Objective-To evaluate secular trends in the incidence and prevalence of rheumatoid arthritis (RA) in Japan. Methods-The incidence and prevalence of RA were determined in a longitudinal population based study in the Kamitonda district, Wakayama, Japan, from 1965 to 1996. Results-In the study area consisting of about 3000 inhabitants, 16 incident cases, satisfying definite RA by the Rome criteria were detected during the study period. The age and sex adjusted incidence in both men and women combined and the age adjusted incidence in women significantly decreased (p<0.025 and p<0.01, respectively). The age and sex adjusted prevalence in all inhabitants tended to decrease (p<0.1), and the age adjusted prevalence in women significantly declined (p<0.025). In men, however, neither incidence nor prevalence showed significant change. Conclusions-The decline of incidence and prevalence of female RA may be reducible to some environmental changes preferentially occurring more obviously in Japanese women than in men. Because the use of oral contraceptives has been extremely low in Japan, the decline should be explained by other factors. (Ann Rheum Dis 1999;58:751-756)

These results suggested the following sequential events for the pathogenesis of the cerebral amyloid angiopathy-associated vascular lesions leading to hemorrhage: (1) damage of the media and adventitia due to severe amyloid deposition results in dilatation of the cortical arteries, (2) the vascular dilatation progresses and is accompanied by thickening of the intima and disruption of the media and adventitia (microaneurysm formation), (3) plasma components invade to the vascular wall (fibrinoid necrosis), and (4) finally, hemorrhage develops.

These findings indicate that abnormal Pi metabolism may also be involved in tight junction molecules such as Cldns that are affected by Npt2b deficiency.

Genetic variants of interleukin-3 (IL-3), a well-studied cytokine, may have a role in the pathophysiology of rheumatoid arthritis (RA); but reports on this association sometimes conflict. A case-control study was designed to investigate association between RA and a single-nucleotide polymorphism (SNP) in the IL-3 promoter region. Comparison of cases of RA versus control individuals yielded a chi(2) value of 14.28 (P=.0002), with a genotype odds ratio of 2.24 (95% confidence interval [95%CI] 1.44-3.49). When female cases with earlier onset were compared with female control individuals, the SNP revealed an even more significant correlation, with chi2=21.75 (P=.000004) and a genotype odds ratio of 7.27 (95%CI 2.80-18.89). The stronger association that we observed in this clinically distinct subgroup (females with early onset), within a region where linkage disequilibrium was not significantly extended, suggested that the genuine RA locus should locate either within or close to the IL-3 gene. Combined genotype data on SNPs on eight other candidate genes were combined with our IL-3 results, to estimate relationships between pairs of loci and RA, by maximum-likelihood analysis. The utility of combining the genotype data in this way to identify possible contributions of various genes to this disease is discussed.