겸상적혈구 혈증에 의한 동통성 발작 1례

김효철,배택환,정윤석,김현수,조준필,김준식,곽연식 대한응급의학회 1995 대한응급의학회지 Vol.6 No.1

The sickle cell disease are a group of hemoglobin disorders characterized by red cells that undergo sickle shape transformation when they are deoxygenated. Sickle cell disease is transmit-ted as an autosomal recessive trait. This unusual property, due to the polymerization of sickle hemoglobin results in anemia and vasoocclusive complication. 1) The most clinically significant of these disease are sickle cell anemia, sickle cell hemoglobin C disease, and sickle cell beta thalassemia. Symptoms of pallor, fever, abdominal and joint pain, enlargement of the liver and spleen, swelling of hands and feet first appear near the latter part of the first year of life. Intravascular sickling affects all organs. For clinical and therapeutic purposes, exacerbations may be classified as vasoocclusive or pain, aplastic, hemolytic or sequestration crisis. we experienced a 22 year old female patient who suffered severe multiple joint pain and back pain thought to be caused by vasoocclussive phenomena.

유방암 환자의 말초혈액에서 역전사효소연쇄중합반응을 이용한 Human Mammaglobin 측정의 임상적 유용성

김재홍,강석윤,송정엽,최태영,임홍석,김선경,김영진,박준성,김현수,최진혁,임호영,김효철 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.2

Background: The mammaglobin gene encodes a novel protein that is secreted from the mammalian epithelium of normal breast tissue as well as malignant breast cancer tissues. In order to ascertain the prognostic value of mammaglobin gene in breast cancer patients, we measured the expression of human mammaglobin (hMAM) by RT-PCR method in various stages of breast cancer patients. Methods: Peripheral blood samples from forty healthy volunteers and 114 breast cancer patients were obtained. Peripheral blood stem cells (PBSC) collected for the purpose of autologous stem cell transplantation in five patients with metastatic breast cancer and ten patient with high risk for relapse and no evidence of disease were used for hMAM assay. Results: All samples from peripheral blood of forty healthy individuals (twenty males and twenty females) were negative for hMAM, whereas 43 of 114 samples (38%) from breast cancer patients were positive for hMAM mRNA. All the normal breast tissues were positive for hMAM mRNA. hMAM mRNA expression was detected in 11 of 42 (26%) in breast cancer patients who underwent for curative resection and had no evidence of disease, in 8 of 25 (34%) with chemo-sensitive relapsed disease, and in 16 of 32 (53%) with chemo-refractory progressive disease. Eight (53%) samples from peripheral blood of 15 breast cancer patients with metastatic disease at diagnosis were positive for hMAM. Three (20%) samples from peripheral blood stem cells of 15 breast cancer patients for high dose chemotherapy were positive for hMAM. Conclusion : In contrast to healthy volunteers, hMAM transcripts were detected in the peripheral blood of breast cancer patients. The frequency of hMAM expression in peripheral blood was correlated with the clinical stages of disease, but, was not significant. The contamination of hMAM expressing cells in the stem cell pool warrants additional effective purging method before the transplantation. The clinical relevance of hMAM RT-PCR-based tumor cell detection in the peripheral blood of breast cancer patients should be further evaluated in prospective studies.

일차적 항암화학요법으로 치료한 복강내 정류고환에서 발생한 거대 정상피종 1례

김성룡,안현수,김세중,김효철,김장희,주희재,이은주 大韓泌尿器科學會 2001 Korean Journal of Urology Vol.42 No.5

Phase II trial of rituximab plus CVP combination chemotherapy for advanced stage marginal zone lymphoma as a first-line therapy: Consortium for Improving Survival of Lymphoma (CISL) study

Kang, Hye Jin,Kim, Won Seog,Kim, Seok Jin,Lee, Je-Jung,Yang, Deok-Hwan,Kim, Jin Seok,Lee, Se-Ryeon,Lee, Gyeong-Won,Kim, Hyo Jung,Kim, Ho Young,Oh, Sung Yong,Kim, Hugh Chul,Eom, Hyeon-Seok,Chung, Joose Springer-Verlag 2012 Annals of hematology Vol.91 No.4

동종조혈모세포 및 배양확장된 간엽모세포 동시이식의 가능성

강석윤,김재홍,박준성,김현수,최진혁,임호영,박상진,양말숙,김영진,김효철 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.2

배경: 사람의 골수내에 두가지 종류의 모세포가 밝혀져 있고 혈액질환에서 간엽모세포 (mesenchymal stem cell)의 역할에 대한 연구가 활발해지고 있다. 이런 간엽모세포들은 조혈기능에 관여하는 싸이토카인을 분비하고, 이식시 조혈모세포들의 생착 및 기능적 분화에 많은 영향을 미치는 것으로 알려져 있으며, 세포의 형태적 변화나 기능의 소실없이 실험실에서 분리하고 배양확장 시킬 수 있는 기술들의 발달로 최근에는 이를 치료에 이용하는 연구들이 확대되고 있다. 현재까지 많은 연구에 있어 조혈모세포의 경우는 이식 후 공여자의 형태로 전환되지만 간엽모세포의 경우에 있어서는 지속적으로 환자의 형태로 남아있음을 보고하고 있다. 본 저자들은 다양한 혈액질환의 치료에 있어 현재까지 사용되고 있는 일반적인 동종조혈모세포 이식술 뿐만 아니라 조혈모세포와 간엽모세포를 동시에 이식하여 이식 후 생착에 도움을 주고 키메리즘에 변화가 있는지를 알아보고자 12명의 환자를 대상으로 연구를 진행하였다. 방법: 12명의 환자에서 9명은 혈연공여자로 부터 동종 조혈모세포이식술을 시행받았고 3명에 있어서는 조혈모세포와 간엽모세포를 동시에 이식하였다. 이식 전 환자 및 공여자의 말초혈액 또는 골수세포로 부터 얻어진 백혈구를 이용하여 키메리즘을 확인하였고 이식 후 3주부터 10개월이 지난 후 공여자의 형태로 전환되었는지를 확인하기 위해 환자의 골수를 채취하여 간엽모세포를 배양하였고 성일치 이식시에는 DNA microsatellite 다형성검사를 성불일치 이식시에는 Y-염샘체를 이용하여 키메리즘의 변화를 확인하였다. 결과: 동종 조혈모세포이식을 받은 환자 9명에 있어서는 이식 후 9일부터 19일까지에 걸쳐 생착 (평균 13.11일)이 되었고 이식 후 3주째부터 10개월째에 걸쳐 시행한 키메리즘 검사상 모든 환자에서 골수는 공여자의 형태로 전환됨이 확인되었으나 배양된 간엽모세포는 지속적으로 환자의 형태로 남아있었다. 동종 조혈모세포와 배양확장된 간엽모세포의 동시이식이 시행된 3명의 환자에서는 평균 10일째 생착이 되었고 이식 후 3주와 4주째 시행한 키메리즘검사에서 골수내 조혈모세포는 모두 공여자의 형태로 바뀌었지만 간엽모세포는 지속적으로 환자의 형태로 확인되었다. 결론: 현재의 이식방법으로는 동종 간엽모세포의 이식이 어렵고 동시이식의 효과도 불명확하므로 향후 기질세포의 생착을 위한 주입양과 주입방법, 환자자신의 골수내 환경을 마련하기 위한 전처치의 방법 등에 대한 연구가 지속되어야 할 것이며 또한 이를 조기에 발견할 수 있는 실험적도구의 개발에 노력해야 할 것으로 사료된다. Background: Human bone marrow contains two kinds of stem cells, hematopoietic stem cells (HSCs) which can differentiate into mature blood cells and multipotential mesenchymal stem cells (MSCs) which are capable of differentiating into a number of mesenchymal cell lineages. We developed an efficient method of isolation and ex vivo expansion of a homogenous population of MSCs from human bone marrow. These MSCs are shown to secrete hematopoietic cytokines and support hematopoietic progenitors ex vivo. Therefore, enrichment of donor MSC in the graft may be useful in the treatment of many hematologic disorders. Methods: To determine if donor derived MSCs can be engrafted in the recipients with hematologic disorders by allogeneic HSC transplantation (CD34+:2.0-16.0×10^(6)/kg) or cotransplantation of both HSC (CD34+:1.98-12.53×10^(6)/kg) and enriched MSC (1.44-13.79×10^(5)/kg) of donor origin, we investigated MSCs after conventional allogeneic HSC transplantation in 9 patients and in 3 patients with cotransplantation of both enriched MSC and HSC at 1 to 10 months after transplantation. Marrow derived MSCs before and after transplantation were genotyped either by polymerase chain reaction using Y chromosome in gender-mismatched or by microsatellite DNA polymorphism in gender-matched transplantation. Results: We found that MSCs isolated from recipients after allogeneic HSC transplantation or cotransplantation remained as the recipient types in all patients, not of donor genotype, despite successful engraftment by donor type hematopoietic cell. Conclusions: These findings indicate that with current allogeneic HSC transplantation or cotransplantation procedures, the stromal compartment of hematopoiesis is not transplantable in humans. Therefore, the reasons for difficulty of engraftment with donor MSCs needs to be further elucidated.

선택적으로 분리된 CD34 양성 자가 조혈모세포이식 후 면역기능의 회복

이은희,김도현,정재학,박준성,김현수,홍대식,박성규,김형준,홍영선,김춘추,김효철,김원석,박찬형 대한조혈모세포이식학회 2002 대한조혈모세포이식학회지 Vol.7 No.2

연구배경: 자가말초혈액 조혈모세포이식에 있어 CD34 양성세포의 선택적 분리로 인해 1~4 logs 정도의 종양세포의 감소를 가져오며, 또한 CD34 양성세포 이식 후의 면역기능의 회복은 선택적으로 분리되지 않은 자가 조혈모세포이식 시와 거의 비슷하다는 것이 보고되어 왔다. 이에 저자들은 선택적으로 분리된 자가 CD34 양성 조혈모세포이식 후의 면역기능의 회복 양상을 알아보기 위해 다기관 연구를 시행하였다. 방법: 15명의 악성 림프종, 유방암, 다발성 골수종 환자들을 대상으로 고용량 항암요법 후 선택적으로 분리된 CD34 양성 자가말초혈액 조혈모세포이식을 시행하였다. 이식 후 1, 2, 4, 6개월에 림프구 표현형 측정과 PHA mitogen induced T세포 증식정도를 측정하였다. 결과: 이식 후 6개월 추적 관찰 시 CD3 양성, CD4 양성 림프구의 수는 정상보다 낮았고, CD8 양성세포는 정상 수준을 보였다. 초기 CD4/CD8 비는 감소되었지만 6개월 후 정상으로 회복되는 경향을 보였으며, CD19 양성, CD56 양성세포수는 정상 수준을 나타냈다. PHA mitogen response는 12개월 추적 관찰 시까지 지속적으로 증가 추세를 보였다. 결론: 선택적으로 분리된 CD34 양성 자가말초혈액 조혈모세포이식은 빠르고 지속적인 혈액학적 생착을 유도하는 것을 알 수 있으며, 이는 기존의 연구에서 선택되지 않은 자가 조혈모세포이식 시와 비교하여 면역기능의 회복에는 유의한 차이가 없다는 보고와 일치하는 결과이다. 그러므로 선택적으로 분리된 CD34 양성 자가말초혈액 조혈모세포이식을 통해 상당한 T 세포의 감소에도 불구하고 면역기능의 회복에 지연 없이 종양세포의 오염을 줄이는 것이 가능함을 확인하였다. Background: Positive selection of autologous peripheral blood stem cells (PBSC) for CD34-expressing cells permits 1 to 4 logs of tumor cell depletion. Hematologic recovery after CD34+ cell transplatation has been reported to be rapid and similar to results achieved in unselected autologous peripheral blood stem cell transplantation (APBSCT). We performed a multi-center study to evaluate the immune reconstitution after CD34+ immunoselected APBSCT. Methods: Fifteen patients with lymphoma, breast cancer, or multiple myeloma received high dose myeloablative chemotherapy followed by an infusion of CD34+ immunoselected PBSC. On 1, 2, 4, and 6 months after transplantation, lymphocyte phenotype was evaluated by flow cytometry and mitogen-induced T cell proliferation were measured. Results: At 6 months after transplantation, CD3+ lymphocyte subset remained below the normal range. CD4+ lymphocytes were depressed while CD8+ lymphocyte subset was in normal range. As a result, inversion of CD4/CD8 ratio was documented for first 4 months, but after 6 months follow up CD4/CD8 ratio was recovered. CD19+ B lymphocyte subset and CD56+ lymphocytes after CD34+ APBSCT were within the normal range. The PHA mitogen induced response was increased during 12 months' follow-up consistently. Phenotypic and functional reconstitution of immune cells after CD34+ cell transplantation were rapid and similar to previous studies. Conclusion: Transplantation of CD34+ immunoselected PBSC allows rapid and sustained hematologic engraftment, and there was no marked delay of immune reconstitution. The selection of CD34+ cells, although causes an extensive depletion of T lymphocytes in the graft does not represent a delayed immune recovery after transplantation.

아급성형 Gaucher 씨 병

김현수(Hyun Soo Kim),신석균(Sug Kyun Shin),한시훈(Si Houn Hahn),김현주(Hyon Ju Kim),김효철(Hugh Chul Kim) 대한내과학회 1996 대한내과학회지 Vol.50 No.2

Gaucher's disease is an inherited metabolic disorder characterized by enzyme defect, cerebroside β-glucosidase and accumulation of glucocerebroside in reticuloendothelial system. There are three subtypes of Gaucher's disease. Type 1(non-neuronopathic) is the chronic form occurring rather frequently and shows hepatosplenomegaly, pancytopenia and bone lesion. Type 2(acute neuronopathic) is uniform in se- verity and progression, showing acute neurologic deterioration and early death. Type 3(subacute neuronopathic) is less rapidly progressive than type 1 disease, but is also a neurovisceral storage disorder. The diagnosis is confirmed by assay of glucocerebrosidase in white cells or fibroblasts. With enzyme assay, however, carrier and subtype determination is unreliable. But it is possible that studies of the gene for glucocerebrosidase and its mutation may lead to more definitive determination. The treatment is divided into two modalities, the first is symptomatic management with splenectomy, the second is enzyme replacement, allogeneic bone marrow transplantation and somatic cell gene transfer. The second modalities are currently experimental. Recently, two sisters of subacute neuronopathic Gaucher's disease who presented with pancytopenia, hepatosplenomegaly and seizure disorder, were diagnosed as type III Gaucher's disease and confirmed by the enzyme assay. Here we reported these cases with literature review.

아급성형 Gaucher 씨 병에서의 동종골수이식과 유세포 분석기를 이용한 Glucocerebrosidase 활성화 추적 1 예

김덕기(Deog Ki Kim),김현수(Hyun Soo Kim),유상용(Sang Yong Yoo),정철권(Cheol Kweon Jeong),박준성(Joon Seong Park),하만준(Mahn Joon Ha),김현주(Hyon Ju Kim),김효철(Hugh Chul Kim) 대한내과학회 2001 대한내과학회지 Vol.61 No.2

Gaucher's disease (GD) is the most common inherited lysosomal storage disease, manifested by generalized accumulation of glucocerebroside in macrophages of the reticuloendothelial system due to a deficient lysosomal β-glucocerebrosidase (GC). It is inherited by an autosomal recessive pattern in which three clinical phenotypes have been described based on the presence and severity of neurologic involvement. GD is treated possible by GC enzyme replacement therapy, allogeneic bone marrow transplantation (BMT), and gene therapy. We here report the experience of successful allogeneic BMT in a 16-year-old female patient with GD type III which was demostrated markedly increased Gaucher cells in bone marrow and absence of GC activity in peripheral blood monocytes by FACS using 5'- pentafluorobenzoylaminofluorescein-di-β-D-glucoside (PFBFDGlu) as substrate. Donor marrow engraftment was confirmed by chromosome analysis using microsatellite and by bone marrow examination. Assay of GC activity using FACS revealed normal level of enzyme activity. She remains alive and well after 12 months of BMT.(Korean J Med 61:195-200, 2001)

혈액질환치료에 있어 동종말초조혈모세포와 배양확장된 간엽모세포(Mesenchymal Stem Cell)의 동시이식 2예

강석윤,김재홍,박준성,김현수,최진혁,임호영,양말숙,김영진,김효철 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.1

Human bone marrow contain two kinds of stem cells. One is hematopoietic stem cell, and the other is multipotential mesenchymal stem cells which are capable of differentiating into a number of mesenchymal cell lineages. These mesenchymal stem cells are shown to secrete hematopoietic cytokines and support hematopietic progenitors in vitro. Animal models suggest that the transplantation of healthy stromal elements, including mesenchymal stem cells, may enhance the ability of the bone marrow microenvironment to support hematopoiesis after stem cell transplantation. Therefore, We hypothesized that cotransplantation of hematopoietic stem cells and mesenchymal stem cells after high dose chemotherapy would facilitate engraftment of hematopietic stem cells and reduce complications caused by delayed engraftments. And we investigated the safety, feasibility, side effects and hematopoietic effects of in vitro-expanded mesenchymal stem cells in hematologic malignancies receiving allogeneic peripheral stem cell transplantation.

악성림프종에서 Phospholipase C의 발현

하만준,황성철,박광화,김현수,강영모,김현주,김효철 아주대학교 의과학연구소 1996 아주의학 Vol.1 No.1

Phosphatidylinositol-specific phospholipase C(PLC) plays a central role in transmembrane signal transduction pathways in response to the interaction between various ligands and cell-surface receptors in most eukaryotic cells. Triggered PLC catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate to yield the intracellular second messengers, diacyiglycerol and inositol 1,4,5-trisphosphate. It has been found that PLC-γ₁ is overexpressed in some cancer cells including breast, liver, and colorectal cancer, but data on the expression of PLC isozymes other than γ₁ have not been reported. Furthermore, there have been no reports on the expression of PLC in lymphomas. In this study, we examined the patterns of PLC isozymes expression in normal lymph node and lymph node samples from 15 patients with malignant lymphoma by western blot analysis and immunohistochemistry. The levels of PLC-β₁ expression were found to be similar between tumor samples and normal lymph node. PLC-β₂ was found to be overexpressed in 12 lymphoma samples showing, marked increase in 4 and slightly increased patterns in 8. PLC-β₃ was abnormally expressed quantitatively and qualitatively in all the lymph nodes from lymphoma patients compared to the normal lymph node. PLC-b3 showed a strong overexpression pattern in the lymphoma tissues, and the mobility of this protein was slightly retarded in all samples on the SDS/polyacrylamide gel. There were no detectable changes in PLC-γ₁ or δ₁ expression, but PLC-γ overexpression was observed in 10 of 15 lymphoma samples. The fact that lymphoma tissues showed an overexpression of PLC-β₂, -β₃, and -γ₂ indicates that the alteration of the signal transduction pathway is associated with the pathogenesis of lymphoma.