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  • 1
    ISSN: 1432-1440
    Keywords: Key words BB rat ; Islet transplantation ; Rejection ; Disease recurrence ; Immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Grafting autoimmune-diabetic recipients with allogeneic islets, graft rejection and disease recurrence as major problems of reaching indefinite survival and tolerance induction have to be solved. Anti-CD25 and anti-CD4 monoclonal antibodies were successfully used after allogeneic islet transplantation in experimentally diabetic rats. A temporary anti-CD25 therapy also prevented disease recurrence in autoimmune-diabetic BB rats, while this was not yet reported for an anti-CD4 treatment. In autoimmune-diabetic NOD mice disease recurrence can be successfully treated using an anti-CD4 monoclonal antibody. We, therefore, compared the efficacy of a short-term anti-CD25 and anti-CD4 treatment regarding the prevention of allograft rejection and disease recurrence in autoimmune-diabetic BB/OK rats. Both monoclonal antibodies were combined with low doses of Cyclosporin A. Untreated BB/OK rats relapsed into hyperglycaemia within 3 weeks independent of the islet donor, LEW.1A, LEW.1BB/OK or BB/OK rats. However, after grafting MHC-identical allogeneic (LEW.1BB/OK) or syngeneic (BB/OK) islets we observed about 30% spontaneous acceptance. Both the anti-CD25 and anti-CD4 therapy significantly prolonged the survival of allogeneic grafted islets. After MHC-identical allogeneic and syngeneic islet transplantation the temporary immunotherapy increased the proportion of permanent acceptors to 63% and 75%, respectively. The efficacy of both treatment strategies in prolonging allograft survival and prevention of disease recurrence was identical. In summary, anti-CD25 as well as anti-CD4 therapy prevented autoimmune but not allogeneic islet destruction in autoimmune-diabetic BB/OK rats. In conclusion, targeting different immune cells by monoclonal antibodies with different specificities can lead to very similar results with respect to an interruption of allograft rejection and autoimmune reaction.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 207 (1983), S. 69-77 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The cellular localization and regional distribution of insulin-and glucagonlike substance, C-peptide-like immunoreactivity, thiol:protein disulphide oxidoreductase, TPO (E.C.1.8.4.2.), and insulin/glucagon-specific proteinase, ISP (E.C.3.4.22.-), are studied in the CNS of man, adult and juvenile rats, mice, tortoises, and frogs by use of immunohistochemistry. Furthermore, the content of immunoreactive insulin, glucagon, and C-peptide was estimated in human cadaver brains by radioimmunoassay.It could be shown that insulinlike immunoreactive material is widely distributed in the human brain and the CNS of juvenile rats as well as in mice, whereas in the CNS of adult rats and nonmammalian animals (frog, tortoises) the polypeptide is restricted to a few nerve cell populations. C-peptide immunoreactivity was demonstrated in human CNS in the same nerve cells as insulin.By use of two different glucagon-antisera it was revealed that gut-type glucagon occurs in many nerve cells of human and mouse brains, as well as in the CNS of juvenile rats. On the other hand, pancreas-type glucagon was less widely distributed in the human brain and nearly not detectable in the CNS of mice and rats.With the exception of neurosecretory nerve cells, there was a high degree of coincidence between the localization of insulin and TPO. The immunoreaction against the ISP antiserum was weak, but correlated well with the distribution of insulin-immunoreactivity.The occurrence of TPO and ISP in the brain demonstrates the ability of nervous tissue to degrade insulin and glucagon. By radioimmunoassay it was established that human brain contains insulin, glucagon and C-peptide at concentrations that exceed blood levels.We conclude from our data that, at least in part, cerebral insulin and glucagon are products of the brain itself.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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