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- Gannedahl, G, et al.
(author)
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Role of antibody synthesis and complement activation in concordant xenograft retransplantation.
- 1994
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In: Transplantation. - 0041-1337 .- 1534-6080. ; 58:3, s. 337-344
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Journal article (peer-reviewed)abstract
- A mouse-to-rat heart retransplantation model was used to study the effects of complement depletion and antibody production with regard to graft survival and anti-donor antibody specificity. Retransplantation was performed 3 weeks after the first transplantation in the presence of absence of 15-deoxyspergualin (DSG) immunosuppression. Untreated animals rejected their first graft after 3 days and retransplantation resulted in a hyperacute rejection within 2 min. A low titer of preformed anti-mouse lymphocytotoxic antibodies of the IgM subclass was found in serum collected from the unoperated rat. The rejection gave rise to a synthesis of IgG antidonor antibodies reacting with both graft endothelium and sarcolemma. Immunofluorescent staining of the rejected first heart graft showed moderate IgM and IgG antibody deposits on the graft vascular endothelium, while only IgG was found in the second graft. There was no C3 deposition found in the first mouse graft, as was the case in the second mouse graft. Anti-mouse antibodies cross-reacted with hamster antigens and a hyperacute rejection of a hamster heart graft occurred in a mouse-sensitized rat. Immunofluorescent staining revealed that the antibodies did not bind to hamster heart endothelium, as was expected, but, instead, to graft sarcolemma. DSG treatment prolonged the survival of the first graft by a median of 8 days. Continuous treatment until retransplantation resulted in a prolongation to 30 (20-127) min of the survival of the second graft and no increase in antibody titers against mouse antigens was observed. However, immunofluorescent staining revealed a weak binding of anti-mouse antibodies of the IgM subclass in the rejected mouse heart graft. Additional complement depletion with cobra venom factor in DSG-treated animals resulted in a prolongation of the median graft survival to 48 hr (6-96). No sign or minimal signs of antibody deposition were found in these grafts, but histology revealed massive mononuclear infiltration. In conclusion, xenograft transplantation in a concordant situation results in a shift of antidonor antibody Ig synthesis from IgM to IgG. If daily DSG treatment is administered from the day of transplantation, this reduces the synthesis of antidonor antibodies, and if complement is also depleted, the survival of the second graft is prolonged. The significance of the mononuclear infiltration remains to be established.
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- Moberg, L, et al.
(author)
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Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation
- 2002
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In: The Lancet. - 1474-547X. ; 360:9350, s. 2039-2045
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Journal article (peer-reviewed)abstract
- Background Intraportal transplantation of pancreatic islets offers improved glycaemic control and insulin independence in type 1 diabetes mellitus, but intraportal thrombosis remains a possible complication. The thrombotic reaction may explain why graft loss occurs and islets from more than one donor are needed, since contact between human islets and ABO-compatible blood in vitro triggers a thrombotic reaction that damages the islets. We investigated the possible mechanism and treatment of such thrombotic reactions. Methods Coagulation activation and islet damage were monitored in four patients undergoing clinical islet transplantation according to a modified Edmonton protocol. Expression of tissue factor (TF) in the islet preparations was investigated by immunohistochemistry, immunoprecipitation, electron microscopy, and RT-PCR. To assess TF activity in purified islets, human islets were mixed with non-anticoagulated ABO-compatible blood in tubing loops coated with heparin. Findings Coagulation activation and subsequent release of insulin were found consistently after clinical islet transplantation, even in the absence of signs of intraportal thrombosis. The endocrine, but not the exocrine, cells of the pancreas were found to synthesise and secrete active TF. The clotting reaction triggered by pancreatic islets in vitro could be abrogated by blocking the active site of TF with specific antibodies or site-inactivated factor Vlla, a candidate drug for inhibition of TF activity in vivo. Interpretation Blockade of TF represents a new therapeutic approach that might increase the success of islet transplantation in patients with type 1 diabetes, in terms of both the risk of intraportal thrombosis and the need for islets from more than one donor.
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- Svensson, G, et al.
(author)
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Quantitative measurements of collateral arterial blood flow in nonarterialized rat liver grafts.
- 1994
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In: Transplant international : official journal of the European Society for Organ Transplantation. - 0934-0874. ; 7:2, s. 136-9
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Journal article (peer-reviewed)abstract
- The early development of arterial blood flow in the grafted liver after orthotopic liver transplantation in the rat without reconstruction of the hepatic artery was studied. Arterial liver blood flow was measured on day 21 after transplantation with NEN-TRAC microspheres (size 15.5 +/- 0.1 microns) and labelled with 103Ru. The arterial liver blood flow in the grafted liver was 0.778 +/- 0.247 ml/min per gram for transplanted rats after 21 days. One day after transplantation, the blood flow was only 0.006 +/- 0.002 ml/min per gram. The results of this study demonstrate that there was no arterial blood flow on day 1 after transplantation, as expected, but that there was a high arterial blood flow in the transplanted liver by day 21. This was also supported by the angiographic findings. The early development of arterial blood flow via collaterals may account for the excellent results that we and others have attained in orthotopic liver transplantation without rearterialization in the rat.
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- Tufveson, G, et al.
(author)
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Organ transplantation in Göteborg with particular reference to kidney transplantation.
- 1993
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In: Clinical transplants. - 0890-9016. ; , s. 243-51
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Journal article (peer-reviewed)abstract
- The limiting factor in organ transplantation is the availability of organs. Continuing work to improve the public's willingness to donate organs and inspire hospital staff to collaborate in organ procurement is essential. Identification of patients who will not benefit from transplantation can also increase the availability of organs. Grafts may also be saved by identification and appropriate treatment of recurrent renal disease. Xenotransplantation may eventually solve the problem, but major obstacles remain. Meanwhile, work in this field may help to clarify mechanisms of rejection. New immunosuppressive drugs may improve graft survival and reduce the incidence and progression of chronic rejection.
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| 37. |
- Wallander, J, et al.
(author)
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Small-bowel transplantation in the rat with a nonsuture cuff technique. Technical and immunological considerations.
- 1988
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In: Transplant International. - 0934-0874 .- 1432-2277. ; 1:3, s. 135-9
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Journal article (peer-reviewed)abstract
- Small-bowel transplantation (SBT) using an nonsuture cuff technique was carried out on 137 rats. Preparation of the donor graft was carried out according to conventional procedures. Graft perfusion was done at a fixed pressure of 35 cm water. The left renal vessels of the recipient were dissected, the native kidney removed, and the graft was connected to the vessels by a nonsuture cuff technique. Of the animals, 92% survived for at least 5 days posttransplant. Three different combinations were investigated: (1) isografts; (2) semisyngeneic grafts from nontreated Lewis----(Lewis x DA) F1 hybrids; and (3) semisyngeneic grafts from rabbit antilymphocyte globulin (ALG)-pretreated Lewis----(Lewis x DA) F1. In group 1, 80% of the grafts were unaffected after 1 month; flow studies showed slight or no impairment of circulation in the graft. In group 2, the recipients developed clinical signs of graft-versus-host disease (GVHD) after 1 week, and at the end of the 2nd week the animals showed signs of severe illness, leading to death due to GVHD. There was also a higher percentage of complications in this group. In group 3, 65% of the animals died. However, 27% showed intact grafts and no signs of GVDH after 1 month, indicating that antibody pretreatment of the donor may successfully prevent GVHD SBT.
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| 38. |
- Wanders, A., et al.
(author)
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Effect of LS-2616 on the graft protection achieved by cyclosporin A, prednisolone, and 15-deoxyspergualin in heart-transplanted rats
- 1992
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In: Transpl Int. ; 5 Suppl 1, s. S462-3
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Journal article (peer-reviewed)abstract
- The immunostimulator LS-2616 abolishes the effect of cyclosporin A in a rat cardiac transplantation model. The present paper compares the characteristics of rejection obtained under different immunosuppressive regimens with and without additional LS-2616 application in the same model. Cyclosporin A (CyA, 10 mg/kg daily), prednisolone (15 mg/kg daily), or 15-deoxyspergualin (2, 5, or 10 mg/kg daily), all given from the day of transplantation until day 9, protected the grafts during the treatment period. The addition of LS-2616 (160 mg/kg, day -1 until stop) resulted in a total abrogation of the immunosuppressive effect of CyA and prednisolone. However, LS-2616 could only partially or not at all reverse the effect of 15-deoxyspergualine. These results show a certain drug selectivity of LS-2616 in promoting rejection of immunosuppressed allografts. Further studies with LS-2616 may be of benefit in evaluating the mode of action of different immunosuppressive compounds and, thus, contribute to finding more effective antirejection therapies.
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| 42. |
- Akyürek, L M, et al.
(author)
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Tolerance induction ameliorates allograft vasculopathy in rat aortic transplants. Influence of Fas-mediated apoptosis.
- 1998
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In: The Journal of clinical investigation. - 0021-9738. ; 101:12, s. 2889-99
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Journal article (peer-reviewed)abstract
- Based on successful induction of donor-specific unresponsiveness by alloantigenic stimulation in several animal models of acute rejection, we hypothesized that similar immune manipulations would also inhibit the evolution of chronic rejection and transplant vasculopathy. To induce immune tolerance, DA rats received a PVG heart allograft and were immunosuppressed with cyclosporine for 30 d. At day 100 the animals were challenged with a PVG aortic allograft after either 1 or 18 h of cold ischemia. 8 wk after the aortic transplantation, the grafts were investigated for morphological changes, infiltrating cells, apoptosis, and Fas-Fas ligand expression. Control allografts showed advanced transplant arteriosclerosis, whereas tolerance-induced aortic allografts displayed reduced neointimal formation, less medial atrophy, fewer apoptotic cells, and fewer Fas- and FasL-expressing cells. Prolonged ischemic storage time did not profoundly alter the morphological changes of the allografts. Fas expression was found in T cells, macrophages, vascular smooth muscle cells, and endothelial cells, whereas FasL was expressed mainly by T cells and macrophages. FasL mRNA expression was evident throughout the entire allograft wall. In conclusion, induction of allospecific tolerance can effectively prevent transplant arteriosclerosis. Cold ischemia damage does not abrogate the beneficial effect of tolerance, but creates a separate identity of mainly endothelial lesions. Furthermore, Fas-mediated apoptosis appears to be involved in the pathological lesions seen in chronic rejection.
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