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Studies on the relationships between cellular immunological parameters and polymorphisms of immune-related genes and their implications in disease development among the A-bomb survivor cohort

Research Project

Project/Area Number 16390190
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Public health/Health science
Research InstitutionRadiation Effects Research Foundation

Principal Investigator

KUSUNOKI Yoichiro  Radiation Effects Research Foundation, Department of Radiobiology/Molecular Epidemiology, Assistant Chief, 放射線生物学/分子疫学部, 副部長 (60333548)

Co-Investigator(Kenkyū-buntansha) HAYASHI Tomonori  Radiation Effects Research Foundation, Department of Radiobiology/Molecular Epidemiology, Chief of Immunology Laboratory, 放射線生物学/分子疫学部, 免疫学研究室長 (70333549)
KYOIZUMI Seishi  Yasuda Women's University, Department of Nutritional Sciences, Professor, 家政学部, 教授 (50333547)
HAKLODA Masayuki  Yasuda Women's University, Department of Nutritional Sciences, Professor, 家政学部, 教授 (70208429)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2005: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2004: ¥5,100,000 (Direct Cost: ¥5,100,000)
KeywordsCohort study / Cellular immunity / Molecular epidemiology / Radiation / Cytokine / Virus hepatitis / Th1 / Th2 / 遺伝子多型 / 炎症 / CD4
Research Abstract

To address whether immunogenetic background may determine individual susceptibility to disease among A-bomb survivors, we examined the relationships between cellular immunological parameters and polymorphisms of immune-related genes and analyzed their associations with disease development. The following results were obtained in this study period.
1.A radiation dose-dependent decrease in percentage of naive CD4 T cells in both Hiroshima and Nagasaki survivors; this is possibly due to radiation-induced suppression of CD4 T-cell production in the thymus.
2.Dose-dependent increases in percentages of the functionally weak and anergic subsets of memory CD4 T cells that were identified by CD43 expression level.
3.Dose-dependent increases in the levels of inflammatory cytokines (IL-6, IFN-γ, and TNF-α) in the blood.
4.Th1-dominant status associated with elevation of inflammatory cytokine levels in individuals with HCV infection as well as in progression of chronic hepatitis.
5.No significant phenotype-genotype association in inflammatory cytokine (IL-6, IFN-γ, and TNF-α) genes ; genotypes of these genes are unlikely to interact with radiation effects.
6.A suggestive association between CD45 exon 6 SNP (A138G) and proportion of Th1/Th2 cells.
A follow-up study regarding disease development will be continued for the subjects in this study. Thus, this study provided not only evidence supporting our hypothesis that A-bomb irradiation has accelerated immunological aging but also a strong basis for further cohort study investigating relationships among radiation exposure, biological endpoints of cellular immunity, genetic backgrounds, and disease risks in a large human population.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (53 results)

All 2007 2006 2005 2004

All Journal Article (50 results) Book (3 results)

  • [Journal Article] Short-term culture and γH2AX flow cytometry determine the difference of individual radiosensitivities in human peripheral T lymphocytes2007

    • Author(s)
      Hamasaki K
    • Journal Title

      Environ Mol Mutagen 48・1

      Pages: 38-47

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Short-term culture and yH2AX flow cytometry determine the difference of individual radiosensitivities in human peripheral T lymphocytes2007

    • Author(s)
      Hamasaki K
    • Journal Title

      Environ Mol Mutagen 48

      Pages: 38-47

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Short-term culture and γH2AX flow cytometry determine the difference of individual radiosensitivities in human peripheral T lymphocytes2007

    • Author(s)
      Hamasaki K
    • Journal Title

      Environmental and Molecular Mutagenesis 48・1

      Pages: 38-47

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification of the NKG2D haplotypes associated with natural cytotoxic activity of peripheral-blood lymphocytes and cancer immunosurveillance2006

    • Author(s)
      Hayashi T
    • Journal Title

      Cancer Res 66

      Pages: 563-570

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A preliminary study measuring the number of T-cell receptor-rearrangement excision circles (TRECs) in peripheral blood T-cell populations of A-bomb survivors and control populations2006

    • Author(s)
      Kubo Y
    • Journal Title

      Cytometry Res 16

      Pages: 33-41

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Levels of antibodies to microorganisms implicated in atherosclerosis and of C-reactive protein among atomic bomb survivors2006

    • Author(s)
      Hakoda M
    • Journal Title

      Radiat Res 166・2

      Pages: 360-366

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 原爆放射線のヒト免疫応答におよぼす影響 第22報 : CD4 T細胞サブセット比率の被ばく放射線量依存性低下は長崎原爆被爆者においても明らかに認められる2006

    • Author(s)
      久保美子
    • Journal Title

      広島医学 59

      Pages: 409-412

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 原爆放射線のヒト免疫応答におよぼす影響 第23報 : 炎症マーカーの長期的上昇2006

    • Author(s)
      森下ゆかり
    • Journal Title

      広島医学 59

      Pages: 413-416

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 原爆放射線のヒト免疫応答に及ぼす影響(第24報) : CD43の発現を指標としたメモリーCD4 T細胞サブセットの測定2006

    • Author(s)
      楠 洋一郎
    • Journal Title

      長崎医学会雑誌 81

      Pages: 350-353

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nakata A, Kamiguchi H associated with natural cytotoxic activity of peripheral-blood lymphocytes and cancer immunosurveillance2006

    • Author(s)
      Hayashi T
    • Journal Title

      Cancer Res 66

      Pages: 563-570

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Levels of antibodies to microorganisms implicated in atherosclerosis and of C-reactive protein among atomic bomb survivors2006

    • Author(s)
      Hakoda M
    • Journal Title

      Radiat Res 166

      Pages: 360-366

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] T-cell homeostasis and inflammatory response among a-bomb survivors2006

    • Author(s)
      Kusunoki Y
    • Journal Title

      Low-Dose Radiation Exposures and BioDefense System. (Ed by Tanaka S, Fujikawa F, Oghiso Y.) 59

      Pages: 409-412

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of atomic-bomb radiation on human immune responses. Report 22 : Radiation-dose-dependent decreases in the percentages of CD4 T-cell subsets are also apparent for survivors in Nagasaki2006

    • Author(s)
      Kubo Y
    • Journal Title

      Journal of the Hiroshima Medical Association 59

      Pages: 409-412

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of A-bomb radiation on human immunological response. 23rd report : Long-term elevation of inflammatory markers2006

    • Author(s)
      Morishita Y
    • Journal Title

      Journal of the Hiroshima Medical Association 59

      Pages: 413-416

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of atomic-bomb radiation on human immune responses. Report 24 : Measurements of memory CD4 T cell subsets using CD43 expression levels as markers2006

    • Author(s)
      Kusunoki Y
    • Journal Title

      Nagasaki Medical Journal 81

      Pages: 350-353

    • NAID

      110006226571

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Principles of flow cytometry(FCM)2006

    • Author(s)
      Kusunoki Y
    • Journal Title

      Diagnosis of hematopoietic tumors using flow cytometry. (K.Mutroi, et al. (edit))(Osaka : Iyuku Jounal Co., Ltd.)

      Pages: 9-20

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Levels of Antibodies to Microor ganisms Implicated in Atherosclerosis and of C-Reactive Protein among Atomic Bomb Survivors2006

    • Author(s)
      Hakoda M
    • Journal Title

      Radiation Research 166・2

      Pages: 360-366

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A preliminary study measuring the number of T-cell receptor-rearrangement excision circles (TRECs)in peripheral blood T-cell populations of A-bomb survivors and control populations2006

    • Author(s)
      Kubo Y
    • Journal Title

      Cytometry Research 16・1

      Pages: 33-41

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification of the NKG2D haplotypes associated with natural cytotoxic activity of peripheral-blood lymphocytes and cancer immunosurveillance2006

    • Author(s)
      Hayashi T, Imai K, Morishita Y, Hayashi I, Kusunoki Y, Nakachi K.
    • Journal Title

      Cancer Res 66

      Pages: 563-570

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A preliminary study measuring the number of T-cell receptor-rearrangement excision circles (TRECs) in peripheral blood T-cell populations of A-bomb survivors and control populations2006

    • Author(s)
      Kubo Y, Yamaoka M, Kusunoki Y
    • Journal Title

      Cytometry Res 16

      Pages: 33-41

    • NAID

      10017967342

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Flow cytometric measurement of mutant T cells with altered expression of TCR : detecting somatic mutations in humans and mice.2005

    • Author(s)
      Kyoizumi S
    • Journal Title

      Methods Mol Biol 291

      Pages: 197-204

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Long-term effects of radiation dose on inflammatory markers in atomic bomb survivors.2005

    • Author(s)
      Hayashi T
    • Journal Title

      Am J Med 118

      Pages: 83-86

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Individual variation of somatic gene mutability in relation to cancer susceptibility : Prospective study on erythrocyte glycophorin A gene mutations of atomic bomb survivors2005

    • Author(s)
      Kyoizumi S
    • Journal Title

      Cancer Res 65

      Pages: 5462-5469

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Individual variation of somatic gene mutability in relation to cancer susceptibility : Prospective study on erythrocyte glycophorin A gene mutations of atomic bomb survivors2005

    • Author(s)
      Kyoizumi S, Kusunoki Y, Hayashi Hakoda, M, Cologne J B, Nakachi K
    • Journal Title

      Cancer Res 65

      Pages: 5462-5469

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Long-term effects of radiation dose on inflammatory markers in atomic bomb survivors.2005

    • Author(s)
      Hayashi T, et al.
    • Journal Title

      Am J Med 118

      Pages: 83-86

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Perspectives on cancer immuno-epidemiology.2004

    • Author(s)
      Nakachi K
    • Journal Title

      Cancer Sci 95

      Pages: 921-929

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Increasing of oxidative stress from mitochondria in type 2 diabetic patients.2004

    • Author(s)
      Nakanishi S
    • Journal Title

      Diabetes Metab Res Rev 20

      Pages: 399-404

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Radiation-induced apoptosis of stem/progenitor cells in human umbilical cord blood is associated with alterations in reactive oxygen and intracellular pH.2004

    • Author(s)
      Hayashi T
    • Journal Title

      Mutat Res 556

      Pages: 83-91

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression characteristics and stimulatory functions of CD43 in human CD4+ memory T cells : Analysis using a monoclonal antibody to CD43 that has a novel lineage specificity.2004

    • Author(s)
      Kyoizumi S
    • Journal Title

      J Immunol 172

      Pages: 7246-7253

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] An association between oxidative stress and radiation-induced lymphomagenesis.2004

    • Author(s)
      Suzuki G
    • Journal Title

      Radiat Res 161

      Pages: 642-647

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Anisomycin downregulates gap-junctional intercellular communication via the p38 MAP-kinase pathway.2004

    • Author(s)
      Ogawa T
    • Journal Title

      J Cell Sci 117

      Pages: 2087-2096

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Estimating the number of hematopoietic or lymphoid stem cells giving rise to clonal chromosome aberrations in blood T lymphocytes.2004

    • Author(s)
      Nakano M
    • Journal Title

      Radiat Res 161

      Pages: 273-281

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Decreases in percentages of naive CD4 and CD8 T cells and increases in percentages of memory CD8 T cell subsets in the peripheral blood lymphocyte populations of A-bomb survivors.2004

    • Author(s)
      Yamaoka M
    • Journal Title

      Radiat Res 161

      Pages: 290-298

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Caspase-2 and caspase-7 are involved in cytolethal distending hoxin-induced apoptosis in Jurkat and MOLT-4 T-cell lines.2004

    • Author(s)
      Ohara M
    • Journal Title

      Infect Immun 72

      Pages: 871-879

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 原爆放射線のヒト免疫応答に及ぼす影響(第21報) : ナイーブおよびメモリーCD8 T細胞サブセットに及ぼす長期的影響2004

    • Author(s)
      山岡美佳
    • Journal Title

      長崎医学会雑誌 79

      Pages: 192-199

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Perspectives on cancer immuno-epidemiology2004

    • Author(s)
      Nakachi K
    • Journal Title

      Cancer Sci 95

      Pages: 921-929

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Anisomycin downregulates gap-junctional intercellular communication via the p38 MAP-kinase pathway2004

    • Author(s)
      Ogawa T
    • Journal Title

      J Cell Sci 117

      Pages: 2087-2096

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Decreases in percentages of naive CD4 and CD8 T cells and increases in percentages of memory CD8T cell subsets in the peripheral blood lymphocyte populations of A-bomb survivors.2004

    • Author(s)
      Yamaoka M
    • Journal Title

      Radiat Res 161

      Pages: 290-298

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Caspase-2 and caspase-7 are involved in cytolethal distending toxin-induced apoptosis in Jurkat and MOLT-4 T-cell lines.2004

    • Author(s)
      Ohara M
    • Journal Title

      Infect Immun 72

      Pages: 871-879

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of atomic-bomb radiation on human immune responses. Report 21 : Long-term effects of radiation exposure on naive and memory CD8 T-cell subsets2004

    • Author(s)
      Yamaoka Y
    • Journal Title

      Nagasaki Medical Journal 79

      Pages: 192-199

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Perspectives on cancer immuno-epidemiology.2004

    • Author(s)
      Nakachi K, et al.
    • Journal Title

      Cancer Sci 95

      Pages: 921-929

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Flow Cytometric Measurement of Mutant T Cells With Altered Expression of TCR : Detecting Somatic Mutations in Humans and Mice.2004

    • Author(s)
      Kyoizumi S, et al.
    • Journal Title

      Methods Mol Biol 291

      Pages: 197-204

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Increasing of oxidative stress from mitochondria in type 2 diabetic patients.2004

    • Author(s)
      Nakanishi S, et al.
    • Journal Title

      Diabetes Metab Res Rev 20

      Pages: 399-404

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Radiation-induced apoptosis of stem/progenitor cells in human umbilical cord blood is associated with alterations in reactive oxygen and intracellular pH.2004

    • Author(s)
      Hayashi T, et al.
    • Journal Title

      Mutat Res 556

      Pages: 83-91

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression characteristics and stimulatory functions of CD43 in human CD4+ memory T cells : Analysis using a monoclonal antibody to CD43 that has a novel lineage specificity.2004

    • Author(s)
      Kyoizumi S, et al.
    • Journal Title

      J Immunol 172

      Pages: 7246-7253

    • Related Report
      2004 Annual Research Report
  • [Journal Article] An association between oxidative stress and radiation-induced lymphomagenesis.2004

    • Author(s)
      Suzuki G, et al.
    • Journal Title

      Radiat Res 161

      Pages: 642-647

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Anisomycin downregulates gap-junctional intercellular communication via the p38 MAP-kinase pathway.2004

    • Author(s)
      Ogawa T, et al.
    • Journal Title

      J Cell Sci 117

      Pages: 2087-2096

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Estimating the number of hematopoietic or lymphoid stem cells giving rise to clonal chromosome aberrations in blood T lymphocytes.2004

    • Author(s)
      Nakano M, et al.
    • Journal Title

      Radiat Res 161

      Pages: 273-281

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Decreases in percentages of naive CD4 and CD8 T cells and increases in percentages of memory CD8 T cell subsets in the peripheral blood lymphocyte populations of A-bomb survivors.2004

    • Author(s)
      Yamaoka M, et al.
    • Journal Title

      Radiat Res 161

      Pages: 290-298

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Caspase-2 and caspase-7 are involved in cytolethal distending toxin-induced apoptosis in Jurkat and MOLT-4 T-cell lines.2004

    • Author(s)
      Ohara M, et al.
    • Journal Title

      Infect Immun 72

      Pages: 871-879

    • Related Report
      2004 Annual Research Report
  • [Book] T-cell homeostasis and inflammatory response among a-bomb survivors. In : Low-Dose Radiation Exposures and BioDefense System.(Ed by Tanaka S, Fujikawa F, Oghiso Y.)2006

    • Author(s)
      Kusunoki Y
    • Publisher
      The Institute for Environmental Sciences
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] フローサイトメトリーを用いた造血器腫瘍の診断(フローサイトメトリー(FCM)の原理)(室井一男他編)2006

    • Author(s)
      楠 洋一郎
    • Publisher
      医薬ジャーナル社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] T-cell homeostasis and inflammatory response among a-bomb survivors. In : Low-Dose Radiation Exposures and BioDefense System. (Ed by Tanaka S, Fujikawa F,Oghiso Y.)2006

    • Author(s)
      Kusunoki Y
    • Publisher
      The Institute for Envronmental Sciences
    • Related Report
      2006 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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