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K Matsuta

Publications and source records attributed to K Matsuta.

45 records · Page 3Linked to original sources
PubMed1981

Neutral proteinases from articular chondrocytes in culture. I. A latent collagenase that degrades human cartilage type II collagen.

Culture media collected from secondary monolayer and spinner cultures of rabbit articular chondrocytes showed evidence of collagenolytic activity by the following criteria: (1) Amicon PM-10 concentrates of culture medium released [14C] glycine from reconstituted rabbit skin collagen fibrils at 37 degrees C; (2) medium concentrated by lyophilization decreased the relative viscosity of human cartilage collagen in solution. The loss in viscosity was partially inhibited if medium was preincubated with o-phenanthroline, and (3) degradation of human cartilage collagen after 60 h incubation at 24 degrees C was characterized primarily by the appearance of 75 000 dalton (TCA) and 25 000 dalton ((TCB) products. The majority of the collagenase (EC 3.4.24.3) from cultured chondrocytes was secreted in latent form, since preincubation with either trypsin or p-aminophenylmercuric acetate significantly increased activity against human cartilage collagen. Chondrocyte collagenase may be important in mediating the normal slow turnover of cartilage collagen and may be particularly active in collagen destruction associated with early stages of synovial joint arthritides, before attack by non-cartilage cells or extra-articular soft tissues.

Animals↗
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Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG.

Rheumatoid arthritis (RA) is a widely prevalent (1-3%) chronic systemic disease thought to have an autoimmune component; both humoral and cellular mechanisms have been implicated. Primary osteoarthritis (OA) is considered to be distinct from rheumatoid arthritis, and here damage is thought to be secondary to cartilage degeneration. In rheumatoid arthritis, immune complexes are present that consist exclusively of immunoglobulin, implying that this is both the 'antibody' (rheumatoid factor [RF]) and the 'antigen' (most commonly IgG). Autoantigenic reactivity has been localized to the constant-region (C gamma 2) domains of IgG. There is no evidence for a polypeptide determinant but carbohydrate changes have been reported. We have therefore conducted a study, simultaneously in Oxford and Tokyo, to compare in detail the N-glycosylation pattern of serum IgG (Fig. 1) isolated from normal individuals and from patients with either primary osteoarthritis or rheumatoid arthritis. The results, which required an evaluation of the primary sequences of approximately 1,400 oligosaccharides from 46 IgG samples, indicate that: (1) IgG isolated from normal individuals, patients with RA and patients with OA contains different distributions of asparagine-linked bi-antennary complex-type oligosaccharide structures, (2) in neither disease is the IgG associated with novel oligosaccharide structures, but the observed differences are due to changes in the relative extent of galactosylation compared with normal individuals. This change results in a 'shift' in the population of IgG molecules towards those carrying complex oligosaccharides, one or both of whose arms terminate in N-acetylglucosamine. These two arthritides may therefore be glycosylation diseases, reflecting changes in the intracellular processing, or post-secretory degradation of N-linked oligosaccharides.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Mode of inheritance of HLA-DRB1 shared epitope in Japanese familial rheumatoid arthritis.

OBJECTIVE: To clarify the mode of genetic contribution of the HLA-DR shared epitope (SE) to the pathogenesis of familial cases of Japanese rheumatoid arthritis (RA). METHODS: Fifty-three unrelated Japanese RA families that had more than 2 affected sibs were selected. The HLA-DR shared epitope typing was carried out by the PCR method and PCR-SSCP (single stranded DNA conformation polymorphism) method. Affected sib pair analysis was carried out using the MAPMAKER/SIB 2.0 program. The mode of inheritance was also calculated based on the sharing of genes identical by descent (IBD) between siblings in each of the 53 affected sib-pairs (propositus and the 2nd affected sib). RESULTS: The maximum LOD score of HLA-DR was 0.437, and the sharing of 2 IBDs, 1 IBD, and no IBDs between affected sibs were 0.330, 0.500, and 0.170, respectively. The sharing distribution of IBD was confirmed to be compatible with the dominant or additive mode since the observed gene frequency of SE was 0.255. CONCLUSION: The HLA-DR shared epitope participated in the pathogenesis of familial cases of Japanese RA. The SE contributes to this pathogenesis in either the dominant or additive mode of inheritance.

Adult↗
PubMedDate not supplied

The genetic contribution of the TNFa11 microsatellite allele and the TNFb + 252*2 allele in Japanese RA.

OBJECTIVES: The contribution of the microsatellite polymorphisms of TNFa and TNFb, and the TNFB + 252 (TNFB) dimorphism to the pathogenesis of rheumatoid arthritis (RA) was studied among Japanese patients. METHODS: The TNFa and TNFb microsatellite polymorphisms, and the TNFB dimorphism were determined in Japanese RA patients and normal subjects using electrophoresis followed by specific PCR amplification. HLA-DRB1*04 typing was carried out by the PCR-SSCP method. RESULTS: The allele frequency of TNFa11 showed a significant increase in RA with DRB1*0405 when compared to that in RA without DRB1*0405 (28.5% Vs 12.9%, respectively, p = 0.022). An association analysis indicated that TNFa11 was not primary, but secondary to the increase in HLA-DRB1*0405, because TNFa11 showed a strong positive association with HLA-DRB1*0405 in Japanese controls. The slight increase in the TNFb4 allele observed in RA with DRB1*0405 (50.0%) may be reflective of the increase in TNFa11 and DRB1*0405. In RA with DRB1*0405, the allele frequency of TNFB*2 significantly increased compared to that of normal controls (75.0% Vs 55.3%, respectively, p = 0.007) and compared to that of RA without DRB1*0405 (45.0%, p = 0.001). No significant positive association of TNFB*2 with HLA-DRB1*0405 or TNFa11 in Japanese controls might suggest that the increase in the TNFB*2 allele might not be secondary to the increase in DRB1*0405, and that TNFB*2 might contribute additively to DRB1*0405-positive RA in Japanese. CONCLUSION: TNFB*2 may contribute additively to Japanese RA with HLA-DRB1*0405, while TNFa11 and TNFb4 are not independent genetic markers of RA among Japanese.

Alleles↗
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Inhibitory effects of gold sodium thiomalate on DNA polymerase alpha.

The usefulness of gold compounds in the therapy of rheumatoid arthritis is well established, however, the pharmacological mechanisms of the compounds are still unclear. In this report, effects of gold compounds on DNA synthesis were examined. Gold sodium thiomalate inhibited DNA synthesis in the HeLa "nuclei system" as well as in the enzyme reaction using DNA polymerase alpha. More precisely, gold sodium thiomalate inhibited the activity of DNA polymerase alpha using activated DNA, poly[d(A-T)] or poly[d(G-C)] for the template, but did not inhibit the activity of DNA polymerase I with each template. The compound had also no inhibitory effect on DNA polymerase beta or gamma. On the other hand, auranofin inhibited the incorporation of [3H]thymidine into HeLa DNA but did not inhibit DNA synthesis in the HeLa "nuclei system". The inhibition of DNA polymerase alpha activity by gold sodium thiomalate was competitive with poly(dA).oligo(dT) for template but noncompetitive with dTTP. Thus, gold sodium thiomalate is a potent and specific inhibitor of DNA polymerase alpha and this inhibitory effect could play an important role in the therapeutic and pharmacological effects of gold sodium thiomalate.

Auranofin↗
PubMedDate not supplied

Positive and negative association of HLA-DR genotypes with Japanese rheumatoid arthritis.

OBJECTIVE: To clarify the relationship between the HLA-DR genotype and susceptibility to rheumatoid arthritis (RA) in Japanese patients. METHODS: HLA-DR typing and DRB1* genotyping were carried out by PCR and PCR-SSCP (single stranded DNA conformation polymorphism), respectively. RESULTS: In RA, the prevalence of HLA-DR4 was significantly higher (57.3%, p < 0.05). In particular, DRB1*0405 was predominantly higher (46.9%, p < 0.05) and DRB1*0401 was also increased although not significantly. HLA-DR8, especially DRB1*0802, was significantly lower (1.0%, p < 0.01). RA patients homozygous for DRB1*0405 showed slightly higher values for the erythrocyte sedimentation rate, gamma-globulin, and IgG, as well as positivity for rheumatoid factor and high titers for the Waalar-Rose test, and a decrease in the albumin/globulin ratio, albumin, and hemoglobin in comparison to patients without RA susceptibility genes, although the difference for each of these parameters was not significant. CONCLUSION: DRB1*0405 and DRB1*0802, which are both rare alleles in Caucasians, are positively and negatively correlated, respectively, with the pathogenesis of RA in Japan.

Alleles↗
PubMedDate not supplied

C4A and C4B null alleles are genetic markers of different types of systemic sclerosis in Japanese patients.

OBJECTIVE: The contribution of the polymorphism of complement C4A and C4B alleles to the pathogenesis of systemic sclerosis (SSc) was studied in Japanese patients. METHODS: C4A and C4B typing was carried out in 44 SSc patients and in 83 normal subjects using electrophoresis followed by immunofixation and immunoblotting. HLA-DR typing and HLA DRB1*15 and *08 genotyping were carried out by the PCR method and the PCR-SSCP method, respectively. RESULTS: In SSc with diffuse scleroderma, the frequency of C4BQ0 was significantly increased (44.4%, p < 0.001, pc < 0.01). In SSc with antitopoisomerase I antibody (a-Scl-70) C4BQ0 was also increased (50.0%, p < 0.001, pc < 0.01). Association analysis indicated that the increase in C4BQ0 was not primary but reflected an increase in HLA-DRB1*1502. In contrast, C4A/Q0 was significantly increased in limited scleroderma (53.8%, p < 0.005, pc < 0.05) and SSc without a-SCL-70 (53.8%, p < 0.005, pc < 0.05). CONCLUSION: Diffuse scleroderma with SSC with a-Scl-70 have different genetical backgrounds from limited scleroderma and SSc without a-Scl-70, respectively, in Japanese patients. C4AQ0 were independent genetic markers for each clinical subgroup and for a a-Scl-70 positivity.

Adult↗