The store-operated Ca(2+) release-activated Ca(2+) (CRAC) channel is activated by diminished luminal Ca(2+) levels in the endoplasmic reticulum and sarcoplasmic reticulum (SR), and constitutes one of the major Ca(2+) entry pathways in various tissues. Tubular aggregates (TAs) are abnormal structures in the skeletal muscle, and although their mechanism of formation has not been clarified, altered Ca(2+) homeostasis related to a disordered SR is suggested to be one of the main contributing factors. TA myopathy is a hereditary muscle disorder that is pathologically characterized by the presence of TAs. Recently, dominant mutations in the STIM1 gene, encoding a Ca(2+) sensor that controls CRAC channels, have been identified to cause tubular aggregate myopathy (TAM). Here, we identified heterozygous missense mutations in the ORAI1 gene, encoding the CRAC channel itself, in three families affected by dominantly inherited TAM with hypocalcemia. Skeletal myotubes from an affected individual and HEK293 cells expressing mutated ORAI1 proteins displayed spontaneous extracellular Ca(2+) entry into cells without diminishment of luminal Ca(2+) or the association with STIM1. Our results indicate that STIM1-independent activation of CRAC channels induced by dominant mutations in ORAI1 cause altered Ca(2+) homeostasis, resulting in TAM with hypocalcemia.

Two cases of acute encephalopathy in young children clearly showed evidence of influenza A virus infection and bilateral thalamic lesions. Influenza-associated encephalopathy with bilateral thalamic lesions has mostly been reported in Japan; it differs from Reye's syndrome in several respects. Other factors in addition to influenza virus infection may have contributed to the etiology of encephalopathy in our case patients.

The virus isolation rates after treatment with each of the NAIs were significantly lower in the A H1N1/09 group, suggesting that the pandemic A H1N1/09 virus was more sensitive to the NAIs than the seasonal A H3N2 virus was. Clinically, there were no significant differences in the effectiveness of the NAIs between the H1N1/09 infected group and H3N2 infected group.

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Increasing research efforts have been directed at determining the contribution of locally synthesized (cell-derived) complement in host defense and inflammation. In the studies presented here, we determined the ability of a continuous cell line of type II pneumocytes (A549) and a cell line of human lung fibroblasts (WI-38) to produce complement components in vitro. Complement biosynthesis by A549 pneumocytes and WI-38 fibroblasts was demonstrated by incorporation of [35S]methionine into immunoprecipitable complement proteins. Using this technique, A549 pneumocytes were demonstrated to synthesize Clr, Cls, C4, C3, C5, C6, C7, C8, C9, Factor B, Factor H, Factor I, and C1s inactivator. In comparison, WI-38 fibroblasts were shown to synthesize Cls, C4, C3, C5, C6, C8, and C9. Because previous work has demonstrated the central role of C3, C5, and their activation products in regulating lung inflammation and tissue injury, we further investigated the production of C3 and C5 by both lung pneumocytes and fibroblasts using enzyme-linked immunospecific assays. A549 cells cultured in the presence of 15% fetal bovine serum (FBS) produced antigenic C3 (135 ng C3/ml/24 h) at a greater rate than did identical cells maintained in serum-free culture conditions (70 ng C3/ml/24 h). Similarly, antigenic C5 production by A549 pneumocytes was greatest in the presence of FBS when compared with cells maintained in serum-free culture conditions (245 ng C5/ml/24 h versus 155 ng C5/ml/24 h).(ABSTRACT TRUNCATED AT 250 WORDS)