Please use this identifier to cite or link to this item: https://olympias.lib.uoi.gr/jspui/handle/123456789/19704
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dc.contributor.authorShapiro, A. M.en
dc.contributor.authorHao, E. G.en
dc.contributor.authorLakey, J. R.en
dc.contributor.authorYakimets, W. J.en
dc.contributor.authorChurchill, T. A.en
dc.contributor.authorMitlianga, P. G.en
dc.contributor.authorPapadopoulos, G. K.en
dc.contributor.authorElliott, J. F.en
dc.contributor.authorRajotte, R. V.en
dc.contributor.authorKneteman, N. M.en
dc.date.accessioned2015-11-24T19:01:32Z-
dc.date.available2015-11-24T19:01:32Z-
dc.identifier.issn0041-1337-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/19704-
dc.rightsDefault Licence-
dc.subjectAnimalsen
dc.subjectBiological Markers/blooden
dc.subjectDiabetes Mellitus, Experimental/physiopathology/surgeryen
dc.subjectDogsen
dc.subjectGlucose Tolerance Testen
dc.subjectGlutamate Decarboxylase/blooden
dc.subjectGraft Rejection/blood/*diagnosisen
dc.subjectIslets of Langerhans/physiopathologyen
dc.subject*Islets of Langerhans Transplantationen
dc.subjectIsoenzymes/blooden
dc.subjectMaleen
dc.subjectRatsen
dc.subjectRats, Inbred Lewen
dc.subjectRats, Inbred WFen
dc.subjectTransplantation, Homologousen
dc.subjectbeta-Galactosidase/blooden
dc.titleNovel approaches toward early diagnosis of islet allograft rejectionen
heal.typejournalArticle-
heal.type.enJournal articleen
heal.type.elΆρθρο Περιοδικούel
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/11455247-
heal.languageen-
heal.accesscampus-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.publicationDate2001-
heal.abstractBACKGROUND: The inability to diagnose early rejection of an islet allograft has previously proved to be a major impediment to progress in clinical islet transplantation. The need to detect early rejection will become even more relevant as new tolerance-inducing protocols are evaluated in the clinic. We explored three novel approaches toward development of early diagnostic markers of islet rejection after islet allotransplantation. METHODS: (a) Canine islet allograft transplant recipients were immunosuppressed for 1 month, then therapy was withdrawn. Serum glutamic acid decarboxylase antigen (GAD65), an endogenous islet protein, was monitored daily with a CO2 release assay. (b) Rodent islets were genetically engineered to express a unique foreign protein (beta-galactosidase) by using adenoviral vectors, and after allograft transplantation, the viral-specific protein was measured in serum using optical luminescence. (c) Rodents receiving islet allografts were immunosuppressed temporarily, and daily glucose tolerance tests were followed until graft failure occurred. RESULTS: (a) Although serum monitoring of GAD65 antigen demonstrated elevated levels preceding loss of graft function in preliminary studies, the effect was not reproducible in all animals. (b) Genetically engineered rodent islets demonstrated normal insulin kinetics in vitro (insulin stimulation index 2.57+/-0.2 vs. 2.95+/-0.3 for control islets, P=ns), and purified viral protein products had a stable half-life of 8 hr in vivo. After islet allotransplantation, there were two peak elevations in serum viral proteins, confirming that an intra-islet "sentinel signal" could be detected serologically during acute rejection. There was no lead-time ahead of hyperglycemia, however. (c) Daily sequential intravenous glucose tolerance (IVGT) tests demonstrated evidence of allograft dysfunction (decline in KG) with a 2-day lead time to hyperglycemia (2.58+/-0.3 vs. 1.63+/-0.2%/min, respectively, P<0.001), with an accuracy of 89%, sensitivity of 78%, and specificity of 95%. CONCLUSIONS: Of the three diagnostic tests, metabolic assessment with an abbreviated IVGT was the most effective method of demonstrating early islet dysfunction due to rejection.en
heal.journalNameTransplantationen
heal.journalTypepeer-reviewed-
heal.fullTextAvailabilityTRUE-
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά) - ΙΑΤ

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