Objective. To elucidate the role played by HLA-B51 in the neutrophil hyperfunction of Behqet's disease, we determined the superoxide production by purified peripheral blood neutrophils from Behqet's disease patients, from HLA-B51 positive healthy individuals, and from HLA-B51 transgenic mice, Methods. Neutrophil function was evaluated by flow cytometric analysis, detecting the conversion of 2',7'-dichlorofluorescin diacetate into dichlorofluorescein, induced by superoxide in the neutrophils.Results. A significant correlation between the neutrophil hyperfunction and the possession of HLA-B51 phenotype, regardless of the presence of the disease, was observed in humans. FMLP-stimulated neutrophils (without in vitro priming) from HLA-BS1 transgenic mice, but not those from HLA-B35 transgenic mice or from nontransgenic mice, produced substantial amounts of superoxide.Conclusion. The HLA-BS1 molecule itself may be responsible, at least in part, for neutrophil hyperfunction in Behqet's disease.

Phenotypic and functional properties of γδ T cells, which play an important role in mucocutaneous immunity, were examined to elucidate whether immunological abnormality in Behc¸et's disease may be related to a specific T cell population. We found that CD45RA+Vγ9+Vδ2+γδ T cells, which constitute a minor population of γδ T cells in healthy individuals, were increased in number in Behc¸et's disease irrespective of disease activity. This CD45RA+ subset of γδ T cells in the active, but not inactive, phase of this disease expressed IL‐2Rβ and HLA‐DR, suggesting that they are activated in vivo in active Behc¸et's disease. In addition, the CD45RA+γδ T cells produced extreme amounts of tumour necrosis factor and contained perforin granules. These data indicate that a phenotypically distinct subset of γδ T cells, CD45RA+CD45RO−Vγ9+Vδ2+, may contribute to immunological abnormalities which may lead to complexity of pathophysiology in Behc¸et's disease.

Abstract

Objective. We have recently found that the presence of autoantibodies against the 70-kd polypeptide of U1 RNP (Ul-70-kd) is associated with HLA-DR4 and DR2. To further characterize this association, we performed a molecular genetic analysis of HLA-DR and DQ genes among patients with autoantibodies against Methods. The polymerase chain reaction (PCR), sequence-specific oligonucleotide hybridization, and U1-70-kd.

In this study, we induced differentiation of CPT II-deficient hiPSCs into mature myocytes in a highly efficient and reproducible manner and recapitulated some aspects of the disease phenotypes of CPT II deficiency in the myocyte disease models. This approach addresses the challenges of modeling the abnormality of FAO in CPT II deficiency using iPSC technology and has the potential to revolutionize translational research in this field.

SUMMARYActivin A not oniy stimulates the synthesis and release of pituitary follicie-stimuiating honnone. but exerts various effects on haematopoietic cetis. embryos, and fibroblasts. In the present study we have examined effects of activin A on lgH synthesis and cytokine production by peripheral blood mononuciear ceiis (PBMt") in normai humans. When PBMC were cultuted in the prcsenee of lL-4. activin A significantiy augmented IgE production induced by IL-4. Activin A did not atlect, however, IgE production from highiy purified B ceiis when they were stimuiated with anti-CD4() MoAb and IL-4. The fact that in the iatter condition IgE synthesis was T ceii-and monocytc-indcpcndent indicated that activin A does not directiy inlluence B ceiis for IgE synthesis. Rather, production as weii as gene expression of IL-6, which is known to enhance IgE syntiiesis by puriiied monoeytes. was induced by activin A aione. In addition, activin A induced other monokines such as lL-l and tutnour necrosis factor (TNF)-a from monoeytes. In contrast, activin A neither induced nor augmented the production of TNF-/i or interferon-gamma (IFN-y). both of which arc known to be cxciusiveiy generated by Tceils. These data indicate that activin A piays a certain role in piiysioiogicat functions for monocyles in normal humans.

No abstract

Objective There is no standardized therapy for renal amyloidosis, which shows rapid progression and poor prognosis. Here, we used