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1996 Fiscal Year Final Research Report Summary

Experimental analysis for reconsruction of inferior vena cava and portal vein in abdominal surgery : endothelial seeding on artificial grafts and insulin gene transfer into endothelial cells.

Research Project

Project/Area Number 07457280
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionShowa University

Principal Investigator

KUMADA Kaoru  Showa University Fujugaoka Hospital, Faculty of Medicine, Chief Professor, 医学部, 教授 (00025602)

Co-Investigator(Kenkyū-buntansha) SORIMACHI Noriko  Tokyo Metropolitan Institute of Medical Science, Department of Immunology, Staff, 免疫研究部門, 研究員 (30217468)
YAMAGUCHI Masahiko  Showa University Fujigaoka Hospital, Faculty of Medicine, Assistant Professor, 医学部, 講師 (00266149)
Project Period (FY) 1995 – 1996
KeywordsVascular reconstruction / Adenovirus vector / gene transfer / Insulin / Vascular endothelial cell / 膵全摘
Research Abstract

Purpose of the study is to investigate the effectiveness of endothelial seeding on the the artificial graft and insulin gene transfer to endothelial cells on the graft, which was interposed in the canine infreior vena cava and portal vein for vascular reconstruction in hepato-biliary-pancreatic surgery.
We could not find any significant difference in patency of the vein grafts, ePTFE grfats, or endothelialized grafts, which were interposed in the IVC or PV.
We performed insulin gene transfer using adenovirus vector carrying human insulin gene (AxIns). AxIns was constructed as follows ; human preproinsulin gene genomic DNA (1.3-kb) containing coding sequence, was inserted into the SwaI site of the full-length replication-deficient adenovirus genome cloned in a cassette cosmid. The cosmid was then co-transfected to 293 cells together with the adenovirus DNA-terminal protein complex digested at several sites with EcoT22I.AxIns was generated by overlapping recombination. AxIns was propagated in 293 cells and concentrated with purification using sequential ultracentrifugation in CsCl step gradients. Transfection of AxIns into endothelial cells induced the expression of preproinsulin mRNA and secret proinsulin. One shot injection of AxIns into the spleen transfered human insulin gene mainly in the liver and produced human insulin enough to decrease blood glucose levels in streptozotosin-induced diabetic rats and to restore the serum levels of total protein and albumin, which were impaired in diabetic rats. AxIns injection into the spleen, but not periodic insulin administration, controled blood glucose levels, restored serum total protein levels, and prolonged survival periods after total pacreatectomy in canine models. Thus we confirmed availability of AxIns for in vivo insulin gene transfer.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Kasano Y, Kumada K, et al.: "Resectable leiomyosarcoma of inferior vene cava extended into right atrium with the use of cardiopulmonary bypass and graft replacement." Surgery. 117. 473-475 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakano H, Kumada K, et al.: "Efficacy of intraportal injection of anti-ICAM-1 monoclonal antibody against liver cell injury following warm ischemia in rats." Am.J.Surg.170. 64-66 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okada Y, Kumada K, et al.: "Long-term follow up of patients with tumor thrombi from renal cell carcinoma and total replacement of the inferior vena cava using an expanded polytetrafluoroethylene tubular graft." J.Urol.155. 444-447 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitamura N, Kumada K, et al.: "Heparin-like glycosaminoglycans inhibit leukocyte adhesion to endotoxin-activated human vascular endothelial cells under nonstatic conditions." Eur Surg Res. 28. 428-435. (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamaguchi M, Kumada K, et al.: "Insulin gene transfer can be a new optional therapy for replacement of Pancreas" Transpl.Proc.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamaguchi M, Kumada K, et al.: "Insulin gene transfer compensated pancreatic β cell function in diabetic rats." Transpl.Proc.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kasano Y,Kumada K,et al.: "Resectable leiomyosarcoma of inferior vene cava extended into right atrium with the use of cardiopulmonary bypass and graft replacement." Surgery. 117. 473-475 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakano H,Kumada K,et al.: "Efficacy of intraportal injection of anti-ICAM-1 monoclonal antibody against liver cell injury following warm ischemia in rats." Am.J.Surg.170. 64-66 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okada Y,Kumada K.: "Long-term follow up of patients with tumor thrombi from renal cell carcinoma and total replacement of the inferior vena cava using an expanded polytetrafluoroethylene tubular graft." J.Urol.155. 444-447 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nomoto S,Kumada K,et al.: "Influence of hepatic mitochondrial redox state on complement biosynthesis and activation during and after cardiopulmonary bypass operations." Eur.J Cardiothorac Surg. 10. 273-278 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitamura M,Kumada K,et al.: "Heparin-like glycosaminoglycans inhibit leukocyte adhesion to endotoxin-activated human vascular endothelial cells under nonstatic conditions." Eur Surg Res.28. 428-435 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamaguchi M,Kumada K,et al.: "Insulin gene transfer can be a new optional therapy for replacement of Pancreas." Transpl.Proc.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamaguchi M,Kumada K,et al.: "Insulin gene transfer compensated pancreatic beta cell function in diabetic rats." Transpl.Proc.(in press).

    • 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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