Biomedical subjects

Yoichiro Takata

Publications and source records attributed to Yoichiro Takata.

8 recordsLinked to original sources

PubMed2007

Distinct expression of mast cell tryptase and protease activated receptor-2 in synovia of rheumatoid arthritis and osteoarthritis.

The objective of this study is to examine the differential expression of mast cell tryptase and its receptor, protease-activated receptor-2 (PAR-2), in the synovium and synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Biochemical and immunohistochemical analyses were performed to determine whether the trypsin-like protease in the synovium is identical to mast cell tryptase. The effects of mast cell tryptase on the proliferation of synovial fibroblast-like cells (SFCs) and the release of IL-8 thereof were evaluated by the [3H]-thymidine incorporation and ELISA, respectively. The trypsin-like protease in the synovium of RA patients was identical to human mast cell tryptase, which was composed of two subunits: 33 and 34 kDa. The 33- and 34-kDa proteins are different glycosylated forms of the 31-kDa protein, which was unglycosylated. Mast cell tryptase activity in RA synovial fluid was significantly higher than that in OA synovial fluid, while their activities and expression in the synovium were similar. Expression of PAR-2 mRNA in the synovium was higher in RA than in OA. Mast cell tryptase containing the unglycosylated 31-kDa subunit was the predominant form in synovial fluid. RA patients had higher amounts of this subunit in their synovial fluid than OA patients. Mast cell tryptase and PAR-2 activating peptide stimulated the proliferation of SFCs and release of IL-8 from these cells. Mast cell tryptase secretion into RA synovial fluid is higher than OA synovial fluid. Mast cell tryptase in synovial fluid stimulates the proliferation of SFCs and the release of pro-inflammatory cytokines via PAR-2, which may contribute to exacerbation of synovitis in RA.

Adult↗

PubMed2007

Genetic association between the PRKCH gene encoding protein kinase Ceta isozyme and rheumatoid arthritis in the Japanese population.

OBJECTIVE: Analyses of families with rheumatoid arthritis (RA) have suggested the presence of a putative susceptibility locus on chromosome 14q21-23. This large population-based genetic association study was undertaken to examine this region. METHODS: A 2-stage case-control association study of 950 unrelated Japanese patients with RA and 950 healthy controls was performed using >400 gene-based common single-nucleotide polymorphisms (SNPs). RESULTS: Multiple SNPs in the PRKCH gene encoding the eta isozyme of protein kinase C (PKCeta) showed significant single-locus disease associations, the most significant being SNP c.427+8134C>T (odds ratio 0.72, 95% confidence interval 0.62-0.83, P = 5.9 x 10(-5)). Each RA-associated SNP was consistently mapped to 3 distinct regions of strong linkage disequilibrium (i.e., linkage disequilibrium or haplotype blocks) in the PRKCH gene locus, suggesting that multiple causal variants influence disease susceptibility. Significant SNPs included a novel common missense polymorphism of the PRKCH gene, V374I (rs2230500), which lies within the ATP-binding site that is highly conserved among PKC superfamily members. In circulating lymphocytes, PRKCH messenger RNA was expressed at higher levels in resting T cells (CD4(+) or CD8(+)) than in B cells (CD19(+)) or monocytes (CD14(+)) and was significantly down-regulated through immune responses. CONCLUSION: Our results provide evidence of the involvement of PRKCH as a susceptibility gene for RA in the Japanese population. Dysregulation of PKCeta signal transduction pathway(s) may confer increased risk of RA through aberrant T cell-mediated autoimmune responses.

Adult↗

PubMed2006

Association study on chromosome 20q11.21-13.13 locus and its contribution to type 2 diabetes susceptibility in Japanese.

Several linkage studies have predicted that human chromosome 20q is closely related to type 2 diabetes, but there is no clear evidence that certain variant(s) or gene(s) have strong effects on the disease within this region. To examine disease susceptibility variant in Japanese, verified SNPs from the databases, with a minor allele frequency larger than 0.15, were selected at 10-kb intervals across a 19.31-Mb region (20q11.21-13.13), which contained 291 genes, including hepatocyte nuclear factor 4alpha (HNF4alpha). As a result, a total of 1,147 SNPs were genotyped with TaqMan assay using 1,818 Japanese samples. By searching for HNF4alpha as a representative disease-susceptible gene, no variants of HNF4alpha were strongly associated with disease. To identify other genetic variant related with disease, we designed an extensive two-stage association study (725 first and 1,093 second test samples). Although SNP1146 (rs220076) was selected as a landmark within the 19.31 Mb region, the magnitude of the nominal P value (P = 0.0023) was rather weak. Subsequently, a haplotype-based association study showed that two common haplotypes were weakly associated with disease. All of these tests resulted in non-significance after adjusting for Bonferroni's correction and the false discovery rate to control for the impact of multiple testing. Contrary to the initial expectations, we could not conclude that certain SNPs had a major effect on this promising locus within the framework presented here. As a way to extend our observations, we emphasize the importance of a subsequent association study including replication and/or meta-analysis in multiple populations.

Aged↗

PubMed2006

MRI signal changes of the pedicle as an indicator for early diagnosis of spondylolysis in children and adolescents: a clinical and biomechanical study.

STUDY DESIGN: Clinical review of pediatric patients with lumbar spondylolysis and biomechanical analysis using finite-element lumbar spine model. OBJECTIVES: To evaluate the usefulness of the signal changes observed on MR images of the pedicle for the early diagnosis of spondylolysis, and to investigate the pathomechanism of the signal changes based on the stresses in pedicles, as predicted using finite-element analyses. Furthermore, to evaluate the usefulness of the signal change to predict the bony healing following conservative treatment. SUMMARY OF BACKGROUND DATA: Since early-stage spondylolysis can achieve osseous healing conservatively, it is important to diagnose this disorder as early as possible. Presently, there is no well-established, noninvasive, and reliable diagnostic tool for the early diagnosis. METHODS: Thirty-seven pediatric patients with spondylolysis were included. Sixty-eight defects were examined and their stages as revealed on CT scans were recorded. High signal changes (HSC) of the pedicles on axial T2-weighted MRI were compared with the CT-based stages of the defect. Among them, 16 patients, including 15 boys and 1 girl, were treated conservatively for at least a 3-month period. Bony healing of the fracture site was evaluated on CT, and the results were compared between two groups with or without HSC at the initial consultation. Using a three-dimensional nonlinear finite-element model of the L3-L5 segment, stress distributions in the pars and pedicle regions were analyzed in response to 400 N compression and 10.6 Nm moment. RESULTS: Based on CTs, 68 pars defects were classified as follows: 8 very early, 24 late-early, 16 progressive, and 20 terminal stages. All defects in very early and late-early stages (100%) showed HSC on T2-weighted MRI at the ipsilateral pedicle. Among 16 progressive stages, eight (50%) showed HSC, while no defects of the terminal stage (0%) were found to have HSC. In total, 29 pars defects were treated conservatively out of 16 patients. In 19 of the HSC positive defects, 15 (79%) showed bony healing after the conservative treatment, whereas none of the 10 HSC negative defects (0%) showed any healing. The results were statistically significant at P < 0.05 (chi). Stress results from the finite-element model indicated that pars interarticularis showed the highest value in all loading modes, and the pedicle showed the second highest. CONCLUSIONS: The correlation between the high stresses in the pedicle and the corresponding HSC suggest that signal changes in MRI could be used as an indicator for early diagnosis of spondylolysis. The HSC of the pedicle provided useful information to diagnose early stage spondylolysis. Furthermore, the HSC may be a good indicator as to whether a bony union will result from conservative treatment.

Adolescent↗

PubMed2006

Association of single-nucleotide polymorphisms in the suppressor of cytokine signaling 2 (SOCS2) gene with type 2 diabetes in the Japanese.

Several previous linkage scans in type 2 diabetes (T2D) families indicated a putative susceptibility locus on chromosome 12q15-q22, while the underlying gene for T2D has not yet been identified. We performed a region-wide association analysis on 12q15-q22, using a dense set of >500 single-nucleotide polymorphisms (SNPs), in 1492 unrelated Japanese individuals enrolled in this study. We identified an association between T2D and a haplotype block spanning 13.6 kb of genomic DNA that includes the entire SOCS2 gene. Evolutionary-based haplotype analysis of haplotype-tagging SNPs followed by a "sliding window" haplotypic analysis indicated SNPs that mapped to the 5' region of the SOCS2gene to be associated with T2D with high statistical significance. The SOCS2 gene was expressed ubiquitously in human and murine tissues, including pancreatic beta-cell lines. Adenovirus-mediated expression of the SOCS2 gene in MIN6 cells or isolated rat islets significantly suppressed glucose-stimulated insulin secretion. Our data indicate that SOCS2 may play a role in susceptibility to T2D in the Japanese.

Adenoviridae↗

PubMed2005

The alpha 2 type IX collagen gene tryptophan polymorphism is not associated with rheumatoid arthritis in the Japanese population.

The aim of this study was to investigate whether the alpha 2 type IX collagen (COL9A2) polymorphism that introduces tryptophan residue into the collagen triple-helix is a marker of susceptibility to, or severity of, rheumatoid arthritis (RA). The study included 749 Japanese patients with RA. One hundred twenty-four unrelated healthy individuals served as the control subjects. The relationship between the COL9A2 gene polymorphism and clinical manifestations of RA was evaluated. For the number of subjects positive for COL9A2 tryptophan polymorphism, there was no statistically significant difference between RA patients and normal controls. Furthermore, we did not detect any association of COL9A2 tryptophan polymorphism with disease status, least erosive subset, more erosive subset, or mutilating disease. The lack of association of COL9A2 tryptophan polymorphism with RA and the clinical findings in our study implies that the polymorphism may not function as a candidate gene marker for screening RA patients.

Adolescent↗

PubMed2005

Association between single-nucleotide polymorphisms in the SEC8L1 gene, which encodes a subunit of the exocyst complex, and rheumatoid arthritis in a Japanese population.

OBJECTIVE: To identify rheumatoid arthritis (RA) susceptibility genes in a Japanese population by conducting a large-scale case-control association analysis and linkage disequilibrium (LD) mapping on chromosome 7q31-34, a candidate susceptibility locus identified in a preliminary genome-wide scan in 53 Japanese families, using single-nucleotide polymorphisms (SNPs). METHODS: We prepared 728 dense, evenly spaced SNPs with a minor allele frequency >0.15 in each gene locus on chromosome 7q31-34. Using these SNPs, a 2-stage case-control analysis was performed on 760 RA patients (157 men and 603 women) and 806 non-RA controls (189 men and 617 women). Haplotypes and LD mapping results were assessed based on SNP genotypes in 380 controls. RESULTS: Forty-eight SNPs showed allele associations (P < 0.05) in the first set of DNA samples (380 RA cases and 380 non-RA controls; first-stage analysis). For 4 of the SNPs in the SEC8L1 gene, the association was replicated (P < 0.05) in the second, independent set of DNA samples (an additional 380 RA cases and 380 non-RA controls; second-stage analysis). When data from the 2 groups were combined, the most significant allele association was observed with SNP 441, an intronic SNP of the SEC8L1 gene (P = 0.000059). The SEC8L1 SNPs with significant allele associations were all located in a single conserved LD block (block 4). Haplotype analysis revealed the disease-risk (P = 0.0015) and disease-protective (P = 0.0000062) haplotypes. Resequencing of coding exons within block 4 did not identify any nonsynonymous SNPs. Real-time quantitative polymerase chain reaction revealed that SEC8L1 was expressed ubiquitously in human tissues, including fibroblast-like synoviocytes from RA patients. CONCLUSION: Our locus-wide association and LD analyses identified intronic SNPs and haplotypes in the SEC8L1 gene that are strongly associated with RA. We propose that SEC8L1, which encodes a component of the exocyst complex, is a candidate susceptibility gene for RA in the Japanese population.

Adult↗

PubMed2005

Asynchronous progressive diaphyseal dysplasia.

We report the case of a 42-year-old Japanese woman with unusual diaphyseal dysplasia of bilateral femora. Radiographs showed thickening and sclerosis of the cortex with resultant enlargement of the diaphysis, unclear demarcation of the surface of the cortex, and no periosteal reaction. These changes were found on the left femur at the first presentation, and those on the right femur developed within several years. Although this patient partly presented characteristics of Ribbing disease and Camurati-Engelmann disease, the focal involvement of bilateral femora suggested an unknown pathogenesis.

Journal Article↗