염증성 관절염에서 NO 의 역할에 관한 연구

배상철(Sang Cheol Bae),김동욱(Dong Yook Kim),김태환(Tae Hwan Kim),전재범(Jae Bum Jun),정성수(Sung Soo Jung),이인홍(In Hong Lee),유대현(Dae Hyun Yoo),김성윤(Seong Yoon Kim),이은영(Eun Young Lee),장성렬(Sung Yeoul Chang) 대한내과학회 1997 대한내과학회지 Vol.52 No.1

N/A Objectives: Nitric Oxide(NO) is a toxic, inorganic, gaseous free radical produced during the metabolism of L-Arginine by NO synthase(NOS). It has been implicated in a rapidly growing number of physiological and pathophysiological processes such as cytotoxic effects against microbes and tumor cells, blood vessel dilation and neurotransmitter. Recently there is growing evidence implicating NO in immune regulation, inflammation, autoimmunity, and arthritis. We performed this study to determine a role for nitric oxide in inflammatory arthritis especially rheumatoid arthritis(RA). Methods: We measured (D the concentrations of nitrite, a breakdown product of nitric oxide, in serum and synovial fluid from patients with RA and osteoarthritis(OA) and in the serum of controls ② the concentrations of nitrite in the supernatant of cultured synovial tissue with RA and OA and ③ determined whether human chondrocytes and synoviocytes can synthesize nitric oxide and if so, how production is regulated by cytokines and antirheumatic drugs. Results: 1) Serum nitrite concentrations in patients with RA and OA were higher than in controls. In both disease groups synovial fluid nitrite was higher than serum nitrite. Serum and synovial fluid nitrite concenrations in RA were higher than those in OA. However, those findings are not statistically significant. 2) Although these findings are not statistically significant, the concentration of nitrite in the supernatant of cultured synavial tissue with RA was higher than that in OA. 3) IL-l5 and TNF-a induced the biosynthesis of NO by chondrocytes and synoviocytes. IGF-1 and TGF-5 failed to provoke the production of NO. The biosynthesis of NO required an induction period of approximately 6 hours and was inhibited by L- NMMA and cycloheximide. Dexamethasone, indomethacin, gold sodium thiomalate and methotrexate had no effect on the induction of NO biosynthesis. Conclusion: These results suggest a role for nitric oxide as an inflommatory mediator in inflammatory arthritis.

Mesna 사용 후 협부 발진양 알레르기 반응을 보인 2예

서정철 ( Jeong Cheol Seo ),배상철 ( Sang Cheol Bae ),심승철 ( Seung Cheol Shim ),김태환 ( Tae Hwan Kim ),전재범 ( Jae Bum Jun ),정성수 ( Sung Soo Jung ),이인홍 ( In Hong Lee ),유대현 ( Dae Hyun Yoo ),김성윤 ( Seong Yoon Kim ) 대한류마티스학회 2000 대한류마티스학회지 Vol.7 No.2

Hemorrhagic cystitis is potentially life-threatening sequellae of chemotherapy using oxazaphosphorine alkylating agents (cyclophosphamide and ifosfamide). Mesna contains a sulfhydryl group that is believed to bind acrolein within the urinary collecting system and reduce the hemorrhagic cystitis without affecting the chemotherapeutic potential. To date, about thirty cases of hypersensitivity or allergic reactions of the delayed and urticarial type associated with mesna have been reported. We reported two patients with systemic lupus erythematosus who developed facial rash and flushing associated with mesna which imitate malar rash.

퇴행성 관절염 환자의 연골 조직에서 콜라겐 변화에 관한 연구

배상철 ( Sang Cheol Bae ),정성수 ( Sung Soo Jung ),이인홍 ( In Hong Lee ),유대현 ( Dae Hyun Yoo ),김성윤 ( Seong Yoon Kim ),정현기 ( Hyun Kee Chung ),최일용 ( Il Yong Choi ) 대한류마티스학회 1994 대한류마티스학회지 Vol.1 No.2

목적: 퇴행성 관절염은 조직학적으로 주로 연골, 활액막, 골조직의 퇴행, 재생, 교정적 변화를 특징으로 하는 질호나으로 이러한 구조적 변화를 정확히 이해하는 것은 유병 기전을 밝히고 질환의 활동도 및 진행 정도를 평가하는데 도움이 된다. 이에 저자들은 연골의 주요 구성성분인 콜라겐의 초직학적 변화를 정확히 펴어가하기 위해 본 연구를 시행하였다. 방법: 정상 대조 연골 조직 l예, 퇴행성 .관절염 연골 조직 10예를 대상으로 ① 제1형, 제2형, 제3형 콜라겐 분포를 조사하기 위해 단일세포성 항체를 이용한 immunoperoxidase법 ② Masson`s trichrome 염색 및 ③ 편광 현미경을 이용한 Picrosirius Red 염색법을 시행하여 비교 관찰하였다 결과: 1) 제2형 콜라겐은 정상 및 퇴행성 관절염 연골 모두에서 전반적으로 말현되어 유의한 차이가 없었다. 제1형 및 제3형 콜라겐은 정상 조직에서는 발현 되지 않으나, 퇴행성 관절염 연골에서는 연골 세포 주위에 발현이 증가되었다, 2) Masson`s trichrome 염색법으로는 정상과 퇴행성 관절염 연골의 콜라겐 분포를 차이를 관찰할 수 없었다 3) Picrosirius Red 염색 후 편광 현미경으로 관찰한 경우, 정상에 비해 퇴행성 관절염 연골은 전반 적으로 복굴절성이 감소되고 불규칙하였으며, 연골 세포 주위의 복굴절성은 증가되어 있었다. 결론: 이상의 결과로, Picrosirius Red 염색법을 이용한 편광현미경 관찰법은 퇴행성 관절염 연골 조직의 콜라겐 변화를 쉽게 관찰 할 수 있는 유용한 방법으로 이용할 수 있을 것으로 사료된다. Objective: Osteoarthritis is a disorder or group of disorders affecting synovial joint, characterized at the tissue level by degenerative, regenerative and reparative structural changes in cartilage, synovium and bone. The histopathological understanding of osteoarthritis would help to clear the pathogenesis and evaluate the activity and progression of the disease. We studied the histochemical distribution of collagen in the search for and accurate morphometric marker for osteoarthritic progression. Methods: The immunohistochemical analysis by monoclonal antibodies to type I, II and III collagen, the Masson`s trichrome stain and the Picrosirius stain and polarization microscopy were performed in 10 osteoarthritis cartilages and 1 normal control cartilage. Results: 1) By the immunohistochemical analysis, type II collagen was diffusely expressed in both normal and osteoarthritis cartilage but the expression of type I and III collagen was only shown around chondrocytes in the osteoarthritis cartilage. 2) There was no difference in Masson`s trichrome stain of the normal and osteoarthritis cartilage. 3) By the Picrosirius stain and polarization microscopy, there was less diffuse birefringence of collagen and increased perichondronal birefringence in the osteoarthritis cartilage in comparison to normal cartilage. Conclusions: The Picrosirius-polarization method may be considered one of the useful morphometriic methods for the progression of osteoarthrits.

류마티스 슬활막염 치료에 있어서 디스프로슘-165의 임상적 시험

배상철 ( Sang Cheol Bae ),김동욱 ( Dong Yook Kim ),김태환 ( Tae Hwan Kim ),전재범 ( Jae Bum Jun ),정성수 ( Sung Soo Jung ),이인홍 ( In Hong Lee ),유대현 ( Dae Hyun Yoo ),김성윤 ( Seong Yoon Kim ),김석준 ( Sug Jun Kim ),이종석 ( Jo 대한류마티스학회 1995 대한류마티스학회지 Vol.2 No.2

연구목적: 류마티스 관절염 치료시 다양한 항 류마티스 제제의 사용에도 불구하고 만성적으로 활막염이 지속되는 경우에는 활막액을 제거해 주는 활막절제술이 치료에 도움이 된다. 방사선 활막절제술 시 과거부터 널리 사용되어 온 Y-90, Au-198은 반감기가 걸고 교질 형태로 방사선 동위원소의 누출이 문제가 되었다. 최근 이러한 단점을 보강한 Dy-165 HMA이 한국 원자력 연구소에 의해 자체 개발하는데 성공하였다. 저자들은 류마티스 관절염 환자에서 만성적으로 지속되는 슬관절염에 대한 Dy-165 HMA의 치료 효과와 안정성을 검증하기 위해 본 연구를 시행하였다. 방법: 류마티스 관절염 환자 중 약물 치료에도 불구하고 계속적으로 슬관절염이 지속되는 300예의 슬관절을 대상으로 하였으며, 그 중 치료 후 6개월 이상 경과한 236예의 슬관절(212예 환자)의 결과를 분석하였다. 한국 원자력 연구소에서 제공한 Dy-165 HMA 250~300mCi를 대상 슬관절에 주사하고, 약 8시간 동안 안정시켰다. 방사선 동위원소의 누출은 혈액 및 요의 방사능 검사와 간, 서혜부, 슬관절의 scintigraphy를 이용하여 검사하였다. 여러 임상적 지표를 이용하여 최종 전반적 판정올 하였다. 결과: 1. 대상 환자의 평균 연령은 49.3세(31-69)였다. 2. 대상 슬관절의 방사선학적 분류는 stage I이 104예, stage II가 124예, stage III이 8예였다. 3. 가장 적당한 방사선량은 260mCi였다. 4. 평균 관찰기간은 50.4주(24-112)였다. 5. 치료 효과는 우수: 4%, 양호: 32%, 불량: 24%로, 전체적으로 76%의 호전율을 보였다. 6. Stage별 호전율은 stage I이 81%, stage II가 78%의 호전율을 보여 양자가 유사하였으며, 우수 반응은 stage I이 54%로 stage II의 39%에 비해 높았다. 7. 치료에 효과를 나타낸 180예의 평균 치료효과 지속기간은 41.4주(24-106)였다. 180예중 10예는 평균 64주(28-80) 후 재발하였다. 8. 관절강 밖으로 Dy-165 HMA누출은 미미하였으며, 주사 초기에 가역적인 슬관절의 팽창(14예) 및 피부 수포(4예)외의 특이한 부작용은 없었다. 결론: 류마티스 슬활막염 치료에 있어서 Dy-165 HMA를 이용한 방사선 활막절제술은 안전하고 효과적인 방법으로 사료되나 향후 장기 추적판찰이 필요하며, 원자로와 거리가 먼 지역에서도 방사선 활막절제술이 가능할 수 있는 반감기가 길고 안전하고 효과적인 동위원소 및 매개체 개발이 필요할 것으로 사료된다. Objectives: To evaluate the efficacy and safety of radiation synovectomy with Dy-165 HMA in chronic rheumatoid synovitis of the knee Methods: Two hundred thirty six knees of 212 patients with rheumatoid arthritis and persistent synovitis of the knee were treated with the intraarticular injection of 250~300 mCi of Dy-165 HMA which was prepared by KAERI. Efficacy was assessed by the following parameters: visual analog scale of the knee pain while walking and resting, circumference of the knee, range of motion of the knee. The final global assessment was classified as good, fair or poor. Estra-articular leakage of Dy-165 HMA was determined by blood pool and urine radioactivity and scintigraphic evaluation of liver, groin, and knee joints. Results: 1) The optimum radiation dose was 260mCi. 2) The mean follow up periods were 50.4(24-112) weeks. 3) Forty four percent of the knees showed good results, 32% fair results, and 24% shwoed good results. 4) In knees with stage I radiographic changes, 81% showed improvement, of which 54% showed good results. In knees with stage II changes, 78% showed improvement including 39% of the patients with good results. There was a direct correlation between the radiographic stage and response to treatment. 5) The mean period of improvement for the 180 knees that reponded to treatment was 41.4(24-106) weeks. Ten of the 180 knees with improvement relapsed after the mean period of 64(28-80) weeks. 6) Leakage of radioactivity from the injected joint was minimal. 7) Adverse reactions were rare (radiation burn: 4, transient postinjection flare: 14). Conclusions: The optimum radiation dose in Korean was somewhat less than of other foreign reports. Dy-165 HMA radiation synovectomy is a safe and useful therapy for chronic synovitis of the knee joint.

국내 류마티스 질환의 유병률 조사 현황

배상철 ( Sang Cheol Bae ) 대한류마티스학회 2010 대한류마티스학회지 Vol.17 No.1

류마티스 관절염 환자에서 N-(2-Mercapto-2-methylpropionyl)- L-cysteine (SA96)의 임상시험

배상철 ( Bae Sang Cheol ),이인홍 ( Lee In Hong ),유대현 ( Yu Dae Hyeon ),김성윤 ( Kim Seong Yun ) 대한내과학회 1993 대한내과학회지 Vol.44 No.3

연구배경 : SA96은 D-penicillamine의 화학구조에서 thiol기를 변형시켜 일본에서 처음으로 개발된 새로운 DMARD의 일종으로, 한국인에 있어서 류마티스 관절염에 대한 SA96의 치료효과 및 안전성을 평가하기 위해 본 연구를 시행하였다. 방법 : 대상환자는 1987년 개정된 ACR 진단기준에 의거한 류마티스 관절염 환자 30명을 대상으로 SA96 100mg를 하루 3회, 총 16주간 투여하였다. 그리고 NSAID 및 경구용 스테로이드(prednisolone 환산량 1일 7.5mg 이하)의 병용요법은 허용하였으나, 관찰기간내 약제의 종류 및 용량은 변경하지 않았다. 결과 : 임상평가 항목 즉, Ritchie 지수, 동통 관절수, 종창 관절수, 아침 강직의 지속시가, 15m 보행시간 및 혈침속도는, 대부분 SA96투여 8주후부터 통계학적으로 유의한 변화를 보였다. 1) 최종 전반 개선도는, 중등도 개선이상을 나타낸 경우 13예(43%), 경도 개선이상을 나타낸 경우는 22예(73%)였다. 2) 개괄 안전도는, 부작용이 없었던 경우가 16예(53%), 약간의 부작용이 있었던 경우가 10예(33%)였다. 3) 유용성은 중등도 유용이상이 10예(34%), 경도유용이상은 16예(54%)였다. 결론 : 이상의 결과를 종합해 볼때, SA96은 류마티스 관절염 치료에 유용한 약물로 사료되나, 보다 광범위하고 장기적인 임상시험이 필요하다고 본다. Background : SA96 is a new antirheumatic drug which was developed in Japan. A number of clinical studies has been demonstrated that SA96 is effective and safe in the treatment of rheumatoid anthritis (RA) with mild adverse reactions. However, there has been no experience in SA96 on RA outside of Japan. This study was performed to evaluate the clinical efficacy and safety of SA96 in patients with RA in Korea. Methods : 30 patients with RA who fulfilled 1987 revised criteria of American College of Rheumatology (ACR) were selected and were given 300mg/day of SA96 for 16 weeks or longer by the non double blind method. And the daily dosage was allowed to change method. And the daily dosage was allowed to change within the range between 100 and 600 mg depending on patients` compliances. Every patient was allowed to take nonsteroidal antiinflammatory drug (NSAID) and/ or steroid (less than 7.5mg/day of prednisolone), provided that the dosage was kept constant for the duration of this clinical trial. Results : In the clinical evaluastion items, it showed statistically significant improvements in Ritchie index, the number of painful joints, the number of swollen joints, morning stiffness, 15m walking time and ESR by the 8th week of drug administration. 1) Final global improvement 4 patients (13%) were assessed as markedly improved, 9(30%) as moderately improved, 9(30%) as slightly improved and 8 (27%) as unchanged. An rating of slightly improved or better was seen in 22 patients (73%). 2) Overall safety Adverse reactions were experienced in 14 patients (47%), mild adverse reactions in 10 (33%), moderate adverse reactions in 2(7%) and severe adverse reactions in 2 (7%). 3) Usefulness Considering final global improvement and overall safety, 3 patients (10%) revealed markedly useful, 7 (24%) moderately useful, 6(20) slightly useful, 9 (30%) indecisive, 3(10%) slightly unfavorble, 1 (3%) moderately unfavorable and 1 (3%) markedly unfavorable. 54% (16 out of 30) revealed mild or better useful. Conclusion : SA96 is expected to be one of the useful DMARDs in the treatment of RA. However, further large scale, long-term follow up clinical trials are required.

전신성 류마티스 질환에서 항인지질항체에 관한 연구

배상철(Sang Cheol Bae),정성수(Sung Soo Jung),송관규(Gwan Gyu Song),이인홍(In Hong Lee),장현규(Hyun Kyoo Jang),유대현(Dae Hyun Yoo),김성윤(Seong Yoon Kim),김신규(Think You Kim) 대한내과학회 1993 대한내과학회지 Vol.45 No.5

N/A Objectives: The antiphospholipid antibodies (APA) are associated with a clinical syndrome of vascular thrombosis, thrombocytopenia, recurrent fetal loss and neurological manifestations. This has been studied by several investigators for systemie lupus erythematosus but no systematic study has been reported for the correlation between a variety of systemic rheumatic diseases including rheumatoid arthritis and antiphospholipid antibodies in Korea. Methods: Authors have used enzyme-linked im-munosorbent assay (ELISA) to detect antibodies to phopholipids and studied the frequencies of antibodies to these antigens and their correlation with clinical and laboratory features in systemic rheumatic diseases. Resulta: 1) 206 patients were investigated for the presence of antibodies to phopholipids and 25 out of 206 patients (12. 1%) had antiphospholipid antibodies. 2) The frequencies of antibodies to phopholipids were 20.7% in patients with systemic lupus erythematosus, 12.3% in rheumatoid arthritis and 16.7% in mixed connective tissue dsease but antibodies to phospholipids were not detected in ankylosing spondylitis, polymyositis/ dermatomyositis, undifferentiated connective tissue disease and Behcet's disease. 3) In patients with systemic lupus erythematosus, no significant association was found between antiphos-pholipid antibodies and clinical and laboratory features except thrombocytopenia and anti-Ro antibody (p=0.003, p=0.036). But patients with antiphopholipid antibodies were likly to have a higher incidence of malar rash, photosensitivity, alopecia, neurologic manifestation, renal disorder, fetal loss and thrombosis than those without antiphospholipid antibodies. 4) In patients with rheumatoid arthritis, no significant association was found between antiphospholipid antibodies and clinical and laboratory features. Conclusions: These results showed that the detection of antibodies to phospholipids by ELISA was expected to be useful as a screening test and suggested that antiphospholipid antibody found in rheumatoid arthritis patients differed from that seen in systemic lupus eryth-ematosus patients. Further studies into the fine specificity of antiphospholipid antibody in various systemic rheumatic diseases are needed.

전신성 류마티스 질환에서 항 ENA 항체에 관한 연구

배상철(Sang Cheol Bae),송관규(Gwan Gyu Song),이인홍(In Hong Lee),유대현(Dae Hyun Yoo),김성윤(Seong Yoon Kim),김신규(Thin Kyou Kim) 대한내과학회 1993 대한내과학회지 Vol.45 No.4

N/A Objectives: Among a variety of nuclear antigens, extractable nuclear antigens(ENA) which can be extracted from nuclei by homogenization in neutral saline contain ribonucleoprotin, Sm, SS-A/Ro, SS-B/La and other antigens. Characterization of anti-ENA anti-bodies provides information about nosology, subset definition within diseases, clinical activity, specific organ involvement and prognosis. Methods: Authors have used double immunodiffusion test to detect antibodies to ENAs and studied the frequencies of autoantibodies to these antigens and their correlation with clinical and laboratory features in systemic rheumatic diseases. Results: 1) 1,063 patients were investigated for the presence of serum antibodies to ENAs and 180 out of 1,063 patients (16.9%) had anti-ENA antibodies. 3,412 tests were performed for the presence of antibodies to Sm, RNP, Ro, La, Scl-70 and Jo-1 respectively and 230 out of 3,412 tests (6.7%) were positive. 2) The profiles of 137 patients who had anti-ENA antibodies are systemic lupus erythematosus (61), rheumatoid arthritis with secondary Sj6gren's syndrome (26) and without secondary Sjogren's syndrom (9), mixed connective tissue disease (18), scleroderma (10), polymyosits/dermatomyositis (6), undifferentiated connective tissue diease (4), gout (1), fibromyalgia syndrome (1) and Hashimoto's thyroiditis (1). 3) The frequencies of antibodes to ENAs were 73.5% in patiets with systemic lupus erythemtosus, 9.6% in rheumatoid arthritis, 100% in mixed connective tissue disease, 71.4% in scleroderma and 46.2% in polymyostis/dermatomyositis. 4) The frequencies of antibodies to Sm, RNP, Ro and La in patients with systemic lupus erythematosus were 18.1%, 41.5% 43.9% and 4.9% respectively. (1) Patients with anti-Sm antbodies had a higher incidence of pleuritis than those without anti-Sm antibodies(p=0.029). (2) Patients with anti-RNP anibodies had a higher incidence of Raynaud's phenomenon and pleuritis and a lower incidence of renal disease than those without anti-RNP antibodies (p=0.008, p=0.019, p=0.029). (3) Patients with anti-Ro antibodies had a higher incidence of thrombocytopenia than those without anti- Ro antibodies. (4) There were no clinical and laboratory differences between patients with anti-La antibodies and without anti-La antibodies. 5) In patients with rheumatoid arthritis, anti-Ro anti-body was likely to be associated wih secondary Sjogren syndrome, although statistically significant association was not found (p=0.063). Conclusions: These results showed that the detection of antibodies to ENAs by double immunodiffusion test was expected to be a useful diagnostic marker and predict some clinical features in systemic rheumatic diseases.

Human Adjuvant Disease 의 임상적 고찰

배상철(Sang Cheol Bae),이인홍(In Hong Lee),유대현(Dae Hyun Yoo),김성윤(Seong Yoon Kim),최희윤(Hee Youn Choi),주경빈(Kyung Bin Joo) 대한내과학회 1992 대한내과학회지 Vol.43 No.2

N/A Background: Human adjuvat disease means the autoimmune disease or autoimmune disease like syndrome developed after plastic surgery using foreign body implantation. After 1st report of HAD by Miyoshi at 1964, a number of cases have been reported especially from Japan. However, there has been no report regarding HAD in Korea. Authors report 12cases of HAD which were experienced recently, Methods: 12patients who represented autoimmune disease or autoimmune disease-like syndrome after plastic surgery using foreign body implantation were evaluated clinically. Results: 1) The mean interval from plastic surgery to onset of HAD was 14.9years. 2) Eight of tweleve patients had undergone rhinoplasty and paraffin was most frequently used. 3) Seven of our patients were given the diagnosis of rheumatoid arthritis and the others were unclassified HAD. 4) Five patients underwent the operation to remove foreign material, Only one was improved. Conclusion: In korea, there has been done a number of plastic surgery using paraffin or silicone, So we have to concern about HAD after plastic surgery using foreign body implantation.

강직성 척추염의 임상적 분석

배상철 ( Sang Cheol Bae ) 대한류마티스학회 1994 대한류마티스학회지 Vol.1 No.1