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Identification of inflammation-mediated oxidized cholesterols as novel biomarkers of the metabolic syndrome

Research Project

Project/Area Number 18509001
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Eating habits, studies on eating habits
Research InstitutionUniversity of Shizuoka

Principal Investigator

OHSHIMA Hiroshi  University of Shizuoka, Department of Food and Nutritional Sciences, Professor (80433209)

Co-Investigator(Kenkyū-buntansha) MASUDA Shuichi  University of Shizuoka, Department of Food and Nutritional Sciences, Assistant Professor (40336657)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,390,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordscholesterol / reactive oxygen and nitrogen species / metabolic syndrome / chronic inflammation / ozone
Research Abstract

The metabolic syndrome is a risk factor for atherosclerosis. Adipocytokines produced by fat cells may activate various inflammatory cells to produce reactive oxygen and nitrogen species, which play important roles in host defenses against pathogens as well as in tissue damage in inflamed tissues. It has recently been reported that human activated neutrophils produce an ozone-like oxidant (s) in vivo, but conflicting experimental results have also been reported. In the present study in order to establish whether human inflammatory cells produce the ozone-like oxidant in vivo, we have investigated the followings using atheronal-A and B, which are oxidized-cholesterols specifically produced by the reaction with ozone: (1) synthesis and characterization of atheronal-A and B, (2) development of a highly sensitive and specific method to detect atheronal-A and B using fluorescent dansyl hydrazine derivatives, (3) elucidation of the mechanism for the formation of atheronal-A and B and also ozo … More ne-like oxidant (s) in vivo by inflammatory cells, (4) biological activities, especially ability to induce apoptotic cell death, and(5)detection of atheronal-A and B in tissues such as the liver of diabetes rats. Our developed method is about one thousand times more sensitive than the previously reported methods and can detect fmol levels of the compounds easily. Using this method, we have shown that increased levels of atheronal-B were formed in human neutrophil-like (HL-60) cells activated with phorbolester, compared to those without activation. As the formation of atheronal-B was inhibited specifically by a compound which inhibits ozone-mediated oxidation, our data strongly suggest that ozone produced by the activated HL-60 is involved in the formation of atheronals. It was also shown that atheronals exhibited strong cytotoxicity. As we also detected elevated levels of atheronals in the liver of diabetes rats, the compounds could be measured as a novel marker for the metabolic syndrome. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (53 results)

All 2008 2007 2006

All Journal Article (28 results) (of which Peer Reviewed: 12 results) Presentation (21 results) Book (4 results)

  • [Journal Article] Increased risk of gastric cancer in Japanese subjects is associated with microsatellite polymorphisms in the heme oxygenase-1 and the inducible nitric oxide synthase gene promoters2008

    • Author(s)
      Sawa, T., Ohshima, H., et. al.
    • Journal Title

      Cancer Letters (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Geographic Distribution of Liver and Stomach Cancers in Thailand in Relation to Estimated Dietary Intake of Nitrate,Nitrite,and Nitrosodimethylamine2008

    • Author(s)
      Mitacek, E.J., Ohshima, H., et. al.
    • Journal Title

      Nutrition and Cancer 60

      Pages: 196-203

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Function alanalyses of neutrophil-like differentiated cell lines under a hyperglycemic condition2008

    • Author(s)
      Oya-lto, T., Masuda, S., et. al.
    • Journal Title

      Molecular Nutrition and Food Research 52(3)

      Pages: 360-369

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Increased risk of gastric cancer in Japanese subjects is associated with microsatellite polymorphisms in the heme oxygenase-1 and the inducible nitric oxide synthase gene promoters2008

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

      Cancer Letters (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Inflammation Induced Carcinogenesis and Chemoprevention2008

    • Author(s)
      H. Ohshima, S. Tomono, Y-L. Lai, N. Miyoshi
    • Journal Title

      Inflammation Induced Carcinogenesis and Chemoprevention (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Geographic Distribution of Liver and Stomach Cancers in Thailand in Relation to Estimated Dietary Intake of Nitrate, Nitrite, and Nitrosodimethylamine2008

    • Author(s)
      Mitacek, E. J., Ohshima, H., et. al.
    • Journal Title

      Nutrition and Cancer 60(2)

      Pages: 196-203

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Functional analyses of neutrophil-like differentiated cell lines under a hyperglycemic condition2008

    • Author(s)
      Oya-Ito T., Masuda, S., et. al.
    • Journal Title

      Molecular Nutrition and Food Research 52(3)

      Pages: 360-369

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Increased risk of gastric cancer in Japanese subjects is associated with microsatellite polymorphisms in the heme oxygenase-1 and the inducible nitric oxide synthase gene promoters.2008

    • Author(s)
      Sawa, T., Mounawar, M., Tatemichi, M., Gilibert, I., Katoh, T. & Ohshima, H.
    • Journal Title

      Cancer Letters (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Geographic Distribution of Liver and Stomach Cancers in Thailand in Relation to Estimated Dietary Intake of Nitrate, Nitrite, and Nitrosodimethylamine.2008

    • Author(s)
      E. J. Mitacek, K. D. Brunnemann, M. Suttajit, L. S. Caplan, C. E. Gagna, K. Bhothisuwan, S. Siriamornpun, C. F. Hummel, H. Ohshima, R. Roy, and N. Martin
    • Journal Title

      Nutrition and Cancer 60

      Pages: 196-203

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional analyses of neutrophil-like differentiated cell lines under a hyperglycemic condition2008

    • Author(s)
      Oya-Ito T., Masuda S., et. al.
    • Journal Title

      Molecular Nutrition and Food Research. 52(3)

      Pages: 360-369

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oxidative and nitrative stress caused by subcutaneous implantation of a foreign body accelerate sarcoma development in Trp53+/-mice2007

    • Author(s)
      Tazawa, H., Ohshima, H., et. al.
    • Journal Title

      Carcinogenesis 28(1)

      Pages: 191-198

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Evaluation of mutagenic activities of leachates inlandfill sites by micronucleus test and comet assay using goldfish2007

    • Author(s)
      Deguchi, Y., Masuda, S., et. al.
    • Journal Title

      Mutat.Res 627(2)

      Pages: 178-185

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] リーブ葉エキス含有食品の抗酸化性、血糖値低減およびAGEs生成抑制効果2007

    • Author(s)
      佐々木 裕、増田 修一, 他
    • Journal Title

      健康・栄養食品研究 10

      Pages: 12-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Oxidative and nitrative stress caused by subcutaneous implantation of a foreign body accelerate sarcoma development in Trp53+/- mice2007

    • Author(s)
      Tazawa, H., Ohshima, H., et. al.
    • Journal Title

      Carcinogenesis 28(1)

      Pages: 191-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Evaluation of mutagenic activities of leachates in landfill sites by micronucleus test and comet assay using goldfish2007

    • Author(s)
      Deguchi, Y., Masuda, S., et. al.
    • Journal Title

      Mutat. Res 627(2)

      Pages: 178-185

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Oxidative and nitrative stress caused by subcutaneous implantation of aforeign body accelerate sarcoma development in Trp53+/- mice2007

    • Author(s)
      Tazawa, H., Tatemichi, M., Sawa, T., Gilibert, I., Ma, N., Hiraku, Y., Donehower, L. A., Ohgaki, H., Kawanishi, S.&Ohshima, H
    • Journal Title

      Carcinogenesis. 28(1)

      Pages: 191-198

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of mutagenic activities of leachates in landfill sites by micronucleus test and comet assay using goldfish2007

    • Author(s)
      Deguchi Y., Masuda S., et. al.
    • Journal Title

      Mutat. Res 627(2)

      Pages: 178-185

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] オリーブ葉エキス含有食品の抗酸化性、血糖値低減およびAGEs生成抑制効果、2007

    • Author(s)
      佐々木裕、増田修一, 他
    • Journal Title

      健康・栄養食品研究 10

      Pages: 12-20

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oxidative and nitrative stress caused by subcutaneous implantation of a foreign body accelerate sarcoma development in Trp53+/- mice2007

    • Author(s)
      Tazawa, H., Ohshima, H., et al.
    • Journal Title

      Carcinogenesis 28(1)

      Pages: 198-198

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Evaluation of mutagenic activities of leachates in landfill sites by micronucleus test and comet assay using goldfish2007

    • Author(s)
      Deguchi, Y., Masuda, S., et al.
    • Journal Title

      Mutat Res. 627(2)

      Pages: 178-178

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 8-Nitroguanine, a product of nitrative DNA damage caused by reactive nitrogen species : formation, occurrence and implications in inflammation and carcinogenesis2006

    • Author(s)
      Ohshima, H., Sawa, T., Akaike, T.
    • Journal Title

      Antioxidants & Redox Signaling 8(5-6)

      Pages: 1033-1033

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Analysis of urinary 8-nitroguanine, a marker of nitrative nucleic acid damage, by high-performance liquid chromatography-electrochemical detection coupled with immunoaffinity purification : Association with cigarette smoking2006

    • Author(s)
      Sawa, T., Ohshima, H., et al.
    • Journal Title

      Free Radic. Biol. Med. 40(4)

      Pages: 711-711

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Nitrative DNA damage in inflammation and its possible role in carcinogenesis2006

    • Author(s)
      Sawa, T., Ohshima, H.
    • Journal Title

      Nitric Oxide : Biol. & Chem. 14(2)

      Pages: 91-91

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Differences in oxidative stress dependence between gastric adenocarcinoma subtypes2006

    • Author(s)
      Bancel, B., Ohshima, H., et al.
    • Journal Title

      World J. Gastroenterol 12(7)

      Pages: 1005-1005

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Utilization study of stems and leaves of Tienchi Ginseng. I. Anti-hypertensive effect of stems and leaves of Tienchi Ginseng on stroke-prone spontaneously hypertensive rat (SHRSP)2006

    • Author(s)
      Yanai, K., Masuda, S., et al.
    • Journal Title

      Biosci Biotechnol Biochem. 70(10)

      Pages: 2501-2501

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Changes in the mutagenic and estrogenic activities of 17beta-estradiol after treatment with nitrite.2006

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

      Biosci Biotechnol Biochem. 70(4)

      Pages: 890-890

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genotoxicity of acrylamide and glycidamide in human lymphoblastoid TK6 cells.2006

    • Author(s)
      Koyama, N., Masuda, S., et al.
    • Journal Title

      Mutat Res. 603(2)

      Pages: 151-151

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effect of Green Tea on the Formation of Nitrosamines, and Cancer Mortality2006

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

      Journal of Health Science 52(3)

      Pages: 211-211

    • Related Report
      2006 Annual Research Report
  • [Presentation] Cholesterol ozonolysis products as a possible biomarker for metabolic syndrome2008

    • Author(s)
      Tomono, S., Iwabuchi, T., Yasue, Y., Niizuma, S., Miyoshi, M., Ohshima, H
    • Organizer
      International symposium on Biomarkers of Oxidative Stress in Health and Diseases
    • Place of Presentation
      Osaka,Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ozonolysis products as a possible biomarker for metabolic syndrome2008

    • Author(s)
      Tomono, S., Iwabuchi, T., Yasue, Y., Niizuma, S., Miyoshi, M., Ohshima, H
    • Organizer
      International symposium on Biomarkers of Oxidative Stress in Health and Diseases
    • Place of Presentation
      (Osaka, Japan), Jan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Cholesterol ozonolysis products as a possible biomarker for metabolic syndrome.2008

    • Author(s)
      Tomono S., Iwabuchi T., Yasue Y., Niizuma S., Miyoshi M., Ohshima H.
    • Organizer
      International symposium on Biomarkers of Oxidative Stress in Health and Diseases
    • Place of Presentation
      Osaka, Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Molecular mechanism of selective cytotoxicity by chemopreventive isothiocyanates.2007

    • Author(s)
      Miyoshi N., Nakamura Y., Ohshima H.
    • Organizer
      International Conference on Food Factors for Health Promotion
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2007-12-27
    • Related Report
      2007 Annual Research Report
  • [Presentation] オゾン酸化コレステロールによるHレ60細胞の細胞傷害分子機構2007

    • Author(s)
      伴野 勧, 新妻 聖子, 岩渕 智恵, 安江 祐佳里, 三好 規之, 大島 寛史
    • Organizer
      第80回日本生化学会大会(Biochemistry and Molecular Biology2007)
    • Place of Presentation
      横浜市(パシフィコ横浜)
    • Year and Date
      2007-12-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] オゾン酸化コレステロールによるHL-60細胞の細胞傷害分子機構2007

    • Author(s)
      伴野勧, 新妻聖子, 岩渕智恵, 安江祐佳里, 三好規之, 大島寛史
    • Organizer
      第80回日本生化学会大会(Biochemistry and Molecular Biology 2007)
    • Place of Presentation
      横浜市(パシフィコ横浜)
    • Year and Date
      2007-12-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] Molecular mechanism of selective cytotoxicity by chemopreventive isothiocyanates2007

    • Author(s)
      Miyoshi, N., Nakamura, Y., Ohshuna, H
    • Organizer
      International Conference on Food Factors for Health Promotion
    • Place of Presentation
      Kyoto,Japan
    • Year and Date
      2007-10-27
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] DNA and protein damage induced by inflammatory oxidnts:role in carcinogenesis2007

    • Author(s)
      Ohshima, H., Sawa, T., Tazawa, H
    • Organizer
      The 2007 International Symposium on Advanced Bioscience
    • Place of Presentation
      Cheongju,Korea
    • Year and Date
      2007-06-15
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] DNA and protein damage induced by inflammatory oxidnts: role in carcinogenesis2007

    • Author(s)
      Ohshima, H., Sawa, T., Tazawa, H
    • Organizer
      Invited speaker at the 2007 International Symposium on Advanced Bioscience
    • Place of Presentation
      Cheongju, Korea
    • Year and Date
      2007-06-15
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] DNA and protein damage induced by inflammatory oxidnts: role in carcinogenesis2007

    • Author(s)
      Ohshima H.
    • Organizer
      The 2007 International Symposium on Advanced Bioscience
    • Place of Presentation
      Cheongju, Korea
    • Year and Date
      2007-06-15
    • Related Report
      2007 Annual Research Report
  • [Presentation] Nitrative DNA damage in inflammation and carcinogenesis2007

    • Author(s)
      Ohshima, H., Sawa, T., Tazawa, H., Kawanishi, S
    • Organizer
      ICoFF2007-International Conference on Food Factors for Health Promotion
    • Place of Presentation
      Kyoto,Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The role of nitrative DNA damage in inflammation-associated2007

    • Author(s)
      Ohshima, H., Sawa, T., Tazawa, H., Kawanishi, S
    • Organizer
      The 1st International Conference on Nitric Oxide(NO)and Cancer
    • Place of Presentation
      Paris,France
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Helicobacter pylori Infection,Oxidative and Nitrative Stress and Stomach Cencer2007

    • Author(s)
      Ohshima H., Sawa, T.Tatemichi, M., Bancel, B., Pignatelli, B
    • Organizer
      The Keystone Symposium on 'Frontiers in Gastrointestinal Cancer:Molecular Genetics, Inflammation, Early Detection and Therapy'
    • Place of Presentation
      Beijing,China
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Molecular mechanism of selective cytotoxicity by chemopreventive isothiocyanates2007

    • Author(s)
      Miyoshi, N., Nakamura, Y., Ohshima, H
    • Organizer
      International Conference on Food Factors for Health Promotion
    • Place of Presentation
      Kyoto
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Molecular mechanism of cell damage by ozonolysis of cholesterol in HL-60 cells2007

    • Author(s)
      Tomono, S., Niiduma, S., Iwabuchi, T., Yasue, Y., Miyoshi, N., Ohshima, H
    • Organizer
      Biochemistry and Molecular Biology 2007
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Nitrative DNA damage in inflammation and carcinogenesis2007

    • Author(s)
      Ohshima, H., Sawa, T., Tazawa, H., Kawanishi, S
    • Organizer
      Invited speaker at the ICoF F2007
    • Place of Presentation
      Kyoto, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The role of nitrative DNA damage in inflammation-associated carcinogenesis2007

    • Author(s)
      Ohshima, H., Sawa, T., Tazawa, H., Kawanishi, S
    • Organizer
      Invited speaker at the 1st International Conference on Nitric Oxide (NO) and Cancer
    • Place of Presentation
      Paris, France
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Helicobacter pylori Infection, Oxidative and Nitrative Stress and Stomach Cancer2007

    • Author(s)
      Ohshima, H., Sawa, T., Tatemichi, M., Bancel, B., Pignatelli, B
    • Organizer
      Invited speaker at the Keystone Symposium on `Frontiers in Gastrointestinal Cancer: Molecular Genetics, Inflammation, Early Detection and Therapy'
    • Place of Presentation
      Beijing, China
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Nitrative DNA damage in inflammation and carcinogenesis2007

    • Author(s)
      Ohshima H.
    • Organizer
      ICoFF2007・International Conference on Food Factors for Health Promotion
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] The role of nitrative DNA damage in inflammation-associated carcinogenesis2007

    • Author(s)
      Ohshima H.
    • Organizer
      The 1st International Conference on Nitric Oxide(NO)and Cancer
    • Place of Presentation
      Paris, France
    • Related Report
      2007 Annual Research Report
  • [Presentation] Helicobacter pylori Infection, Oxidative and Nitrative Stress and Stomach Cancer.2007

    • Author(s)
      Ohshima H.
    • Organizer
      The Keystone Symposium on 'Frontiers in Gastrointestinal Cancer: Molecular Genetics, Inflammation, Early Detection and Therapy'
    • Place of Presentation
      Beijing, China
    • Related Report
      2007 Annual Research Report
  • [Book] Inflammation Induced Carcinogenesis and Chemoprevention2008

    • Author(s)
      Ohshima, H., Tomono, S., Lai, Y-L., Miyoshi, N
    • Publisher
      Knasmuller,S.DeMarini,D.M.,Johnson,IT.& Gerhauser(In press)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] がん予防『酸化ストレスの医学』2008

    • Author(s)
      大島 寛史, 三好 規之
    • Publisher
      診断と治療社(印刷中)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Inflammation Induced Carcinogenesis and Chemoprevention.2008

    • Author(s)
      H. Ohshima, S. Tomono, Y-L. Lai, and N. Miyoshi
    • Publisher
      Knasmuller, S. DeMarini, D.M., Johnson, I.T. & Gerhauser(in press)
    • Related Report
      2007 Annual Research Report
  • [Book] がん予防『酸化ストレスの医学』2008

    • Author(s)
      大島寛史, 三好規之
    • Publisher
      診断と治療社(印刷中)
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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