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Methylmercury is an environmental pollutant that induces potent neurotoxicity. We previously identified transcription factor 3 (TCF3) as a transcription factor that is activated in the brains of mice treated with methylmercury, and reported that methylmercury sensitivity was increased in cells in which TCF3 expression was suppressed. However, the mechanisms involved in the activation of TCF3 by methylmercury and in the reduction of methylmercury toxicity by TCF3 remained unclear. We found that treatment of mouse neuronal C17.2 cells with methylmercury increased TCF3 protein levels and promoted the binding of TCF3 to DNA consensus sequences. In cells treated with actinomycin D, a transcription inhibitor, an increase in TCF3 protein levels was also observed under methylmercury exposure. However, in the presence of cycloheximide, a translation inhibitor, methylmercury delayed the degradation of TCF3 protein. In addition, treatment with MG132, a proteasome inhibitor, increased TCF3 protein levels, and there was not significant increase in TCF3 protein levels by methylmercury under these conditions. These results suggest that methylmercury may activate TCF3 by increasing its levels through inhibition of TCF3 degradation by the proteasome. It has been previously reported that the induction of apoptosis in neurons is involved in methylmercury-induced neuronal damage in the brain. Although apoptosis was induced in C17.2 cells treated with methylmercury, this induction was largely suppressed by overexpression of TCF3. These results indicate that TCF3, which is increased in the brain upon exposure to methylmercury, may be a novel defense factor against methylmercury-induced neurotoxicity.

To manage hepatocellular carcinoma (HCC) patients surviving for a long term, the treatment strategy for recurrent cancer is as important as that for the initial treatment. However, no prognostic scoring system has been available for patients with HCC recurrence. The purpose of this study was to develop a new staging system for deciding the treatment strategy not only for first-time diagnosed patients but also for recurrent patients.

The evaluation of Gd-DTPA contrast enhancement (CE) in high intensity tissues on Tl-weighted magnetic resonance images, such as fat and bone marrow, is quite difficult. In this study, we used subtraction and subtracted color images in an attempt to show more clearly the Gd-DTPA CE. In addition, we also carried out sequential post-Gd-DTPA imaging to assess the changes in enhancement of lesions with time. Twenty patients were studied with these methods and our results are illustrated.

Growth factor receptor‐bound protein‐2 (GRB‐2) is a protein linking receptor tyrosine kinase and Sos (Son of Sevenlessgene; Ras GDP/GTP exchange protein), leading to activation of the Ras‐mitogen‐activated protein kinase (MAPK) cascade. So far, it remains unclear how GRB‐2 plays a role in signal transduction pathways evoked by hepatotrophic factors. This study was attempted to evaluate the involvement of GRB‐2 in signalling in rat hepatocyte growth. Using rat cultured hepatocytes stimulated by hepatotrophic factors and regenerating livers after partial hepatectomy (PH) we examined GRB‐2‐mediated linkage of hepatotrophic factor receptors to signal transducing molecules such as Sos or dynamin‐II by immunoprecipitation and western blot analysis. In primary cultured hepatocytes stimulated with hepatocyte growth factor (HGF) or epidermal growth factor (EGF), GRB‐2 linked HGF receptor or EGF receptor, respectively, to Sos which activated the mitogen‐activated protein kinase (MAPK) cascade. In contrast, in primary cultured hepatocytes stimulated with insulin, GRB‐2 linked insulin receptor substrate‐1 (IRS‐1) to dynamin‐II as well as Sos. In the early phase after PH, GRB‐2 activated the Ras‐MAPK cascade by linking HGF receptor, IRS‐1, or EGF receptor to Sos. In the late phase after PH, a complex of IRS‐1‐GRB‐2 associated with dynamin‐II, indicating that GRB‐2 may transduce signals from IRS‐1 to dynamin‐II. We conclude that GRB‐2 may play a role in transmitting signals from hepatotrophic factors to not only MAPK but also to other signalling pathways in hepatocyte growth.

Proper evaluation of the wheel-rail contact is necessary to understand the dynamics of railway vehicles and the causes of wear and damage to components such as wheels and rails. Numerical methods are often used to evaluate the dynamic contact condition between the wheel and rail; however, there are few promising methods for experimental evaluation. It is important to develop a measurement method because the wheel-rail contact is easily changed owing to vehicle-track dynamic interactions. In this study, we used a film-based pressure sensor equipped with force-sensitive resistors to measure the contact area between the wheel and rail during vehicle operation. Using the film-based pressure sensor, we evaluated the geometry of the contact area and position. The validity of the measured contact position is evaluated by comparing it with the contact position based on the cross-sectional profiles of the wheel and rail and the wheelset displacement during a vehicle running.

Methylmercury precipitates heart failure by increasing Drp1-mediated mitochondrial fission.

Filamin enhances Drp1-mediated mitochondrial fission and cellular senescence after myocardial infarction.