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Research of Osteoclastogenesis in Priodontium induced by mechanical stress and its Clinical Application

Research Project

Project/Area Number 12671984
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 矯正・小児・社会系歯学
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

MIKI Mirei  TOHOKU UNIVERSITY, GRADUATE SCHOOL OF DENTISTRY, ASSISTANT PROFESSOR, 大学院・歯学研究科, 助手 (10236820)

Co-Investigator(Kenkyū-buntansha) MITANI Hideo  TOHOKU UNIVERSITY, GRADUATE SCHOOL OF DENTISTRY, PROFESSOR, 大学院・歯学研究科, 教授 (50014220)
KAGAYAMA Manabu  TOHOKU UNlVERSITY, GRADUATE SCHOOL OF DENTISTRY, PROFESSOR, 大学院・歯学研究科, 教授 (60004610)
SHIMIZU Yoshinobu  TOHOKU UNlVERSITY, GRADUATE SCHOOL OF DENTISTRY, PROFESSOR, 大学院・歯学研究科, 助教授 (20005078)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsOsteoclasts / Peiodontium / Bone resorption / Periodontal ligament / Mechanical stress / Orthodontic tooth movement / RANKL / OPG / 破骨細胞 / 歯周組織 / 骨吸収 / 歯根膜細胞 / メカニカルストレス / 歯科矯正学的歯の移動 / メカニカルストレス受容 / Osteoprotegerin
Research Abstract

The periodontal tissue that is subject to mechanical loading during occlusion and mastication. The purpose of this study are to clarify the effects of mechanical stress on the osteoclastogenesis induced at a local site of stress, such as orthodontic tooth movement, and to search for there clinical application. Following results were obtained.
1. The first molar of rat were moved by fixed orthodontic wire experimentally. lmmunohistochemical staining revealed that osteoprotegerin (OPG) protein accumulated adjacent to bone resorption area including osteoclasts and resorption lacunae at the compressive site of periodontal ligament. Furthermore, receptor activator of NF kappa B ligand (RANKL) protein was expressed strongly on the fibroblasts of compressive cite.
2. As progenitors of osteoclasts, peripheral blood mononuclear cells (PBMCs) and human promyelocytic leukemia cell line, HL-60 were cultured directly with PDL cells. Formed multinucleated cells had osteoclastic characteristics and res … More orptive activity. Furthermore, PDL cells expressed both RANKL and OPG mRNA.
3. Fifteen clones derived from periodontal ligament of SV40 tsA58 transgenic rat were established, and compared the characteristics of these cell lines by RT-PCR. RANKL and OPG were seen in 0 and 8 clones respectively and expression were changed in 3 and 0 clones respectively afler 1,25α(0H)_2D_3 (10^<-8>M) treatment.
4. PDL cells under mechanical stress up-regulated osteoclastogenesis from PBMCS. Furthermore, the expression of RANKL mRNA and protein in PDL cells increased with compressive force. Cyclooxygenase 2 mRNA expression and prostaglandin E_2 production were also induced, and indomethacin inhibited the RANKL up-regulation resulting from compressive force. OPG expression remained constant.
5. The number of TRAP-positive multinucleated cells cultured in the presence of conditioned media from stimulated PDL cells by tension force were reduced significantly. Tension force up-regulated OPG, RANKL and TGFβ mRNA expression in PDL cells, and increased OPG and TGFβ protein production from PDL cells. Less

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (71 results)

All Other

All Publications (71 results)

  • [Publications] Okazaki, M.: "Expression of heat shock proteins induced by cyclical stretching stress in human periodontal ligament fibroblasts"Tohoku University Dental Journal. 19. 108-115 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chiba, M.: "Mechanical stress induced both NO and PGE2 in POL cells"Journal of Dental Research. 79・suppl. 145 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanzaki, H.: "ODF and OCIF mRNA expressed by mechanical stress"Journal of Dental Research. 79・suppl. 590 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 戸塚 実: "骨格筋細胞に対する機械的伸展刺激の影響に関する研究"歯科基礎医学会雑誌. 42・3. 233-244 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 久保田 衛: "Oncogenet ransgenic ratを用いた歯根膜不死化細胞の樹立"歯科基礎医学会雑誌. 42・5. 590 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 千葉美麗: "In vivo electroporationやadenovirus vectorを用いた歯周組織への遺伝子導入法の確立-歯周疾患遺伝子治療法の基礎的検討-"歯科基礎医学会誌. 43巻5号. 540 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Kubota: "Estblishment of Immortalized Periodontal ligament cell lines and gene expression"Journal of Dental Research. 80. 585 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.Yamaguchi: "Mechanical stress induces c-fos mRNA expression in human PDL-fibroblasts"Journal of Dental Research. 80. 585 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanzaki: "Dual regulation of osteoclast differentiation by periodontal ligament cells through ODF stimulation and OPG inhibition"Journal of Dental Research. vol.80, No.3. 887-891 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanzaki.H: "Periodontal Ligament Cells Under Mechanical stress Induce Osteoclastogenesis by Receptor Activatior of Nuclear Factor κ B Ligand Up-Regulation via Prostaglandin E2 Synthesis"Journal of Bone and Mineral Research. vol.17, No.2. 210-220 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamaguchi N: "The induction of c-fos mRNA expression by mechanical stress in human periodontal ligament cells"Archives of Oral Biology. 47. 465-471 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.KANZAKI: "RANKL Upregulation in the Compressed Area of Periodontal Ligament induces Orthodontic Tooth Movement"Journal of Dental Research. 81. A-135 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] C.MAISUMOTO: "Synergistic human Osteoclast differentiation inducing by the combined use of 1.25(OH)2D 3, RANKL. and M-CSF"Journal of Dental Research. 81. A105 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.NISHIMURA: "The Expression of Osteoprotege in the Periodontal Ligament in Experimental Tooth Movement"Journal of Dental Research. 81. A135 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.TSUCHIYA: "Gene transfer into periodontal tissue by in vivo electroporation"Journal of Dental Research. 81. A-452 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.CHIBA: "Molecular biological review on bone remodeling based on mechanical stress"the Ouintessence. 21. 931-938 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.CHIBA: "Establishing Immortalized Periodontal Ligament Cells from Oncogene Transgenic Rat and Gene Expression of Bone Metabolic Markers"Journal of Bone and Mineral Research. 17. S223 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chiba M.: "Mechanical tension force inhibits osteoclastogenesis via osteoprotegerin production from periodontal ligament cells"Bone. 32. S197 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Goga, Y.: "Continuous compressive force induces apoptosis in human osteoblast-like cells"Bone. 32. S138 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 糠塚世毅: "ヒト歯根膜線維芽細胞の骨吸収制御機構に対する機械的伸展力の影響"歯科基礎医学会雑誌. 44巻5号. 113 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okazaki, M., Shimlzu, Y., Chiba, M., Mitani, H.: "Expression of heat shock proteins induced by cyclical stretching stress in human periodontal ligament fibroblasts."Tohoku University Dental Journal. 19. 108-115 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chlba, M., Yamaguchi N., lgarashi K., Kanzaki H., Yamada S., Mitani H.: "Mechanical stress induced both NO and PGE2 in PDL cells"Journal of Dental Research. 791. 145 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanzaki, H., Chida M., Shimizu Y., Mitani H.: "ODF and OCIF mRNA expressed by mechanlcal stress"Journal of Dental Research. 79. 590 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Totsuka M., Chiba M., Mitani H.: "The effect of mechanical stretching on skeletal muscle organogenesis in vitro"Japanese Journal of Oral Biology. 42. 233-244 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kubota M., Chiba M, Kanzaki H., Mitani H.: "Establishment of immortalized periodontal ligament cells derived from oncogene transgenic rat."Japanese Journal of Oral Biology. 42. 590 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chiba M., Tsuchiya S, Kanzaki H., Kubota M., Mitani H.: "Establishment of the gene transfer technique by in vivo elevtroporation or adenovirus vector.-Basic study for the gene therapy of periodontal disease."Japanese Journal of Oral Biology. 43. 540 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Kubota, M. Chiba, H. Knzaki, N. Yanai, M. Obinata, S. Ueda, H. Mitani: "Establishment of Immortalized Periodontal ligament cell lines and gene expression"Journal of Dental Research. 80. 585 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N. Yamaguchi, M. Chiba, H. Mitani: "Mechanical stress induces c-fos mRNA expression in human PDL-fibroblasts."Journal of Dental Research. 80. 585 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanzaki, H., Chiba, M., Shimizu, Y., Mitani, H.: "Dual regulation of osteoclast differentiation by periodontal ligament cells through ODF stimulation and OPG inhibition."Journal of Dental Research. 80. 887-891 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanzaki, H., Chiba, M., Shimizu, Y., Mitani, H.: "Periodontal Ligament Cells Under Mechanical stress induce Osteoclastogenesis by Receptor Activatior of Nuclear Factor κB Ligand Up-Regulation via Prostaglandin E2 Synthesis."Journal of Bone and Mineral Research. 17. 210-220 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamaguchi, N., Chiba, M., Mitani, H.: "The induction of c-fos mRNA expression by mechanical stress in human periodontal ligament cells"Archives of Oral Biology. 47. 465-471 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanzaki, H., Chiba, M., Nishimura, M., Mitani, H.: "RANKL Upregulation in the Compressed Area of Periodontal Ligament induces Orthodontic Tooth Movement"Journal of Dental Research. 81. A-135 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsumoto, C., Chiba, M., Kanzaki H., Kubota, M., Mitani, H.: "Synergistic human osteoclast differentiation inducing by the combined use of 1.25(OH)2D 3, RANKL, and M-CSF"Journal of Dental Research. 81. A-105 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishimura, M., Chiba, M., Kanzaki, H., Mitani, H.: "The Expression of Osteoprotegerin in the Periodontal Ligament in Experimental Tooth Movement"Journal of Dental Research. 81. A-135 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuchiya, S., Chiba, M., Kishimoto, K., Nakamura, H., Mitani, H.: "Gene transfer into periodontal tissue by in vivo electroporation"Journal of Dental Research. 81. A-452 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chiba, M.: "Molecular biological review on bone remodeling based on mechanical stress."the Quintessence. 21. 931-938 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chiba M., Kubota M., Obinata M., and Mitani H.: "Establishing Immortalized Periodontal Ligament Cells from Oncogene Transgenic Rat and Gene Expression of Bone Metabolic Markers"Journal of bone and mineral research. 17. S223 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chiba M., Nukatsuka S., Kanzaki H., Matsumoto C., Mitani H.: "Mechanical tension force inhibits osteoclastogenesis via osteoprotegerin production from periodontal ligament cells"Bone. 32. S197 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Goga, Y., Shimizu Y., Chiba M., Mitani H.: "Continuous campressive force induces apoptosis in human osteoblast-like cells"Bone. 32. S138 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nukatsuka S., Chiba M., Kanzaki H., Mitani H.: "Effect of mechanical stretching on the regulatory mechanism of bone resorption in human periodontal ligament cells."Japanese Journal of Oral Biology. 44. 113 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.KANZAKI: "RANKL Upregulation in the Compressed Area of Periodontal Ligament induces Orthodontic Tooth Movement"Journal of Dental Research. 81. A-135 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] C.MATSUMOTO: "Synergistic human osteoclast differentiation inducing by the combined use of 1,25(OH)2D 3,RANKL, and M-CSF"Journal of Dental Research. 81. A-105 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.NISHIMURA: "The Expression of Osteoproteger in in the Periodontal Ligament in Experimental Tooth Movement"Journal of Dental Research. 81. A-135 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.TSUCHIYA: "Gene transfer into periodontal tissue by in vivo electroporation"Journal of Dental Research. 81. A-452 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kanzaki, H.: "Periodontal Ligament Cells Under Mechanical stress Induce Osteoclastogenesis by Receptor Activatior of Nuclear Factor κ B Ligand Up-Regulation via Prostaglandin E2 Synthesis"Journal of Bone and Mineral Research. vol.17,No.2. 210-220 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamaguchi N.: "The induction of c-fos mRNA expression by mechanical stress in human periodontal ligament cells"Archives of Oral Biology. 47. 465-471 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.CHIBA: "Establishing Immortalized Periodontal Ligament Cells from Oncogene Transgenic Rat and Gene Expression of Bone Metabolic Markers"Journal of Bone and Mineral Research. 17. S223 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 糠塚世毅: "ヒト歯根膜線維芽細胞の骨吸収制御機構に対する機械的伸展力の影響"歯科基礎医学会雑誌. 44巻5号. 113 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 千葉美麗: 日本実験力学学会第2回バイオメカニクス分科会講演論文集. No.2-1. 44-47 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.CHIBA: "Molecular biological review on bone remodeling based on mechanical stress"the Quintessence. 21. 931-938 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 千葉美麗: "メカニカルストレスによる歯根膜細胞の初期応答"日本機会学会 第13回バイオエンジニアリング講演会講演論文集. No.00-35. 192-193 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Kubota: "Estblishment of Immortalized Periodontal ligament cell lines and gene expression"Journal of Dental Research. 80. 585 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 山口希実: "メカニカルストレスによる歯根膜線維芽細胞の転写因子c-fosの発現誘導"日本実験力学学会 第一回研究発表講演会講演論文集. No.1. 83-86 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 千葉美麗: "1,25(OH)2D3, RANEL, M-CSF併用によるstage-specificなヒト破骨細胞分化誘導相乗作用"日本骨代謝学会誌. 19巻2号. 99 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 千葉美麗: "In vivo electroporationやadenovirus vectorを用いた歯周組織への遺伝子導入法の確立-歯周疾患遺伝子治療の基礎的検討-"歯科基礎医学会誌. 43巻5号. 540 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.KANZAKI: "RANKL Upregulation in the Compressed Area of Periodontal Ligament induces Orthodontic Tooth Movement"Journal of Dental Research. 81(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] C.MATSUMOTO: "Synergistic human osteoclast differentiation inducing by the combined use of 1,25(OH)2D 3, RANKL, and M-CSF"Journal of Dental Research. 81(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.NISHIMURA: "The Expression of Osteoprotegerin in the Periodontal Ligament in Experimental Tooth Movement"Journal of Dental Research. 81(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.TSUCHIYA: "Gene transfer into periodontal tissue by in vivo electroporationon"Journal of Dental Research. 81(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kanzaki: "Dual regulation of osteoclast differentiation by periodontal ligament cells through ODF stimulation and OPG inhibition"Journal of Dental Research. vol.80, No.3. 887-891 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kanzaki.H: "Periodontal Ligament Cells Under Mechanical stress induce Osteoclastogenesis by Receptor Activatior of Nuclear Factor κ B Ligand Up-Regulation via Prostaglandin E2 Synthesis"Journal of Bone and Mineral Research. vol.17, No.2. 210-220 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamaguchi N: "Mechanical stress induces c-fos mRNA expression in human periodontal ligament cells"Archives of Oral Biology. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 千葉美麗: "メカニカルストレスによる歯根膜細胞の初期応答"日本機械学会[No.00-35]第13回バイオエンジニアリング講演会講演論文集. 192-193 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 戸塚実: "骨格筋細胞に対する機械的伸展刺激の影響に関する研究"歯科基礎医学会雑誌. 42・3. 233-244 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Chiba,M.: "Mechanical stress induced both NO and PGE2 in PDL cells."Journal of Dental Research. 79・suppl. 145 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kanzaki,H.: "ODF and OCIF mRNA expressed by mechanical stress."Journal of Dental Research. 79・suppl. 590 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 菅崎弘幸: "メカニカルストレスによる歯根膜線維芽細胞のODF mRNA発現増強とPGE2の関与"日本骨代謝学会雑誌. 18・2. 200 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 久保田衛: "Oncogene transgenic ratを用いた歯根膜不死化細胞の樹立"歯科基礎医学会雑誌. 42・5. 590 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kanzaki,H.: "Dual regulation of osteoclast differentiation by periodontal ligament cells through RANKL stimulation and OPG inhibition."Journal of Dental Research. 80(In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kubota,M.: "Establishment of immortalized periodontal ligament cell lines and gene expression."Journal of Dental Research. 80・suppl(In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamaguchi,M.: "Mechanical stress induces c-fos mRNA expression in human PDL-fibroblasts."Journal of Dental Research. 80・suppl(In press). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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