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제 2형 콜라겐에 의해 경구관용 유도된 DBA/1 mice에서의 세포면역반응
양형인 ( Hyung In Yang ),김완욱 ( Wan Uk Kim ),민도준 ( Do Jun Min ),박성환 ( Sung Hwan Park ),홍연식 ( Yeon Sik Hong ),이상헌 ( Sang Heon Lee ),조철수 ( Chul Soo Cho ),김호연 ( Ho Youn Kim ) 대한류마티스학회 2000 대한류마티스학회지 Vol.7 No.4
Objective: To investigate the dosage of bovine type II collagen (BnCII) for the induction of oral tolerance in CIA animals, and to verify the changes of immune response and TGF-β production of mesenteric lymph node cells in tolerized CIA animals. Methods: Oral tolerance was induced by feeding of variable doses (5㎍, 10㎍, 20㎍ and 40㎍) of BnCII to DBA/1 mice 4 times per week during 2 weeks, and control mice were given ovalbumin (1000㎍), before immunization. We examed clinical assessment; incidence of arthritis, severity of arthritis, arthritic limb by visual analysis. IgG antibodies to BnCII were measured by ELISA, T cell responses to BnCII and PHA were quantified by antigen (CII)-induced 3H-thymidine incorporation into lymphocytes of mesenteric lymph node, draining lymph node, and spleen. TGF-β in supernatants obtained from lymph node culture medium was measured by ELISA. Results: Arthritis limbs were observed in 100% of control at 5 weeks after subcutaneous BnCII injection. The incidences of CIA in all tolerized group were significantly lower than that in control 5 weeks after immunization (control 100% vs. 5㎍ feeding group: 50%, 10㎍ feeding group: 50%, 20㎍ feeding group: 50%, 40㎍ feeding group: 55.5%, P<0.01). In comparison to control, mean articular indices were lower in all tolerized groups (control 5.13: 5㎍ feeding group 3.50, 10㎍ feeding group 2.75, 20㎍ feeding group 2.87, 40㎍ feeding group 2.63, P<0.05). Arthritic limbs were also significantly lower in tolerized groups (control 58.3: 5㎍ feeding group 20.8, 10㎍ feeding group 16.7, 20㎍ feeding group 20.8, 40㎍ feeding group 20.8, P<0.05). The titers of IgG antibody to CII were lower in tolerized group than that in control [tolerized group; median 10 (min. 0, max. 48), control; median 33 (min. 8.6, max. 101), P<0.05]. The proliferative responses to BnCII were significantly suppressed in tolerized (control 8010±2319cpm, tolerized group 4500±2060cpm, P<0.01). High TGF-β production was noted in tolerized group (control; 28pg/ml, BnCII feeding group; 73pg/ml). Conclusion: Oral tolerance in DBA/1 mice was successfully induced from low doses of BnCII (5㎍) and suppressed T and B cell function in conjunction with increased TGF-β production may play an important role for the induction of CII induced oral tolerance in DBA/1 mice.
류마티스 질환에서 혈청 Soluble Fas Ligand (sFasL), FasL-Fas 복합체, FasL-IgG 복합체 측정
민준기 ( Jun Ki Min ),민소연 ( So Youn Min ),조미라 ( Mi Ra Cho ),정재연 ( Jae Yeon Jeong ),주대명 ( Dae Myung Jue ),민도준 ( Do June Min ),조철수 ( Chul Soo Cho ),김호연 ( Ho Youn Kim ) 대한류마티스학회 2000 대한류마티스학회지 Vol.7 No.4
Objective: To quantify the soluble Fas ligand (sFasL) and to measure FasL-Fas complex and FasL-IgG complex in the sera of patients with various rheumatic diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), and adult onset Still`s disease (AOSD). Methods: Serum samples were obtained from 37 patients with SLE, 40 with RA, 30 with SSc, 20 with AOSD, and 40 healthy controls. The serum sFasL, FasL-Fas complex, and FasL-IgG complex were measured using a sandwich enzyme-linked immunoabsorbent assay. Hospital medical records were retrospectively reviewed for clinical and laboratory characteristics in patients with SLE. Disease activity in SLE patients was assessed by the SLE Disease Activity Index (SLEDAI) score. Results: In patients with SLE, serum sFasL levels (383.1±208.9pg/ml) were significantly higher (p<0.001) than those of healthy controls (192.0±84.7pg/ml). sFasL levels in patients with RA (150.8±30.7pg/ml, p=0.014), SSc (115.4±13.5pg/ml, p<0.001), and AOSD (137.5±12.9pg/ml, p=0.001) were significantly lower compared with healthy controls. The frequencies of positive FasL-Fas complex and FasL-IgG complex were higher in patients with SLE (56.8%, 56.8% respectively) than in healthy controls (2.5%, 0% respectively) (p<0.001). All patients with RA or AOSD were negative for FasL-Fas complex and FasL-IgG complex. No patients with SSc were positive for FasL-Fas complex. On the other hand, the positive frequency of FasL-IgG complex was greater in patients with SSc (16.7%) than in healthy controls (0%) (p=0.012). Serum levels of FasL-IgG complexes in active SLE patients (OD 0.467±0.050) were tended to be lower than those in inactive SLE patients (OD 0.509±0.055) (p=0.060). SLEDAI score was tended to be negatively correlated with the serum levels of FasL-IgG complex in patients with SLE (r=-0.308, p=0.068). Conclusion: These results suggest that FasL may possibly play a role in the pathogenesis of SLE.
한국인 류마티스 관절염 환자에서 Susceptible Allele 의 빈도 조사와 질병 진행정도에 미치는 영향
민준기(Jun Ki Min),민도준(Do Jun Min),추교영(Kyo Young Choo),양형인(Hyeong In Yang),박성환(Sung Hwan Park),이상헌(Sang Heon Lee),조철수(Chul Soo Cho),김태규(Tai Gyu Kim),김호연(Ho Youn Kim) 대한내과학회 1995 대한내과학회지 Vol.49 No.1
N/A Objectives: To identify the HLA-DR4 subtypes and the influence of susceptibility alleles on disesase severity in Korean patients with rheumatoid arthritis. Methods: Ninty five patients with RA and one hundred eighteen normal controls were examined for HLA-DR genotyping by reverse dot hybridization. We compared clinical manifestationes such as bony erosion, joint deformity, anemia, subcutaneous nodule, vasculitis and pulmonary symptoms and signs according to the presence of susceptibility epitopes or not. Results: The frequency of HLA-DRBI*04 was significantly increased among RA patients (60.0% versus 31.4%, relative risk 3.28, p<0,005). HLA-DR6 was decreased in RA patients(16.8% vewsus 32.2%, RR=0.39, p<0.05). Forty two of 57 DR4 positive patients(71.9%) possesed the DRHI*0405. The DRBI *0405 is the most common DRBI allele and strongly associated with RA(44.2% vesrsus 11.9% of controls, relative risk 5.88, p<0.05). The frequencies of the inferred amino acid sequences, QRRAA, QKRAA, and RRRAA at position 70-74 on the third hypervariable regoins in HLA-DRBI alleles which are known to be the RA susceptible allele are higer in patients group(69.5% versus 29.7% of controls, relative risk 4.07, p<0.05). Among predisposing epitopes, there was increase in the percentage of patients who possessed the QRRAA sequence(64.2% versus 25.4% of controls, relative risk 4.03, p<0.05). Bony erosion, joint deformity, and extraarticular manifestations such as anemia, vasculitis, pulmonary manifestations were associated with suscep-tible allele, but subcutaneous nodule was not associated with susceptible allele signficantly. Conclusion: These results showed that the most common HLA-DRBI 0405. High frequencies of susceptible alleelepitops are associated with bony erosion, joint deformity, and extraarticular manifestations such as anemia, vasculitis, and pulmonary manifestations. Screening of sesceptible allele might be one of useful tools to predict the progression of disease and prognosis.
민준기 ( Jun Ki Min ),민도준 ( Do June Min ),홍연식 ( Youn Sik Hong ),이상헌 ( Sang Heon Lee ),박성환 ( Sung Hwan Park ),조철수 ( Chul Soo Cho ),김호연 ( Ho Youn Kim ) 대한류마티스학회 2000 대한류마티스학회지 Vol.7 No.4
Objective: To determine the causative organisms and predisposing factors of bacteremia in patients with systemic lupus erythemaosus (SLE). Methods: We retrospectively evaluated medical records of 358 patients with SLE who were followed in Kangnam St. Mary`s Hospital from 1992 to 1997. Bacteremic SLE patients were compared to non-bacteremic SLE patients in terms of laboratory and clinical variables. Results: Twenty-nine episodes of bacteremia in 27 patients with SLE (26 women, 1 man) were identified. The episode of community acquired bacteremia (n=21, 72.4%) was more frequent than that of hospital acquired bacteremia (n=8, 27.6%). Isolated bacterial organisms from blood were as follows: gram negative organisms (n=14); Salmonella species (n=8), E. coli (n=4), P. mirabilis (n=1), K. pneumonia (n=1). gram positive organisms (n=15); S. aureus (n=6) , Streptococcus pneumoniae (n=2), coagulase negative Staphylococci(n=2), Bacillus species (n=1), Streptococcus viridans (n=1), Streptococcus pyogenes (n=1), Entero-coccus faecalis (n=1), Listeria monocytogenes (n=1). SLE was the most common underlying condition among Salmonella bacteremic patients. One of twenty seven bacteremic SLE patients (3.8%) died in spite of antibiotic therapy. Logistic regression analysis of the laboratory and clinical variables between bacteremic SLE patients and non-bacteremic SLE patients (n=140) showed that bacteremic SLE patients were more frequently associated with thrombocytopenia (p=0.008, odds ratio (OR)=7.8, 95% confidence interval (CI), 1.7 to 35.9), lupus nephritis (p=0.023, OR=5.3, 95% CI, 1.1 to 26.8), and high dose steroid therapy (prednisolone >0.5mg/kg/day, p=0.008, OR=12.1, 95% CI 2.5 to 58.6) than non-bacteremic SLE patients. Conclusion: Our data suggested that Salmonella was the single most frequent isolate from the blood of SLE patients. Lupus nephritis and high dose steroid therapy were independent predisposing factors for the development of bacteremia in SLE patients.
베체트 환자에서의 monocyte chemoattractant protein-1의 상승
도주호 ( Do Ju Ho ),정지현 ( Jeong Ji Hyeon ),박찬석 ( Park Chan Seog ),고지송 ( Go Ji Song ),김순섭 ( Kim Sun Seob ),최현철 ( Choe Hyeon Cheol ),손장명 ( Son Jang Myeong ),민도준 ( Min Do Jun ),박성환 ( Park Seong Hwan ),조철수 ( 대한내과학회 2003 대한내과학회지 Vol.65 No.4
목적: 베체트병에서는 림프구, 단핵구, 호중구에 의한 염증성 혈관염이 흔하게 발생하는데 특히 단핵구의 활성화와 충원을 책임지는 MCP-1과 같은 케모카인의 증가가 조직 내 염증세포의 충원과 침윤에서 중요한 역할을 할 것으로 생각되나 아직까지 이에 대한 연구는 없는 실정이다. 저자들은 본 연구에서 베체트병 환자의 혈청 혹은 세포배양액에서 MCP-1의 표현을 조사하고 RANTES, MIP-1α IL-8 등 다른 케모카인들과의 연관성을 조사하였다. 방법: 7 Background: Monocyte chemoattractant protein-1 (MCP-1) belongs to C-C subfamily of chemokines, which stimulates the migration of monocytes. MCP-1 exerts various effects on the monocytes, including the induction of integrin and tissue factor, and synthesis
β-Cyclodextrin Piroxicam의 약역동학적 연구와 골관절염 환자에서의 치료효과
이상헌 ( Sang Heon Lee ),민도준 ( Do Jun Min ),박성환 ( Sung Hwan Park ),조철수 ( Chul Soo Cho ),박동준 ( Dong Jun Park ),김호연 ( Ho Youn Kim ) 대한류마티스학회 1994 대한류마티스학회지 Vol.1 No.2
연구배경: 소염진통제는 골관절염환자의 통증을 완화시키고 염증을 감소시키는데 대표적인 약제이다. 이런 약제들을 장기간 복용할 경우 위장관에 심각한 부작용이 일어날 수 있다. piroxicam은 널리 사용되고 있는 소염진통제이다. 이 약제를 β-cyclodextrin으로 분자 포접하여 개발한 β-cyclodextrin-piroxicam(Brexin(R))의 약역동학적인 조사와 골관절염 환자에서의 소염진통효과 및 위장관에 대한 내성을 알아보기 위하여 본 연구를 시행 하였다. 방법: 1993년 7월부터 가톨릭의대부속 강남성모병원 류마티스 크리닉을 내원한 환자중 슬관절의 골관절염 환자 30명에서 β-cycloextrin-piroxicam 1일 20mg씩 약 8주간 투여후 임상적 효과 및 부작용을 조사하였다. 그리고 4명의 건강성인에서 이 약제의 약역동학을 조사하기 위해 투여직전, 투여후 15분, 30분, 60분, 2시간, 3시간, 24시간에 각각의 혈장내 농도를 HPLC로 측정하여 이를 piroxicam과 비교하였다. 결과: 약물을 투여받은 환자들중 90%에서 임상적 호전을 보였으며, 휴식시 동통, 운동시 동통, 압통 및 부종의 의미있는 감소를 나타내었다. 부작용은 위장관 부작용이 3예로 가장 많았으며 이중 1예에서는 약물을 중단하였으나, 그외 특이한 부작용은 발견되지 않았다. 약역동학적 조사에서는 기존의 piroxicam제제에 비해 흡수가 빠르게 나타났고 24시간 동안 지속적으로 높은 혈중 농도를 보였다. 결론: β-cyclodextrin-piroxicam은 골관절염 및 여러 류마티스 질환을 가진 환자에서 특히 위장관 부작용이 우려되는 경우 유용한 치료 약제로 생각된다. Objectives: To evaluate the efficacy, safety and pharmacokinetics of β-cyclodextrin-piroxicam in patients with osteoarthritis of knee. Methods: Thirty patients with osteoarthritis (28 women, 2 men) were enrolled in the study. β-cyclodextrin-piroxicam 20mg was administered orally, once daily for 8 weeks. The indices of efficacy (evaluation of the pain, joint swelling, tenderness and functional limitation) were evaluated at 0, 2, 4, 8 weeks. Piroxicam plasma concentrations were determined by HPLC over 24 hours in 4 healthy volunteers, and were compared with those of reference formulation. Results: There were statistically significant improvement in the indices of efficacy between entry and end of the study. The majority of side effects were related to the gastrointestinal tract, but the symptoms were mild except 1 drop-out case. According to pharmacokinetic study, the bioavailability and absorption rate of piroxicam were improved in β-cyclodextrin-piroxicam group. Peak plasma piroxicam concentrations were higher in β-cyclodextrin-piroxicam group than were in reference group. Conclusions: β-cyclodextrin-piroxicam is efficacious and well tolerated in patients with osteoarthritis. Because of its rapid absorption, good bioavailability and fewer gastrointestinal disturbance, it seems to be a useful drug for long-term management of osteoarthritis.