Abstract. CD8 + CD25 + -activated cytotoxic T cells and anti-thyroglobulin antibodies (TgAb) are independently involved in the severity of Hashimoto's disease (HD). Interferon γ (IFN-γ) activates cytotoxic T cells. To evaluate the hypothesis that the functional +874A/T polymorphism in the gene encoding IFN-γ is associated with the severity of HD, we examined the frequencies of this polymorphism in 34 HD patients who developed hypothyroidism (severe HD); 22 untreated, euthyroid HD patients (mild HD); 49 patients with intractable Graves' disease (GD); 16 GD patients in remission; and 57 healthy volunteers. Frequency of the +874T allele, which is associated with high IFN-γ production, was higher in patients with severe HD than in those with mild HD (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.0-12.4; p = 0.047), but there was no difference in the frequency between GD patients. The difference in the frequency of +874T was observed in the subset of patients with HD negative for TgAb (OR, 8.4; 95% CI, 1.2-57.3; p = 0.029) but not in the subset of patients with HD positive for TgAb. Our data indicate that the +874A/T polymorphism in the IFN-γ gene is associated with severity of HD.

Microparticles (MPs) which are micro vesicles shed from the membrane of vascular and blood cells are considered as one of the causes of endothelial dysfunction in the diabetic vascular complications. In this study, we examined the effect of MPs derived from diabetes mice on vascular function, focusing on extracellular signal-regulated kinases (ERK)1/2-conteining MPs. MPs were prepared from streptozotocin (STZ)-induced diabetic mice (STZ), controls (Cont) and STZ and Cont mice treated with ERK1/2 inhibitor, PD98059 (PD). Vascular reactions and protein expressions were examined. STZ-derived MPs (STZ MPs) were found to have increased amounts of MP and to be attached to the endothelial cells as compared to Cont-derived MPs (Cont MPs). Furthermore, we found that ERK1/2 was contained in the MPs, especially STZ MPs. In addition, ERK1/2 activity and expression were increased in Cont vessels treated with STZ MPs. STZ PDMPs (PD-treated STZ derived MPs) improved the attenuated endothelial dependent relaxation in aortic rings. On the other hand, direct treatment of PD in STZ aortic rings did not improve the attenuated endothelial dependent relaxation. These results suggested that ERK1/2-containing MPs regulate ERK1/2 activity in blood vessels and cause endothelial dysfunction during diabetes. Student Sessions