Proceedings of the Japan Academy, Series B
Online ISSN : 1349-2896
Print ISSN : 0386-2208
ISSN-L : 0386-2208
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Reviews
  • Akihiko YOSHIMURA, Daisuke AKI, Minako ITO
    2021 Volume 97 Issue 6 Pages 277-291
    Published: June 11, 2021
    Released: June 11, 2021
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    Cytokines are important intercellular communication tools for immunity. Most cytokines utilize the JAK-STAT and Ras-ERK pathways to promote gene transcription and proliferation; however, this signaling is tightly regulated. The suppressor of cytokine signaling (SOCS) family and SPRED family are a representative negative regulators of the JAK-STAT pathway and the Ras-ERK pathway, respectively. The SOCS family regulates the differentiation and function of CD4+ T cells, CD8+ T cells, and regulatory T cells, and is involved in immune tolerance, anergy, and exhaustion. SPRED family proteins have been shown to inactivate Ras by recruiting the Ras-GTPase neurofibromatosis type 1 (NF1) protein. Human genetic analysis has shown that SOCS family members are strongly associated with autoimmune diseases, allergies, and tumorigenesis, and SPRED1 is involved in NF1-like syndromes and tumors. We also identified the NR4a family of nuclear receptors as a key transcription factor for immune tolerance that suppresses cytokine expression and induces various immuno-regulatory molecules including SOCS1.

  • Yasuki NAGAI
    2021 Volume 97 Issue 6 Pages 292-323
    Published: June 11, 2021
    Released: June 11, 2021
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    Interest has been growing in the development of medical radioisotopes used for noninvasive nuclear medicine imaging of disease and cancer therapy. Especially the development of an alternative production scheme of 99Mo, the mother radioisotope of 99mTc used for imaging, is required, because the current supply chain of the reactor product 99Mo is fragile worldwide. We have proposed a new production scheme of 99Mo as well as therapeutic radioisotopes, such as 64Cu and 67Cu, using accelerator neutrons provided by the natC(d,n) reaction. Based on this scheme we have obtained high-quality 99mTc, 64Cu, and 67Cu suitable for clinical use by developing both production and separation methods of the radioisotopes. We proposed a new facility to constantly and reliably produce a wide variety of high-quality, carrier-free radioisotopes, including 99Mo, with accelerator neutrons. We report on the development of the proposed scheme and future prospects of the facility toward the domestic production of medical radioisotopes.

  • Yoichiro KAMATANI, Yusuke NAKAMURA
    2021 Volume 97 Issue 6 Pages 324-335
    Published: June 11, 2021
    Released: June 11, 2021
    JOURNALS FREE ACCESS FULL-TEXT HTML

    As we look so different, our genomic sequences vary enormously. The differences in our genome, genetic variations, have played very significant roles in medical research and have contributed to improvement of medical managements in the last 2–3 decades. Genetic variations include germline variations, somatic mutations, and diversities in receptor genes of rearranged immune cells, T cells and B cells. Germline variants are in some cases causative of genetic diseases, are associated with the risk of various diseases, and also affect drug efficacies or adverse events. Some somatic mutations are causative of tumor development. Recent DNA sequencing technologies allow us to perform single-cell analysis or detailed repertoire analysis of B and T cells. It is critically important to investigate temporal changes in immune environment in various anatomical regions in the next one to two decades. In this review article, we would like to introduce the roles of genetic variations in medical fields in the past, at present and in the future.

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