The Keio Journal of Medicine
Online ISSN : 1880-1293
Print ISSN : 0022-9717
ISSN-L : 0022-9717
Volume 59, Issue 3
Displaying 1-4 of 4 articles from this issue
COMMEMORATIVE LECTURE
  • Fred H. Gage
    2010 Volume 59 Issue 3 Pages 79-83
    Published: September 25, 2010
    Released on J-STAGE: October 01, 2010
    JOURNAL FREE ACCESS
    Adult neural stem cells (NSCs) are a potential endogenous source for neuronal cell replacement in the diseased adult central nervous system (CNS). However, the recruitment of adult NSCs for repair is hampered by the current lack of knowledge about the cellular and molecular mechanisms that control their behavior in vivo. We have previously demonstrated that environment-derived signals control the fate choice of adult NSCs. More recently we have provided evidence that in the adult hippocampal dentate gyrus - one of the two neurogenic regions of the adult CNS - specialized astrocytes provide signals that instruct NSCs to adopt a neuronal fate. In this review I will examine in vitro and in vivo the molecular mechanisms underlying the neuronal fate instruction of adult NSCs by the local astrocyte population in the adult hippocampus. In particular, I will focus on the Wnt family of proteins, which we have found to be expressed in adult hippocampal astrocytes; our preliminary studies have also shown that these proteins enhance the generation of neurons from adult NSCs in vitro.
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REVIEWS
  • Koichi Hayashi, Koichiro Homma, Shu Wakino, Hirobumi Tokuyama, Naoki S ...
    2010 Volume 59 Issue 3 Pages 84-95
    Published: September 25, 2010
    Released on J-STAGE: October 01, 2010
    JOURNAL FREE ACCESS
    Voltage-dependent Ca channels are classified into several subtypes based on the isoform of their α1 subunits. Traditional Ca channels blockers (CCBs), including nifedipine and amlodipine, act predominantly on L-type Ca channels, whereas novel CCBs such as efonidipine, benidipine and azelnidipine inhibit both L-type and T-type Ca channels. Furthermore, cilnidipine blocks L-type and N-type Ca channels. These CCBs exert divergent actions on renal microvessels. L-type CCBs preferentially dilate afferent arterioles, whereas both L-/T-type and L-/N-type CCBs potently dilate afferent and efferent arterioles. The distinct actions of CCBs on the renal microcirculation are reflected by changes in glomerular capillary pressure and subsequent renal injury: L-type CCBs favor an increase in glomerular capillary pressure, whereas L-/T-type and L-/N-type CCBs alleviate glomerular hypertension. The renal protective action of L-/T-type CCBs is also mediated by non-hemodynamic mechanisms, i.e., inhibition of the inflammatory process and inhibition of Rho kinase and aldosterone secretion. Finally, a growing body of evidence indicates that T-type CCBs offer more beneficial action on proteinuria and renal survival rate than L-type CCBs in patients with chronic kidney disease (CKD). Similarly, in CKD patients treated with renin-angiotensin blockers, add-on therapy with N-type CCBs is more potent in reducing proteinuria than that with L-type CCBs, although no difference is found in the subgroup with diabetic nephropathy. Thus, the strategy for hypertension treatment with CCBs has entered a new era: treatment selection depends not only on blood pressure control but also on the subtypes of CCBs.
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  • David A. Cook
    2010 Volume 59 Issue 3 Pages 96-103
    Published: September 25, 2010
    Released on J-STAGE: October 01, 2010
    JOURNAL FREE ACCESS
    Education scholarship and research are critically important in extending our ability to teach and assess effectively. Those considering a scholarly project in medical education should consider the following tips, learned from personal experience and supported by literature: 1) get some training, 2) find a mentor, 3) ask important questions, 4) start small and grow, 5) aim high, 6) don't wait for the perfect study, 7) plan for adequate time and other resources, 8) attend to ethical issues, 9) network with others in the field, and 10) recognize that this is hard work. By following these steps and planning ahead, scholars will be better poised to make meaningful contributions to the art and science of medical education.
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LECTURE
  • Yuji Sato, Keisuke Koyama
    2010 Volume 59 Issue 3 Pages 104-109
    Published: September 25, 2010
    Released on J-STAGE: October 01, 2010
    JOURNAL FREE ACCESS
    The volume of clinical research carried out in Japan is relatively small by global standards, especially when compared with the country's contributions to basic research. Although the academic quality of the clinical research done here is generally high, its relative paucity has had a number of alarming consequences, e.g., delays in the approval of important new drugs and medical devices caused by difficulties in clinical trials, leading to the limited availability of novel treatments for Japanese patients. This article aims to present an overview of current clinical research activities in Japan and to summarise the historical, socio-cultural and regulatory issues underlying the current situation. Suggestions are made as to how the present problems might be resolved and how a brighter future for clinical research might be achieved.
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