Hearts from alpha1,3-galactosyltransferase knockout pigs (GalT-KO, n = 8) were transplanted heterotopically into baboons using an anti-CD154 monoclonal antibody-based regimen. The elimination of the galactose-alpha1,3-galactose epitope prevented hyperacute rejection and extended survival of pig hearts in baboons for 2-6 months (median, 78 d); the predominant lesion associated with graft failure was a thrombotic microangiopathy, with resulting ischemic injury. There were no infectious complications directly related to the immunosuppressive regimen. The transplantation of hearts from GalT-KO pigs increased graft survival over previous studies.

The use of animal organs could potentially alleviate the critical worldwide shortage of donor organs for clinical transplantation. Because of the strong immune response to xenografts, success will probably depend upon new strategies of immune suppression and induction of tolerance. Here we report our initial results using alpha-1,3-galactosyltransferase knockout (GalT-KO) donors and a tolerance induction approach. We have achieved life-supporting pig-to-baboon renal xenograft survivals of up to 83 d with normal creatinine levels.

It remains to be established whether TM is related to a very low level of natural preformed or T-cell-induced antibody deposition on the graft, inducing endothelial activation and injury, or to molecular incompatibilities in the coagulation mechanisms between pig and baboon, or to both. However, function of a pig organ in a baboon for a period approaching six months, which has not been reported previously, lends encouragement that the barriers to xenotransplantation will eventually be overcome.

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In conclusion, despite the absence of the Gal epitope, acute and chronic antibody and cell-mediated rejection developed in grafts, maintained by chronic immunosupression, presumably due to de novo responses to non-Gal antigens.

Situs solitus refers to the normal arrangement of body organs. Situs inversus totalis is a complete mirror image or reverse isomeric form of the thoracic and abdominal viscera. Any arrangement of organs between these two extremes is designated by heterotaxia. Several patterns of vascular and visceral abnormalities are associated with heterotaxia, and two loosely defined syndromes of splenic anomalies (asplenia and polysplenia) are most common. We present the case of a 71-year-old woman with situs inversus totalis and polysplenia syndrome who developed synchronous double cancer originating from the stomach and rectum. Abdominal manifestations were situs inversus totalis combined with multiple lobulated spleen, azygous continuation of the interrupted inferior vena cava, direct drainage of hepatic vein to left atrium, preduodenal portal vein, short pancreas, incomplete rotation of the colon, and malrotation of the intestine. Histologically, gastric cancer was diagnosed as papillary adenocarcinoma and rectal cancer, as moderately differentiated adenocarcinoma. The patient was successfully treated with total gastrectomy for gastric cancer and low-anterior resection of the rectum for rectal cancer.

This is the first demonstration of the long-term acceptance of fully MHC-mismatched cardiac allografts in large animals.

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