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C Ricordi

Publications and source records attributed to C Ricordi.

At least 217 records · Page 12Linked to original sources
PubMed1993

Chimerism after liver transplantation for type IV glycogen storage disease and type 1 Gaucher's disease.

BACKGROUND: Liver transplantation for type IV glycogen storage disease (branching-enzyme deficiency) results in the resorption of extrahepatic deposits of amylopectin, but the mechanism of resorption is not known. METHODS: We studied two patients with type IV glycogen storage disease 37 and 91 months after liver transplantation and a third patient with lysosomal glucocerebrosidase deficiency (type 1 Gaucher's disease), in whom tissue glucocerebroside deposition had decreased 26 months after liver replacement, to determine whether the migration of cells from the allograft (microchimerism) could explain the improved metabolism of enzyme-deficient tissues in the recipient. Samples of blood and biopsy specimens of the skin, lymph nodes, heart, bone marrow, or intestine were examined immunocytochemically with the use of donor-specific monoclonal anti-HLA antibodies and the polymerase chain reaction, with preliminary amplification specific to donor alleles of the gene for the beta chain of HLA-DR molecules, followed by hybridization with allele-specific oligonucleotide probes. RESULTS: Histopathological examination revealed that the cardiac deposits of amylopectin in the patients with glycogen storage disease and the lymph-node deposits of glucocerebroside in the patient with Gaucher's disease were dramatically reduced after transplantation. Immunocytochemical analysis showed cells containing the HLA phenotypes of the donor in the heart and skin of the patients with glycogen storage disease and in the lymph nodes, but not the skin, of the patient with Gaucher's disease. Polymerase-chain-reaction analysis demonstrated donor HLA-DR DNA in the heart of both patients with glycogen storage disease, in the skin of one of them, and in the skin, intestine, blood, and bone marrow of the patient with Gaucher's disease. CONCLUSIONS: Systemic microchimerism occurs after liver allotransplantation and can ameliorate pancellular enzyme deficiencies.

Adult↗
PubMed1993

Donor cell chimerism permitted by immunosuppressive drugs: a new view of organ transplantation.

One line of thought in organ transplantation feels that immunosuppressive drugs can lead to tolerance induction by allowing a previously unrecognized common mechanism of cell migration and microchimerism to occur, persist, and in some cases, become drug independent. It has been recognized that there is a spectrum of susceptibility of different organs to cellular rejection and that the variable ability of these organs to induce donor-specific nonreactivity reflects their comparative content of migratory leukocytes. Here, Thomas Starzl and colleagues discuss how many of the enigmas of transplantation immunology can be explained by this chimerism.

Animals↗
PubMed1993

Donor cell chimerism permitted by immunosuppressive drugs: a new view of organ transplantation.

One line of thought in organ transplantation feels that immunosuppressive drugs can lead to tolerance induction by allowing a previously unrecognized common mechanism of cell migration and microchimerism to occur, persist, and in some cases, become drug independent. It has been recognized that there is a spectrum of susceptibility of different organs to cellular rejection and that the variable ability of these organs to induce donor-specific nonreactivity reflects their comparative content of migratory leukocytes. Here, Thomas Starzl and colleagues discuss how many of the enigmas of transplantation immunology can be explained by this chimerism.

Animals↗
PubMed1993

Frequency of kidney rejection in diabetic patients undergoing simultaneous kidney and pancreatic islet cell transplantation.

An increased frequency of kidney rejection has been reported in diabetic patients who have simultaneous pancreas and kidney transplantation compared with patients who have a kidney transplant alone. Kidney graft outcome is similar in the two groups. The mechanism for increased kidney graft rejection with a simultaneous pancreas graft is not clear. It is ascribed to the immunogenicity of the exocrine pancreas that initiates migration of activated cells from the peripheral blood that are entrapped in the kidney. Since the volume of the transplanted tissue is less in islet transplantation (usually < 2 ml) than in pancreas transplantation, one might not expect an increased frequency of kidney rejection in islet cell recipients. We looked at biopsy-proven kidney rejection episodes in patients who had combined kidney and islet transplants and compared this with the frequency of rejection in diabetic and nondiabetic patients who underwent a kidney transplant alone under the same immunosuppression. Diabetic patients who had kidney islet transplants (n = 9) had a higher frequency of rejection (100%) compared with diabetic patients (n = 107, 55.1%) and nondiabetic patients (n = 327, 65%) who had a kidney transplant alone. The 1-year graft and patient survival rates were not different among the groups. Although the number of patients is small, it would appear that transplantation of a low volume of islet cells with high purity can lead to an increased frequency of kidney rejection. This is unlikely to be explained solely on the basis of fewer antigen matches in these recipients but may reflect the inherent immunogenicity of the purified islet preparations. Alternatively, there may be an effect of their direct infusion into the portal vein.

Adrenal Cortex Hormones↗
PubMed1993

Chimerism and donor-specific nonreactivity 27 to 29 years after kidney allotransplantation.

Chimerism was demonstrated with immunocytochemical and/or polymerase chain reaction techniques in kidney allografts and in the native skin, lymph nodes, or blood of 5 of 5 patients who received continuously functioning renal transplants from 1 or 2 haplotype HLA mismatched consanguineous donors (4 parents, 1 aunt) 27-29 years ago. In the 4 cases where the kidney donor still was alive to provide stimulator lymphocytes for testing, these provoked no (n = 2) or modest (n = 2) MLR in contrast to vigorous MLR to third party lymphocytes. In all 4 cases, the donor cells failed to generate in vitro cytotoxic effector cells (cell-mediated lymphocytotoxicity). These findings are in accord with the hypothesis that cell migration, repopulation, and chimerism are seminal events that define graft acceptance and ultimately can lead to acquired donor-specific nonresponsiveness (tolerance).

Adult↗
PubMed1993

Nicotinamide is a potent inducer of endocrine differentiation in cultured human fetal pancreatic cells.

The effects of nicotinamide (NIC) on human fetal and adult endocrine pancreatic cells were studied in tissue culture. Treatment of the fetal cells with 10 mM NIC resulted in a twofold increase in DNA content and a threefold increase in insulin content. This was associated with the development of beta cell outgrowths from undifferentiated epithelial cell clusters and an increase in the expression of the insulin, glucagon, and somatostatin genes. DNA synthesis was stimulated only in the undifferentiated cells. Half-maximal doses for the insulinotropic and mitogenic effects of NIC were 5-10 and 1-2 mM, respectively. Islet-like cell clusters cultured with NIC responded to glucose stimulation with a biphasic increase in insulin release (fourfold peak), whereas control cells were unresponsive to glucose. Both control and NIC-treated cells developed into functional islet tissue after transplantation into athymic nude mice. As compared with adult islets, the insulinotropic action of NIC could only be demonstrated in the fetal cells. Our results indicate that NIC induces differentiation and maturation of human fetal pancreatic islet cells. This model should be useful for the study of molecular mechanisms involved in beta cell development.

Adult↗
PubMed1993

The effect of prednisone on pancreatic islet autografts in dogs.

Prednisone was shown to induce hyperglycemia in dogs submitted to total pancreatectomy and pancreatic islet autotransplantation. The hyperglycemia caused by a 10-day course of prednisone, 1 mg/kg/day, starting on the day of operation was reversible within 1 week after steroid discontinuance. Three weeks after prednisone was stopped, there was no detectable adverse effect on glucose homeostasis as judged by fasting blood sugar levels and intravenous glucose tolerance test results. Four months after transplantation, glucose disappearance was delayed in animals previously treated with the prednisone compared with those previously treated with prednisone plus insulin or control animals. This was accompanied by lower insulin values on intravenous glucose tolerance testing and suggests a long-term subtle effect on islet function. The mechanism of the steroid effect is not known. However, this model could be used to test the diabetogenicity of other immunosuppressive agents including cyclosporine, FK 506, and azathioprine.

Animals↗
PubMed1992

Systemic chimerism in human female recipients of male livers.

We have previously reported data from clinical and laboratory animal observations which suggest that organ tolerance after transplantation depends on a state of balanced lymphodendritic cell chimerism between the host and donor graft. We have sought further evidence to support this hypothesis by investigating HLA-mismatched liver allograft recipients. 9 of 9 female recipients of livers from male donors had chimerism in their allografts and extrahepatic tissues, according to in-situ hybridisation and molecular techniques 10 to 19 years posttransplantation. In 8 women with good graft function, evidence of the Y chromosome was found in the blood (6/8), skin (8/8), and lymph nodes (7/8). A ninth patient whose transplant failed after 12 years from recurrent chronic viral hepatitis had chimerism in her lymph nodes, skin, jejunum, and aorta at the time of retransplantation. Although cell migration is thought to take place after all types of transplantation, the large population of migratory cells in, and the extent of their seeding from, hepatic grafts may explain the privileged tolerogenicity of the liver compared with other organs.

ABO Blood-Group System↗