초임계 이산화탄소를 이용한 약용식물 성분의 선택적 추출

최영해,박은정,김영림,진영원,전성호,정승남,유기풍,김진웅,Choi, Young-Hae,Park, Eun-Jung,Kim, Young-Leem,Chin, Young-Won,Jeon, Seong-Ho,Joung, Seung-Nam,Yoo, Ki-Pung,Kim, Jin-Woong 한국생약학회 1999 생약학회지 Vol.30 No.1

Supercritical fluid extraction (SFE) technique was applied to extract cytotoxic substances from five medicinal plants including Angelica gigas, Angelica acutiloba, Aralia cordata, Spirodela polyrhiza, Bupleurum falcatum, and Acanthopanax sessiliflorus. The cytotoxicities against P388, A549, and HL-60 cell lines were determined for the supercritical carbon dioxide extracts of five plant materials employed and were compared with those of the conventional organic solvent extracts such as n-hexane, $CHCl_{3}$, and MeOH to evaluate the SFE as an alternative method to conventional organic solvent extraction. In most cases, the SFE extracts of plant materials showed enhanced cytotoxicities when compared with those of other organic solvent extracts. In addition, the optimum temperature and pressure of SFE for extraction of the cytotoxic substances were largely affected by both the plant species and the cell lines tested. These results suggested that SFE could be an alternative to the conventional organic solvent method for the selective extraction of cytotoxic compounds from plants.

급성 골수성 백혈병에서 busulfan, thiotepa, 그리고 melphalan 3제 알킬화제제 전처치를 이용한 동종 골수이식

박수정(Soo Jeong Park),민우성(Woo Sung Min),김희제(Hee Je Kim),박은정(Eun Joung Park),엄기성(Ki Seong Eum),엄현석(Hyeon Seok Eum),민창기(Chang Ki Min),김동욱(Dong Wook Kim),이종욱(Jong Wook Lee),진종률(Jong Yul Jin),한치화(Chi Wha Ha 대한내과학회 2001 대한내과학회지 Vol.60 No.2

N/A Background : The purpose of this study was to evaluate the toxicity and efficacy of high-dose chemotherapy with busulfan, thiotepa and melphalan (BTM) as a myeloablative regimen in allogeneic bone marrow transplantation (allo-BMT) for patients with acute myelogenous leukemia (AML). Methods : Twenty-seven patients with AML were enrolled; Sixteen patients had standard risk (SR) diseases (first complete remission (CR1) and de novo AML) and eleven patients had high risk (HR) diseases (second, or subsequent remission, secondary AML, relapsed, or refractory AML, CR marrow with persisting extramedullary manifestation (chloroma), or hypoplastic acute leukemia). The conditioning regimen included busulfan 4 mg/kg/day for a total dose of 12 mg/kg; thiotepa 250 mg/m2/day for a total dose of 500 mg/m2; and melphalan 50 mg/m2/day for a total dose of 100 mg/m2. Cyclosporine A and short-course methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. Results : The median time to recovery a granulocyte count of 0.5 x 109/L was 14 days (range 10∼25 days) and platelet transfusion independence was 30 days (range 12∼49 days). The major regimen-related toxicities were gastrointestinal-related symptoms including oral mucositis, nausea, vomiting, and diarrhea. All patients experienced oral mucositis (≥ grade 1) and the patients with oral mucositis of equal and greater than grade 3 were 44% in SR and 45% in HR. The toxicities associated with lung, skin, heart and brain were minimal. Three (11%) patients had severe or fatal veno-occlusive disease (VOD). There were five treatment-related death (19%) (hepatic VOD with multiorgan failure (n=3), pneumonia and ARDS (n=2)) within the first 100 days after allo-BMT. There was not a significant difference between SR and HR group (p=0.167). The incidence of acute GVHD equal or greater than grade II was less than 10%. The actual survival at 2 year was 70.4%(95% confidence interval (CI), 54.7%∼86.1%)(SR; 81.3% (95% CI; 63.4∼99.1%) vs HR; 54.6% (95% CI; 28.7∼80.4%), p=0.154). After a median follow-up of 630 days, 18 of 27 (67%, 355∼1062 days) patients are alive without evidence of disease. Three of the 27 patients relapsed (SR; 0% vs HR; 55.6% (95% CI; 19.6∼71.3%), p=0.004). Conclusion : The BTM regimen followed by allo-BMT is associated with acceptable toxicity and appears to have significant activity in patients with AML. It should be used with caution in patients with prior hepatopathy or refractory state who have an increased risk of severe VOD. Busulfan, thiotepa, and melphalan is an effective and alternative myeloablative regimen for patients with AML.(Korean J Med 60:156-166, 2001)

여성가장가계의 재무구조 및 사회적 지원방안 - 편모가계 연구를 중심으로 -

김나연(Kim Na Youn),박은정(Park Eun-joung) 한국지역사회생활과학회 2003 한국지역사회생활과학회지 Vol.14 No.1

강원도내 일부 초,중,고등학교의 금연에 대한 건강증진정책의 조사연구

김춘배 ( Chun Bae Kim ),박준호 ( Jun Ho Park ),안정숙 ( Joung Sook Ahn ),허혜경 ( Hea Kung Hur ),박은정 ( Eun Jung Park ),전은표 ( Eun Po Jeon ),지역보건연구회 ( Community Health Service Research Group ) 한국보건행정학회 2003 보건행정학회지 Vol.13 No.3

The purpose of this study was to investigate the current status of health promotion policies about antismoking, and the relationship between policy status, enforcement of smoking restrictions and perceptions of smoking behaviour among teachers. A representative sample of 173 teachers·school inspectors from 150 elementary·middle·high schools in Gangwon-do was surveyed during Gangwon-do Office of Education`s antismoking and temperance training course in 2002 (response rate 60.7%). One staff member from each school was also analyzed regarding school antismoking polices for students and teachers in several locations within and outside the school building. The results showed that 118 elementary·middle·high schools (78.7%) had an antismoking policy and more schools had a written policy on student antismoking than on teacher antismoking. Most schools (92.4%) in the sample banned smoking by students, but 52 schools (44.1%) allowed smoking by teachers in restricted areas. However, teachers reported seeing smoking sometimes in the toilets (42.7%) or the playground (40.0%) among students and sometimes in the staff room (31.3%) or about every day on school premises (52.7%) among teachers. Irrespective of the type of policy or restrictions on smoking, the association between having a ban on student/teacher smoking and teachers` perceptions of student/teacher smoking in school was not significant. In conclusion, we suggest that most schools must have explicitly an antismoking policy on both students & teachers and enforce consistently a ban in promoting a healthy school environment (smoke-free schools).

일본어의 기점표현과 우리말의 착점표현

박은정 한국일어일문학회 1999 日語日文學硏究 Vol.34 No.1

本稿は, 移動動詞構文における日本語と韓國語の表現の相違についてである. 調査の結果, 移動動詞構文では韓國語に着點表現が多いのに比べて日本語には起點表現が多くみられた. 日本語の起點表現は韓國語では「로」格を用いた起點表現, または經路表現となる場合がある. そして, 韓國語では場所表現が省略されないのであるが, 日本語では省略されることが多かった. 場所の省略は, 移動動詞の動きをより鮮明にするためである. 日本語は, 韓國語に比べて起點表現を好む傾向にあると言える. これにより韓國語が日本語の起點表現に比べて相對的に着點表現を好む傾向にあることが증明されたと言える. 日本語の起點表現は, 池上(1980)も言ったように起點表現の不安定性が斷定的でない言い方になり, これが-つの丁寧な表現として好まれるのではないかと思われる. これに比べて, 韓國語は不安定な表現である起點表現よりは着點表規を好んでいる. 日本語の「から」格が用いられる起點表現と韓國語の着點表現の對應は, 日本語においてなぜ起點表現が好まれる傾向にあるのかについての答を導き出すものであった. 次の二つの理由にその答えが求められる. それは起點表現の斷定的でないことからくる日本語らしい丁寧さと, 助詞「で」でなく「から」格を用いて移動の動きを表わした動的な起點表現が可能であるというものである. 一方, 韓國語は日本語の起點表現に對應して着點, あるいは「에서」格を用いている. 着點表現は起點表現より安定性のある表現であるので, 明確に意思を傳達することができる. そして, この「에서」格を用いて場所內での移動行爲を表わすことにより, 韓國語が場所を重視していることが증明されたと言える.

고위험군의 원발성 전신성 유전분증 1례 보고 및 조혈모세포이식에 대한 문헌고찰

심준,박수정,엄현석,김기영,박은정,강인중,조병식,이안희,한치화 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.2

저자 등은 클론성 형질세포질환과 동반된 젊은 연령의 원발성 전신성 유전분증 환자를 진단하였기에 다발성 골수종과의 감별 진단, 치료 , 예후 및 고용량 항암화학요법과 조혈모세포이식에 관하여 문헌고찰과 함께 보고하는 바이다. Primary systemic amyloidosis (AL) is a rapidly fatal disorder related to plasma cell dyscrasia. Conventional dose of melphalan, which prolongs the duration of survival by about 10 months, does not improve the functions of impaired organs in most cases. The high dose chemotherapy followed by autologous hematopoietic stem cell rescue for AL, in spite of its high treatment-related mortality, is a new approach to achieve high response rate and better survival. We experienced a 35-year old man with AL(involving heart, liver, stomach, kidneys, peripheral nerve, and rectum) who did not respond to the standard schedule of melphalan plus prednisone and had rapidly fatal course with organ failure. Hence, we evaluate its availability by reviewing the recent reports of high dose chemotherapy in AL.

성인 급성 림프구성백혈병 고위험군에서 일차관해시 동종 및 자가 조혈모세포이식의 성적 비교 : 단일기관 치료경험 A Single Center Experience

이석,민우성,민창기,김동욱,이종욱,김유진,박은정,박윤희,김춘추 대한조혈모세포이식학회 2000 대한조혈모세포이식학회지 Vol.5 No.2

배경:성인 ALL에서 동종 조혈모세포이식은 전처치요법 및 이식편대백혈병 효과에 의한 효과적인 백혈병세포의 제거가 가능하다는 측면에서 활발히 시행되고 있으나 자가 조혈모세포이식과 화학요법과의 비교 연구에서는 대상환자의 다양성 등으로 인하여 상이한 결과가 보고되었다. 그러나 최근 진단당시 환자의 임상적·세포생물학적 특성 및 관해유도요법 후의 백혈병세포의 제거 속도 등을 기준으로 한 위험인자가 정의되면서 이를 근간으로 위험도에 따른 관해 후 치료방침의 결정이 타당성 있는 접근방법으로 제시되고 있고, 특히 고위험군에서의 동종 조혈모세포이식의 역할이 강조되고 있다. 방법: 성인 ALL 고위험군에서 일차 완전관해시 동종 조혈모세포이식의 역할을 규명하기 위해 최근 5년간 가톨릭의대 조혈모세포이식센터에서 ALL로 진단 후 일차 완전관해 상태에서 동종 및 자가 조혈모세포이식을 시행받고 임상적 특성과 세포면역학적 특성 및 세포유전학적 검사결과가 모두 확인 가능하였던 환자 중 고위험군에 해당된 50례를 대상으로 후향적 분석을 시행하였다. 고위험군은 진단시 연령이 30세 이상인 경우, 백혈구수가 30,000/μL 이상인 경우, 관해유도기간이 30일 이상 소요된 경우, Ph 혹은 t(4;11)이 동반된 경우 중 하나 이상의 인자를 갖고 있는 경우로 정의하였다. 결과: 대상환자의 중앙연령은 30세(15~43세)이었고, 남녀 비는 27:23이었다. FAB 분류상 L1 29례(58.0%), L2 21례(42.0%)였으며, precursor B-lineage 항원이 양성인 경우는 36례(72.0%), T-세포 항원이 양성인 경우는 9례(18.0%), 골수구계 항원이 동시에 발현된 경우는 5례(10.0%)였다. 세포유전학적 검사상 23례(46.0%)에서 불량한 염색체유형 [Ph 19례, t(4;11) 4례]이 동반되었다. 전체 환자 중 31례에서 동종 조혈모세포이식을 시행하였으며, 19례에서는 자가 조혈모세포이식이 시행되었다. 동종 및 자가 조혈모세포이식 환자군간의 임상적 특성은 양군간의 유의한 차이가 없었다. 대상환자의 중앙 추적관찰기간은 27개월(7~72개월)이었고, 전체 환자의 2년 무병생존율 및 전체생존율은 각각 59.0±7.6%, 68.2±7.1%이었다. 조혈모세포이식에 따른 치료성적을 비교한 결과 전체생존율은 동종 조혈모세포이식군 71.4±8.6%, 자가 조혈모세포이식군 62.7±12.4%로 양군간의 유의한 차이가 없었던 반면, 재발율은 동종 조혈모세포이식군에서 유의하게 낮은 빈도를 보였으며(25.8% vs 52.6%, P=0.05), 무병생존율에 있어서도 각각 70.6±9.0%, 42.1±12.2%로 동종 조혈모세포이식군에서 보다 높은 경향을 보였다(P=0.07). 이식 후 생존율에 영향을 주는 위험인자를 분석한 결과, 진단시 연령, 백혈구수, 관해유도기간에 따른 차이는 관찰되지 않았다. 다만 Ph 혹은 t(4;11)이 동반된 경우에서 무병생존율이 동종(28.5±16.0% vs 94.4±5.4%, P=0.0002) 및 자가 조혈모세포이식군(18.1±11.6% vs 80.0±17.8%, P=0.0046) 모두에서 유의하게 감소되었다. 결론: 본 연구를 통하여 일차관해시 조혈모세포이식을 시행받은 고위험군 성인 ALL에서는 관해 후 치료법으로써 동종 조혈모세포이식이 우선적으로 고려될 수 있는 치료법임을 확인할 수 있었다. 이는 추후 국내에서도 보다 장기간의 추적관찰을 통한 전향적 임상연구를 시행하여 보다 정립된 관해 후 치료방침의 결정 필요성을 제시하였다는 측면에서 임상적 의의가 있을 것으로 사료된다. Background:Optimal postremission therapy remains controversial in adult patients with acute lymphoblastic leukemia (ALL). In this study, we compared allogeneic bone marrow transplantation (alloBMT) with autologous peripheral blood stem cell transplantation (autoPBSCT) using the result of the human leukocyte antigen typing (HLA). Methods:Patients were eligible if they were in first remission (CR1) and had either: adverse cytogenetics [Philadelphia chromosome (Ph), t(4;11)], age >30 years, required more than 1 induction course to achieve remission (time-to-CR1 >30 days) or presenting WBC >30,000/μL. From July 1994 to June 1999, 50 consecutive adult patients with high-risk ALL underwent HLA-matched alloBMT (n=31) or autoPBSCT (n=19) at the Catholic Hemopoietic Stem Cell Transplantation Center. Results:There were 27 males and 23 females with median age 30 (range, 15~43) years. The distribution of phenotype was as follows: L1 (n=29), L2 (n=21), precursor B (n=36), T (n=9), myeloid marker coexpression (n=5). Adverse cytogenetic abnormalities at diagnosis were shown in 23 (46.0%) cases. All pretransplant characteristics were well balanced between these two groups. Most patients were treated with total body irradiation containing regimen as part of the conditioning. With a median follow-up of 27 months in both groups, disease-free survival (DFS) and overall survival probabilities at 2 years were 59.0±7.6% and 68.2±7.1%, respectively. The relapse rates were significantly different between alloBMT and autoPBSCT groups (25.8% vs 52.6%, P=0.05). There was no significant difference in overall survival between the two groups. However, alloBMT had a trend toward better DFS (70.6±9.0% vs 42.1±12.2%, P=0.07). None of the pretransplant characteristics significantly affected outcome after transplantation, except adverse cytogenetics. Prognosis of ALL with Ph or t(4;11) was significantly poorer than that of the remaining high-risk ALL patients (P<0.01). Conclusion: We conclude that alloBMT appears to be more effective than autoPBSCT in prolonging initial CR for high-risk ALL patients. Prospective studies addressing additional clinical variables are needed to guide clinical decision making about transplant choices for adult patients with ALL. New therapeutic strategies for the management of ALL with adverse cytogenetics will be also required.

Fludarabine을 근간으로 한 저용량 전처치 동종 조혈모세포 이식

박수정,민우성,김희제,박은정,엄기성,민창기,이석,김동욱,이종욱,김춘추 대한조혈모세포이식학회 2000 대한조혈모세포이식학회지 Vol.5 No.1

배경:동종 골수이식은 혈액학적 악성 질환들에서 완치를 위한 치료법이지만 이식관련 사망률이 높은 제한점이 있다. 부분골수제거 조혈모세포 이식은 전처치에 의한 동종골수 이식의 문제점인 이식관련 사망률을 낮추고 이식편대 백혈병 효과를 증대시킬 목적으로 전처치의 강도를 낮추고 면역억제를 증대시킨 새로운 개념의 이식법으로 최근 관심을 끌고 있다. 본 센터에서는 전골수제거 동종 골수이식이 불가능한 고령 및 장기부전을 동반한 환자들을 대상으로 부분골수제거 조혈모세포 이식을 시행하여 이식편의 생착, 이식관련 독성, 이식편대 숙주병의 발생정도, 그리고 이식편대 백혈병 효과 등을 알아보고자 하였다. 방법:가톨릭 조혈모세포 이식센터에서 추적 관찰하였던 환자들 중 주장기 부전이 동반된 만성 골수성 백혈병 환자 3명, 급성 림프구성 백혈병 환자 3명, 그리고 급성 골수성 백혈병 환자 1명을 대상으로 하였다. 환자들은 모두 주장기 기능부전이 있었으며 2명은 환자의 나이가 50세 이상 이었다. 전처치는 fludarabine을 근간으로 busulfan/ATG (4명), G-CSF 가동화 fludarabine/cytarabine (2명), fludarabine/melphalan (1명) 조합 중 선택하여 사용하였다. 조혈모세포원은 G-CSF로 가동화한 말초혈액 조혈모세포를 이용하였으며 면역억제는 표준 cyclosporine과 methotrexate를 사용하였으나 조기 감량 및 중단계획에 따라 이식 90일에 대부분 중단하였다. 이식 후 키메리즘 추적은 RFLP 방법을 사용하였고 이식편대 숙주병이 발생하지 않거나 잔류 질환이 증가하는 증거가 있는 경우는 공여자 림프구 수혈을 계획에 따라 시행하였다. 결과:생착은 모든 환자에서 이식 21일 이내에 되었으며 이식관련 독성은 미미하였다. 호중구 수가 0.5×10^(9)/L 이상 회복되는 데 걸린 기간의 중간값은 12일(10~18일) 이었으며 혈소판 수혈없이 혈소판이 20×10^(9)/L 유지하는 데 걸린 기간의 중간값은 16일(14~19일) 이었다. 추적기간 중간값은 232일(216~356일) 이었다. 3명은 무병 생존 중이며 4명은 각각 재발, 급성 이식편대 숙주병, 공여자 림프구 수혈 후 발생한 이식편대 숙주병, 그리고 기저 간질환의 악화로 사망하였다. 결론:부분 골수제거 조혈모세포 이식은 전골수제거 동종 골수이식이 어려운 고령, 혹은 주장기 부전 환자들에서 비교적 안전하고 효과적인 방법이다. 향후 보다 많은 환자들을 대상으로 장기간 추적 관찰을 통하여 이 치료에 반응 할 수 있는 적응증 및 이식 후 완치를 위한 추가적인 치료계획의 확립이 필요할 것으로 사료된다. Background:Allogeneic stem cell transplantation (allo-SCT) is the only curative approach but it is associated with a high incidence of transplant-related mortality (TRM). Non-myeloablative stem cell transplantation, so called mini-transplantation is a novel approach with reducing conditioning related TRM and enhancing graft-versus-leukemia (GVL) effect in these patients. We have introduced the use of non-myeloablative conditioning in patients with elderly, organ dysfunction, or combining advanced disease status. Methods:Seven patients were enrolled in this study. Three patients had CML (aged man combining organ dysfunction, 1 chronic phase, 2 blastic crisis), 3 patients had ALL (organ dysfunction with CR1), and 1 patients had AML (aged man, relapse after autoPBSCT). The median age was 38 years (range, 32 to 54 years). Coexisting medical problems before SCT were cardiac failure (n=3), CVA (n=2), and chronic liver disease (n=2). Two patients had two more than medical problems. Four patients received fludarabine with busulfan and ATG, one patient received fludarabine with melphalan, and two patients received G-CSF primed fludarabine with cytarabine. After non-myeloablative conditioning, G-CSF mobilized peripheral blood stem cell was infused. GVHD prophylaxis consisted of standard cyclosporine and short term methotrexate. Patients without GVHD on day 45 had their cyclosporine tapered by 25% weekly and discontinued on day 90. Chimerism and evidence of minimal residual disease were determined by conventional cytogenetics and restriction fragment length polymorphisms (RFLPs). Results:All patients achieved an engraftment within day 21. Non-myeloablative conditioning regimens were extremely well tolerated without regimen-related toxicities. The duration of neutropenia <500/ul ranged between 10 and 18 days (median, 12 days), and the duration to achieve self-sustaining platelet counts > 20,000/ul between 14 and 19 days (median, 16 days). Median follow-up is 232 days (216 to 356 days). Four patients (3 without GVHD, 1 with early relapse) received DLI (donor lymphocyte infusion). Three patients alive without relapse. Four patients died: 1 relapse and intracranial hemorrhage, 1 acute GVHD, 1 post-DLI GVHD, 1 underlying hepatitis flare up. Conclusion: These preliminary data shows that non-myeloablative regimens were tolerable and could be used in patients who are not candidate for conventional allo-SCT especially, due to major organ dysfunction and old age. Many patients with more long-term follow-up period should be needed to document the incidence of GVHD and GVL effect.

급성 신부전과 심한 단백뇨가 동반된 급성 다발성 세균성 신염 1예

정은선,김영옥,박은정,윤선애,박준일,김세희,방병기,양철우 대한내과학회 1999 대한내과학회지 Vol.57 No.3

Acute multifocal bacterial nephritis is a severe form of acute renal infection in which heavy leucocytic infiltrates occurs throughout kidney. Therefore, in contrast to uncomplicated acute pyelonephritis, it frequently causes acute renal failure. We here report an unusual case of acute multifocal bacterial nephritis which caused acute real failure and massive proteinuria. A 44-year old man was referred to our hospital because of high fever and both flank pain and non-oliguric acute renal failure. He had pyuria and massive proteinuria(5.87g/day), and serum creatinine level of 3.6mg/dL. We initially suspected hemorrhagic fever with renal syndrome. But immunofluorescent antibody for Hantavirus was negative and E. coli was isolated at urine. Computed tomography showed multifocal areas of wedge-shaped low densities in both kidneys. Kidney biopsy revealed tubulointerstitial infiltration of leucocyte without glomerular change. After treatment of antibiotics, proteinuria completely disappeared and serum creatinine level decreased to 1.0mg/dL. (Korean J Med 57:375-379, 1999)

사혈치료 중 다발성 비장경색을 동반한 진성다혈증 1 례

김현숙,김재영,한지연,박은정,이경식,조돈현 대한내과학회 1998 대한내과학회지 Vol.55 No.6

Polycythemia vera(PV) is a chronic myeloproliferative disease characterized by an increase in the total mass of red cells. Leukocyte and platelet counts are often elevated as well. The most common complication is thrombosis, which usually involves brain, heart, gastrointestinal tract, and kidneys, but rarely involves spleen. The cornerstone of therapy for this disease is phlebotomy and it is associated with an increased risk of thrombosis, especially for patients older than 70 years, those with a history of thrombosis, and those requiring an increased frequency of phlebotomy. Concurrent treatment with myelosuppressive agents decreases the risk of thrombotic complications. Recently we experienced a case of multiple splenic infarction in PV treated phlebotomy alone in a 42-year old woman who had complained of massive splenomegaly, left upper quadrant abdominal pain and fever. CT scan of abdomen showed multiple hypodense areas suggesting splenic infarction. She was managed with hydroxyurea and salicylate instead of phlebotomy and showed a clinical improvement with lowering the platelet count and reducing splenomegaly. PV with a massive splenomegaly is prone to thrombosis and phlebotomy in such patients may contribute to the thrombotic complications by increasing platelet counts. When it is necessary to lower the platelet count or reduce splenomegaly, hydroxyurea may be more useful than phlebotomy.