Yuko Matsuda

Wako Urano; Atsuo Taniguchi; Hisashi Yamanaka; Eiichi Tanaka; Hiroshi Nakajima; Yuko Matsuda; Hideto Akama; Yutaka Kitamura; Naoyuki Kamatani

5,10-Methylenetetrahydrofolate reductase (MTHFR), a key enzyme involved in folate metabolism, has two common polymorphisms that affect enzyme activity. The objective of this study was to examine whether there was a correlation between the genotype or haplotype of the MTHFR gene and the efficacy or toxicity of methotrexate (MTX) in the treatment of rheumatoid arthritis. MTX-treated rheumatoid arthritis patients (n = 106) were selected from outpatient clinics and used for a retrospective study to examine the correlation between genotypes or haplotypes concerning polymorphisms of the MTHFR gene, and the efficacy or toxicity of MTX. Estimation of the haplotype frequencies was performed by maximum likelihood estimation based on expectation maximization algorithm. Single locus analysis examining each locus separately showed that patients with 1298C were receiving significantly lower doses of MTX compared to patients without [P < 0.05, relative risk (RR) = 2.18, 95% confidence interval (CI) 1.17-4.06], while a higher rate of overall MTX toxicity was observed in patients with 677T than those without (P < 0.05, RR = 1.25, 95% CI 1.05-1.49). An estimation of haplotype frequencies showed that there was no 677T-1298C haplotype in the population. Posterior distribution of the diplotype configuration for each individual was concentrated on a single configuration. Patients with the 677C-1298C haplotype were receiving lower doses of MTX than those without (P < 0.05, RR = 2.14, 95% CI 1.13-4.07), while subjects with 677T-1298A had a higher frequency of side-effects from MTX (P < 0.05, RR = 1.42, 95% CI 1.11-1.82). Both single locus and haplotype analyses suggest that polymorphisms within the MTHFR gene are associated with both the efficacy and toxicity of MTX in rheumatoid arthritis patients. Pharmacokinetic studies are necessary to prove the association.

Hisashi Yamanaka; Yuko Matsuda; Michi Tanaka; Wako Sendo; Hiroshi Nakajima; Atsuo Taniguchi; Naoyuki Kamatani

OBJECTIVE To evaluate whether matrix metalloproteinase 3 (MMP-3), a proteinase that is expressed in rheumatoid synovial tissue and shows potent activity in degrading the proteoglycan of cartilage, plays a pivotal role in the joint destruction seen in early rheumatoid arthritis (RA). METHODS In a prospective study of patients with early RA, the relationship between the serum concentration of MMP-3, as determined by a sandwich enzyme immunoassay system, and the progression of joint destruction in patients with early RA, as measured by the Larsen radiologic score, was investigated. RESULTS Serum MMP-3 levels were elevated in the RA patients compared with healthy controls, not only in the late stage, but also in the early stage of the disease in patients whose duration of RA was <4 months. The serum MMP-3 level at entry into the study had a strong correlation with the Larsen score at 6 months and 12 months after entry (r = 0.58 and r = 0.49, respectively). Similarly, the serum MMP-3 level at 12 months and 24 months after entry showed a positive association with the Larsen score in the subsequent 6-12 months. Suppression of the serum MMP-3 level in the first year led to a decline in joint damage in the second year. CONCLUSION The serum concentration of MMP-3 is a useful marker for predicting bone damage in the early stage of RA, and the suppression of MMP-3 production may be an effective therapeutic approach for patients with early RA.

Zuzana Uhrin; Benjamin W. E. Wang; Yuko Matsuda; Samuel Strober; Mark C. Genovese

OBJECTIVE Total lymphoid irradiation (TLI) has been used to treat rheumatoid arthritis (RA) since the 1970s. This study reviews long-term (15-20-year) mortality outcomes of patients treated with TLI for RA at Stanford University Medical Center and compares these outcomes with those in patients treated with disease-modifying antirheumatic drugs (DMARDs). METHODS Fifty-three patients with RA were treated with full-dose TLI at Stanford University Medical Center. All had failed previous therapy with gold salts and penicillamine. One hundred six control patients were selected from the Arthritis, Rheumatism, and Aging Medical Information Systems database and were matched with the patients for age, sex, disease duration, and mean Health Assessment Questionnaire (HAQ) score. Survival was analyzed using Kaplan-Meier methods and Cox proportional hazards regression. RESULTS No significant difference in age and sex was found between TLI-treated patients and controls. TLI-treated patients had more education (mean 13.4 years versus 11.8 years; P = 0.016) and received more DMARDs prior to TLI (mean 2.1 versus 1.3; P = 0.0001). TLI-treated patients had lower mean HAQ scores at the time of TLI (2.0 versus 2.4; P = 0.0002). TLI had no significant overall effect on survival in treated patients compared with controls (P = 0.62). The survival curves appeared to cross over at approximately 11 years of followup, with better early survival in the TLI group and better late survival in the control group. There was a total of 25 deaths in the TLI group. There were 45 deaths in the control group, with causes of death available for 20 patients. There were 3 patients with lymphoma and 2 with myelodysplastic syndrome in the TLI group, and none in the control group. The most common cause of death in both groups was infection. CONCLUSION TLI had no significant effect on overall survival, with trends toward higher early mortality in controls and trends toward higher late mortality in TLI-treated patients. Overall, there was no difference in mortality, but it appears that there may have been more lymphoproliferative malignancies in the TLI cohort. We would recommend that TLI be used cautiously for patients with refractory RA in whom the benefits outweigh the risks.

Yuko Matsuda; Gurkirpal Singh; Hisashi Yamanaka; Eiichi Tanaka; Wako Urano; Atsuo Taniguchi; Terunobu Saito; Masako Hara; Taisuke Tomatsu; Naoyuki Kamatani

Wako Urano; Hisashi Yamanaka; Hiroshi Tsutani; Hiroshi Nakajima; Yuko Matsuda; Atsuo Taniguchi; Masako Hara; Naoyuki Kamatani

Eiichi Tanaka; Atsuo Taniguchi; Wako Urano; Hiroshi Nakajima; Yuko Matsuda; Yutaka Kitamura; Masayuki Saito; Hisashi Yamanaka; Terunobu Saito; Naoyuki Kamatani

Yuko Matsuda; Hisashi Yamanaka; Higami K; Kashiwazaki S

Kenshi Higami; Masayuki Hakoda; Yuko Matsuda; Hiroyuki Ueda; Sadao Kashiwazaki

Hiroshi Kajiyama; Hideto Akama; Hisashi Yamanaka; Akira Shoji; Yuko Matsuda; Eiichi Tanaka; Ayako Nakajima; Chihiro Terai; Masako Hara; Taisuke Tomatsu; Terunobu Saitoh; Naoyuki Kamatani

Eiichi Tanaka; Hisashi Yamanaka; Yuko Matsuda; Wako Urano; Hiroshi Nakajima; Atsuo Taniguchi; Terunobu Saito; Naoyuki Kamatani