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S Momohara

Publications and source records attributed to S Momohara.

16 recordsLinked to original sources
PubMed2006

Haplotype analysis revealed no association between the PTPN22 gene and RA in a Japanese population.

OBJECTIVE: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene is a member of the PTPs that negatively regulate T-cell activation. A missense single nucleotide polymorphism (SNP) in the PTPN22 gene known as R620W was recently reported to be associated with several autoimmune diseases including rheumatoid arthritis (RA). The association was confirmed repeatedly in the populations of North European ancestry. However, the SNP was reported to be non-polymorphic in the Asian populations. Because the gene confers an impact on autoimmune diseases, we attempt to explore an association between PTPN22 gene and RA in a Japanese population without restricting to the SNP, R620W. METHODS: We studied 1128 RA patients and 455 controls. In addition to the SNP, R620W, we selected eight testing SNPs spanning 45 kb over the PTPN22 gene using the International HapMap Project. Genotyping was performed using the TaqMan fluorogenic 5' nuclease assay. Associations between RA and each of the SNPs were estimated by the Fisher's exact test. Haplotype was constructed using the expectation-maximization algorithm. RESULTS: R620W was not polymorphic enough in both the patients and the controls, and was therefore excluded from further analysis. Each allele frequency for the eight other SNPs in both groups was compared and no association was detected. Haplotype analysis also revealed that PTPN22 gene was not associated with RA in a Japanese population. CONCLUSION: We found no association between PTPN22 and RA in a Japanese population. The result suggests that the PTPN22 gene is associated with RA only in a specific ethnic group.

Arthritis, Rheumatoid↗
PubMed2006

Association between PADI4 and rheumatoid arthritis: a meta-analysis.

OBJECTIVE: Polymorphisms and haplotypes of the peptidylarginine deiminase type 4 gene (PADI4) have been reported to be associated with rheumatoid arthritis (RA) in a Japanese population. However, subsequent replication studies showed conflicting results. The aim of this study was to determine whether meta-analysis would prove the existence of the association. METHODS: PubMed was searched using the term 'PADI4' for articles from the publication of the first study to December 2005. Replication studies that tested the association between PADI4 and RA were reviewed for meta-analysis. The Breslow-Day test for homogeneity across the studies was calculated. The Mantel-Haenszel procedure was used to pool odds ratios (OR) with 95% confidence intervals (CI) to evaluate the association. RESULTS: Six replication studies, one from Japan and five from Europe and North America, fulfilled the selection criteria for inclusion in the meta-analysis. Homogeneity was confirmed across the replication studies. The common OR was 1.14 (95% CI = 1.07-1.21) for allelic distribution. The association was confirmed when only five replication studies in the European descent populations were combined (P = 0.0096, common OR = 1.10). CONCLUSIONS: Our meta-analysis showed a positive association between PADI4 and RA not only in the Japanese population but also in populations of European descent.

Arthritis, Rheumatoid↗
PubMed2006

Raised monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebrospinal fluid of patients with neuropsychiatric lupus.

BACKGROUND: An imbalance in cytokine homoeostasis is thought to have a key role in the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE), and recently, a role for chemokines has been noted. OBJECTIVE: To compare concentrations of monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebral spinal fluid (CSF) of patients with SLE, and with and without neuropsychiatric symptoms. METHODS: CSF was obtained from 185 patients with SLE: 96 with NPSLE and 89 patients with SLE without neuropsychiatric symptoms (non-NPSLE patients). MCP-1/CCL2 concentrations were measured with an ELISA. RESULTS: The average concentration of CSF MCP-1/CCL2 in patients with NPSLE was 1959 pg/ml, and in non-NPSLE patients 712 pg/ml. The average MCP-1/CCL2 concentration was significantly higher in the NPSLE group than in the non-NPSLE group (p<0.001). In one representative patient with NPSLE, MCP-1/CCL2 levels in the CSF decreased in parallel with a decline in neuropsychiatric symptoms. CONCLUSIONS: CSF MCP-1/CCL2 levels are higher in patients with NPSLE than in non-NPSLE patients. MCP-1/CCL2 may have an important role in the expression of NPSLE. These results indicate that CSF MCP-1/CCL2 reflects an inflammatory activity in the brain, suggesting that it might be used as a diagnostic tool and a monitor for therapeutic responses in patients with NPSLE.

Adolescent↗
PubMed2005

Monocyte chemoattractant protein-4 (MCP-4)/CCL13 is highly expressed in cartilage from patients with rheumatoid arthritis.

OBJECTIVES: To study the role of monocyte chemoattractant protein-4 (MCP-4)/CCL13 in the pathogenesis of rheumatoid arthritis (RA), we analysed the expression of MCP-4/CCL13 in chondrocytes, synovial fluid and serum from patients with RA and investigated the effect of MCP-4/CCL13 on the proliferation of synovial cells. METHODS: Human articular cartilage specimens were obtained from joints from RA and osteoarthritis (OA) patients and normal joints (controls). Transcript levels of MCP-4 in cartilage were determined by real-time polymerase chain reaction. Protein levels were measured by enzyme-linked immunoassay. Cultured fibroblast-like synoviocytes (FLS) were treated with various concentrations of recombinant MCP-4/CCL13 protein, and cell proliferation was evaluated with a viability assay. RESULTS: The gene expression of MCP-4 was significantly higher in cartilage from RA patients than in that from OA patients (P = 0.00902) and in normal cartilage (P = 0.00902). The concentration of MCP-4/CCL13 protein in serum from RA patients (mean 94.7 +/- 37.6 pg/ml) was significantly higher than in serum from OA patients (mean 49.2 +/- 31.2 pg/ml, P = 0.0051) and controls (mean 32.6 +/- 23.9 pg/ml, P = 0.0001). The concentration of MCP-4/CCL13 protein in synovial fluid from RA patients (mean 247.2 +/- 161.2 pg/ml) was also significantly higher than in that from OA patients (mean 29.6 +/- 50.5 pg/ml, P = 0.000019). Moreover, MCP-4/CCL13 enhanced the proliferation of FLS in a dose-dependent manner. CONCLUSIONS: MCP-4/CCL13 is highly expressed in RA joints at the mRNA and protein levels. Our results suggest that MCP-4/CCL13 is secreted from chondrocytes and activates the proliferation of rheumatoid synovial cells, thereby leading to joint destruction in RA.

Arthritis, Rheumatoid↗
PubMed2005

Supportive evidence for a genetic association of the FCRL3 promoter polymorphism with rheumatoid arthritis.

BACKGROUND: An association between susceptibility to rheumatoid arthritis and the Fc receptor-like 3 gene (FCRL3) has been reported in a Japanese population. A case-control study showed that the strongest evidence of the association was derived from a polymorphism in the promoter region of FCRL3, which has a regulatory effect on the expression of the gene. OBJECTIVE: To validate the findings of this previous report by examining the -169C-->T single nucleotide polymorphism (SNP) in a large cohort. METHODS: 752 unrelated cases and 940 controls were genotyped. All the samples were from the same ethnic background as the original study. Genotyping was done using 5' allelic discrimination assays. Association between susceptibility to rheumatoid arthritis and -169C-->T SNP was examined by chi(2) testing. RESULTS: As in the previous study, the SNP showed significant differences between cases and controls (p = 0.022, odds ratio = 1.18, 95% confidence interval 1.02 to 1.35). CONCLUSIONS: This result supports a genetic association of the FCRL3 promoter polymorphism with rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed2005

Single nucleotide polymorphisms in the gene encoding the major histocompatibility complex class II transactivator (CIITA) in systemic lupus erythematosus.

BACKGROUND: The major histocompatibility complex (MHC) class II transactivator (CIITA) is a master switch of antigen presentation and activates expression of the MHC II gene. Insufficient up regulation of MHC class II molecules is reported to be one of the major immunological mechanisms in systemic lupus erythematosus (SLE). OBJECTIVE: To examine the association between single nucleotide polymorphisms (SNPs) in the human CIITA gene (MHC2TA) and SLE. METHODS: Promoters and coding regions of MHC2TA were evaluated for polymorphisms in 100 patients with SLE and 100 healthy donors. Eight oligonucleotide primer sets that covered the coding region and each promoter region were used for genomic analysis of SNPs. RESULTS: Allele frequencies of previously reported SNPs did not differ between healthy donors and patients with SLE. Additionally, a new polymorphism in an intronic region at nt 485 (A-->A/G) was identified, which is close to the polymorphism at nt 474 that has been associated with one of the disease causing CIITA cDNA mutations in bare lymphocyte syndrome. This SNP was found in 11% of patients with SLE and in 3% of healthy donors, suggesting it may have a role in the pathogenesis of SLE. CONCLUSIONS: A newly identified polymorphism in an intronic region at nt 485 (A-->A/G) may have an important role in the pathogenesis of SLE.

Adolescent↗
PubMed2001

[A questionnaire-based survey on the Internet concerning optimal timing for knee surgery in a patient with rheumatoid arthritis].

To investigate the differences between orthopedists and internists in indications for surgical management in patients with rheumatoid arthritis (RA), a questionnaire-based survey was performed on the Internet with the presentation of a case of progressive RA along with serial X-ray films of the knee. Ninety-three doctors (43 orthopedists and 50 internists, average age: 49.2 years) answered the questionnaire. Most of the doctors who viewed the X-ray film showing Larsen's grade IV chose that as the optimal time for total knee arthroplasty. No difference was noted in their choice between orthopedists and internists. Opinions varied widely, however, among younger doctors, but there was agreement among older doctors, suggesting the effect of the study and experience. On the other hand, some doctors recommended arthroscopic synovectomy for knees in the earlier stages of RA, but others did not recommend the arthroscopic surgery itself. Although this new methodology might include possible biases, we believe it should be considered in the research of rheumatology.

Arthritis, Rheumatoid↗
PubMed2000

[Radiological evaluation of foot deformities in rheumatoid arthritis].

Deformities of the feet are common in patients with rheumatoid arthritis (RA). We investigated whether there was any correlation among forefoot deformities, flat foot or articular destruction of the midfoot and hindfoot, in 146 feet of 73 RA patients whose age varied from 26 to 81 years (mean 58.5 years). In all patients, anteroposterior (AP) and lateral radiographs of the feet with weight bearing were obtained. The hallux valgus angle (HVA), the intermetatarsal angle between the 1st and 2nd metatarsals (M 1 M 2), and the intermetatarsal angle between the 1st and 5th metatarsals (M 1 M 5) were measured on AP radiographs. On slateral radiographs, the height of the arch was measured and articular destruction of the talocalcaneal, talocrural, talonavicular, cuneonavicular and cuneometatarsal joints was measured and classified using Steinbrocker's classification. The average HVA was 23.4 degrees, the average M 1 M 2 was 11.1 degrees, and the average M 1 M 5 was 28.4 degrees. There was no correlation between forefoot deformities and flat foot. There were significant correlations between arthritic destruction of the cuneometatarsal joint and HVA, M 1 M 2 and M 1 M 5. The correlations between arthritic destruction of the cuneonavicular joint and HVA or M 1 M 2 were also significant, although weaker. Thas, we found some relationships between forefoot deformity and arthritics destruction of midfoot joints. Especially, the correlations between arthritic destruction of the cuneonavicular and cuneometatarsal joints and forefoot deformities were significant. Many radiographic methods for the assessment of RA have been reported, however, it is difficult to assess sarthritic destruction of rheumatoid feet with the existing methods. Accordingly, a new method should be established.

Adult↗
PubMed1999

[Arthritic manifestations in ulcerative colitis].

Ulcerative colitis (UC) is commonly associated with peripheral joint disease which correlates with the activity and extent of the inflammatory bowel disorder. They are generally divided into three clinical categories; peripheral arthritis, spondylitis, and sacroiliitis. The arthritis is usually pauciarticular, generally asymmetric, transient, and nondestructive. However, the peripheral arthritis becomes chronic and destructive in some cases. Rheumatoid arthritis has been reported to be seldom associated with UC. Inflammatory joint disease is considered an enteropathic arthritis if the gastrointestinal tract is directly involved in the pathogenesis. The occurrence of rheumatologic manifestations in UC is reviewed in this paper.

Arthritis↗
PubMed1998

A new culture system to study the metabolism of the intervertebral disc in vitro.

STUDY DESIGN: This study determined whether entrapment of a rabbit intervertebral disc in alginate gel helped to promote the retention of normal metabolic activities by the nucleus pulposus and anulus fibrosus in tissue culture. OBJECTIVES: To establish an in vitro culture system to study the metabolism of the intervertebral disc as a whole integral organ. SUMMARY OF BACKGROUND DATA: In vitro studies of the metabolism of intervertebral discs have been scarce because of the difficulties involved in maintaining the integrity of the tissues, especially that of the nucleus pulposus, in culture medium. METHODS: Rabbit intervertebral discs were embedded in alginate gel and maintained in culture for as long as 1 month. At weekly intervals, experiments were performed to measure the rate of proteoglycan synthesis and to characterize proteoglycans newly synthesized by cells in the anulus fibrosus and nucleus pulposus. In addition, at these same time intervals, the contents of sulfated proteoglycans, antigenic keratan sulfate, hyaluronan, and collagen in these two intervertebral disc tissues were measured to evaluate tissue integrity. Intervertebral discs cultured in medium alone were used as controls and analyzed in parallel. RESULTS: The anulus fibrosus and nucleus pulposus of intervertebral discs cultured in alginate gel sustained a higher rate of proteoglycan synthesis and maintained a higher content of extracellular matrix components than the respective controls at all times. CONCLUSIONS: This new alginate tissue culture system should prove useful for studying the metabolism of whole intervertebral discs.

Alginates↗
PubMed1997

Elastase from polymorphonuclear leukocyte in articular cartilage and synovial fluids of patients with rheumatoid arthritis.

Objective was to study the significance and the mechanism of action of elastase from polymorphonuclear leukocyte (PMN elastase) in patients with rheumatoid arthritis (RA). The experiments conducted consisted of two phases. Firstly, articular cartilage and synovia from 8 patients with RA undergoing total knee replacement were obtained, and the gelatinolytic enzyme activity was extracted with 2M guanidine hydrochloride. The gelatinolytic activity of each tissue was measured to confirm that the activity was due to PMN elastase by using an antihuman leukocyte elastase antibody. Secondly, the levels of PMN elastase-alpha 1 proteinase inhibitor complex (EIC) in the blood and synovial fluid of 170 patients with RA were measured by immunoassay. The results were as follows: 1. Gelatinolytic activity was shown to be mainly due to PMN elastase, and found to be highest in cartilage and synovia in RA joints. 2. The EIC levels in plasma of RA patients were significantly higher than those in gout and osteoarthritis (OA), and the EIC levels increased according to the stage of articular cartilage destruction. Moreover, the EIC levels in synovial fluid of RA patients were higher compared to those of OA patients. The activity of PMN elastase was elevated in destructive joints of RA. With the progression of articular cartilage destruction, EIC levels in plasma of RA patients increased as well. We suggest that PMN elastase may play a significant role in RA disease.

Adult↗
PubMed1994

[Osteoporosis in collagen diseases].

The pathogenesis of osteoporosis in patients with rheumatic diseases, especially rheumatoid arthritis (RA), is poorly understood. The duration of the disease, the severity of the inflammatory process, gender, age, steroid therapy and menopause have been suggested as risk factors for osteoporosis in patients with RA. Although these factors may contribute to the development of osteoporosis, the influence of one specific factor is difficult to evaluate. It is said that the treatment with steroids has a deleterious effect on bone turnover, but this effect has been controversial. The dose margin of prednisone that will lead to osteoporosis is not known but has been estimated to be 10 mg per day. Fractures and stress fractures in patients with RA are probably much more common. Further study concerning osteoporosis in rheumatic diseases is necessary.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Synovial histology in three Behçet's disease patients with orthopedic surgery.

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.

Adult↗
PubMedDate not supplied

Inhibition of NF-kappaB signaling by fenofibrate, a peroxisome proliferator-activated receptor-alpha ligand, presents a therapeutic strategy for 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.

Animals↗