Biomedical subjects

Daisuke Hamada

Publications and source records attributed to Daisuke Hamada.

10 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 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↗

PubMed2006

Effects of monofilament nylon coated with basic fibroblast growth factor on endogenous intrasynovial flexor tendon healing.

PURPOSE: We developed a monofilament nylon thread that can release various growth factors to enhance intrinsic reparative processes after flexor tendon injury. We evaluated the properties of this thread in vitro and in vivo. METHODS: Nylon threads were coated with gelatin that subsequently was cross-linked in glutaraldehyde. The thread was soaked in basic fibroblast growth factor (bFGF) solution (400 microg/mL). Exogenous bFGF in the thread was released constantly over the course of 1 week. The biologic activity of bFGF and the biomechanical strength of the thread were examined in vitro and its efficacy was investigated in an in vivo rabbit tendon repair model after early flexion exercises. The sutured sites were examined histologically (hematoxylin-eosin, immunohistochemistry, in situ hybridization), biochemically (Western blot test), and biomechanically (ultimate load) after surgery. RESULTS: This gelatin-coated thread absorbed iodine 125-labeled bFGF in a time-dependent manner. The total amount of bFGF absorbed by the thread within the tendon tissue was between 3 and 15 mug depending on the concentration of bFGF solution. Basic fibroblast growth factor protein was delivered selectively-not in the surrounding scar but in the repaired tendon-for 3 weeks. Histologic analysis showed that the cellular density at the repaired site increased in accordance with the expression of bFGF messenger RNA and protein in the tendon. Endogenous bFGF expression seemed to be enhanced transiently by exogenous bFGF during the first few weeks. The epitenon showed a vigorous fibroblastic response to the coated thread and the ultimate load also was increased significantly at 3 weeks after surgery. CONCLUSIONS: This bFGF-coated nylon suture gave excellent results in delivering a drug selectively to tendon; it also induced an increase of biomechanical strength and a thickening of the epitenon layer in vivo during a 3-week period, thereby accelerating cellular proliferation, initially peripherally and later centrally. This system may become a therapeutic tool to be used in hand surgery.

Animals↗

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

Long-term outcome of patients with rheumatoid arthritis treated by multiple arthroplasty.

We conducted a study of 82 patients with rheumatoid arthritis (RA) who had undergone multiple arthroplasty and investigated their clinical findings and clinical courses. We reviewed the significance of multiple arthroplasty in the treatment of RA, its problems, and measures to solve them. All patients initially regained and maintained good walking capacity. However, the walking capacity of many patients again decreased over the long term; in the tenth year, 79% of patients were capable of a practical gait. The causes of decreased walking capacity included complications of artificial joints, cervical lesions, and vertebral compression fractures. Fractures were observed in as many as nine patients, indicating that it is important to prevent and treat their cause, that is, osteoporosis. The survival rate was 71% in 10 years. In RA patients, particularly those who have undergone multiple arthroplasty, the major causes of death are infection and rheumatic disease, suggesting that prevention of such diseases should be considered paramount. Appropriate systemic treatment of RA, patient education, and measures against osteoporosis for prevention of complications may preserve the worth of multiple arthroplasty for RA patients with multiple joint destruction.

Journal Article↗

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↗

PubMed2005

Total hip arthroplasty in osteopetrosis using computer-assisted fluoroscopic navigation.

Hybrid total hip arthroplasty with computer-assisted fluoroscopic navigation was performed on a patient with osteoarthritis due to an autosomal dominant form of osteopetrosis. The surgical procedures were difficult because the bone was extremely hard and brittle with obliteration of the medullary cavity. Especially, preparation of a femoral canal for the stem was technically challenging and required changes from a conventional surgical procedure. Therefore, we used a computer-assisted fluoroscopic navigation system to create the femoral cavity for the stem, and an accurate placement of the prosthesis was achieved. Navigation guidance can be a useful tool when performing arthroplasty in patients with hip osteoarthritis associated with osteopetrosis.

Arthroplasty, Replacement, Hip↗

PubMed2003

Intracapsular hip fractures in patients with rheumatoid arthritis.

We reviewed the treatment of 43 patients with rheumatoid arthritis and femoral neck fracture. Patients' average age was 66.4 (36-80) years and average duration of RA was 20.3 (4-42) years. Thirteen patients were treated with primary total hip arthroplasty (THA), and the clinical results were comparable to patients treated conservatively or by osteosynthesis. Eighteen patients were treated with primary bipolar hip prosthesis and after an average of 6.1 (1-13) years there was no acetabular destruction. However, long-term results were inferior to patients treated with THA. Nine patients were treated with osteosynthesis, of which two later had a hip prosthesis. Three cases with impacted fractures were treated conservatively with successful union in all.

Adult↗