Incidence of herpes zoster in Japanese patients with rheumatoid arthritis from 2005 to 2010.

Objective: To clarify the incidence and the risks of herpes zoster infection in Japanese patients with rheumatoid arthritis (RA).

Methods: By using a self-report of occurrence of herpes zoster in patients with RA in a large observational cohort study from 2005 to 2010, the standardized incidence rate was calculated. A Cox model was used to analyze risk factors for occurrence of herpes zoster.

Effect of genetic polymorphisms on development of gout.

Objective: To validate the association between genetic polymorphisms and gout in Japanese patients, and to investigate the cumulative effects of multiple genetic factors on the development of gout.

Methods: Subjects were 153 Japanese male patients with gout and 532 male controls. The genotypes of 11 polymorphisms in the 10 genes that have been indicated to be associated with serum uric acid levels or gout were determined.

Two young-adult female cases of dermatomyositis with antibodies for transcriptional intermediary factor 1-γ.

A variety of myositis-specific autoantibodies (MSAs) have been detected in patients with dermatomyositis (DM). We analyzed MSAs in 20 cases with DM. Eleven of the 20 cases were positive.

Comorbidities in patients with gout.

Gout is one of the most important diseases associated with hyperuricemia. Gout is characterized by acute monoarthritis with frequent flares. Some patients with gout have gouty tophi that are composed of monosodium urate crystals and inflammatory cells.

Incidence of serious respiratory infections in patients with rheumatoid arthritis treated with tocilizumab.

We aimed to demonstrate the incidence of serious respiratory infections in patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ) monotherapy. We analyzed the incidence of serious respiratory infections in 601 RA patients enrolled in TCZ clinical trials and their extension studies (TCZ cohort) and in 601 age- and sex-standardized RA patients treated in daily clinical practice at Tokyo Women's Medical University (IORRA subsample cohort). The rates of serious respiratory infections were 1.

Functional analysis of human sodium-phosphate transporter 4 (NPT4/SLC17A3) polymorphisms.

We analyzed the functional properties of five nonsynonymous single nucleotide polymorphisms (SNPs) in the sodium-phosphate transporter NPT4 gene (SLC17A3) using the Xenopus oocyte expression system. NPT4 variants carrying SNP V257F, G279R, or P378L exhibited reduced transport of [(14)C]para-aminohippurate, [(3)H]bumetanide, [(3)H]estrone sulfate, and [(14)C]urate, when each variant clone was expressed in the plasma membrane of oocytes. This study suggests the possibility that the genetic variation of NPT4 contributes to inter-individual differences in disposition of anionic drugs such as diuretics as well as certain endogenous organic anions such as urate.

Functional Analysis of Human Sodium-Phosphate Transporter 4 (NPT4/SLC17A3) Polymorphisms.

We analyzed the functional properties of five nonsynonymous single nucleotide polymorphisms (SNPs) in the sodium-phosphate transporter NPT4 gene (SLC17A3) using the Xenopus oocyte expression system. NPT4 variants carrying SNP V257F, G279R, or P378L exhibited reduced transport of [C]para-aminohippurate, [H]bumetanide, [H]estrone sulfate, and [C]urate, when each variant clone was expressed in the plasma membrane of oocytes. This study suggests the possibility that the genetic variation of NPT4 contributes to inter-individual differences in disposition of anionic drugs such as diuretics as well as certain endogenous organic anions such as urate.

Human sodium phosphate transporter 4 (hNPT4/SLC17A3) as a common renal secretory pathway for drugs and urate.

The evolutionary loss of hepatic urate oxidase (uricase) has resulted in humans with elevated serum uric acid (urate). Uricase loss may have been beneficial to early primate survival. However, an elevated serum urate has predisposed man to hyperuricemia, a metabolic disturbance leading to gout, hypertension, and various cardiovascular diseases.

Sodium-dependent phosphate cotransporter type 1 sequence polymorphisms in male patients with gout.

Objectives: Molecular biological approaches have recently identified urate transporters in renal proximal tubular cells. Human sodium-dependent phosphate cotransporter type 1 encoded by SLC17A1 is a urate transporter localised to the renal proximal tubular cells and candidate molecule to secret urate from renal tubular cells to urine. This study investigated the roles of SLC17A1 in the development of gout.

Associations between methotrexate treatment and methylenetetrahydrofolate reductase gene polymorphisms with incident fractures in Japanese female rheumatoid arthritis patients.

Several case reports have described associations between pathological nonvertebral fractures and low-dose methotrexate (MTX) in rheumatoid arthritis (RA) patients. Furthermore, a significant association between the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene and incident fractures has been reported in postmenopausal women. We attempted to determine whether MTX use and MTHFR polymorphisms are associated with incident fracture risk in Japanese female RA patients.

Validation of the associations between single nucleotide polymorphisms or haplotypes and responses to disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a proposal for prospective pharmacogenomic study in clinical practice.

Background: For prevention of joint destruction in rheumatoid arthritis, optimal management of therapy with disease-modifying antirheumatic drugs is essential. Pharmacogenomic evidence, if reliable, may be incorporated in the treatment of rheumatoid arthritis to achieve a more efficient activity control with minimized adverse events.

Methods: We conducted retrospective studies to validate our previous three different results about the association between adverse events or efficacy of two different disease-modifying antirheumatic drugs and genomic variations.

[Pharmacogenomics of antirheumatic drugs and personalized medicine for rheumatoid arthritis].

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints. The inflammatory process causes a significant disability and may involve internal organs. The efficacy of disease modifying anti rheumatic drugs is widely accepted.

Prevalence of Helicobacter pylori infection and risk of upper gastrointestinal ulcer in patients with rheumatoid arthritis in Japan.

We evaluated the prevalence of Helicobacter pylori infection and the association of H. pylori infection and/or nonsteroidal anti-inflammatory drug (NSAID) use with upper gastrointestinal (UGI) ulcers in a cohort of Japanese patients with rheumatoid arthritis (RA). Using the clinical database of the cohort of RA patients and the serum titers of H.

Validation of a Japanese version of the Stanford Health Assessment Questionnaire in 3,763 patients with rheumatoid arthritis.

Objective: To develop and validate a self-administered instrument for measuring functional status in Japanese-speaking rheumatoid arthritis patients.

Methods: We translated the Stanford Health Assessment Questionnaire (HAQ) into Japanese (original HAQ), and then made a tentative Japanese version of the HAQ (J-HAQ) with culturally appropriate modifications of the arising, eating, and reach category questions. The questionnaire was then administered to 3,763 RA patients (82.

[Pharmacogenetics of disease modifying anti-rheumatic drugs].

There are large differences in the effectiveness of disease modifying anti-rheumatic drugs(DMARD) from one person to the next. Adverse drug reactions caused by DMARD can also occur to some patients, but do not occur to others. One possible cause of the differences in the effectiveness and adverse drug reactions is genetic variation in how individuals metabolize drugs.

Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene.

Objective: N-acetyltransferase 2 (NAT2) is a key enzyme for the acetylation of sulfasalazine (SSZ). We examine whether there was a correlation between diplotype configurations (combinations of 2 haplotypes for a subject) at the NAT2 gene and the adverse effects of SSZ used for the treatment of rheumatoid arthritis (RA).

Methods: The findings from 144 patients with RA who had been treated with SSZ were collected from our outpatient department and used for a retrospective study.

The inflammatory process in the mechanism of decreased serum uric acid concentrations during acute gouty arthritis.

Objective: To clarify the mechanism of decreased serum uric acid (SUA) concentrations during acute gouty arthritis.

Methods: Data from patients with acute gouty arthritis during and after an attack were investigated retrospectively. Other investigations, including changes in urinary excretion and biochemical markers, were performed prospectively.

Comparison of the Rau method and the Larsen method in the evaluation of radiographic progression in early rheumatoid arthritis.

Objective: To investigate the usefulness of the radiographic scoring method proposed by Rau, et al for evaluation of joint damage in patients with early rheumatoid arthritis (RA).

Methods: Radiographs of hands and feet of 30 prospectively observed patients with early RA were assessed by the Rau method, the Larsen method, and count of erosive joints. The standardized response mean (SRM) was used to estimate the sensitivity to change of each method of assessment.

Polymorphisms in the methylenetetrahydrofolate reductase gene were associated with both the efficacy and the toxicity of methotrexate used for the treatment of rheumatoid arthritis, as evidenced by single locus and haplotype analyses.

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.