Chilliness in Japanese middle-aged women is associated with anxiety and low n-3 fatty acid intake.

Objective: This cross-sectional study investigated chilliness, which is the most prevalent sexual-vasomotor symptom in middle-aged Japanese women.Methods: First-visit records of 475 Japanese women (age 40-65 years) enrolled in the health and nutrition education program at a menopause clinic were analyzed. Chilliness was estimated based on responses to the Menopausal Symptom Scale. Effects of age, menopausal status, body composition, cardiovascular parameters, resting energy expenditure, physical fitness, menopausal symptoms, lifestyle, and estimated daily intake of nutrients were assessed using a multivariate logistic regression analysis.Results: Severe chilliness was found in 28.4% of women. It was not related to age, menopausal status, body mass index, or body fat percentage. The anxiety subscale score of the Hospital Anxiety and Depression Scale was the sole background characteristic independently associated with severe chilliness (adjusted odds ratio, 1.09; 95% confidence interval, 1.04-1.15 per point). Daily intakes of vitamin D and n-3 fatty acids were significantly lower in women with severe chilliness. Daily intake of n-3 fatty acids was negatively associated with severe chilliness after adjustment (odds ratio, 0.54; 95% confidence interval, 0.29-0.95 per g/1000 kcal intake).Conclusions: Chilliness is associated with anxiety and low intake of n-3 fatty acids.

A novel non-polyglutamable anti-folate, MX-68, inhibits the induction of experimental autoimmune uveitis in rats.

MX-68 is a novel antifolate which is chemically designed not to undergo intracellular polyglutamation thus preventing the development of adverse effects. The present study was carried out to examine both the in vitro and in vivo effects of MX-68 on experimental autoimmune uveitis (EAU) and to compare its effect on collagen-induced arthritis (CIA) in rats. EAU was induced by injecting Lewis rats with retinal S-antigen in complete Freund's adjuvant. Either MX-68 or methotrexate (MTX), which forms several polyglutamates intracellularly, was orally administered five days a week for three weeks beginning on the day of immunization. In vivo, both MX-68 and MTX significantly delayed the onset of EAU and inhibited the antibody response to S-antigen in a dose-dependent manner. High dose MX-68 (2.5 mg kg-1 day-1) completely abrogated the induction of EAU. No adverse effects were observed in either MX-68- or MTX-treated rats. However, the cessation of MX-68 administration after a period of three weeks resulted in the induction of EAU. In contrast, both MX-68 and MTX suppressed the severity of CIA without affecting the onset of the disease and inhibited anti-collagen antibody production in a dose-dependent fashion. Discontinuation of the drugs did not result in the recurrence of CIA. In vitro, both MX-68 and MTX significantly suppressed the proliferation of S-antigen- and Con A-stimulated lymph node cells obtained from immunized rats in a dose-dependent fashion. These data suggest that MX-68 may be useful for the treatment of autoimmune diseases including EAU and that the pathophysiology of EAU could be different from that of CIA.

Enhanced expression of nucleobindin in lymphatic organs of lupus-prone mice.

Nucleobindin (Nuc) was originally identified as a 55 kDa protein that enhanced anti-DNA antibody production in cultures of autoimmune MRL/lpr mouse spleen cells. cDNA cloning and the production of recombinant protein (rNuc) have revealed that rNuc binds to DNA and Ca2+ by means of leucine zipper and EF-hand motif structures. In vitro and in vivo effects of rNuc to induce autoantibodies including anti-dsDNA antibody in normal mice have been demonstrated; however, whether Nuc is involved in the state of autoimmunity occurred in MRL/lpr, C3H/gld and male BXSB mice has not been elucidated. Here we report that the expression of Nuc mRNA is upregulated with age in the lymphatic organs and is positively correlated to the serum levels of Nuc in these lupus-prone strains of mice. Upon immunization with KLH in Freund's complete adjuvant, normal BALB/c mice also showed an elevated level of Nuc in their serum and elevated Nuc mRNA in their lymphatic organs. In addition, in vitro stimulation of BALB/c splenocytes with Con A or LPS remarkably enhanced Nuc mRNA expression. These results suggest that upregulation of Nuc mRNA in lymphatic organs and serum Nuc of lupus-prone mice is related to spontaneous activation of immunocompetent cells; the present data are also consistent with our previous hypothesis on the role of Nuc in the induction or enhancement of autoimmunity in lupus models of mice.

The human immunoglobulin V(H) gene repertoire is genetically controlled and unaltered by chronic autoimmune stimulation.

The factors controlling immunoglobulin (Ig) gene repertoire formation are poorly understood. Studies on monozygotic twins have helped discern the contributions of genetic versus environmental factors on expressed traits. In the present experiments, we applied a novel anchored PCR-ELISA system to compare the heavy chain V gene (V(H)) subgroup repertoires of mu and gamma expressing B lymphocytes from ten pairs of adult monozygotic twins, including eight pairs who are concordant or discordant for rheumatoid arthritis. The results disclosed that the relative expression of each Ig V(H) gene subgroup is not precisely proportional to its relative genomic size. The monozygotic twins had more similar IgM V(H) gene repertoires than did unrelated subjects. Moreover, monozygotic twins who are discordant for RA also use highly similar IgM V(H) gene-subgroup repertoires. Finally, the V(H) gene repertoire remained stable over time. Collectively, these data reveal that genetic factors predominantly control V(H) gene repertoire formation.

Comparison of diagnosis and treatment of Sjögren's syndrome in Japan and United States.

Today, as with western countries, diagnosis and treatment of Sjögren's syndrome (SS) patients in Japan are carried out by a team effort. The clinical manifestations of Japanese SS patients are quite similar also. There are, however, several minor modifications in the diagnosis and treatment of SS patients in Japan, which are presented in this article.

Increased production of endothelin-1 in patients with inflammatory arthritides.

OBJECTIVE: Endothelin-1 (ET-1) is a potent vasoconstrictive peptide, but its precise mechanism of action in vivo has remained unknown. METHODS: We measured ET-1 activity by radioimmunoassay, in both plasma and synovial fluid from patients with inflammatory arthritides. RESULTS: ET-1-like immunoreactivity was found in synovial fluid, at levels severalfold higher than those in plasma. Reverse-phase high-performance liquid chromatography showed an elution profile corresponding to actual ET-1. A single class of high-affinity binding sites for ET-1 in cultured synovial cells was also detected. Furthermore, ET-1 induced mild DNA synthesis in synovial cells. CONCLUSION: Taken together, these results indicate that ET-1 might contribute to the synovial proliferation seen in inflammatory arthritides, in an autocrine/paracrine manner.