Effect of Histone H1 on Collagen Induced Arthritis in Mice

Objective : Besides the functions of histones in the nucleus of the cells, there is growing evidence that histones have many other extra-cellular or extra-nuclear functions, such as stabilizing axonemal microtubule of sea urchin sperm flagella. This microtule assembly function of the histone is similar to that of taxol, which has an effect of controlling joint inflammation. In this study, a possible suppressive effect of histones on a mouse collagen-induced arthritis(CIA) model was investigated. Methods : A DBA/1 mouse were injected intradermally with emulsified chicken type II collagen. Three weeks after immunization, histone H1 was injected intraperitoneally twice a week. Clinical incidences of arthritis and arthritis index were measured. Anti-collagen antibodies and stimulation index of the splenocytes of mice were measured. IL-10 and TNF-α in the supernatants of the cultured splenocytes were measured by ELISA. IL-10 and TNF-α in the supernatants of the cultured U937 cells stimulated with histone H1 were measured by ELISA. mRNA expression of IL-10 and TNF-α in the U937 cells stimulated with histone H1 were observed. Results : Histone H1 appears to be an effective suppressor of CIA in mice. When delivered intravenously, this suppressive effect of histone H1 was most effective compared to intraperitoneal or intradermal injections. The anti-collagen antibody level of the histone H1 treated group was significantly lower than that of the control group. A remarkable increase in the level of IL-10 was observed from the cultured supernatant of the splenocytes treated with histone H1. Also, an increase of IL-10 level was observed from the cultured supernatant of the U937 cells treated with histone H1. Conclusion : According to these results, histone H1 appears to have a suppressive effect on CIA. The mechanism of the suppressive effect of histone may be a stimulation of IL-10 production.ope

Effect of a Flavon Extracted from Artemisia absinthium on Collagen Induced Arthritis in Mice

PURPOSE: In this study, a possible suppressive effect of a flavon extracted from Artemisia absinthium on a mouse collagen-induced arthritis (CIA) model was investigated.0aMETHODS: DBA/1 mice were injected intradermally with emulsified chicken type II collagen. Three weeks after immunization, a flavon was introduced p.o. everyday. Clinical incidences of arthritis and arthritis index were measured. Measurement of anti-collagen antibodies and a stimulation index of the splenocytes of the mice were measured. IL-10 and TNF-alpha in the supernatants of the mice sera were measured by ELISA. mRNA expression for IL-10 and TNF-alpha in the splenocytes were tested.0aRESULTS: Flavon extracted from Artemisia absinthium appears to be an effective suppressor of CIA in mice. The serum anti-collagen antibody level and stimulation index of the cultured splenocytes showed no significant differences among the three experimental groups. Also serum IL-10 and TNF-alpha levels did not show any significant differences among the three experimental groups. An increased expression of mRNA for IL-10 was observed in the splenocytes treated with flavon.0aCONCLUSION: With these results, flavon extracted from Artemisia absinthium appears to have a suppressive effect of CIA. The mechanism of the suppressive effect of flavon extracted from Artemisia absinthium may be from a stimulation of IL-10 production.ope

Expression of Toll-like Receptor-2 on the Peripheral Blood Monocytes in Kawasaki Disease Patients

Objective : Toll like receptor(TLR) is known to be involved in innate immunity. Many microbial antigens stimulate TLR, and as a result of intracellular signal transduction, they activate nuclear factor-kB which produces diverse inflammtory cytokines. Until now, many research topics in Kawasaki disease focused on cytokine increasement. In this study, we aim to reveal TLR increasement which might be associated with initiation of inflammatory response. Methods : We obtained the peripheral blood of ten patients who were diagnosed with Kawasaki disease in Yonsei University College of Medicine from March 2003 to August 2003, as well as those of a febrile control group and the same number of a normal control group. Flow cytometry was done in all samples for quantification of TLR-2 expression in CD14 positive monocyte. And we also extracted total RNA of periphral monocyte and quantificated expression of TLR-2 mRNA by RT- PCR. Results : The expression of TLR-2 in Kawasaki disease increased significantly compared with the normal control group but not when compared with the febrile control group. And the expression decreased slightly in the subacute phase of Kawasaki disease compared with the acute phase, but this was statistically insignificant. mRNA expression of TLR-2 in peripheral blood monocyte also increased in the acute phase of Kawasaki disease. Conclusion : Expression of TLR-2 in Kawasaki disease increased when compared with the normal control group, which means that innate immunity is associated with the pathogenesis of Kawasaki disease.ope

Statistical Analysis of 1,000 Cases of Kawasaki Disease Patients Diagnosed at a Single Institute

Purpose : To find the risk factors associated with coronory artery lesions, non-responsiveness to intravenous immunoglobulin(IVIG) treatment, and recurrences in Kawasaki disease patients. Methods : We retrospectively analyzed 1,000 Kawasaki disease patients who were admitted to Yonsei University Medical Center from September 1990 to December 2003. We compared between responder and non-responder groups to IVIG treatment as well as between relapsed and non-relapsed groups, and as to the relapsed group, we also compared variables between patients in their first and second attack states. Finally, factors associated with longer-fever duration from disease onset were evaluated. Results : Longer fever durations before and after IVIG treatment, male sex, lower Hgb and Hct level, higher WBC count and segmented WBC proportion, and higher CRP and Harada's score were related with coronary artery lesions. Non-responsiveness was related to higher WBC count, segmented WBC proportion, CRP, SGPT, Harada's score, and pyuria. Moderate-to-severe coronary artery dilatations and recurrences were more commonly seen among the non-responder group. No significant predictive factors for recurrence were found. In the relapsed group, lower WBC count, CRP, and shorter fever duration from disease onset were observed in their second attack state. Fever duration from disease onset showed positive correlation with WBC count, CRP, and Harada's score and negative correlation with Hgb levels. Conclusion : Higher WBC count, CRP, and higher Harada's score were related to both higher incidences of coronary artery lesions and non-responsiveness to IVIG treatment, and these factors were also related with longer fever duration. Non-responders to IVIG treatment showed higher recurrence rate and more moderate-to-severe coronary artery dilatations than responders.ope

A Clinical Study of Infective Endocarditis in Childhood

Purpose : Advances in the treatment of congenital heart disease and a decline in the incidence of rheumatic fever has led to changes in the causative organisms and the clinical outcome of infective endocarditis(IE). We sought to analyze the clinical outcome, prognostic factors, causative organisms and corresponding antibiotic sensitivity in IE. Methods : Retrospective analysis of medical records of 104 children diagnosed and treated with IE at Severance Hospital, Yonsei University College of Medicine from January 1986 to June 2003 was undertaken. According to the Duke criteria, 55 patients were classified into the definite group(DG) and possible group(PG). Results : Thirty one cases(56.4%) fulfilled the criteria for the definite group in the Duke criteria, whereas 24 cases(43.6%) fulfilled the criteria for the possible group. The most common chief complaint on admission was fever(93%). The most common infecting organism was Staphylococcus aureus, which was found in 14 cases(48.3%). Three cases(21.4%) of this organism were methicillin- resistant S. aureus(MRSA). Other causative organisms were α-streptococcus(seven cases, 24.1%), Staphylococcus epidermidis(three cases, 10.3%), Citrobacter freundii(one case, 3.8%), Enterococcus faecium(one case, 3.4%) and Candida albicans(three cases, 10.3%). Penicillin-resistant organisms were found in 90.5%(19/21) of total cases and the most sensitive antibiotics were vancomycin(13/13, 100 %) and teicoplanin(12/12, 100%). One case of IE due to MRSA unresponsive to vancomycin was treated with Arbekacin. Conclusion : The incidence of IE caused by S. aureus, especially MRSA, is increasing. Multi-drug resistant organisms are also emerging as a frequent cause of IE. Thus, in patients strongly suspected of having IE in patients with underlying heart disease, glycopeptides such as vancomycin combined with aminoglycosides should be considered, and if fever and positive blood cultures continue despite treatment with glycopeptides, a consideration of the use of new antibiotics may improve the treatment results.ope