equilibria of quatemary liquid-liquid extraction system composed 2-propanol-water-binary solvent at 25℃. Ethyl acetate(EAc)-toluene was used as binary solvents. Binodal curve, tie-line, distribution and selectivity for quatemary system have been determined in order to investigate the effect of using binary solvent in extracting 2-propanol from aqueous solotion. And this experimental tie-line data was also compared with the values predicted by UNIFAC model. It was shown that UNIFAC model is capable of predicting the tie-line in this quaternary system within an average RMSD of 1.93 mol%.

셀레콕시브 및 그 합성유도체들의 항암활성 스크리닝

박정란,강진형,구효정,노지영,류형철,박상욱,고동현,조일환,이주영,황다니엘,김인경 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.2

Selective COX (cyclooxygenase)-2 inhibitors including celecoxib have been shown to induce apoptosis and cell cycle changes in various tumor cells. New inhibitors are recently being developed as chemomodulating agents. We evaluated celecoxib and screened 150 synthetic compounds for anti-proliferative activities in vitro. Effects of celecoxib on COX activity, cell growth, cell cycle distribution, and apoptosis induction were determined in A549 COX-2 overexpressing human non-small cell lung cancer (NSCLC) cells. The COX inhibition of celecoxib increased with concentration up to 82% at 1μM after 24 hr exposure. Forty μM and 50μM of celecoxib induce G_1 arrest, and TUNEL-positive apoptotic cells, respectively. Among 150 compounds, several compounds were selected for having greater COX-2 inhibitory activity and higher selectivity than celecoxib with growth inhibitory activity. Celecoxib showed concentration-dependent COX inhibitory activity, and ability to induce cell cycle arrest and apoptosis in human NSCLC cells in vitro. Among synthetic analogues screened, several compounds showed promising in vitro activity as COX-2 inhibitory anticancer agents, which warrant further evaluation in vitro and in vivo.

각종 난치성 혈액 질환에서의 비혈연간 골수이식

김동욱,한훈,김정아,김희제,민창기,엄현석,최정현,이종욱,한치화,홍영선,최일봉,신완식,민우성,김학기,김춘추,김원일,김동집 대한조혈모세포이식학회 1997 대한조혈모세포이식학회지 Vol.2 No.1

목적: 비혈연간 골수이식은 혈연내에 적절한 골수공여자가 없는 만성골수성백혈병, 고위험군의 급성별혁병, 면역억제치료에 실패한 재생불량성빈혈 및 각종 난치성 조혈모세포질환의 완치를 위한 표준적인 치료방법으로 정착되고 있다. 혈연간 표준적인 동종 이식에 비하여 비혈연간 이식시에는 생착부전, 이식편대숙주반응과 감염이 더 빈번하게 발생하며, 국내에서는 아직까지 체계적인 임상연구결과가 보고된 바 없었다. 이에 본 센터에서는 1995년 10월 이후로 약 20개월간 26예의 비혈연간 골수이식을 시행하였으며 3개월 이상의 추적관찰이 가능하여 이식초기 합병증의 관찰 및 분석이 가능하였던 20예의 환자를 대상으로 이식성적 및 문제점을 보고함으로써 새롭게 확대되고 있는 이 분야의 임상연구 및 진료의 활성화를 꾀하고자 한다. 방법: 각종 혈액 종양질환으로 비혈연간 이식을 시행한 총 26예의 환자중 3개월이상의 추적관찰이 가능하였던 20예를 대상으로 후향적으로 임상경과를 분석한 후 생존 분석을 시행하였고, 환자의 연령, 성별, 질병의 상태, 조식 적합 항원의 일치정도, 이식편대 숙주 반응의 유무와 생존기간과의 상관관계를 살펴보았다. 또한 표준위험군과 고위험군으로 나누어 생존율을 비교하였고 이식과 관계된 생착 부전, 이식편대숙주반응, 감염의 발생과 양상 그리고 그 합병증을 관찰하였다. 결과: 1. 환자와 공여자간에 HLA 불일치가 20예 중 4예에서 있었으며, 생착여부의 확인이 가능했던 17예 중 16예에서 생착이 확인되어 94.1%의 생착율을 보였다. 2. 급성이식편대숙주반응은 62.5%(10/16예)에서 발생하였으며 111도 이상의 급성의 이식편대숙주 반응은 25%(4/16예)에서 발생하였다. 만성이식편대숙주반응은 40%(2/5예)의 환자에서 발생하였으며 이들 모두 국소형으로 중증의 진행형 만성이식편대숙주반응이 관찰된 환자는 없었다. 3. 호흡기 합병증은 10예(50%)에서 발생하였으며 감염성 폐렴을 포함한 호흡기 합병증이 가장 흔한 일차적인 사망 원인이었다. 호흡기 합병증이 발생했던 10예중 6예가 감염에 의한 폐렴이 의심되었고 나머지 4예는 특발성 간질성 폐렴이었다. 4. 8.5개월의 중앙추적기간 중 35%의 생존율을 관찰할 수 있었고, 생존기간은0.5개월에서 15개월 (중앙치:4개월)이었다. 한편 고위험군은 25%(3/12예), 표준위험군은 50%(4/8)의 생존율을 관찰할 수 있었다. 5. 가장 흔한 사망 원인은 감염성 폐렴을 포함한 호흡기 합병증(6예)이었고, 이외의 사망 원인으로는 급성 이식편대숙주반응과 다장기부전이 각각 2예, 생착 부전, 간정맥 폐쇄, 그리고 재발이 각각 1예였다. Unrelated bone marrow transplantation(UBMT) has been increasingly recognized as the standard treatment for cure of chronic myelogenous leukemia, high risk acute leukemia, aplastic failed on immunotherapy, and the variety of refractory hematologic diseases in patients lacking a related donor. However, as compared to HLA identical sibing transplantation, UBMT carries higher incidence of graft failure, graft versus host disease(GVHD), and infection. In our center, 26 patients underwent UMBT between October 1995 and June 1997. The minimum follow-up of 3 months was possible in 20 patients, for whom early complications and clinical outcomes were assessed. The median age of the 20 patients was 24 years. 8 patients had standard risk disease and 12 patients had high risk disease. All patients received various preparative regimens including total body irradiation according to disease and disease status. 19 patients received CsA + short course MTX for GVHD prophylaxis. One patient received marrow that was depleted of T cells ex vivo using avidinbiotin column. The class I loci were typed by serological methods and HLA-A, HLA-B and HLA-DRB1. 3 additional pairs were one minor mismatched at the HLA-B locus. Another one patients was one major mismatched at the DRBI alleles. 17 patients were evaluable for engraftment. Successful enfraftment was confirmed in 16 patients(94.1%). Only one patient who was performed one major DRBI mismatched transplants experienced graft rejection. 16 patients were evaluable for acute GVHD. The overall incidence of acute GVHD developed in 4 patients(25%). Five patients were evaluable for the development of Ⅳ acute GVHD developed in 4 patients (25%). Five patients were evaluanle for the development of chronic GVHD. 2 patients(40%) developed limited chronic GVHD. Respiratory complications including pulmonary infection developed in 10 patients(50%) and these complications were the most common primary cause of death. Of these 10patients, 6 had pneumonia due to fungus(4 patients), pacterial (1 patient), and CMV infection (1 patient) and 4(20%) had idiopathic interstitial pneumonitis and/or adult respiratory distress syndrome. The duration of median follow- up was 8.5 months and 7 of 20 patients(35%) are alive at the time of this analysis with survival duration of 0.5 to 15 months(median survival duration: 4 months). The overall survival was 25% (3/12 patients) in high risk group and 50%(4/8 patients) in standard group. From these results, we can predict that the incidence and severity of GVHD in Korea are lesser than multiracial countries and the long-term survival of patients with standard risk disease can approach that of HLA matched sibling transplants. For the past two years, the performance of UBMT has been rapidly increasing and it will be possible to analyze much larger number of patients soon in Korea. In the future the problems of graft failure, GVHD, and infection due to long lasting immunocompromised status will need to be overcome by continued medical research. In addition, the volunteer donor pool will have to be expanded by the promotion of the national awareness of its need.

중년기 우울증 여성의 생활사건, 대처방식, 사회적 지지 및 가족관계

김동인,이진욱,김임,이선미,은헌정 大韓神經精神醫學會 1997 신경정신의학 Vol.36 No.4

국문초록본 연구는 중년기 우울증 여성의 생활사건 스트레스, 대처 방식, 사회적 지지, 가족 관계 등의 정신사회적 요인들을 알아보기 위한 것으로 각 변인들이 어떻게 우울과 관계가 있는지를 우울증 환자 집단과 정상인 집단으로 나누어서 비교 연구하였다. 이를 위해 35세 이상 64세 이하의 116명의 우울증 환자와 113명의 정상인을 대상으로 Beck 우울 질문지(BDI), 생활사건 질문지, 대처방식 척도, 대인관계 지지 평가척도(ISEL), 가정환경척도 등의 검사를 하였고 다음과 같은 결과를 얻었다. 1) 최고 스트레스는 환자 집단의 경우 결혼생활 스트레스(42명, 36.2%), 정상인 집단의 경우는 가정생활 스트레스(44명, 38.9%)였다. 2) 소극적 대처(t=0.93, p=.35)만을 제외하고 환자 집단과 정상인 집단에서 BDI 우울 점수(t=15.94, p<.0001), 생활사건 스트레스 점수(t=4.73, p<.0001), 적극적 대처점수(t=6.29, p<.0001), 사회적 지지점수(t=7.20, p<.0001), 가족 관계 점수(t=5.75, p<.0001)에서 유의한 차이를 보였다. 3) 우울증 환자 집단에서 BDI 우울 점수는 생활사건 스트레스(r=.24, p<.01) 변인과 유의한 정적 상관을 보였고, 적극적 대처(r= -.22, p<.01) 변인, 사회적 지지(r= -.35, p<.001) 변인, 가족관계(r= -.30, p<.001) 변인과는 유의한 역 상관을 보였다. 4) 우울증 환자 집단에서 BDI 우울에 대한 각 변인들의 중다회귀분석은 사회적 지지(12.3%, β= -.281, T= -3.162, P=.002, 생활사건 스트레스(5.1%, β=.279, T=3.195, P=.002), 적극적 대처(3.5%, β= -.204, T= -2.225, P=.028) 변인이 합하여 20.9%의 설명력을 나타냈다. 5) 중년기 여성에서 생활사건 스트레스는 가족 관계에서 겪는 스트레스가 가장 큰 스트레스였고, 대처방식은 우울과의 관계에서 일관성이 부족하였으며, 사회적 지지는 우울에 영향을 주는 가장 중요한 요인이었고, 가족관계는 양 집단에서 유의한 차이는 있었으나 우울에 대하여 의미있게 설명하지 못하고 있다. ABSTRACTLife Events, Coping Styles, Social Support, and Family Relationships of Middle-Aged Depressed Women Jin-Wook Lee, M.D., Yim Kim, M.D., Sun-Mi Yi, M.S., Dong-In Kim, M.D., Heon-Jeong Eun, M.D. Department of Neuropsychiatry, Presbyterian Medical Center, Chonju The objective of this study was to explore the psychosocial factors such as life events, coping styles and family relationships in middle-aged depressed women. This study was designed to compare how different variables relate to depression in two different test groups : a depressed patient group and a normal group. The Beck Depression Inventory(BDI), The Ways of Coping Checklist, Interpersonal Support Evaluation List(ISEL), Family Environment Scale were administered to 116 depressed patients and 113 normal persons between the ages of 35 and 64. The results were as follows : 1) The highest stress was marital stress(n=42, 36.2%) in patient group and family stress(n=44, 38.9%) in normal group, respectively. 2) There were significant differences between patient group and normal group in BDI scores(t=15.94, p<.0001), life events(t=4.73, p<.0001), active copinig(t=6.29, p<.0001), social support(t=7.20, p<.0001), and family relationships(t=5.75, p<.0001) except for passive coping(t=0.93, p=.35). 3) In depressed patient group, BDI scores had a significantly positive correlation with the scores of the life events(r=.24, p<.01) and negative correlation with active coping(r= -.22, p<.01), social support(r= -.35, p<.001) and family relationships(r= -.30, p<.001). 4) In depressed patient group, multiple regression analysis showed that social support(12.3%, β= -.281, T= -3.162, P=.002), life events(5.1%, β=.279. T=3.195, P=.002), and active coping(3.5%, β= -.204, T= -2.225, P=.028) had predictability on the BDI scores and the total predictability was 20.9%. 5) Stress experienced in family relationships were highest in life events and there was a lack of consistency(in the BDI scores of the coping styles). Social support was the most important factor and there were no significant differences between the two groups in family relationships.

용액분산촉진 초임계 공정을 이용한 라이소자임 나노 입자의 제조 및 그 특성

김동현,박희준,강선호,전승욱,김민수,이시범,박정숙,황성주 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.2

The micron or nano-sized lysozyme as a model protein drug was prepared using solution enhanced dispersion by supercritical fluid (SEDS) process at various conditions (e.g., solvent, temperature and pressure) to investigate the feasibility of pulmonary protein drug delivery. The lysozyme particles prepared were characterized by laser diffraction particle size analyzer, scanning electron microscopy (SEM) and powder X-ray diffractometry (PXRD). The biological activity of lysozyme particles after/before SEDS process was also examined. Lysozyme was precipitated as spherical particles. The precipitated particles consisted of 100 -200 nm particles. Particle size showed the precipitates to be agglomerates with primary particles of size 1 - 5 μm. The biological activity varied between 38 and 98% depending on the experimental conditions. There was no significant difference between untreated lysozyme and lysozyme after SEDS process in PXRD analysis. Therefore, the SEDS process could be a novel method to prepare micron or nano-sized lysozyme particles, with minimal loss of biological activity, for the pulmonary delivery of protein drug.