[Studies on disease susceptibility and disease resistance in Behçet's disease].
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Biomedical subjects
Publications and source records attributed to S Kotake.
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Interferon induces oligo-2',5'-adenylate synthetase in cells. In various diseases, interferon was detectable in the circulation or was produced spontaneously from peripheral blood mononuclear leukocytes. The oligo-2',5'-adenylate synthetase activity in peripheral blood mononuclear leukocytes was examined in various diseases, including systemic lupus erythematosus, sarcoidosis, Vogt-Koyanagi-Harada disease, and Behcet's disease. The activity of this enzyme was significantly increased in systemic lupus erythematosus (P less than 0.01), sarcoidosis (P less than 0.01), and Vogt-Koyanagi-Harada disease (P less than 0.01) compared with that in controls, but the increase of activity was not significant in Behcet's disease (P greater than 0.05).
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The interaction of a large number of ATP and ADP analogs with nitrogenase from Azotobacter vinelandii, Klebsiella pneumoniae, and Clostridium pasteurianum has been examined. Only 1,N6-etheno-ATP and 2'-deoxy-ATP served as substrates for acetylene reduction. Other triphosphates including GTP, ITP, 8-Br-ATP, alpha,beta-methylene ATP, beta,gamma-methylene ATP, 6-chloropurine riboside triphosphate, and AMP-PNP were inert, showing less than 50% inhibition at levels up to two- to fivefold greater than ATP. Xanthosine triphosphate behaved simply as a chelator of magnesium, activating the enzyme at low levels but strongly inhibiting at high levels. When nucleotide diphosphates were tested as inhibitors with enzyme from A. vinelandii, GDP, dGDP, and 6-chloropurine riboside diphosphate were ineffective, XDP was three- to fivefold less effective, and dADP and 1,N6-etheno-ADP were about equally as effective as ADP. With enzyme from C. pasteurianum, dADP was twofold less effective than ADP, XDP was fivefold less effective, and IDP and 1,N6-etheno-ADP appeared to be ineffective. Results with enzyme from K. pneumoniae were very similar to those obtained with A. vinelandii. Different metal ions were tested in the presence of both ATP and ADP to determine whether preferential binding to one nucleotide or the other might alter the ADP/ATP ratio needed for 50% inhibition of activity. Magnesium and manganese gave the same ratio, while with Fe and Co, slightly less ADP was required for equivalent inhibition. Nickel appeared to reduce the sensitivity of A. vinelandii nitrogenase to ADP inhibition while increasing that of C. pasteurianum, but both effects were less than twofold. Calcium, strontium, and aluminum ions were inert with enzymes from these organisms. Cd and Zn were also ineffective with K. pneumoniae. Two isomers of ATP beta S were prepared by enzymatic synthesis from ADP beta S. The A form was a more potent inhibitor of A. vinelandii nitrogenase.
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The polyoncogenic prototype human papovavirus BKV (Gardner's strain) produced clear, small and large plaques. Two small-plaque isolates (wt-500 and wt-502), as well as a large-plaque-forming isolate (wt-501), induced frequent brain tumors and occasional osteosarcomas (but no insulinomas) in hamsters. The large-plaque former (wt 501) was more tumorigenic than the two small-plaque mutant (pm-525), which had been rescued from hamster tumor cell lines and have small deletion near the origin of DNA replication, induced frequent brain tumors and insulinomas. Mutant 522 was about five times more tumorigenic than wt-501. These results support the hypothesis that the polyoncogenicity of prototype BKV is accounted for by the presence of BKV mutants.
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A mouse tumor cell line (MCT) persistently infected with mumps virus (strain Urabe) was obtained. No antibody or chemicals were required for establishment or maintenance of the infected cell line (M-MCT). No difference was observed by light microscopy between MCT and M-MCT cells, except for cytoplasmic inclusion bodies in 10--20% of the M-MCT cells. Hemadsorption of chicken erythrocytes, which did not necessarily coincide with inclusion positive cells was shown by 10--20% of the M-MCT cells. Immunofluorescence staining revealed that almost all M-MCT cells contained mumps virus antigens, which were seen mainly in the cytoplasm as fine granules, dots, or large clumps. Infectious mumps virus was consistently detected in the culture fluid and the released virus showed some temperature sensitivity when assayed at 34 degrees C and 40 degrees C. M-MCT was resistant to superinfection with homologous virus and showed some resistance to heterologous viruses. Thirty one clones of M-MCT were isolated by the soft agar method. Some, but not all, clones had viral antigen and all those with antigen released virus into the culture medium. The growth rates of MCT and M-MCT cells as monolayer cultures in vitro were similar, but the transplantability of M-MCT cells in syngeneic C57BL/6 mice was lower than that of MCT cells.
PURPOSE: The new microemulsion preconcentrate (MEPC) formulation of ciclosporin has been developed to reduce problems in intestinal absorption and to stabilize fluctuations in blood levels. A multicenter, open-label clinical trial of MEPC was conducted to assess its efficacy and safety in Behçet's disease patients with ocular involvement. METHODS: The patient population comprised 17 de novo patients (patients not previously treated with ciclosporin in the currently available formulation) and 30 patients whose ciclosporin formulation was switched from the conventional formulation to MEPC. The patients were treated with the test formulation for 16 weeks in the former (de novo) group and for 12 weeks in the latter (switched) group. RESULTS: In the de novo group, ocular attacks decreased significantly as compared to the pretreatment incidence in 11 of the 14 patients (78.6%) evaluated after MEPC therapy. Ocular attacks also decreased significantly in the switched group. In the de novo group, visual acuity improved with MEPC therapy in 20 of the 28 eyes (71.4%) examined, and the overall efficacy evaluation was "improved" or "markedly improved" in 13 of the 16 patients evaluated (81.3%). The one case each of onset of neuro-Behçet's disease and intestinal Behçet's disease observed in the de novo group were regarded as adverse reactions. CONCLUSION: It was concluded that ciclosporin MEPC is useful for controlling the ocular symptoms of Behçet's disease, and that it can be used as effectively and safely as the conventional formulation.
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Specimens of synovial tissues from 5 affected joints of 3 patients with Behçet's disease were available for histopathological examination. All specimens were infiltrated by lymphocytes and neutrophils, and exhibited marked vascularity and infiltration of lymphoid cells among the vessels. Marked plasma cell infiltration and lymphoid follicle formation were found in one synovial tissue sample. There was no evidence of infection or vasculitis. These findings suggest that the histopathological characteristics of synovial tissue in Behçet's disease may have a wide range, some of which may even resemble the synovial tissue of rheumatoid arthritis.
OBJECTIVES: Inflammatory mediators such as interleukin-6 and tumor necrosis factor-alpha play an important role in the pathogenesis of rheumatoid arthritis (RA) by promoting chronic inflammation and joint damage. NF-kappaB is a transcriptional activator of genes for these cytokines. It also plays an important role in the regulation of osteoclast differentiation which plays a key role in joint destruction in RA. Ligands for peroxisome proliferator-activated receptor (PPAR) -gamma have recently been reported to inhibit the development of RA. In this study, we investigated the role of PPARalpha in RA. METHODS: We analyzed the protein expression of PPAR-alpha and -gamma in rheumatoid synovial fibroblasts (RSF) from RA patients and analyzed the effects of ligands for PPAR-alpha and -gamma on cytokine production from RSF NF-kappaB activations in RSF and osteoclast differentiation from osteocalst progenitor in the peripheral blood. Moreover, we analyzed the effects of oral administration of PPAR-alpha and -gamma ligands on the development of adjuvant-induced arthritis (AIA) in female Lewis rats. RESULTS: We confirmed the expression of PPAR-alpha in RSF and also demonstrated that fenofibrate, a ligand for PPAR-alpha, inhibited cytokine production from RSF, NF- kappaB activation in RSF, and osteoclast differentiation from osteoclast progenitor cells. Furthermore, we demonstrated that fenofibrate inhibits the development of arthritis in a rat model of human RA. CONCLUSIONS: These results indicate that fenofibrate suppresses the development of arthritis by inhibition of NF-kappaB signaling; therefore, this compound offers possible anti-rheumatic drug.
We describe two cases, a 28-year-old woman and a 46-year-old man, with mouth and genital ulcers with inflamed cartilage (chondritis of the nose and ears) (MAGIC syndrome). The conditions of both patients were resolved by treatment with corticosteroid and colchicine. We also review the English literature related to this rare syndrome.