Phosphorylation of the histone family is not only a response to cell signaling stimuli, but also an important indicator of DNA damage preceding apoptotic changes. While astrocytic degeneration, including DNA damage, has been reported in Alzheimer disease (AD), its pathogenetic significance is somewhat unclear.In an effort to clarify this, we investigated the expression of γH2AX as evidence of DNA damage in astrocytes to elucidate the role of these cells in the pathogenesis of AD. In response to the formation of double-stranded breaks in chromosomal DNA, serine 139 on H2AX, a 14-kDa protein that is a member of the H2A histone family and part of the nucleosome structure, becomes rapidly phosphorylated to generate γH2AX. Using immunocytochemical techniques, we found significantly increased levels of γH2AX in astrocytes in regions know to be vulnerable in AD, i.e., the hippocampal regions and cerebral cortex. These results suggest that astrocytes contain DNA damage, possibly resulting in functional disability, which in turn reduces their support for neurons. These findings further define the role of astrocyte dysfunction in the progression of AD.
Angiomyolipoma is a common tumor of the kidney but has rarely been found in the mediastinum. We report a case of angiomyolipoma of the posterior mediastinum in a 62-year-old woman. She experienced exertional dyspnea and intermittent cough at admission. Computed tomography indicated a tumor located at the left paravertebral and upper posterior mediastinum and MRI imaging demonstrated a mass with low signal intensity in T1-weighted image at T4-5 level. Thoracotomy was done for surgical removal of the tumor and histologic examination revealed a mesenchymal tumor composed of mature fat, capillaries and smooth muscle fibers. The tumor was immunohistochemically positive for CD34 and factor-VIII (for vascular component) smooth muscle actin (for smooth muscle component) and S-100 protein (for fat component). There have been four case reports about mediastinal angiomyolipoma, namely three Japanese cases and one French case. It is suggested that angiomyolipoma could be considered for the differential diagnosis of mediastinal tumors.
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