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Establishment of hematopoietic cytokine therapy with a combination of hematopoietic factors for hematologic diseases of childhood

Research Project

Project/Area Number 02454269
Research Category

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

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionShinshu University

Principal Investigator

KOMIYAMA Atsushi  Shinshu Univ. School Med., Dept. Pediatrics, Professor, 医学部, 教授 (50020798)

Co-Investigator(Kenkyū-buntansha) KOIKE Kenichi  Shinshu Univ. School Med., Dept. Pediatrics, Assistant Professor, 医学部, 講師 (40143979)
KAWAI Hiroshi  Shinshu Univ. School Med., Dept. Pediatrics, Assistant Professor, 医学部附属病院, 講師 (70126671)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1990: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordshematopoietic factors / erythropoietin / colony-stimulating factor / anemia of prematurity / aplastic anemia / neutropenia / leukemia
Research Abstract

The present studies were conducted to establish hematopoietic cytokine therapy with a combination of hematopoietic factors for hematologic diseases of childhood with cytopenia. To make better hematopoietic cytokine therapy, synergic effects of hematopoietic factors and mechanisms for cytopenia were first studied in anemia of prematurity, aplastic anemia, chronic neutropenia, and acute leukemia. Then., hematopoietic factors (G-CSF, GM-CSF, H-CSF, erythropoietin) were administered in combination.
1. Synergic effects of hematopoietic factors in vitro
(1) G-CSF and GN-CSF acted synergically on the production of neutrophils.
(2) A combination of G-CSF and IL-3 increased the production of neutrophil and monocytes in a synergic fashion.
(3) A combination of IL-3 anf IL-6 or IL-3 anf inteferon-gamma had synergic effects on the production of megakaryocytes/platelets.
2. Mechanisms for cytopenia in hematologic diseases of childhood
(1) In anemia of prematurity, serun erythropoietin levels were low as … More expected based on the hemoglobin concentrations. The erythroid precursors could proliferate and differentiate normally in the presence of erythropoietin.
(2) In vitro hematopoiesis was poor in aplastic anemia. The addition of sufficient amounts of hematopoietic factors to thecultures improved the hematopoiesis in some but not in the others.
(3) In vitro granulopoiesis was normal in chronic neutropenia. In half of the patients, anti-neutrophil antibodies were detectable, which indicates the involiiement of such antibodies in the neutropenia.
3. Hematopoietic cytokine therapy with a combination of hematopoietic factors
(1) Erythropoietin was effective for anemia of prematurity. We designed a protocol with a combination of erythropoietin and G-CSF in case of the development of neutropenia as reported by other investigators, but neutropenia did not develop in the patients studied.
(2) G-CSF or Gbl-CSF was. effective in five of 1 1 patients with aplastic anemia. Acombination of G-CSF and GM-CSF was effective in two of them.
(3) In chronic neutropenia, G-CSF alone yielded satisfactory clinical improvements with a increase in neutrophil counts. After the therapy., anti-neutrophil antibodies decreased in the titer.
(4) A combination of G-CSF and M-CSF was effective for intractable mycosis occurred at the neutropenic stage after chemotherapy in acute leukemia. Less

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (76 results)

All Other

All Publications (76 results)

  • [Publications] Komiyama,A.: "Natural killer cell immunodeficiency in siblings:Defective killing in the absence of natural killer cytotoxic factor activity in natural killer and lymphokine-activated killer cytotoxicities." Pediatrics. 85. 323-330 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yabuhara,A.: "Castleman's disease and interleukin 6." Leukemia and Lymphoma. 2. 369-380 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tsuda,T.: "Transient abnormal myelopoiesis and diffuse hepatic necrosis in Down's syndrome with prominent bleeding diathesis." Acta Paediatrica Scandinavica. 79. 241-244 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yasui,K.: "An increase in polymorphonuclear leukocyte chemotaxis accompanied by a change in the membrane fluidity with age during childhood." Clinical Experimental Immunology. 81. 156-159 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Agematsu,K.: "Successful bone marrow transplantation in a patient with severe pretransplant pneumonia." Transplantation. 50. 326-327 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Agematsu,K.: "Detection of engraftment and chimerism after bone marrow transplantation by ib situ hybridization using a Y-chromosome specific probe." American Jounal of Hematology. 33. 255-260 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yabuhara,A.: "Development of natural killer cytotoxicity during childhood:Marked increases in number of natural killer cells with adequate cytotoxic ability during infancy to early childhood." Pediatric Research. 28. 316-322 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Aonuma,K.: "Pseudo-Chediak-Higashi anomaly in acute myeloid leukemia (M2) of childhood." Acta Paediatrica Japonica. 32. 651-655 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 小宮山 淳: "好中球減少症のサイトカインによる治療" 小児科. 31. 553-561 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 小宮山 淳: "GーCSF,MーCSFによるcompromised hostの感染対策" 小児感染免疫. 2. 75-77 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 小宮山 淳: "顆粒球減少症" 小児科. 31. 1450-1452 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 小宮山 淳: "好中球遊走能異常症" 小児内科. 22. 734-739 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 小宮山 淳: "成長ホルモンと白血病" 小児科診療. 53. 1847-1853 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 小宮山 淳: "NK細胞およびLAK細胞における標的細胞障害機構の電顕的観察" 日本臨床. 48. 227-231 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 岡村 純: "遺伝子組み換えヒト型顆粒球刺激因子(rhGーCSF KRN8601)の小児科領域における臨床的検討ー抗癌剤投与後の二次性好中球減少症に対する有効性,安全性の検討" 日本小児血液学会雑誌. 4. 428-435 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ichikawa,M.: "Functional p75 interleukin-2 receptor expression on the fresh blast cells in childhood acute lymphoblastic leukemia with natural killer cell properties." American Journal of Hematology. 36. 259-264 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yamada,S.: "Decreased cytotoxic potential of fresh and recombinant interlerkin 2-cultured large granular lymphocytes in childhood acute lymphoblastic leukemia." Leukemia Research. 15. 367-372 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yamada,S.: "Effect of radiotherapy on natural killer activity in childhood acute lymphoblastic leukemia and lymphoma." Leukemia and Lymphoma. 4. 343-349 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yamada,S.: "Decrease in number of CD16(Leu 11)^+CD45RA(2H4)^+ cells and defective production of natural killer cytotoxic factor in childhood acute lymphblastic leukemia." Leukemia Research. 15. 785-790 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ishiguro,A.: "Induction of granulocyte and granulocyte-macrophage colony-stimulating factors from human monocytes stimulated by Fc fragments of human IgG." British Journal of Haematology. 79. 14-21 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yamada,S.: "Impaired cytotoxic activity of interleukin 2(IL 2)-cultured large granular lymphocytes (LGL)in childhood acute lymphoblastic leukemia.Quantitative measurement of IL 2 receptor expression of IL 2-cultured LGL." Leukemia and Lymphoma. 6. 65-73 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Agematsu,K.: "Spontaeors production of interleukin-6 by ki-1-positive large-cell anaplastic lymphoma with extensive bone destruction." Blood. 77. 2299-2301 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Koike,K.: "Interferon-gamma inhibits proliferation,but not commitment,of murine granulocyte-macrophage-progenitors."

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 小宮山 淳: "小児における造血因子療法" 日本小児科学会雑誌. 95. 2093-2096 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 小宮山 淳: "Transient abnormal myelopoiesis(TAM)." 病理と臨床. 9. 78-78 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 中村 友彦: "未熟児貧血に対するリコンビナント・ヒト・エリスロポェチンの臨床効果" 日本小児科学会雑誌. 95. 1105-1109 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 赤羽 太郎: "小児科学ー血液および造血器疾患" 奥田 六郎,日本医事新報社, 766 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 小宮山 淳: "今日の小児診断指針第2版ー反復性発熱" 前川 喜平ほか,医学書院, 533 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 小宮山 淳: "小児科学年鑑1991「小児科の進歩11」ー血液疾患の遺伝子組換えヒト造血因子による治療" 前川 喜平ほか,診断と治療社, 284 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 小宮山 淳: "救急医療ハンドブック,改訂第3版ー小児の発熱" 清野 誠一ほか,南山堂, 464 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Komiyama, A., et al: "Natural killer cell immunodeficiency in siblings : Defective killing in the absence of natural killer cytotoxic factor activity in natural killer and lymphokineactivated killer cytotoxicities" Pediatrics. 85. 323-330 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yabuhara, A., et al: "Castleman's disease and interleukin 6" Leukemia and Lymphoma. 2. 369-380 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tsuda, T., et al: "Transient abnormal myelopoiesis and diffuse hepatic necrosis in Down's syndrome with prominent bleeding diathesis." Acta Paediatrica Scandinavica. 79. 241-144 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yasui, K., et al: "An increase in polymorphonuclear leukocyte chemotaxis accompanied by a change in the membrane fluidity with age during childhood." Clinical Experimental Immunology. 81. 156-159 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Agematsu, K., et al: "Successful bone marrow transplantation in a patient with severe pretransplant pneumonia." Transplantation. 50. 326-327 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Agemastu, K., et al: "Detection of engraftment and chimerism after bone marrow transplantation by in situ hybridization using a Y-chromosome specific probe." American Journal of Hematology. 33. 255-260 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yabuhara, A., et al: "Development of natural killer cytotoxicity during childhood : Marked increases in number of natural killer cells with adequate cytotoxic abilities during infancy to early childhood." Pediatric Research. 28. 316-322 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ichikawa, M., et al: "Functional p75 interleukin-2 receptor expression on the fresh blast cells in childhood acute lymphoblastic leukemia with natural killer cell properties." American Journal of Hematology. 36. 259-264 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yamada, S., et al: "Decreased cytotoxic potential of fresh and recombinant interleukin 2-cultured large granular lymphocytes in childhood acute lymphoblastic leukemia." Leukemia Research. 15. 367-372 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yamada, S., et al: "Decrease in number of CD16 (Leu 11)^+ CD45RA (2H4)^+ cells and defective production of natural killer cytotoxic factor in childhood acute lymphoblastic leukemia." Leukemia Research. 15. 785-790 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ishiguro, A., et al: "Induction of granulocyte and granulocyte-macrophage colony-stimulating factors from human monocytes stimulated by Fc fragments of human IgG." British Journal of Hamatology. 79. 14-21 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Agematsu, K., et al: "Spontaneous production of interleukin-6 by Ki-1-positive large-cell anaplastic lymphoma with extensive bone destruction." Blood. 77. 2299-2301 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Koike, K., et al: "Interferon-gamma inhibits proliferation, but not commitment, of murine granulocyte-macrophage progenitors."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ichikawa,M.: "Functional p75 interleukinー2 receptor expression on the fresh blast cells in childhood acute lymphoblastic with natural killer cell properties" American Jounal of Hematology. 36. 259-264 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yamada,S.: "Decresed cytotoxic potential of fresh and recombinant interleukinー2ーcultured large granular lymphocytes in chlldhood acute lymphoーblastic leukemia" Leukemia Research. 15. 367-372 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yamada,S.: "Effect of radiotherapy on natural killer activity in chilhood acute lymphoblastic leukemia and lymphoma" Leukemia and Lymphoma. 4. 343-349 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yamada,S.: "Decrease in number of CD16(Leuー11)^+CD45RA(2H4)^+ cells and defective production of natural killer cytotoxic factor in childhood acute lymphoblastic leukemia" Leukemia Research. 15. 785-790 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ishiguro,A.: "Induction of granulocyte and granulocyteーmacrophage colonyーstimulating factors from human monocytes stimulated by Fc fragments of human IgG" British Jounal of Haematology. 79. 14-21 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Aonuma,K.: "Threeーdimensional ultrastructure of abnormal granulation in childhood acute myelogenous leukemia with maturation(M2)" Jounal of Clinical Electron Microscopy. 24. 163-168 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tsuchida,M.: "Treatment of acute lymphoblastic leukemia in the Tokyo Children's Cancer Study GroupーPreliminary results of L84ー11 protocol" Acta Paediatrica Japonica. 33. 522-532 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yamada,S.: "Impaired cytotoxic activity of interleukin 2 (LLー2)ーcultured large granular lymphocytes (LGL)in childhood acute lymphoblastic leukemia.Quantitative measurement of ILー2 receptor expression expression of ILー2ーcultured LGL" Leukemia and Lymphoma. 6. 65-73 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Agematsu,K.: "Spontaneous production of interleukinー6 by Kiーlーpositive largeーcell anaplastic lymphoma with extensive bone destruction" Blood. 77. 2299-2301 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 小宮山 淳: "小児における造血因子療法" 日本小児科学会権誌. 95. 2093-2096 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 小宮山 淳: "Transient abnormal myelopoiesis(TAM)" 病理と臨床. 9. 78-78 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 天野 芳郎: "小児急性白血病" クリニカ. 18. 214-220 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 渡辺 昌: "成長ホルモンと白血病" ホルモンと臨床. 39. 365-373 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 中村 友彦: "長野県における未熟児貧血に対する輸血の現況" 信州医学雑誌. 39. 375-379 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 中村 友彦: "未熟児貧血に対するリコンビナント・ヒト・エリスロポエチンの臨床効果" 日本小児科学会雑誌. 95. 1105-1109 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 杉山 ひろみ: "著明な骨髄壊死が先行した急性骨髄性白血病の1例" 臨床血液. 32. 991-995 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 中沢 良樹: "肺炎罹患後,呼吸心不全をきたしたマルチコア病の1小児例" 脳と発達. 24. 81-82 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 小宮山 淳: "救急医療ハンドブック 改訂第3版ー小児の発熱" 清野誠一ほか,南江堂, 199-204 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 小宮山 淳: "小児科学年鑑1991 小児科の進歩11ー血液疾患の遺伝子組換之ヒト造血因子による治療" 前川喜平ほか,診断と治療社, 58-65 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Komiyama,A.: "Natural killer cell immunodeficiency in siblings:Defective killing in the absence of natural killer cytotoxic factor activity in natural killer and lymphokineーactivated killer cytotoxicities." Pediatrics. 85. 323-330 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yasui,K.: "An increase in polymorphonuclear leukocyte chemotaxis accompanied by a change in the membrane fluidity with age during childhood." Clinical Experimental Immunology. 81. 156-159 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Agematsu,K.: "Successful bone marrow transplantation in a patient with severe pretransplant pneumonia." Transplantation. 50. 326-327 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Agematsu,K.: "Detection of engraftment and chimerism after bone marrow transplantation by in situ hybridization using a Yーchromosome specific probe" American Journal of Hematology. 33. 255-260 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yabuhara,A.: "Development of natural killer cytotoxicity during childhood:Marked increases in number of natural killer cells with adequate cytotoxic abilities during infancy to early childhood." Pediatric Research. 28. 316-322 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 小宮山 淳: "好中球減少症のサイトカインによる治療" 小児科. 31. 553-561 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 小宮山 淳: "GーCSF,MーCSFによるcompromised hostの感染対策" 小児感染免疫. 2. 75-77 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 村田 敬寛: "骨髄炎を契機に発見されたlazyーleukocyte syndromeの1乳児例" 小児科臨床. 43. 2411-2414 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ichikawa,M.: "The p75 interleukin 2 receptor expression on the fresh blasts cells in childhood acute lymphoblastic leukemia with natural killer cell properties." American Journal of Hematology.

    • Related Report
      1990 Annual Research Report
  • [Publications] Yamada,S.: "Effect of radiotherapy on natural killer activity in childhood acute lymphoblastic leukemia and lymphoma." Leukemia and Lymphoma.

    • Related Report
      1990 Annual Research Report
  • [Publications] Yamada,S.: "Decreased cytotoxic potential of fresh and recombinant interleukin 2ーcultured large granular lymphocytes in childhood acute lymphoblastic leukemia." Leukemia Research.

    • Related Report
      1990 Annual Research Report
  • [Publications] 中村 友彦: "未熟児貧血に対するリコンビナント・ヒトエリスロポエチンの臨床効果" 日本小児科学会雑誌.

    • Related Report
      1990 Annual Research Report
  • [Publications] 小宮山 淳: "血液疾患の遺伝子組み換えヒト造血因子による治療" 小児科の進歩11(小児科学年鑑).

    • Related Report
      1990 Annual Research Report
  • [Publications] 赤羽 太郎: "小児科学" 奥田 六郎,日本医事新報社, 766 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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