We demonstrated that there is increased SNHL in patients with RA, which may result from systemic inflammation and tissue injury, and increased latent-type CHL caused by stiffness of the middle ear system whose mechanisms are not yet clear.

The Y chromosome of the BXSB mouse has been shown to be responsible for the acceleration of lupus-like autoimmune syndrome in inbred BXSB mice and in their F1 hybrids with NZB or NZW mice. To further define the role of this as yet unidentified gene linked to the BXSB Y chromosome, designated Yaa (Y chromosome-linked autoimmune acceleration), the Y chromosome was transferred from the BXSB strain to nonautoimmune C57BL/6 (B6) mice. The effect of the Yaa gene on the autoantibody formation and the development of glomerulonephritis was investigated in B6 mice and in their F1 hybrids with NZW mice. The presence of the BXSB Y chromosome was not able to induce significant autoimmune responses in B6 mice. However, (NZW x B6)F1 males bearing the BXSB Y chromosome developed a severe lupus-like autoimmune syndrome, as documented by the production of anti-DNA antibodies and gp70-anti-gp70 immune complexes and the development of lethal lupus nephritis. Both sexes of (NZW x B6)F1 hybrids without the BXSB Y chromosome were essentially normal. Our results suggest that (a) the BXSB Y chromosome by itself is not sufficient to initiate autoimmune responses in nonautoimmune B6 mice, and (b) it is able to induce autoimmune responses in mice potentially capable of developing the disease, but whose autosomal abnormality by itself is not sufficient to develop autoimmune diseases.

The accelerated development of lupus-like autoimmune disease in male BXSB mice (H-2b, I-E-) is associated to the presence of a mutant gene, designated Yaa, located on their Y chromosome. To investigate whether the H-2b haplotype and/or the lack of expression of I-E molecules play any role in the Yaa-linked acceleration of autoimmune disease, an I-E+ BXSB.H-2d congenic strain was created by backcross procedures. We compared the development of autoimmune disease in the novel BXSB.H-2d (I-E+) strain to that of BXSB.H-2b (I-E-) and BXSB.H-2b/d (I-E+) heterozygous mice. Male BXSB.H-2d (I-E+) mice exhibited only a limited production of autoantibodies and a lower incidence of glomerulonephritis with a markedly prolonged survival rate, which were essentially identical to those of female BXSB mice of both-H-2b and H-2d haplotypes. However, BXSB.H-2b/d (I-E+) heterozygous males developed an accelerated disease comparable to that of conventional BXSB.H-2b (I-E-) male mice. These results indicate that the expression of I-E molecules and consequent clonal deletion or anergy of I-E reactive T cells does not appear to be responsible for the prevention of accelerated autoimmune disease in BXSB.H-2d (I-E+) male mice. The finding that the Yaa gene-induced acceleration of lupus-like autoimmune disease is modulated by gene(s) within or closely linked to the H-2 complex underlines the crucial role of the major histocompatibility complex and the polygenetic nature of autoimmune disease in BXSB mice.

These findings indicate that PLGA nanoparticles can be an useful drug carrier to the cochlea via local application.

These results suggest that the present strategy is useful to advance the clinical application of PGE(1) as a therapeutic agent for vascular disorders.

No abstract

Epidermal basal cell injury with colloid body formation is a characteristic feature of lichen planus. Infiltrated cells are thought to be responsible for the epidermal injury. Ultrastructural findings of colloid bodies are typical of apoptosis. Granzymes in cytotoxic T lymphocytes are involved in apoptosis probably together with perforin. Based on this background, we analyzed the role of granzyme B in the mechanisms of epidermal injury in lichen planus. On electron microscopy, basal and suprabasal cells showed condensed chromatin and fragmented nuclei which are typical morphological features of apoptosis. Nuclei of colloid bodies were positively stained by the in situ nick end labeling technique indicating that colloid bodies are subsequently formed in the process of apoptosis. Immunohistochemical staining showed CD8-positive infiltrating cells to contain granzyme B. Cells undergoing exocytosis also contained granzyme B. By immunoelectron microscopy, granzyme B molecules were observed to be secreted from a lymphocyte to an apoptotic keratinocyte. These findings suggest that granzyme B-positive CD8 cells seem to induce apoptosis of keratinocytes in lichen planus.

A decision tree model that includes hepatic steatosis, LDL-C, age, blood sugar, and GGT may be useful for the prediction of response before PEG-IFN plus RBV therapy, and has the potential to support clinical decisions in selecting patients for therapy and may provide a rationale for treating metabolic factors to improve the efficacy of antiviral therapy.