We performed histological and immunohistochemical analyses of the removed thymus in 20 elderly (onset age >60 years) and 23 young (onset age <40 years) patients with myasthenia gravis (MG) who showed positive anti-acetylcholine receptor (AChR) antibodies in serum without associated thymoma. In the elderly group nine (45%) demonstrated accumulations of lymphocytes indicating atrophied thymus without the basic structure. The elderly MG patients with atrophied thymic tissues showed higher titers of the anti-AChR antibody (59.6 81.0 nmol/l) than those with adipose tissue alone (20.1 20.9 nmol/l). In immunohistochemistry both the young group and elderly patients with atrophied thymic tissues showed significantly higher levels of CD20 on image analysis than the age-matched controls (p<0.005). Atrophied thymic tissues as often seen immunohistochemically in young MG patients might be found also in the elderly ones, particularly in those with high titers of the anti-AChR antibody, even though fat infiltration is remarkable.

Malignant pleural mesothelioma (MPM) is an aggressive tumor that is characterized by dysregulated growth and resistance to apoptosis. Reactive oxygen species (ROS)-generating NADPH oxidase (Nox) family enzymes have been suggested to be involved in neoplastic proliferation. Both the antioxidant N-acetylcysteine (NAC) and the inhibitor of flavoprotein-dependent oxidase, diphenylene iodonium (DPI), inhibited the cell viability of MPM cells in a dose-dependent manner. To examine whether Nox-mediated ROS generation confers antiapoptotic activity and thus a growth advantage to MPM cells, we analyzed the mRNA expression of Nox family members using quantitative RT-PCR in 7 MPM cell lines and a normal mesothelial cell line. Nox4 mRNA was expressed in all of the examined MPM cell lines, whereas little or no Nox2, Nox3 and Nox5 mRNA expression was detected. In 2 MPM cell lines, Nox4 mRNA expression was significantly higher than that in a normal mesothelial cell line. siRNAs targeting Nox4 suppressed ROS generation and cell viability in the MPM cell lines. In addition, DPI treatment and knockdown of Nox4 attenuated phosphorylation of AKT and ERK. Taken together, our results indicate that Nox4-mediated ROS, at least in part, transmit cell survival signals and their depletion leads to apoptosis, thus highlighting the Nox4-ROS-AKT signaling pathway as a potential therapeutic target for MPM treatment.