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한국인에서 류마토이드 관절염과 제 2 형 조직적합항원과의 연관성에 관한 연구
유대현(Dae Hyun Yoo),서정대(Jeong Dai Suh),배상철(Sang Cheol Bae),김성윤(Seong Yoon Kim),김목현(Mok Hyun Kim),김신규(Thin Kyou Kim),주경빈(Kyung Bin Joo) 대한내과학회 1991 대한내과학회지 Vol.40 No.5
N/A Rheumatoid arthritis is a chronic inflammatory disease characterized as destructive polyarthritis and has evidence of immunogenetic and environmental elements in its etiologic factors. Many studies document that one of the key genetic elements is closely linked to the class II major histocompatibility complex located in chromosome 6. Although it is not. known precisely how HLA genes contribute to disease susceptibility, many studies document a close association between rheumatoid arthritis and the specific histocompatibility marker, HLA-DR4. However, studies of HLA-DR4 in disease severity have yielded conflictiing results. Association between HLA- DR4 and the rheumatoid factor, earlier age of onset, increased general disease severity and more erosive radiographic changes have been reported, but these associations have not been confirmed in other studies. In addition, there has been no report regarding the association between rheumatoid arthritis and class II MHC in Koreans. Therefore this is the first epidemiologic study regarding the association between rheumatoid arthritis and class II MHC. The disrtibution of class II major histocompatibility complex and association between HLA- DR4 and disease severity were analyzed in 206 Korean patients with rheumatoid arthritis in this study. The results were as follows: 1) HLA-DR4 was associated with rheumatoid arthritis in 61.6% of the patients studied. The relative risk and etiologic fraction of HLA-DR4 were 2.47 and 0.367, respectively. HLA-DR1 was positive in 11.1% and the etiologic fraction of HLA-DR1 was 0.008. Therefore HLA-DR4 was associated strongly with rheumatoid arthritis in Koreans, similar to other ethnic populations, but HLA-DR1 was not associated with rheumatoid arthritis in Koreans. 2) HLA-DR2 was positive in 19.9% and the preventive fraction of HLA-DR2 was 0.205. HLA-DR7 was positive in 4.3% and the preventive fraction of HLA- DR7 was 0.011. Hence HLA-DR2 was the most preventive class II MHC against the development of rheumatoid arthritis in this study. 3) HLA-Dgw3 was positive in 62.1% and the relative risk of HLA-DQw3 was 1.65, HLA-DQw7, which was known as HLA-DQw3.1, was positive in 20.5% and HLA-DR4 Dgw7 haplotype was positive in 15% of the total number of patients. 4) HLA-DR4 was significantly associated with a more advanced ARA anatomical grade and more severe radiographic changes, including bony erosion, joint space, narrowing and total radiographic score. 5) The rheumatoid facor was positive in 84.3% of the HLA-DR4 positive patients and positive in 82.3% of the HLA-DR4 negative patients. HLA-DR4 v as positive in 62.2% of the 172 seropositive patients and positive in 58.8% of the 34 seronegative patients. Therefore HLA-DR4 was not associated significantly with the presence of a rheumatoid factor in this study. 6) HLA-DR4 was not associated significantly with joint count (Ritchie index), ARA functional class, ESR, C-reactive protein or other demographic data. HLA-DR4 was not associated significantly with the positive rate of ANA, cryoglobulin. 7) Homozygous HLA-DR4 patients were 31 out of 127 DR4-positive patients and showed more advanced ARA anatomical stage and radiographic changes than heterozygous DR4 patients, but the difference was statistically insignificant. In summary, HLA-DR4 was significantly associated with rheumatoid arthritis in Koreans, similar to other ethnic populations, Also HLA-DR4 was significantly associated with more destructive arthritis, but not associated with rheumatoid factor positivity and the parameters representing disease activity of rheumatoid arthritis.
류마티스 관절염과 퇴행성 관절염의 활액막조직에서 VLA 항원의 발현에 관한 연구
유대현(Dae Hyun Yoo),정성수(Sung Soo Jung),이인홍(In Hong Lee),배상철(Sang Cheol Bae),김성윤(Seong Yoon Kim),김목현(Mok Hyun Kim),정현기(Hyun Kee Chung),최일용(Il Yong Choi) 대한내과학회 1994 대한내과학회지 Vol.46 No.5
N/A Objective: The adhesion molecule that mediate cell-cell and cell-extracellular matrix provides very important role in various physiologic and pathologic conditions, VLA integrin is heterodimeric transmembrane glycoprotein which participate in cell-cell and cell-extracellular matrix, especially collagen, laminin and fibronectin. Rheumatoid arthritis is important prototype of chronic inflammatory disease. Continuous emigration and anchorage of chronic inflammatory cells are prerequisite for the perpetuation of disease. Transient episode of inflammatory synovitis could be found in osteoarthritis also. Although the notion that VLA-integrin play a major role in the initiation and perpetuation of arthritis would be possible, distribution of VLA integrin in synovial tissue of rheumatoid arthritis and osteoarthritis was investigated by immunohistochemistry. Methods: Immunohistochemical analysis of synovial tissue utilizing avidin-biotin complex method was con- ducted. Applied monoclonal antibodies were CD49a-f, CD29, CD51, and CD61. The pattern of expression was scored by semiquantitative grading system. Results: 1) The expression of CD29 was diffuse and intense at synovial lining cells, endothelium and infiltrating inflammatory cells. Endothelial stain was evident with VLA-1, 6, CD51 and negative with VLA-4. Inflammatory cells expressed VLA-4, 5 intesively and synoviocytes expressed VLA-3, 5, 6 and CD51 as ligand for fibronectin and laminin. 2) CD29 expression of inflammatory cells were prominent around small blood vessles which showed strong stain of CD29 and located just beneath the synovial lining cells. 3) VLA-integrin expression in synvoium of osteoarthritis was smimilar to that of rheumatoid arthritis except little inflammatory cell infiltratilon and little proliferation of microvasculature. Conclusion: It was able to presume from above findings that VLA-integrin has been doing some role in the development and perpetuation of synovitis. Future perspectives in field of VLA-integrin may be exact process of intracellular signalling, functional aspect of integrin and regulation of expression by some cytokines and growth factors.
유대현(Dae Hyun Yoo),변정원(Jeong Won Byeon),이오영(Oh Young Lee),김태화(Tae Hwa Kim),김성윤(Seong Yoon Kim),강종명(Chong Myung Kang),김목현(Mok Hyun Kim),박문향(Moon Hyang Park) 대한내과학회 1989 대한내과학회지 Vol.37 No.4
N/A The renal lesions in ankylosing spondylitis are known as renal injury due to nonsteroidal anti-inflamatory drugs, renal amyloidosis and golomrelonephritis, but the accurate incidence of renal lesions in ankylosing spondylitis has not been determined. After the first report of IgA nephropathy associated with ankylosing spondylitis by Sisson et al., several investigators have reported a few cases of IgA nephropathy associated with ankylosing spondylitis and related spondyloarthritides. Elevated serum IgA and IgA circulating immune complexes are noted in ankylosing spondylitis and play a major role in the pathcogenesis of ankylosing spondylitis. lgA nephropathy is characterized by predominant deposition of IgA at the mesangium and renal injury is caused by circulating immune complexes in IgA nephropathy. Because of the similarity of the suggested pathogenesis between ankylosing spondylitis and IgA nephropathy, a few investigators have proposed that ankylosing spondylitis and IgA nephropathy are related. We experienced a case of IgA nephropathy associated with ankylosing spondylitis in a 34-year-old male patient and report this with a review of the literature.
Gamma - Interferon 에 의하여 유도된 류마토이드 활액막세포와 T 임파구 유착
김성윤(Seong Yoon Kim),김목현(Mok Hyun Kim) 대한내과학회 1987 대한내과학회지 Vol.33 No.5
N/A Rheumatoid synovium is characterized by the proliferation of synovial membrane and subsynoivial infiltration of lymphocytes clustered around Ia+ synovial cell. We performed this study to investigate the effect of gamma-interferon (gamma-IFN) on lymphocyte adhesion to rheumatoid synovial cells in vitro. Adherent synovial cells (SC) obtained from rheumatoid synovium by enzyme digestion were cultured at a low density with various concentration of gamma-IFN and then were incubated with freshly isolated peripheral blood T-lymphocytes. Gamma-IFN induced HLA-DR antigen and significant lymphocyte adhesion to SC. The lymphocyte adhesion to SC were enhanced in the dose-response pattern of gamma-IFN, whereas the intensity of DR antigen or the number of DR+ SC showed plateau at higher concentration of gamma-IFN, and were not correlated with adhesion index. Additionally, there was remarkable changes of intracellular fibronectin morphology. These findings suggest that gamma-IFN induced DR antigen on SC plays a central role in adhesion of lymphocyte to SC, however changes of fibronectin may have additive effect on binding enhancement.
류마토이드 활액막내 혈관내피와 말초 단핵세포간의 유착에 관한 연구
변정원(Jeong Won Byeon),유대현(Dae Hyun Yoo),이오영(Oh Young Lee),권기운(Ki Woon Kwon),김태화(Tae Hwa Kim),김성윤(Seong Yoon Kim),김목현(Mok Hyun Kim),최일용(Il Yong Choi) 대한내과학회 1989 대한내과학회지 Vol.36 No.6
N/A Lymphocyte migration is an essential event in the pathogenesis of rheumatoid arthritis. Lymphocyte accumulation in the diseased tissue is a modification of lymphocyte traffic from blood to lymphoid tissue. But the mechanism by which lymphocytes enter synovia is poorly understood. In our study, sections of rheumatoid arthritis and osteoarthritis synovium were overlaid with human peripheral blood mononuclear cells, and the binding of these cells to blood vessels was examined. Rheumatoid arthritis synovia that had lymphocyte-rich areas only contained blood vessels adhesive for mononuclear cells. These reactive vessels showed striking similarities to high endothelial venules of the paracortical region of normal lymph nodes where normal lymphocyte-endothelial cell adhesion and lymphocyte emigration into tissue occurs. Between 13.8 and 9.4% of the high endothelial venule-like vessels were reactive vessels and each vessel had a mean of 2~5 cells bound to it. These results suggest that the key cellular event in the pathogenesis of inflammatory rheumatic disease is adhesive interaction between circulating mononuclear cells and high endothelial venule-like structures found in inflamed synovium.
정상 한국인의 저주지역별 조직적합 항원의 출현빈도 및 이들 산호간의 유전적 거리
이재호(Jae Ho Lee),김태화(Tae Hwa Kim),김성윤(Seong Yoon Kim),김목현(Mok Hyun Kim) 대한내과학회 1987 대한내과학회지 Vol.32 No.6
N/A We studied the HLA antigen frequencies in Korean and then, genic distance was calculated by Nei et al equation to identify the route of racial immigration, Total sampling number was 355 and classified by three groups. Group-I (220 Korean living in overall south Korean peninsula), group-II (95 Korean living in Shenyang), group-III (40 Korean living in Honam region of Korean peninsula). The method was microcytotoxicity of NIH by use of antisera received from 3rd AOHWS. The followings are the results. 1) Korean, living in Shenyang, might have been migrated from all over the Korean peninsula. This is in accord with historical fact that most of them were migrated in early this centry during Japanese domination. 2) Korean in Honam might have some special experiences historically in communicating with surrounding countries and this might be reflected in some genetic differences from overall Korean. However, this should be confirmed in future, because present data from Honam is too small, and also this data should be compared with the data from surrounding countries.