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류마티스 관절염 환자에서 Hydroxychloroquine 이 혈중지질에 미치는 영향
장대국(Dae Kuk Chang),전재범(Jae Bum Jun),정성수(Sung Soo Jung),이인홍(In Hong Lee),배상철(Sang Cheol Bae),유대현(Dae Hyun Yoo),김성윤(Seong Yoon Kim) 대한내과학회 1994 대한내과학회지 Vol.47 No.5
N/A Objectives: Antimalarial drug have been used in the treatment of rheumatoid arthritis and systemic lupus erythematosus. They are inhibitors of platelet aggregation and adhesion whose prophylactic effects in thromboembolism have been demonstrated. Recently, profound decreases in serum cholesterol levels were reported in rheumatoid arthritis patients treated with chloroquine. The mechanism by which hydoxychloroquine may lower serum lipid is not clear, although chloroquine has multiple effects on hepatic cholesterol metabolism. We investigated the effects of hydroxychloroquine on serum lipid levels. Methods: We studied 62 female patients diagnosed as rheumatoid arthritis from Feburary 1993 to August 1993, prospectively. Patients were excluded from the study if they were diabetic, had nephrotic syndrome, or were taking antihyperlipidemic agents. A total of 62 female wer divided into following treatment groups: Group A; HCQ(n=46) Group B; sulfasalazine (n=16) We measured the lipid profile before therapy and after 3 months. Results: The hydoxychloroquine-treated group had lower cholesterol and LDL-cholesterol levels than those receiving sulfasalazine. The significant changes in lipid profile including lowering of serum cholesterol and LDL-cholesterol, were especially evident in the middle aged(age 41 to 60 years) group of patients. Conclusions: The lipid lowering effects of hydroxychloroquine on serum lipid levels may have a good reference for selection of antirheumatic drugs in patients with rheumatoid arthritis.
CD40와 종양괴사인자 수용체에 의한 B림프구 Fas항원 발현과 세포사멸 유도에 관한 연구
장대국 ( Dae Kook Chang ),유대현 ( Dae Hyun Yoo ),김성윤 ( Seong Yoon Kim ) 대한류마티스학회 2001 대한류마티스학회지 Vol.8 No.1
Objective: CD40 and the TNFR belong to the NGF/TNFR supergene family. Ligation of CD40 on B cells induces activation signals leading to proliferation, Ig isotype class switching, germinal center formation but also induces Fas antigen expression. In addition, CD40 ligation induces pro-inflammatory cytokines including TNF-α and LT-α gene transcription by human B cell. TNF-α is a pleiotropic cytokine and also induces Fas antigen expression on various cells. Lately it has been known that TNF-α plays an important role in the pathogenesis of chronic inflammatory diseases, including rheumatoid arthritis, or chronic inflammatory bowel diseases. However there have been occurrence of autoantibodies, or autoimmune disease such as lupus after use of anti TNF-α blocking agents. In this report, we tested the relationship and biological significance of CD40 ligation and TNFR signaling with respect to Fas antigen expression on human B cells. Methods: Ramos Burkitt`s lymphoma B cell was used as a prototype of germinal center B lymphocyte, and R2G6 cell was utilized as a model of activated germinal center B cell. CD40 Igation was performed by the coculture with CD40 ligand bearing L-293 cells, or anti-CD40 monoclonal antibody, whereas control was obtained with CD-8-L-293 cells or control antibody. Expression of Fas antigen was determined with flow cytometer. Apoptosis assay was conducted by two ways. Alamar blue reduction assay after sIgM cross linking or anti-Fas anti-body, in the presence or absence of CD40 ligation or TNF-α In addition, DNA content assay was utilized to make sure the proportion of apoptotic Ramos B cells by various treatments. Results: 1) CD40 and TNF-α induced Fas antigen expression on Ramos B cell line cells and rendered them susceptible to Fas-mediated apoptosis. 2) CD40 and TNFR signaling upregulate Fas antigen independently. 3) Both TNFR and CD40 signaling rescue sIgM crosslink induced apoptosis of Ramos B cell line cells, only CD40, but not TNFR, signaling rescues Ramos cells from Fas-mediated apoptosis. Conclusion: Taken together, these results demonstrate that B cell signaling via two distinct members of the NGF/TNFR superfamily, CD40 and TNFR, independently engage the Fas pathway and provide mechanisms for eliminating B cells. Acting alone, both signals will ready B cells for Fas-mediated apoptosis. In concert with sIg signaling, the rescue effect provided uniquely by CD40 ligation assures the selective survival of only those B cells which have bound antigen and presented it to antigen-specific T(h) cells.
장대국 ( Dae Kook Chang ),김태환 ( Tae Hwan Kim ),정성수 ( Sung Soo Jung ),이인홍 ( In Hong Lee ),배상철 ( Sang Cheol Bae ),유대현 ( Dae Hyun Yoo ),김성윤 ( Seong Yoon Kim ),오영배 ( Young Bae Oh ),전재범 ( Jae Bum Jun ),고희관 ( 대한류마티스학회 1999 대한류마티스학회지 Vol.6 No.1
Hypothyroidism may be accompanied by different rheumatic syndromes such as neuropathy, arthropathy and myopathy. Severe myopathy with high elevations of creatine kinase (CK) is rarely seen in hypothyroidism. Authors experinced a case of myopathy with hypothyroidism, similar to rheumatoid arthritis or polymyositis-like syndrome. We have treated with thyroid hormone replacement (Levothyroxine sodium 100ug/day) for 10 months. The initial serology resulted in: free T4 0.51ng/dl, TSH 110uIU/ml, LDH 465 units, and CK 4385 units. After treatment, we gained free T4 1.60ng/dl, TSH 0.14uIU/ml, LDH 110 units, and CK 80 units and musculoskeletal symptoms are much improved. We report this patient with a review of literatures.