The aim of the present study was to assess the survival of adult porcine islets transplanted into baboons receiving either (I) conventional triple drug immunosuppressive therapy or (2) a non-myeloablative regimen and an anti-CD154 monoclonal antibody (mAb) aimed at tolerance-induction. Group 1 baboons (n = 3) were pancreatectomized prior to intraportal injection of 10,000 porcine islet equivalents (IE)/kg and immunosuppressed with anti-thymocyte globulin (ATG), cyclosporine and azathioprine. In Group 2 (n = 2), non-pancreatectomized baboons underwent induction therapy with whole body and thymic irradiation, and ATG. Extracorporeal immunoadsorption (EIA) of anti-Galalpha1,3Gal (Gal) antibody was carried out. Maintenance therapy was with cobra venom factor, cyclosporine. mycophenolate mofetil, methylprednisolone and anti-CD154 mAb. Porcine islets were injected intraportally (14,000 and 32,000 IE/kg, respectively) and high-dose pig mobilized peripheral blood progenitor cells (3 x 10(10) cells/kg) were infused into a systemic vein. Porcine islets were also implanted in the sternomastoid muscle to facilitate subsequent biopsies. In both groups. porcine C-peptide was measured, and histological examination of liver or sternomastoid muscle biopsies was performed at regular intervals. In Group 1, total pancreatectomy reduccd human C-peptide to < 0.1 ng/ml and induced insulin-requiring diabetes. The transplantation of porcine islets was followed by normalization of glycemia for 15-24 h. Porcine C-peptide was detected only transiently immediately after porcine islet injection (maximum 0.12 ng/ml). Histological examination of liver biopsies taken between days 2 and 19 did not reveal viable islets, but necrotic cell structures with mononuclear cell infiltrates were identified in portal venules. In Group 2, injection of porcine islets into non-pancreatectomized recipients induced a transient hypoglycemia (2-4 h) requiring concentrated intravenous dextrose administration. Porcine C-peptide was detectable for 5 and 3 days (maximum 2.8 and 1.0 ng/ml), respectively. Baboon #4 died on day 12 from small bowel intussusception. Liver and sternomastoid muscle biopsies showed well-preserved porcine islets, staining positive for insulin and glucacon, without signs of rejection. In baboon #5, viable islets were detected in the sternomastoid muscle biopsy on day 14, but not on day 28 or thereafter. A progressive mononuclear cell and macrophage infiltration was seen in the biopsies. In conclusion, conventional immunosuppression allowed survival of porcine islets in baboons for < 24 h. The non-myeloablative regimen prolonged survival of porcine islets for > 14 days. However, despite depletion of T cells, anti-Gal antibody and complement, and CD154-hlockade, porcine islets were rejected by day 28. These results suggest that powerful innate immune responses are involved in rejection of discordant xenogencic islets.

CTG triplet expansion was studied in lymphocytes and thyroid tissue in a patient with myotonic dystrophy (DM) and associated thyroid nodular disease. An approximately 7 fold larger amplification was found in abnormal thyroid tissue compared to lymphocytes, suggesting that anomalies in the putative DM kinase gene might contribute to thyroid dysfunction.

The International Pancreas Transplant Registry data base was analyzed for the effect of HLA and mismatching on pancreas survival rate. Typing data was available for both donor and recipient at the A, B and DR loci in 524 of 855 cadaver cases reported since 1982 and in 37 related cases. For cadaver cases, the 1-year functional survival rates for grafts mismatched at less than or equal to 3 (N = 163) versus greater than or equal to 4 (N = 361) A, B and DR antigens were 49% versus 39% (P = 0.121); for technically successful (TS) cases the rates were 66% (N = 123) versus 54% (N = 257) (P = 0.038). An effect was seen at A, B and DR loci, but the differences were not significant when considered separately. THe analysis of TS related donor transplants showed a 1-year graft survival rate of 89% for HLA mismatched donors (N = 11) and of 80% for HLA identical donors (N = 11). The survival rate of the latter is significantly higher (P = 0.046) than that of the TS cadaver donor transplants (59% at 1 year, N = 361). The data suggest that the results of pancreas transplantation will be improved by minimizing HLA mismatches. However, a reanalysis with a more complete data base is needed before firm conclusions can be drawn.

Annals of the New York Academy of SciencesVolume 475, Issue 1 p. 359-360 Aberrant Expression of HLA-DR Determinants on Human Thyroid Cells Treated with Phytohemagglutinin and γ-Interferon and on Human Melanoma Cells Demonstration with a Binding Assay Using a New Potent 125I-Monoclonal Antibody against the HLA-DR β-Chain (MAb 03-D7) P. DE MEYTS, P. DE MEYTS Hormone and Metabolic Research UnitSearch for more papers by this authorS. HALLEZ, S. HALLEZ Hormone and Metabolic Research UnitSearch for more papers by this authorJ. L. GU, J. L. GU Hormone and Metabolic Research UnitSearch for more papers by this authorM. MERCHEZ, M. MERCHEZ Hormone and Metabolic Research UnitSearch for more papers by this authorI. ECONOMIDIS, I. ECONOMIDIS Hormone and Metabolic Research UnitSearch for more papers by this authorG. G. ROUSSEAU, G. G. ROUSSEAU Hormone and Metabolic Research UnitSearch for more papers by this authorJ. van SNICK, J. van SNICK Experimental Medicine Unit International Institute of Cellular and Molecular Pathology Avenue Hippocrate, 75 B-1200, Brussels, BelgiumSearch for more papers by this authorC. SPINEL, C. SPINEL Department of HistologySearch for more papers by this authorJ. P. SQUIFFLET, J. P. SQUIFFLET Department of Experimental SurgerySearch for more papers by this authorA. M. RAVOET, A. M. RAVOET Department of Hematology Catholic University of Louvain Medical School B-1200 Brussels, BelgiumSearch for more papers by this authorM. de BRUYERE, M. de BRUYERE Department of Hematology Catholic University of Louvain Medical School B-1200 Brussels, BelgiumSearch for more papers by this authorK. WILLARD, K. WILLARD Ludwig Cancer Institute B-1200 Brussels, BelgiumSearch for more papers by this authorF. VESSIERE, F. VESSIERE Ludwig Cancer Institute B-1200 Brussels, BelgiumSearch for more papers by this authorC. LEMOINE, C. LEMOINE Ludwig Cancer Institute B-1200 Brussels, BelgiumSearch for more papers by this authorT. BOON, T. BOON Ludwig Cancer Institute B-1200 Brussels, BelgiumSearch for more papers by this authorH. TOYODA, H. TOYODA Department of Molecular GeneticsSearch for more papers by this authorF. CHEN, F. CHEN Department of Immunology Beckman Research Institute of the City of Hope Duarte, California 91010Search for more papers by this authorJ. SHIVELY, J. SHIVELY Department of Immunology Beckman Research Institute of the City of Hope Duarte, California 91010Search for more papers by this author P. DE MEYTS, P. DE MEYTS Hormone and Metabolic Research UnitSearch for more papers by this authorS. HALLEZ, S. HALLEZ Hormone and Metabolic Research UnitSearch for more papers by this authorJ. L. GU, J. L. GU Hormone and Metabolic Research UnitSearch for more papers by this authorM. MERCHEZ, M. MERCHEZ Hormone and Metabolic Research UnitSearch for more papers by this authorI. ECONOMIDIS, I. ECONOMIDIS Hormone and Metabolic Research UnitSearch for more papers by this authorG. G. ROUSSEAU, G. G. ROUSSEAU Hormone and Metabolic Research UnitSearch for more papers by this authorJ. van SNICK, J. van SNICK Experimental Medicine Unit International Institute of Cellular and Molecular Pathology Avenue Hippocrate, 75 B-1200, Brussels, BelgiumSearch for more papers by this authorC. SPINEL, C. SPINEL Department of HistologySearch for more papers by this authorJ. P. SQUIFFLET, J. P. SQUIFFLET Department of Experimental SurgerySearch for more papers by this authorA. M. RAVOET, A. M. RAVOET Department of Hematology Catholic University of Louvain Medical School B-1200 Brussels, BelgiumSearch for more papers by this authorM. de BRUYERE, M. de BRUYERE Department of Hematology Catholic University of Louvain Medical School B-1200 Brussels, BelgiumSearch for more papers by this authorK. WILLARD, K. WILLARD Ludwig Cancer Institute B-1200 Brussels, BelgiumSearch for more papers by this authorF. VESSIERE, F. VESSIERE Ludwig Cancer Institute B-1200 Brussels, BelgiumSearch for more papers by this authorC. LEMOINE, C. LEMOINE Ludwig Cancer Institute B-1200 Brussels, BelgiumSearch for more papers by this authorT. BOON, T. BOON Ludwig Cancer Institute B-1200 Brussels, BelgiumSearch for more papers by this authorH. TOYODA, H. TOYODA Department of Molecular GeneticsSearch for more papers by this authorF. CHEN, F. CHEN Department of Immunology Beckman Research Institute of the City of Hope Duarte, California 91010Search for more papers by this authorJ. SHIVELY, J. SHIVELY Department of Immunology Beckman Research Institute of the City of Hope Duarte, California 91010Search for more papers by this author First published: July 1986 https://doi.org/10.1111/j.1749-6632.1986.tb20893.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume475, Issue1Autoimmunity: Experimental and Clinical AspectsJuly 1986Pages 359-360 RelatedInformation