Microtubule-associated protein 1B (MAP1B), one of the microtubule-associated proteins (MAPs), is a major component of the neuronal cytoskeleton. It is expressed at high levels in immature neurons during growth of their axons, which indicates that it plays a crucial role in neuronal morphogenesis and neurite extension. To better define the role of MAP1B in vivo, we have used gene targeting to disrupt the murine MAP1B gene. Heterozygotes of our MAP1B disruption exhibit no overt abnormalities in their development and behavior, while homozygotes showed a slightly decreased brain weight and delayed nervous system development. Our data indicate that while MAP1B is not essential for survival, it is essential for normal time course development of the murine nervous system. These conclusions are very different from those of a previous MAP1B gene–targeting study (Edelmann, W., M. Zervas, P. Costello, L. Roback, I. Fischer, A. Hammarback, N. Cowan, P. Davis, B. Wainer, and R. Kucherlapati. 1996. Proc. Natl. Acad. Sci. USA. 93: 1270–1275). In this previous effort, homozygotes died before reaching 8-d embryos, while heterozygotes showed severely abnormal phenotypes in their nervous systems. Because the gene targeting event in these mice produced a gene encoding a 571–amino acid truncated product of MAP1B, it seems likely that the phenotypes seen arise from the truncated MAP1B product acting in a dominant-negative fashion, rather than a loss of MAP1B function.

PurposeTo establish a new medical information database network (designated MID‐NET®) to provide real‐world data for drug safety assessments in Japan.MethodsThis network was designed and developed by the Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency in collaboration with 23 hospitals from 10 healthcare organizations across Japan. MID‐NET® is a distributed and closed network system that connects all collaborative organizations through a central data center. A wide variety of data are available for analyses, including clinical and administrative information. Several coding standards are used to standardize the data stored in MID‐NET® to allow the integration of information originating from different hospitals. A rigorous and consistent quality management system was implemented to ensure that MID‐NET® data are of high quality and meet Japanese regulatory standards (good post‐marketing study practice and related guidelines).ResultsMID‐NET® was successfully established as a reliable and valuable medical information database and was officially launched in April 2018. High data quality with almost 100% consistency was confirmed between original data in hospitals and the data stored in MID‐NET®. A major advantage is that approximately 260 clinical laboratory test results are available for analysis.ConclusionsMID‐NET® is expected to be a major data source for drug safety assessments in Japan. Experiences and best practices established in MID‐NET® may provide a model for the future development of similar database networks.

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The mechanisms underlying mitochondrial impairment in the failing heart are not yet clearly defined. In the present study, we examined the involvement of changes in small heat shock proteins (HSPs) such as HSPB1, HSPB5 and HSPB8 in mitochondrial dysfunction of the failing heart. Hemodynamic parameters of rats with myocardial infarction at the 2nd and 8th weeks (2W- and 8W-) after coronary artery ligation (CAL) were measured. The 8W-CAL rats, but not the 2W-CAL ones, showed the signs of the chronic heart failure concomitant with a reduced mitochondrial oxygen consumption rate. In the mitochondrial fraction prepared from the heart of the 2W-CAL animals, the contents of small HSPs and phosphorylated small HSPs were increased, suggesting that these increases contributed to the preservation of the mitochondrial energy-producing ability. In the failing heart, HSPB1 and HSPB8 contents and phosphorylated small HSP contents in the mitochondrial fraction were decreased, suggesting that a reduction in mitochondrial translocation of these small HSPs led to impaired mitochondrial energy-producing ability. To further define the submitochondrial locations of these small HSPs, we performed mitochondrial subfractionation. The contents of small HSPs in the 2W-CAL rats were increased in the mitochondrial inner-membrane fraction, whereas those of the 8W-CAL rats were reversed to those of the control animals. These findings suggest that small HSPs, at least in part, play an important role in the development of the impaired mitochondrial energy-producing ability that leads to heart failure after a myocardial infarction.