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1996 Fiscal Year Final Research Report Summary

Pathophisiological study of acinar cell proliferation and apoptosis

Research Project

Project/Area Number 08670609
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

KASHIMA Kei  Kyoto Prefectural University of Medicine, Department of Internal Medicine, Professor, 医学部, 教授 (30079818)

Co-Investigator(Kenkyū-buntansha) KATAOKA Keisho  Kyoto Prefectural University of Medicine, Department of Internal Medicine, Assis, 医学部, 助手 (70185792)
SAKAGAMI Junichi  Kyoto Prefectural University of Medicine, Department of Internal Medicine, Resea
Project Period (FY) 1996 – 1997
KeywordsProliferation / Apoptosis / CCK / PCNA / BrdU / Cell cycle / Western blot / Cyclin D_1
Research Abstract

We investigated acinar cell proliferation and apoptosis during the pancreatic reconstruction after acinar hyperplasia or acute pancreatitis. We applied two different experimental models as camostat-induced pancreatic hyperplasia and as arginine-induced acute pancreatitis in rats. Plasma cholecystokinin (CCK) reached the highest peak at 30 min after single oral administration of camostat (50mg/kg BW) and gradually declined to control level by 9 hrs. Pancreatic DNA content significantly increased at 1 day affer camostat administration. Pancreatic wet weight, protein content, and RNA content significantly increased at day 2, all of which described above decreased to control level by day 5. In this model, we can estimate both pancreatic trophism and involution. BrdU labeling indices (LI) of acinar cells markedly increased at day 1, thereafter rapidly decreased. On the other hand, TUNEL-positive acinar cells significantly increased during day 1 to day 5. Observed number of acini possessing … More both BrdU-positive cell and apoptotic cell were significantly low compared to expected number of acini calculated by using binominal distribution (p<0.001) or Poisson's distribution (p<0.001). We administered BrdU (4mg/hr) to conscious rats intravenously during 12 to 36 hrs after camostat administration when the DNA synthesis of acinar cell is prominent. These animals were killed at day 5. Approximately 12% of acinar cells were labeled with BrdU and were seemed to exist focally. We also observed BrdU-positive mitosis which indicates acinar cell is able to replicate at least twice. Acute pancreatitis was made by single administration of L-arginine monohydrochloride (4.5g/kg BW) intraperitoneally. At 12 hrs after induction of acute pancreatitis, PCNA-positive acinar cells markedly increased, Whereas the BrdU LI remained low level. PCNA is known as a nuclear protein that shows striking increase during late G_1 through S phase of cell cycle. Therefor, we suspect that acinar cell death during the progressing phase of pancreatitis occurs subsequent to entering G_1 phase. The results of western blotting indicated that augmented PCNA of acinar cell during the progressing phase of pancreatitis exists as polymeric structure or as complex consistent with G_1 cyclins (e.g.cyclin D_1). During the regenerative period of acute pancreatitis. acinar cell apoptosis as well as proliferation significantly increased. Similar to the resu of our first experiment, Observed number of acini possessing both BrdU-positive cell and apoptotic cell were significantly low compared to expected number of acini calculated by using binominal distribution (p<0.0001) or Poisson's distribution (p<0.0001). Although a cinar cell proliferation and apoptosis occurs at random when searched for separately, these might be spatially controlled as acinar unit Less

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 加嶋 敬: "慢性膵炎の診断と治療" 日本内科学会雑誌. 86(3). 406-410 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加嶋 敬 他: "膵機能検査" 内科. 79(3). 491-493 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 阪上 順一 他: "アルギニン急性膵炎モデルとアポトーシス" 胆と膵. 18(1). 37-40 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 片岡 慶正 他: "慢性膵炎の新しい診断基準-機能的診断基準-" 診療と治療. 85(11). 1974-1978 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K Umehava, et al: "Comparative distribution of nitric cxide synthase(NOS) in pancreas of the dog and rat,Immunocytochemistry of neuronal type NOS and histochemistry of NADPH-diaphorase" Buain Rescarch Bulltin. 42(6). 469-478 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Kataoka, et al: "Diagnosis of chronic pancreatitis using honinvasive tests of exocrine pancreatic function-comparison to duodenal intubation tests." Paucreas. 15(4). 409-415 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Sakagami, et al: "Relation ship of plasma CCK to acivar cell regenetion in Autts paucethからas studiesl By perlifatasys cell wsclear autigen." Dig.Dis.Sci. 41・9. 1828-1837 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加嶋 敬: "Annual Review 消化器 1996" 中外医学社, 4 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Junichi SAKAGAMI: "Relationship of plasma CCK to acinar cell regeneration in acute pancreatitis as studied by proliferating cell nuclear antigen." Dig Dis Sci. 41. 1828-1837 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Junichi SAKAGAMI: "Acinar cell proliferation and apoptosis related to endogenous CCK following camostat administration in rats." Gut Hormone. XIV. 23-29 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Keisho KATAOKA: "CCK receptor antagonist as a new treatment for patients with chronic pancreatitis." KAN-TAN-SUI. 33. 363-370 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Junichi SAKAGAMI: "Role of cholecystokinin on pancreatic Pathophysiology." Shokakika. 23. 76-83 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kei KASHIMA: "Diagnosis and treatment of chronic pancreatitis." J Jpn Soc Intern Med. 406-410 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Junichi SAKAGAMI: "The role of apoptosis in the regenerative period of arginine-induced acute pancreatitis in the rat." J Bil Panc. 18. 37-40 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaori UMEHARA: "Comparative distribution of nitric oxide synthase (NOS) in pancreas of the dog and rat : Immunocytochemistry of neuronal type NOS and histochemistry of NADPH-diaphorase." Brain Research Bulletin. 42. 469-478 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Keisho KATAOKA: "Diagnosis of chronic pancreatitis using noninvasive tests of exocrine pancreatic function-Comparison to duodenal intubation tests." Pancreas. 15. 409-415 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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