著者
Shinichi Kuriyama Nobuo Yaegashi Fuji Nagami Tomohiko Arai Yoshio Kawaguchi Noriko Osumi Masaki Sakaida Yoichi Suzuki Keiko Nakayama Hiroaki Hashizume Gen Tamiya Hiroshi Kawame Kichiya Suzuki Atsushi Hozawa Naoki Nakaya Masahiro Kikuya Hirohito Metoki Ichiro Tsuji Nobuo Fuse Hideyasu Kiyomoto Junichi Sugawara Akito Tsuboi Shinichi Egawa Kiyoshi Ito Koichi Chida Tadashi Ishii Hiroaki Tomita Yasuyuki Taki Naoko Minegishi Naoto Ishii Jun Yasuda Kazuhiko Igarashi Ritsuko Shimizu Masao Nagasaki Seizo Koshiba Kengo Kinoshita Soichi Ogishima Takako Takai-Igarashi Teiji Tominaga Osamu Tanabe Noriaki Ohuchi Toru Shimosegawa Shigeo Kure Hiroshi Tanaka Sadayoshi Ito Jiro Hitomi Kozo Tanno Motoyuki Nakamura Kuniaki Ogasawara Seiichiro Kobayashi Kiyomi Sakata Mamoru Satoh Atsushi Shimizu Makoto Sasaki Ryujin Endo Kenji Sobue the Tohoku Medical Megabank Project Study Group Masayuki Yamamoto
出版者
日本疫学会
雑誌
Journal of Epidemiology (ISSN:09175040)
巻号頁・発行日
pp.JE20150268, (Released:2016-07-02)
参考文献数
64
被引用文献数
1 41

The Great East Japan Earthquake (GEJE) and resulting tsunami of March 11, 2011 gave rise to devastating damage on the Pacific coast of the Tohoku region. The Tohoku Medical Megabank Project (TMM), which is being conducted by Tohoku University Tohoku Medical Megabank Organization (ToMMo) and Iwate Medical University Iwate Tohoku Medical Megabank Organization (IMM), has been launched to realize creative reconstruction and to solve medical problems in the aftermath of this disaster. We started two prospective cohort studies in Miyagi and Iwate Prefectures: a population-based adult cohort study, the TMM Community-Based Cohort Study (TMM CommCohort Study), which will recruit 80 000 participants, and a birth and three-generation cohort study, the TMM Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study), which will recruit 70 000 participants, including fetuses and their parents, siblings, grandparents, and extended family members. The TMM CommCohort Study will recruit participants from 2013 to 2016 and follow them for at least 5 years. The TMM BirThree Cohort Study will recruit participants from 2013 to 2017 and follow them for at least 4 years. For children, the ToMMo Child Health Study, which adopted a cross-sectional design, was also started in November 2012 in Miyagi Prefecture. An integrated biobank will be constructed based on the two prospective cohort studies, and ToMMo and IMM will investigate the chronic medical impacts of the GEJE. The integrated biobank of TMM consists of health and clinical information, biospecimens, and genome and omics data. The biobank aims to establish a firm basis for personalized healthcare and medicine, mainly for diseases aggravated by the GEJE in the two prefectures. Biospecimens and related information in the biobank will be distributed to the research community. TMM itself will also undertake genomic and omics research. The aims of the genomic studies are: 1) to construct an integrated biobank; 2) to return genomic research results to the participants of the cohort studies, which will lead to the implementation of personalized healthcare and medicine in the affected areas in the near future; and 3) to contribute the development of personalized healthcare and medicine worldwide. Through the activities of TMM, we will clarify how to approach prolonged healthcare problems in areas damaged by large-scale disasters and how useful genomic information is for disease prevention.
著者
Kei Segawa Miki Watanabe-Matsui Toshitaka Matsui Kazuhiko Igarashi Kazutaka Murayama
出版者
Tohoku University Medical Press
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.247, no.3, pp.153-159, 2019 (Released:2019-03-09)
参考文献数
30

Heme is one of the key factors involved in the oxidative stress response of cells. The transcriptional repressor Bach1 plays an important role in this response through its heme-binding activity. Heme inhibits the transcriptional-repressor activity of Bach1, and can occur in two binding modes: 5- and 6-coordinated binding. The Cys-Pro (CP) motif has been determined to be the heme-binding motif of Bach family proteins. The sequence of Bach1 includes six CP motifs, and four CP motifs are functional. With the aim of elucidating the molecular mechanism of heme-Bach1 regulation, we conducted biophysical analyses focusing on the C-terminal region of mouse Bach1 (residues 631-739) which is located after the bZip domain and includes one functional CP motif. UV-Vis spectroscopy indicated that the CP motif binds heme via 5-coordinated bond. A mutant, which included a cysteine to alanine substitution at the CP motif, did not show 5-coordination, suggesting that this binding mode is specific to the CP motif. Surface plasmon resonance revealed that the binding affinity and stoichiometry of heme with the Bach1 C-terminal region were KD = 1.37 × 10–5 M and 2.3, respectively. The circular dichroism spectrum in the near-UV region exhibited peaks for heme binding to the CP motif. No significant spectral shifts were observed in the far-UV region when samples with and without heme were compared. Therefore, disordered-ordered transition such as “coupled folding and binding” is not involved in the Bach1-heme system. Consequently, the heme response of this C-terminal region is accomplished by disorder-disorder conformational alteration.
著者
Yuki Sato Hiroki Kato Risa Ebina-Shibuya Ari Itoh-Nakadai Ryuhei Okuyama Kazuhiko Igarashi
出版者
東北ジャーナル刊行会
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.241, no.3, pp.175-182, 2017 (Released:2017-02-18)
参考文献数
37
被引用文献数
1

Bach2 is a transcription factor which represses its target genes and plays important roles in the differentiation of B and T lymphoid cells. Bach2-deficient (KO) mice develop severe pulmonary alveolar proteinosis, which is associated with increased numbers of granulocytes and T cells. Bach2 is essential for the regulation of T cells, but its role in the regulation of granulocytes is not clear. Here, we observed increased numbers of eosinophils but not neutrophils in the bone marrow, spleen, peripheral blood, and bronchoalveolar lavage fluids of Bach2 KO mice compared with those of wild-type (WT) mice. Upon co-transplantation of the bone marrow cells from CD45.2 Bach2 KO and CD45.1/CD45.2 double-positive WT mice to irradiated WT CD45.1/CD45.2 mice, the reconstituted numbers of eosinophils were similar between Bach2 KO and WT cells. These results showed that the deficiency of Bach2 in eosinophils did not directly drive the differentiation of eosinophils. To investigate the effect of Bach2 KO CD4+ T cells upon eosinophils, we analyzed Rag2/Bach2-double deficient (dKO) mice which lack lymphocytes including CD4+ T cells. Rag2/Bach2 dKO mice did not show any increase in the numbers of eosinophils. Importantly, Bach2 KO mice showed an increase of interleukin-5 (Il-5) in the sera compared with WT mice. These results suggest that up-regulated functions of CD4+ T cells including secretion of Il-5 resulted in proliferation and/or migration to peripheral tissues of eosinophils in Bach2 KO mice. We propose that Bach2 controls homeostasis of eosinophils via restricting the production of Il-5 in CD4+ T cells.