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Mechanism of delayed phase of increased vascular permeabitity in acute inflammation

Research Project

Project/Area Number 09470065
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKumamoto University

Principal Investigator

YOSHINAGA Masaru  Department of Pathology, Kumamoto University School of Medicine, Professor, 医学部, 教授 (90040196)

Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2000: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1997: ¥3,200,000 (Direct Cost: ¥3,200,000)
KeywordsINFLAMMATION / INCREASED VASCULAR PERMEABILITY / CYTOKINE / TNFα / IL-8 / IL-1β / IL-1ra / GRO / TNAα
Research Abstract

To investigate the mechanism of increased vascular permeability (IVP) in acute inflammation, we developed the recombinant cytokines, including interleukin (IL)-1β, tumor necerosis factor-α (TNFα), IL-1receptor antagonist (IL-1a), IL-8, growth stimulating oncogene (GRO), monocyte chemoattractant protein-1 (MCP-1) and their antibodies, together with immunoassay systems. Using rabbits with LPS-induced pleurisy as well as the above mentioned materials and methods, we determined interleukin (IL)-8 as a direct mediator for delayed phase of IVP in acute inflammation on the basis of the following series of evidence ; (1) We reconfirmed that the IVP showed biphasic pattern in the LPS-induced pleurisy similarly to the other types of acute inflammation, and the immediate phase is mediated by histamine. (2) Either blocking of TNFα or IL-8 with corresponding antibodies, resulted in disappearance of the delayed permeability, while the duration and the degree of intensity of immediate permeability was not affected. IL-1ra did not suppress the delayed IVP.(3) The delayed permeability was not observed in neutro-phil-depleted rabbits, but the production of TNFα was maintained. (4) Intrapleural injections of either rabbit recombinant TNFα or IL-8 induced a delayed type of IVP that was not inhibited with antihistamine. (5) Injection of TNFα induced the production of IL-8. (6) IL-8 but not TNFα induced the delayed type IVP in the neutrophil-depleted rabbits. (7) GRO induced a delayed type of IVP via inducing the production of TNFα. Thus, TNFα-induced IL-8 is responsible for the mediation of delayed IVP in LPS-induced pleurisy of rabbits. This mechanism may generally be applicable to many types of acute inflammations, because similar IVP was also observed in inflammations at different site of the body, i.e. articular cavity and vitreal space as well as the inflammation with a different stimuli, i.e. urea crystal in rabbits.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (61 results)

All Other

All Publications (61 results)

  • [Publications] Akihiro Matsukawa 他: "Analysis of the inflammatory cytokine network among TNFα, IL-1β, IL-1 receptor antagonist and IL-8 in LPS-induced rabbit arthritis."Laboratory Investigation. 76. 629-638 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akihiro Matsukawa 他: "IL-1 receptor antagonist in tissues from healthy rabbits and in endotoxemia-related changes. IL-1 receptor antagonist has the potential to regulate over-actions of IL-1 in health and disease."Cytokine. 9. 307-315 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazuhiko Miyamoto 他: "IL-8 is involved in homologous TNFα-, but not in IL-1β-induced neutrophil infiltration in rabbits."Inflammation Research. 46. 472-477 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sumitaka Imamura 他: "Involvement of tumor necrosis factor-α, interleukin-1β, interleukin-8, and interleukin-1 receptor antagonist in acute lung injury caused by local Shwartzman reaction."Pathology International. 47. 16-24 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Makoto Kimura 他: "Blocking of TNF-α and IL-1 inhibits leukocyte infiltration at early, but not at late stage of Staphylococcus aureus-induced arthritis and concomitant cartilage destruction in rabbits."Clinical Immunology and Immunopathology. 82. 18-25 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Junsong Mo 他: "Involvement of TNFα, IL-1β and IL-1 receptor antagonist in LPS-induced rabbit uveitis."Experimental Eye Research. 66. 547-557 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeshi Ujioka 他: "Interleukin-8 as an essential factor in the human chorionic gonadotropin-induced rabbit ovulatory process : Interleukin-8 induces netrophila accumulation and activation in ovulation."Biology of Reproduction. 58. 526-530 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeshi Ujioka 他: "Analysisof the cytokine interaction among interleukin-1β, interleukin-8 and interleukin-1 receptor antagonist in rabbit ovulatory process."Fertility and Sterility. 70. 759-765 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takumi Fukumoto 他: "IL-8 is an essential mediator of the increased delayed-phase vascular permeability in LPS-induced rabbit pleurisy."Journal of Leukocyte Biology. 63. 584-590 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akihiro Matsukawa 他: "Analysis of the cytokine network among tumor necrosis factor α, interleukin-1β, interleukin-8 and interleukin-1 receptor antagonist in monosodium urate crystal-induced rabbit arthritis."Laboratory Investigation. 78. 559-569 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akihiro Matsukawa 他: "Production and regulation of monocyte chemoattractant protein-1 in lipopolysaccharide-or monosodium urate crystal-induced arthritis in rabbits : Roles of tumor necrosis factor α, interleukin-1, and interleukin-8."Laboratory Investigation. 78. 973-985 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akihiro Matsukawa 他: "Involvement of growth related protein (GRO) in lipopolysaccharide-induced rabbit arthritis : Cooperation between GRO and interleukin (IL)-8, and interrelated regulation among tumor necrosis factor-α, IL-1, IL- 1 receptor antagonist, IL-8 and GRO."Laboratory Investigation. 79. 591-600 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akihiro Matsukawa 他: "Cytokine network in the joint inflammation."Current Trends in Immunology. 1. 159-167 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Junsong Mo 他: "Role and regulation of IL-8 and MCP-1 in LPS-induced uveitis in rabbits."Experimental Eye Research. 68. 333-340 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akihiro Matsukawa 他: "Neutrophils as a source of cytokines in inflammation."Histology and Pathology. 14. 511-516 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shin-ichi Miyazaki 他: "Neutrophil infiltration as a craucial step for monocyte chemoattractant protein-1 to attract monocytes in lipopolysaccharide-induced arthritis in rabbits."Inflammation Research. 49. 673-678 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jun-Song Mo 他: "CXC chemokine GRO is essential for neutrophil infiltration in LPS-induced uveitis in rabbits."Experimental Eye Research. 70. 221-226 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshihiro Takahashi 他: "Erythromycin attenuates an experimental model of chronic bronchiolitis via augmenting MCP-1."European Respiratory Journal. (印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Matsukawa, T.Yoshimura, K.Miyamoto, S.Ohkawara, and M.Yoshinaga: "Analysis of the inflammatory cytokine network among TNFα, IL-1β, IL-1 receptor antagonist and IL-8 in LPS-induced rabbit arthritis."Lab.Invest.. 76. 629-638 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Matsukawa, T.Fukumoto, T.Maeda, S.Ohkawara, and M.Yoshinaga: "Detection and characterization of IL-1 receptor antagonist in tissues from healthy rabbits : IL-1 receptor antagonist is probably involved in health."Cytokine. 9. 307-315 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Miyamoto, A.Matsukawal, S.Ohkawara, K.Takagi, and M.Yoshinaga: "IL-8 is involved in homologous TNFα-, but not in IL-1β-induced neutrophil infiltration in rabbits."Inflammation Res.. 46. 472-477 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Imamura S, Matsukawa A, Ohkawara S, Kagayama M, and Yoshinaga M: "Involvement of tumor necrosis factor-a, interleukin-1b, interleukin-8, and interleukin-1 receptor antagonist in acute lung injury caused by local Shwartzman reaction."Pathology International.. 47. 16-24 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Kimura, A.Matsukawa, S.Ohkawara, K.Takagi and M.Yoshinaga: "Blocking of TNF-α. and IL-1 inhibits leukocyte infiltration at early, but not at late stage of Staphylococcus aureus-induced arthritis and concomitant cartilage destruction in rabbits."Clin.Immunol.Immunopathol.. 82. 18-25 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Mo, A.Matsukawa, M.Yoshinag: "Involvement of TNFα, IL-1β and IL-1 receptor antagonist in LPS-induced rabbit uveitis."Exp.Eye Res.. 66. 547-557 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Ujioka, A.Matsukawa, N.Tanaka, K.Matsuura, M.Yoshinaga and H.Okamura: "Interleukin-8 as an essential factor in the human chorionic gonadotropin-induced rabbit ovulatory process : Interleukin-8 induces netrophila accumulation and activation in ovulation."Biol.Reproduct.. 58. 526-530 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Ujioka, A.Matsukawa, N.Tanaka, K.Matsuura, M.Yoshinaga, H.Okamura: "Analysis of the cytokine interaction among interleukin-1β, interleukin-8 and interleukin-1 receptor antagonist in rabbit ovulatory process."Fertility and Sterility. 70. 759-765 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Fukumoto, , A.Matsukawa, T.Yoshimura, S.Edamitsu, S, Ohkawara, K.Takagi. and M.Yoshinaga: "IL-8 is an essential mediator of the increased delayed-phase vascular permeability in LPS-induced rabbit pleurisy."J.Leuko.Biol.. 63. 584-590 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Matsukawa, T.Yoshimura, T.Maeda, T.Takahashi, S.Ohkawara and M.Yoshinaga: "Analysis of the cytokine network among tumor necrosis factor α, interleukin-1β, interleukin-8 and nterleukin-1 receptor antagonist in monosodium urate crystal-induced rabbit arthritis."Lab.Invest.. 78. 559-569 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Matsukawa, S.Miyazaki, T.Maeda, S.Tanase, L.Feng, S.Ohkawara, M.Yoshinaga and T.Yoshimura: "Production and regulation of monocyte chemoattractant protein-1 in lipopolysac-charide-or monosodium urate crystal-induced arthritis in rabbits : Roles of tumor necrosis factor a, interleukin-1, and interleukin-8."Lab.Invest.. 78. 973-985 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Matsukawa, T.Yoshimura, K.Fujiwara, T.Maeda, S.Ohkawara and M.Yoshinaga: "Involvement of growth related protein (GRO) in lipopolysaccharide-induced rabbit arthritis : Cooperation between GRO and interleukin (IL)-8, and interre-lated recrulation among tumor necrosis factor-a, IL-1, IL-1 receptor antagonist, IL-8 and GRO."Lab.Invest.. 79. 591-600 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsukawa A and Yoshinaga M: "Cytokine network in the joint inflammation."Current Trends in Immunol. 1. 159-167 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] J.Mo, A.Matsukawa, S.Ohkawawa and M.Yoshinaga: "Role and regulation of IL-8 and MCP-1 in LPS-induced uveitis in rabbits."Exp.Eye Res.. 68. 333-340 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Matsukawa and M.Yosinaga: "Neutrophils as a source of cytokines in inflammation."Histol.Pathol.. 14. 511-516 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Furue, K.Kuwabara, K.Mikawa, K.Nishina, M.Shiga, N.Maekawa, M.Ueno, Y.Chikazawa, T.Ono, Y.Hori, A Matsukawa, M.Yoshinaga and H.Obara: "Crucial role of group IIA phospholipase A2 in oleic acid-induced acute lung injury in rabbits."Am.J.Repri.Crit.Care Med.. 160. 1291-1302 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyazaki, S, Matsukawa A, Ohkawara S, Takagi K and Yoshinaga M: "Neutrophil infiltration as a craucial step for monocyte chemoattractant protein-1 to attract monocytes in lipopolysaccharide-induced arthritis in rabbits."Inflam.Res.. 49. 673-678 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] J.Mo, A.Matsukawa, S.Ohkawara and M.Yoshinaga: "CXC chemokine GRO is essential for neutrophil infiltration in LPS-induced uveitis in rabbits."Exp.Eye res.. 70. 221-226 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shibata, M, Uno, T, Kajihara, M, Ohkawara, S and Yoshinaga, M: "Enhanced LPS-fever following hyperthermic stress in rabbits."J.Thermal Biology. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takahashi T., Suga M., Matsukawa A., Sato K., Okamoto T., Ichiyasu H., Ohkawara S., Yohsinaga M.and Ando M.: "Eryth-romycin attenuates an experimental model of chronic bronchiolitis via augmenting MCP-1."Eur.Resp.J.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akihiro Matsukawa 他: "Adenoviral-mediated overexpression of monocyte chemoattractant protein-1 differentially alters the development of Th1 and Th2 type responses in vivo."Journal of Immunology. 164. 1699-1704 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akihiro Matsukawa 他: "Expression and contribution of endogenous IL-13 in an experimental model of sepsis."Journal of Immunology. 164. 2738-2744 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akihiro Matsukawa 他: "Pivotal role of the CC chemokine, macrophage-derived chemokine, in the innate immune response."Journal of Immunology. 164. 5362-5363 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shin-ichi Miyazaki 他: "Neutrophil infiltration as a craucial step for monocyte chemoattractant protein-1 to attract monocytes in lipopolysaccharide-induced arthritis in rabbits."Inflammation.Research. 49. 1-6 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Jun-Song Mo 他: "CXC chemokine GRO is essential for neutrophil infiltration in LPS-induced uveitis in rabbits."Experimental Eye Research. 70. 221-226 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Toshihiro Takahashi 他: "Erythromycin attenuates an experimental model of chronic bronchiolitis via augmenting MCP-1."European Respiratory Journal . (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akihiro Matsukawa 他: "Involvement of growth-related protein in lipopolysaccharide-induced rabbit arthritis: cooperation between growth-related protein and IL-8 and interrelated regulation among TNFalpha, IL-1, IL-1 receptor antagonist, IL-8 and growth-related protein."Laboratory Investigation. 79. 591-600 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Junsong Mo 他: "Role and regulation of IL-8 and MCP-1 in LPS-induced uveitis in rabbits"Experimental Eye Research. 68. 333-340 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akihiko Matsukawa 他: "Neutrophils as a source of cytokines in inflammation."Histology and Pathology. 14. 511-516 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sinichi Frue 他: "Crucial role of group IIA phospholipase A2 in oleic acid-induced acute lung injury in rabbits."American J. Repriratory & Critical Care Medicine. 160. 1291-1302 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takeshi Ujioka: "Interleukin-8 as an essential factor in the human chorionic gonadotropin-induced rabbit ovulatory process:Interleukin-8 induces netrophila accumulation and activation in ovulation." Biology Reproduction. 58. 526-530 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Junsong Mo: "Involvement of TNFα,IL-1β and IL-1 receptor antagonist in LPS induced rabbit uveitis." Experimental Eye Research. 66. 547-557 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takeshi Ujioka: "Analysis of the cytokine interaction among interleukin-1b,Interleukin-8 and Interleukin-1 receptor antagonist in rabbit ovulatory process." Fertility and Sterility. 70. 759-765 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takumi Fukumoto: "IL-8 is an essential mediator of the increased delayed-phase vascular permeability in LPS-induced rabbit pleurisy." J.Leukocyte Biology. 63. 584-590 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Akihiro Matsukawa: "Analysis of the cytokine network amoung tumor necrosis factor α,Interleukin-1β,Interleukin-8 and Interleukin-1 receptor antagonist in monosodium urate crystal-induced rabbit arthritis." Laboratory Investigation. 78. 559-569 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Akihiro Matsukawa: "Sequential generation of cytokines during the initiative phase of inflammation,with reference tu neutrophils." Inflammation Research. 47. S137-S144 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Akihiro Matsukawa: "Production and regulation of monocyte chemoattractant protein-1 in lipopolysaccharide-or monosodium urate crystal-induced arthritis rabbits:Roles of tumor necrosis factor α,Interleukin-1,and Interleukin-8." Laboratory Investigation. 78. 973-985 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Akihiro Matsukawa: "Analysis of the inflammatory cytokine network among TNFα, IL-1β, IL-1 receptor antagonist and IL-8 in LPS-induced rabbit arthritis." Laboratory Investigation. 76. 629-638 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Akihiro Matsukawa: "IL-1 receptor antagonist in tissues from healthy rabbits and in endotoxemia-related changes, IL-1 receptor antagonist has the potential to regulate over-actions of IL-1 in health and disease." Cytokine. 9. 307-315 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sumitaka Imamura: "Involvement of tumor necrosis factor-α, interleukin-1β, interleukin-8, and interleukin-1 receptor antagonist in acute lung injury caused by local Shwartzman reaction." Pathology International. 47. 16-24 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Makoto Kimura: "Blocking of TNF-α and IL-1 inhibits leukocyte infiltration at early, but not at late stage of Staphylococcus aureus-induced arthritis and concomitant cartilage destruction in rabbits." Clinical Immunology and Immunopathology. 82. 18-25 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazuhiko Miyamoto: "IL-8 is involved in homologous TNF-α-, but not in IL-1β-induced neu-trophil infiltration in rabbits." Inflammation Research. 46. 472-477 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takeshi Ujioka: "Interleukin-8 as an essential factor in the human chorionic gonadotropin-indused rabbit ovulatory process : Interleukin-8 induces netrophila accumulation and activation in ovulation." Biology Reproduction. 58. 526-530 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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