Proceedings of the Japan Academy, Series B
Online ISSN : 1349-2896
Print ISSN : 0386-2208
ISSN-L : 0386-2208
Special Issue
Volume 88, Issue 3
Displaying 1-6 of 6 articles from this issue
Reviews
  • Tomohisa KUZUYAMA, Haruo SETO
    2012 Volume 88 Issue 3 Pages 41-52
    Published: March 09, 2012
    Released on J-STAGE: March 09, 2012
    JOURNAL FREE ACCESS
    Isoprenoids are a diverse group of molecules found in all organisms, where they perform such important biological functions as hormone signaling (e.g., steroids) in mammals, antioxidation (e.g., carotenoids) in plants, electron transport (e.g., ubiquinone), and cell wall biosynthesis intermediates in bacteria. All isoprenoids are synthesized by the consecutive condensation of the five-carbon monomer isopentenyl diphosphate (IPP) to its isomer, dimethylallyl diphosphate (DMAPP). The biosynthetic pathway for the formation of IPP from acetyl-CoA (i.e., the mevalonate pathway) had been established mainly in mice and the budding yeast Saccharomyces cerevisiae. Curiously, most prokaryotic microorganisms lack homologs of the genes in the mevalonate pathway, even though IPP and DMAPP are essential for isoprenoid biosynthesis in bacteria. This observation provided an impetus to search for an alternative pathway to synthesize IPP and DMAPP, ultimately leading to the discovery of the mevalonate-independent 2-C-methyl-D-erythritol 4-phosphate pathway. This review article focuses on our significant contributions to a comprehensive understanding of the biosynthesis of IPP and DMAPP.

    (Communicated by Teruhiko BEPPU, M.J.A.)
    Download PDF (353K)
  • Hiroshi MAEDA
    2012 Volume 88 Issue 3 Pages 53-71
    Published: March 09, 2012
    Released on J-STAGE: March 09, 2012
    JOURNAL FREE ACCESS
    Tumor and inflammation have many common features. One hallmark of both is enhanced vascular permeability, which is mediated by various factors including bradykinin, nitric oxide (NO), peroxynitrite, prostaglandins etc. A unique characteristic of tumors, however, is defective vascular anatomy. The enhanced vascular permeability in tumors is also distinctive in that extravasated macromolecules are not readily cleared. We utilized the enhanced permeability and retention (EPR) effect of tumors for tumor selective delivery of macromolecular drugs. Consequently, such drugs, nanoparticles or lipid particles, when injected intravenously, selectively accumulate in tumor tissues and remain there for long periods. The EPR effect of tumor tissue is frequently inhomogeneous and the heterogeneity of the EPR effect may reduce the tumor delivery of macromolecular drugs. Therefore, we developed methods to augment the EPR effect without inducing adverse effects for instance raising the systemic blood pressure by infusing angiotensin II during arterial injection of SMANCS/Lipiodol. This method was validated in clinical setting. Further, benefits of utilization of NO-releasing agent such as nitroglycerin or angiotensin-converting enzyme (ACE) inhibitors were demonstrated. The EPR effect is thus now widely accepted as the most basic mechanism for tumor-selective targeting of macromolecular drugs, or so-called nanomedicine.

    (Communicated by Takashi SUGIMURA, M.J.A.)
    Download PDF (1788K)
  • Ryo KOMINAMI
    2012 Volume 88 Issue 3 Pages 72-87
    Published: March 09, 2012
    Released on J-STAGE: March 09, 2012
    JOURNAL FREE ACCESS
    Bcl11b is a lineage-specific transcription factor expressed in various cell types and its expression is important for development of T cells, neurons and others. On the other hand, Bcl11b is a haploinsufficient tumor suppressor and loss of a Bcl11b allele provides susceptibility to mouse thymic lymphoma and human T-cell acute lymphoblastic leukemia. Although there are many transcription factors affecting both cell differentiation and cancer development, Bcl11b has several unique properties. This review describes phenotypes given by loss of Bcl11b and roles of Bcl11b in cell proliferation, differentiation and apoptosis, taking tissue development and lymphomagenesis into consideration.

    (Communicated by Shigekazu NAGATA, M.J.A.)
    Download PDF (431K)
  • Yasuo SUZUKI, Noriyuki MIYOSHI, Mamoru ISEMURA
    2012 Volume 88 Issue 3 Pages 88-101
    Published: March 09, 2012
    Released on J-STAGE: March 09, 2012
    JOURNAL FREE ACCESS
    Green tea is manufactured from the leaves of the plant Camellia sinensis Theaceae and has been regarded to possess anti-cancer, anti-obesity, anti-atherosclerotic, anti-diabetic, anti-bacterial, and anti-viral effects. Many of the beneficial effects of green tea are related to the activities of (−)-epigallocatechin gallate (EGCG), a major component of green tea catechins. For about 20 years, we have engaged in studies to reveal the biological activities and action mechanisms of green tea and EGCG. This review summarizes several lines of evidence to indicate the health-promoting properties of green tea mainly based on our own experimental findings.

    (Communicated by Takao SEKIYA, M.J.A.)
    Download PDF (535K)
  • Hiroto OKAYAMA
    2012 Volume 88 Issue 3 Pages 102-119
    Published: March 09, 2012
    Released on J-STAGE: March 09, 2012
    JOURNAL FREE ACCESS
    The 1970s and the following decade are the era of the birth and early development of recombinant DNA technologies, which have entirely revolutionized the modern life science by providing tools that enable us to know the structures of genes and genomes and to dissect their components and understand their functions at the molecular and submolecular levels. One major objective of the life sciences is to achieve molecular and chemical understandings of the functions of genes and their encoded proteins, which are responsible for the manifestation of all biological phenomena in organisms. In the early 1980s, I developed, together with Paul Berg, a new technique that enables the cloning of full-length complementary DNAs (cDNAs) on the basis of their functional expression in a given cell of interest. I review the development, application and future implications in the life sciences of this gene-cloning technique.

    (Communicated by Shigetada NAKANISHI, M.J.A.)
    Download PDF (1656K)
Original Article
  • Eizi HIROTA
    2012 Volume 88 Issue 3 Pages 120-128
    Published: March 09, 2012
    Released on J-STAGE: March 09, 2012
    JOURNAL FREE ACCESS
    A new spectroscopic method of triple resonance is proposed for studying chirality of a molecule of C1 symmetry. Each enantiomer of such a molecule is of mixed parity and thus exhibits all three a-, b-, and c-types of rotational spectra. The present study concludes, by using time-dependent perturbation theory, that the transition probability between two of the three rotational levels under triple resonance differs for different enantiomer. This result can thus be of some significance for enantiomer differentiation.

    (Communicated by Toshimitsu YAMAZAKI, M.J.A.)
    Download PDF (233K)
feedback
Top