r-Gamma-Glutamyltransferase 의 조직내 분포에 관한 연구 - 단일클론항체의 효소면역측정법 , 방사면역측정법 , 면역조직화학검사 , 자가방사기록검사 적용에 관하여 -

김명곤(Meyoung Kon Kim),박윤규(Youn Kyu Park),류총근(Chong Kun Ryu) 대한핵의학회 1994 핵의학 분자영상 Vol.28 No.1

N/A y-Glutamyltransferase (GGT: E.C. 2.3.2.2.) is a glycoprotein enzyme which is involved in glutath- ione metabolism and amino acid transport through the plasma membrane. It is distributed widely in several organs including liver and kidney. Several isozymes of GGT have been reported and some of the isozymes may be associated with hepatocarcinogenesis. We have produced six monoclnal antibodies (mAbs) against GGT purified from the liver of 2-acetamidofluorene (AAF) treated rats. All of the six mAbs were obtained by immunizing mice with liver GGT. Six hybridomas which produced anti-GGT Abs were extensively subcloned and injected into the peritoneal cavity of BALB/c mice to obtain large quantities of Abs. These mAbs were purified from ascites by ammonium sulfate precipitation and protein A sepharose CL-4B column chromatography. Using these mAbs we proformed enzyme-linked immunosorbent assay (ELISA), radioimmvnoassay (RIA), immunohistochemistry (IHC), and autoradiography (ARG) to study the distribution of GGT isozyme in tissue. The results indicate that GGT-mAb 1 is specific for the AAF treated liver GGT, GGT-mAb 5 for the normal liver GGT, and GGT-mAb 6 for the normal kindey GGT. These mAbs may be used to evaluate the distribution of GGT isozymes in different tissues.

4차 산업혁명과 인문예술교육 - 의료 분야를 중심으로 -

김승현 ( Kim Seung Hyun ),김명곤 ( Kim Meyoung Kon ) 성균관대학교 인문학연구원(성균관대학교 인문과학연구소) 2018 人文科學 Vol.0 No.69

본 논문은 자본경제와 정보산업 체제를 거치면서 비인간적으로 고도화하고 있는 의료 분야가 4차 산업혁명을 맞아 의료의 근본 가치인 인간성을 회복할 수 있는 방법을 찾는 것을 목표로 한다. 그 방법으로 4차 산업혁명과 의료분야의 특성을 살펴보고, 비판적 포스트휴머니즘의 관점에서 인간주체의 개념과 인문예술교육의 역할을 고찰하였다. 4차 산업혁명은 ‘다양한 분야의 기술 융합’과 ‘매우 빠른 발전 속도’로 특징지을 수 있다. 융합과 속도는 광범위한 창조와 파괴를 예고하며 전례 없는 희망과 불안을 낳고 있다. 의료도 예외가 아니다. 의료분야는 4차산업혁명과의 결합이 용이치 않은 특성을 가지고 있음에 불구하고, 자본경제체제는 신기술들을 앞세워 얼마 남지 않은 공적 보호 장치마저 파괴해 나갈 것이 자명해 보인다. 반면에 의료계는 4차 산업혁명의 기술융합과 AI의 도움을 받아 인간성을 회복하고 인간이 가져야 할 본연의 창조성 발휘의 기회를 가질 수도 있다. 이를 위한 방법으로 본 논문에서는 인문예술교육을 의과대학 커리큘럼에 적극적으로 도입할 것을 제안하였다. 인문예술교육은 인간성이란 무엇이며, 의료의 주체가 과학이 아닌 인간이어야 하는 근본적인 이유에 대해 설명하고, 의사로서의 공감 능력과 창의적이고 혁신적인 사고 배양에 기여할 수 있다. 그리고 AI와 공생하는 미래에서 인간 생존에 필요한 힘과 복잡한 윤리적인 문제에 대하여 균형 있는 판단의 준거를 제공할 것이다. The goal of this paper is to find methods to enable the medical field, which has developed ― without ever caring for humanity ― along with capital economy and the information industry, to help restore humanity, which is at the root of medical care in the age of the Fourth Industrial Revolution. As a method, the characteristics of the Fourth Industrial Revolution and the medical field were examined and the concept of human subjects and the role of the education of humanities and arts were considered from the viewpoint of critical post-humanism. The Fourth Industrial Revolution can be characterized by ‘technological convergence in diverse fields’ and the ‘ultra-high developing speed.’ The convergence and speed give birth to the creation and destruction and bring about an unprecedented hope and anxiety. Despite that the medical field has a characteristic that it cannot be easily combined with the Fourth Industrial Revolution, it seems clear that the capitalist economy system will destroy even a few remaining public protection devices by actively introducing newly developed technologies. On the contrary, the medical circles and doctors can have the opportunity to restore humanity and display the original creativity that human beings should have with the help of the Fourth Industrial Revolution technologies and AI. As a method to that end, this paper proposed to actively introduce the education of humanities and arts into the curriculums at medical colleges. Humanities and arts education can explain what humanity is, examine the fundamental reason why human beings ― not science ― should be the principal agents of medical treatment, contribute to the cultivation of the empathic ability as doctors and cultivation of innovative thinking, and provide grounds for balanced judgments on the power necessary for human survival and complex ethical issues in the future when human beings will coexist with AI.

자궁경부암의 방사선치료 및 방사선항암화학 병용치료에 따른 유전자발현 조절양상

이규찬(Kyu Chan Lee),김명곤(Meyoung-kon Kim),김주영(Jooyoung Kim),황유진(You Jin Hwang),최명선(Myung Sun Choi),김철용(Chul Yong Kim) 대한방사선종양학회 2003 Radiation Oncology Journal Vol.21 No.1

목적 : 동시에 대량으로 유전자발현 양상을 검사할 수 있는 cDNA microarray 기법을 이용하여 자궁경부암에서 특징적으로 나타나는 유전자발현 양상을 알아보고, 방사선치료 및 방사선 항암화학요법 병용치료시의 유전자발현 변화양상을 파악하고자 한다. 대상 및 방법 : 자궁경부 편평상피암으로 확진된 후 근치목적 방사선치료를 단독으로 시행한 8명과 항암화학요법을 병행한 8명에서 채취한 종양조직을 대상으로 하고, 정상 자궁경부 3례를 대조군으로 하였다. 조직 생검은 치료 전과 외부 방사선치료 16.2~27 Gy에 두 번하였다. 항암화학요법을 병용한 경우, 5-FU 1000 mg/㎡을 제 1일부터 5일까지 정주하고, cisplatin 60 mg/㎡을 제 1일에 정주하였다. cDNA microarray는 종양조직에서 추출한 total RNA를 역전사(reverse transcription)방법을 이용하여 [P-33]을 표지한 cDNA를 제작, nylon membrane에 hybridization하였다. 이후 membrane을 phosphor-imager screens에 옮겨 1~5일 동안 노출시킨 후 이미지를 스캔하였다. 유전자의 발현정도는 각 스팟(spot)들의 방사능 강도로 나타나는데, 각 스팟의 픽셀(pixel)을 Arrayguage?潁? 사용하여 산출한 후 엑셀파일로 저장하였다. 유전자의 발현정도 비교는 원 자료(original data)를 Z-변환을 통해 보정(normalized)한 후 Z-ratio값을 산출하여 시행하였다. 결과 : 대조군에 비해 자궁경부암에서 Z-ratio 2.0 이상으로 유의한 발현증가를 보인 유전자들은 integrin-linked kinase, CDC28 protein kinase 2, Spry 2, ERK 3 등 15개롤 주로 세포성장과 증식, 세포주기, 신호전달 등에 관련된 유전자들이었으며, Z-ratio -2.0 이하의 유의한 발현감소는 G protein-coupled receptor kinase 6외 6개였다. 방사선 단독치료를 시행한 후 Z-ratio 2.0 이상 발현이 증가한 것은 cyclic nucleotide gated channel외 3개의 Expressed sequence tags (EST)들이었고, Z-ratio -2.0 이하의 발현감소를 보인 것들에는 치료전 종양세포에서 발현이 증가되었던 세포성장과 증식, 세포주기, 신호전달 등에 관련된 유전자들이 포함되었다. 방사선치료와 항암화학요법을 병용했을 때는 방사선 단독치료에 비하여 세포성장과 증식 및 신호전달 관련 유전자들이 상대적으로 높게 발현되었으며, 이외에도 혈관형성(angiopoietin-2), 면역반응(formyl peptide receptor-like 1), DNA 손상회복에 관련된 (cAMP phosphodiesterase)의 발현은 증가되고 세포고사(death associated protein kinase)에 관련된 유전자는 발현 감소를 보였다. 결론 : 자궁경부암에서 분열과 증식 및 신호전달에 관여하는 여러 종류의 유전자들 발현이 동시다발적으로 증가되어 있다는 것과 방사선치료를 시행하면 이들 유전자의 발현이 감소하여 종양세포의 분열과 증식이 저해된다는 것을 확인하였다. 방사선 단독치료와 항암화학요법 병용치료를 비교하면 그 유전자 발현양상이 다르므로 향후 이번 연구에서 나타난 유전자들에 대한 추가 연구가 필요하며, 이는 개별화된 맞춤형 치료법을 개발하는데 기초자료로 사용될 수 있을 것으로 기대된다. Purpose : To analyze the gene expression profiles of uterine cervical cancer, and its variation after radiation therapy, with or without concurrent chemotherapy, using a cDNA microarray. Materials and Methods : Sixteen patients, 8 with squamous cell carcinomas of the uterine cervix, who were treated with radiation alone, and the other 8 treated with concurrent chemo-radiation, were included in the study. Before the starting of the treatment, tumor biopsies were carried out, and the second time biopsies were performed after a radiation dose of 16.2~27 Gy. Three normal cervix tissues were used as a control group. The microarray experiments were performed with 5 groups of the total RNAs extracted individually and then admixed as control, pre-radiation therapy alone, during-radiation therapy alone, pre-chemoradiation therapy, and during-chemoradiation theapy. The 33P-labeled cDNAs were synthesized from the total RNAs of each group, by reverse transcription, and then they were hybridized to the cDNA microarray membrane. The gene expression of each microarrays was captured by the intensity of each spot produced by the radioactive isotopes. The pixels per spot were counted with an Arrayguage??, and were exported to Microsoft Exel??. The data were normalized by the Z transformation, and the comparisons were performed on the Z-ratio values calculated. Results : The expressions of 15 genes, including integrin linked kinase (ILK), CDC28 protein kinase 2, Spry 2, and ER K 3, were increased with the Z-ratio values over 2.0 for the cervix cancer tissues compared to those for the normal controls, Those genes were involved in cell growth and proliferation cell cycle control, or signal transduction. The expressions of the other 6 genes, including G protein coupled receptor kinase 6, were decreased with the Z-ratio values of below -2.0. After the radiation therapy, most of genes, with a previously increase expressions, represented the decreased expression profiles, and the genes, with the Z-ratio values of over 2.0, were cyclic nucleotide gated channel and 3 Expressed sequence tags (EST). In the concurrent chemo-radiation group, the genes involved in cell growth and proliferation, cell cycle control, and signal transduction were shown to have increased expression compared to the radiation therapy alone group. The expressions of (angiopoietin-2), immune reactions (formyl peptide receptor-like 1), and DNA repair (cAMP phosphodiesterase) were increased, however, the expression of gene involved in appoptosis (death associated protein kinase) was decreased. Conclusion : The different kinds of genes involved in the development and progression of cervical cancer were identified with the cDNA microarray, and the proposed theory is that the proliferation signal starts with ILK, and is amplified with Spry 2 and MAPK signaling, and the cellular mitoses are increased with the increased expression of Cdc 2 and cell division kinases. After the radiation therapy, the expression profiles demonstrated the evidence of the decreased cancer cell proliferation. There was no significant difference in the morphological findings of cell death between the radiation therapy alone and the chemo-radiation groups in the second time biopsy specimen, however, the gene expression profiles were markedly different, and the mechanism at the molecular level needs further study.

봉사교육과정의 개발과 시행 후 평가

최윤선(Youn Seon Choi),김대균(Dae Gyeun Kim),안덕선(Duck Sun Ahn),이영미(Young Mee Lee),김창덕(Chang Duck Kim),천병철(Byung Cheol Chun),김명곤(Meyoung-Kon Kim),김옥주(Ock-Joo Kim) 한국의학교육학회 2006 Korean journal of medical education Vol.18 No.1

Purpose: This paper reports on the development a program to foster good doctors who care for their patients with humanism and self-directed learning ability. Methods: In order to develop the program, Korea University College of Medicine established educational committees. In collaboration, these committees discussed the direction for curriculum reorganization, performed a needs analysis of specified programs, and built realistic strategies for program management. Based upon the needs analyses, through literature review and survey studies, committee discussions and benchmarking of other medical schools, three programs were developed for rearing humanism and self-directed learning ability in medical students were developed: Service learning by experiential learning; Doctoring by small group activities; and Communication skills program by various small group activities. Results: The evaluation by the pre-medical students who participated in the service learning program for one week reveals that through service learning, pre-medical students had an opportunity to obtain the attitudes that encompass the sanctity and dignity of human life and an understanding of cultural, social and religious customs and beliefs that differ from his or her own. In addition, the pre-medical students came to realize that patients most difficult problems might be caused by non-medical factors as well as medical factors. Conclusion: It is needed to grope for the way that leads the active participation of students in the continuous linkage of substantial post-work evaluation and next learning of volunteering in order to make the program of educating the public spirit more than self-learning of experience.

의대생의 자기효능감과 환경요인, 성격, 학업성취도 관련성

이영미(Young-Mee Lee),함병주(Byung-Joo Ham),이경아(Kyung-A Lee),안덕선(Duck-Sun Ahn),김명곤(Meyoung-Kon Kim) 한국의학교육학회 2006 Korean journal of medical education Vol.18 No.3

Purpose: The purpose of this study was to explore the relation of self-efficacy with environmental factors, personality, and academic achievement in medical students. Methods: Study subjects consisted of 141 first-year medical students at Korea University Medical School during one academic year (2003~2004). All participants completed a 24-item questionnaire on self-efficacy beliefs, a 16-item questionnaire asking demographic and socioeconomic data, and the Temperament and Character Inventory (TCI). Spearman sorrelation of selfefficacy with other variables was generated. The differences of self-efficacy scores according to the level of satisfaction with school life, total family income per month and the reasons for entering medical college were analyzed by ANOVA. Results: Age and overall satisfaction with school correlated with self-confidence and total family income per month was related to self-regulation. Students who entered medical college due to the socioeconomic stability of medicine showed significantly lower preference for task difficulty than those who had other reasons for entering medical college. The GPAs of premedical studies correlated with self-regulation and the GPAs of Med 1 and the cumulative GPAs of premedical and Med I were related to the preference for task difficulty. Conclusion: This result supports that self-efficacy beliefs were related with some environmental factors, personality and academic achievements in medical students.

방사성동위원소 표지 치료용 올리고뉴클레오티드를 이용한 나노핵폭파 유전자 치료법 소개

최재걸(Jae Gol Choe),이희영(Hee Young Lee),박길홍(Gil Hong Park),류총근(Chong Kun Ryu),김명곤(Meyoung Kon Kim) 대한핵의학회 2001 핵의학 분자영상 Vol.35 No.3

N/A

肝癌細胞의 γ-Glutamyltranspeptidase에 對한 Monoclonal antibody에 關한 硏究

金明坤,柳總根 고려대학교 의과대학 1992 고려대 의대 잡지 Vol.29 No.2

This study was devised to produce monoclonal antibody against hepatocelullar carcinoma speclfic γ-glutamyltranspeptidase (HCC GGT), which proceeded by first purifying the HCC GGT using ion exchange chromatography and immunoaffinity chromatography. Subsequently, a mouse was immunized with the purified enzyme, and then spleen cells taken from the immunized mouse was fused with mouse myeloma cells (SP2-Ag 14) to form the hybridoma. The following results were obtained by characterization of the monoclonal antibody of the hybridoma using immunoglobulin isotyping and immunoblot. 1. The purification of HCC GGT by means of ion exchange chromatography and immunoaffinity chromatogiaphy produced a yield of 29.41%, a purification fold of 167.87, and final specific activity of 21units per mg of protein. 2. Direct enzyme linked immunoadsorbent assay (ELISA) method was used to measure the antibody level against HCC GGT. An antibody titration of the blood sample taken from the mouse immunized with the above enzyme showed value over 1:5, 120. 3. The cell fusion of the mouse myeloma cell and the spleen cell of the immunized mouse was generated 14 positive wells in 221 wells. (specific fusion efficacy of 6.33%) Only one IgG2a monoclonal antibody was determined by both repetitive cloning procedures and immunoglobulin subisotyplng. 4. A antigen-antibody cross matching after the western blot revealed a specific reaction between the HCC GGT antigen at the 40Kd band and the monoclonal antibody of the hybridoma. And the monoclonal antibody did not react with GGT derived from normal liver or kidney.

단일클론 항γ-Glutamyltransferase항체를 이용한 효소 및 방사 면역측정법 적용에 관한 연구

金明坤,柳總根 고려대학교 의과대학 1994 고려대 의대 잡지 Vol.31 No.1

γ-Glutamyltransferase (GGT: E. C. 2. 3. 2. 2.) is a glycoprotein enzyme which is involved in glutathione metabolism and amino acid transport through the plasma membrane. It is distributed widely in several organs including liver and kidney. Several isozymes of GGT have been reported and some of the isozymes may be associated with hepatocarcinogenesis. We have produced six monoclnal antibodies (mAbs) against GGT purified from the liver of 2-acetamidofluorene (AAF) treated rats. All of the six mAbs were obtained by immunizing mice with liver GGT. Liver GGT from AAF treated rats was biochemically purified to a specific activity of 125.6 units per mg of protein. The overall purification was 551 folds and the final yield was 20. 8. Six hybridomas which produced anti-GGT Abs were extensively subcloned and injected into the peritoneal cavity of BALB/c mice to obtain large quantities of Abs. These mAbs were purified from ascites by ammonium sulfate precipitation and protein A sepharose CL-4B column chromatography. Using these mAbs we performed enzyme linked immunosorbent assay (ELISA), radioimmunoassay (RIA), immunohistochemistry (IHC), and autoradiography (ARG) to study the distribution of GGT isozymes in tissue. The results indicate that GGT-mAb 1 is specific for the AAF treated liver GGT, GGT-mAb 5 for the normal liver GGT, and GGT-mAb 6 for the normal kidney GGT. These mAbs may be used to evaluate the distribution of GGT isozymes in different tissues.

단일클론 항 γ-Glutamyltrasferase(GCT) 항체를 이용한 혈뇌장벽 내 GGT의 분포에 관한 연구

이병규,김명곤,신규만,류총근 대한신경외과학회 1995 Journal of Korean neurosurgical society Vol.24 No.3

γ-Glutamyltransferase(GGT: E.C. 2.3.2.2.) is a glycoprotein enzyme which is involved in glutathione metabolism and amino acid transport through the plasma membrane. It is distributed widely in several organs including liver, kidney, pancrease and brain. GGTs derived from the brain of Wister rats and BALB/c mice were biochemically purified to a specific activity of 4246.2, 862.1 units per mg of protein, a purification folds 93.7, 43.8 and the final yield 65.8, 44.0% respectively. Electrophoretic pattern of purified GGTs from rats and mice brain shows very similar protein fraction each other. We have produced six monoclonal antibodies(GGT-MAb 1-6) against 2-acetamidofluorene treated rat liver GGT. Using these GGT-MAb 1-6 we performed immunohistochemistry(IHC) to study the distribution of GGY isozymes in normal tissues of rat brain and in ncoplastic tissues of human brain. The results indicated that human brain GGT was localized in pericytes of blood-brain barrier, especially in the blood-rich portion of the brain(e.g. cerebellum of rat, meningioma and craniopharyngioma of human). Therefore these MAbs may be used to evaluate the distribution of GGT isozymes in different tissues.

신경정신 의학분야의 방사성동위원소 표지 cDNA 마이크로어레이

최재걸,신경호,이민수,김명곤 대한핵의학회 2003 핵의학 분자영상 Vol.37 No.1

Microarray technology allows the simultaneous analysis of gene expression patterns of thousands of genes, in a systematic fashion, under a similar set of experimental conditions, thus making the data highly comparable. In some cases arrays are used simply as a primary screen leading to downstream molecular characterization of individual gene candidates. In other cases, the goal of expression profiling is to begin to identify complex regulatory networks underlying developmental processes and diseases states. Microarrays were originally used with cell lines or other simple model systems, More recently, microarrays have been used in the analysis of more complex biological tissues including neural systems and the brain. The application of cDNA arrays in neuropsychiatry has lagged behind other fields for a number of reasons. These include a requirement for a large amount of input probe RNA in fluorescent-glass based array systems and the cellular complexity introduced by multicellular brain and neural tissues. An additional factor that impacts the general use of microarrays in neuropsychiatry is the lack of availability of sequenced clone sets from model systems. While human cDNA clones have been widely available, high quality rat, mouse, and drosophilae, among others are just becoming widely available. A final factor in the application of cDNA microarrays in neuropsychiatry is cost of commercial arrays. As academic microarray facilitates become more commonplace custom made arrays will become more widely available at a lower cost allowing more widespread application. In summary, microarray technology is rapidly having an impact on many areas of biomedical research. Radiosotope-nylon based microarrays offer alternatives that may in some cases be more sensitive, flexible, inexpensive, and universal as compared to other array formats such as fluorescent-glass arrays. in some situations of limited RNA or exotic species, radioactive membrane microarrays may be the most practical experimental approach in studying psychiatric and neurodegenerative disorders, and other complex questions in the brain. (Korean J Nucl Med 2003;37:43-52)