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Biomedical subjects

Y Mullen

Publications and source records attributed to Y Mullen.

122 records · Page 7Linked to original sources

Characteristics of specific unresponsiveness toward kidney and skin allografts in adult rats inoculated at birth with allogenic bone marrow or kidney cells across a strong H-1 barrier.

Specific unresponsiveness inducible in newborn Lewis (Le) rats by injection of bone marrow or kidney cells from (Bu x Le)F1 hybrids was tested in adults by allografting of skin or kidneys from strongly incompatible Buffalo (Bu) strain donors. High doses of bone marrow cells (10(7) or more) proved quite effective in procuring indefinite survival of subsequent Bu kidney allografts, but not Bu skin allografts. Kidney allografts remained fully functional without modulation of their inherent immunogenicity regardless whether skin allografts were acutely rejected before or after kidney grafting on bone marrow-tolerant recipients. Lower doses of bone marrow cells were either near threshold for induction of specific Bu kidney allograft tolerance (5 x 10(6)) or, conversely, led to increased immunity(1-5 x 106). A strikingly different pattern of reactivity was found in adult Le recipients of Bu skin allografts as shown by only a moderate, but stepwise increase in survival times as a function of increasing allogeneic cell dosage at birth. Allogeneic kidney cells at all doses were surprisingly ineffective in inducing tolerance of either kidney or skin allografts, so the existence of kidney-specific transplantation antigens remains problematical. Lymphocytes from kidney allograft-tolerant recipients showed much reduced but still significant antidonor activity in several tests of cell-mediated immunity in vitro and in vivo. Blocking antibody activity was also demonstrable in these animals. Acquired tolerance (i.e., essential nonreactivity) may not only exist in degrees in either T or B cell pathways but may coexist with specific immunoblocking reactions in a dynamic equilibrium. Instead of tolerance versus enhancement, a new concept of selective specific immunoregulation emerges.

Animals↗

Control of experimental diabetes mellitus in rats by transplantation of fetal pancreases.

Experimental diabetes mellitus in young adult Lewis rats was successfully treated by transplantation of fetal pancreases from syngeneic fetuses. Complete or partial control lasting up to 165 days was achieved in 64 percent of recipients by using two to three pancreases of fetal age (15 to 18(1/2) days) placed under each kidney capsule. Islets of Langerhans without exocrine elements were present in the transplants.

Animals↗

The fasciovascular flap: a new vehicle for islet transplantation.

In order to determine whether pancreatic islets could be neovascularized by a fasciovascular flap (FVP), islet transplant studies were conducted in Lewis rats. Islets from two donors were isolated by collagenase digestion and discontinuous gradient centrifugation on Ficoll. These islets were injected in syngeneic recipients either into random groin SC fat as a control, or into a flap composed of fascia and fat elevated from the groin based on the superficial inferior epigastric vessels. After two wk, islet viability was assessed by histological analysis. The degree of neovascularization of the islet tissue was evaluated with India ink injection through the vascular pedicle. Whereas control islets degenerated and did not show clear signs of neovascularization, FVP-islets showed rich neovascularization and viability as a large sheet of islet clusters. These results have demonstrated that the FVP-flap is a novel recipient site which can support a large quantity of islet tissue. This model constitutes a unique neo-endocrine pancreas flap, which can be subsequently transplanted at will to transfer the established neo-endocrine pancreas to a desired site using microvascular surgical technique.

Adipose Tissue↗

Protection of mouse islet isografts from nonspecific inflammatory damage by recipient treatment with nicotinamide and 15-deoxyspergualin.

The major cause of primary nonfunction of transplanted islets is nonspecific inflammation associated with the transplantation procedures. Using mouse islet isografts, we attempted to prevent graft loss mediated by nonspecific inflammation using recipient treatment with nicotinamide (NA) and 15-deoxyspergualin (DSG). Newborn BALB/c islets, ranging in numbers between 1200 and 1500, were transplanted into syngeneic adult mice made diabetic by intravenous injection of 200 mg/kg streptozotocin. Recipient mice were divided into the following four groups, based on the treatment protocol of NA and DSG: intraperitoneal injection (IP) of normal saline (Group 1), IP injection of 2500 mg/kg NA (Group 2), IP injection of 5 mg/kg DSG (Group 3), and IP injection of NA + DSG (Group 4). Treatment started Day -1 and continued until Day 9 (Day 0 is day of transplantation). Blood and urine glucose, body weight, and intravenous glucose tolerance tests (IV-GTT) were examined after transplantation. Reversal of diabetes, as indicated by normoglycemia and negative urine glucose, was higher in Groups 2 (75%), 3 (50%), and 4 (85.7%), compared to Group 1 (11.1%). Especially in Group 4, the endocrine function and morphology of grafted islets were well preserved as shown by K values of IV-GTT and histological studies. These results suggest the importance of islet protection from irreversible damage by nonspecific inflammation at earlier stages of implantation, and the effectiveness of a short course of treatment with NA and DSG.

Animals↗