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Biomedical subjects

L J Dumble

Publications and source records attributed to L J Dumble.

At least 19 recordsLinked to original sources
PubMed1993

Variable rejection patterns of cultured keratinocyte allografts in the rabbit.

There are many conflicting reports on the survival of cultured keratinocyte allografts (CKAs). Studies were performed in the rabbit model to elucidate further the fate of CKAs. Of 24 CKAs, 7 were identified as technical failures, 13 displayed classical macroscopic evidence of rejection with a prolonged mean survival time of 2.8 days, compared to non-cultured allograft controls (p < 0.01), and 4 failed to display typical macroscopic evidence of rejection. Furthermore, the time to eventual wound healing of the classically rejected CKAs were delayed by 6.0 days (p < 0.0001), compared to identical non-grafted control wounds.

Animals↗
PubMed1993

15 AU81, a prostacyclin analog, potentiates immunosuppression and mitigates renal injury due to cyclosporine.

15 AU81, a synthetic prostacyclin analog, inhibits human mixed lymphocyte culture responses in a dose-dependent manner at concentrations within a range [0.1 to 10.0 micrograms/ml] similar to that of cyclosporine, methylprednisolone, antilymphocyte serum, and prostaglandin E1 and E2 analogs. Using the median-effect analysis to dissect immunosuppressive interactions, 15 AU81 and cyclosporine were shown to produce synergistic effects on human peripheral blood lymphocyte activation upon phytohemagglutinin or anti-CD3 monoclonal antibody stimulation. In vivo, 15 AU81 potentiated the effect of cyclosporine to prolong the survival of rabbit renal allografts using concentrations of each agent that were individually ineffective. Furthermore, addition of 15 AU81 mitigated functional damage of rabbit kidneys due to high-dose cyclosporine therapy. These observations suggest that the addition of 15 AU81 may broaden the therapeutic window of cyclosporine by potentiating immunosuppression and mitigating nephrotoxic effects.

Animals↗
PubMed1990

In vitro culture of disaggregated rabbit keratinocytes.

A technique is described for the culture of disaggregated rabbit keratinocytes and the production of confluent sheets of immunologically pure keratinocytes suitable for use in transplantation studies. The benefits of various feeder layers, nutrients and growth hormones were examined by the use of paired controls. The ability of the cultured keratinocyte sheets to be removed from the culture vessel intact and survive as viable autografts was demonstrated, thus establishing a new animal model for the investigation of allograft rejection responses to cultured keratinocytes. The benefits of using the rabbit model for such studies and the advantages of this culture technique over a previously described method of rabbit keratinocyte cell culture are discussed.

Animals↗
PubMed1990

The immunosuppressive properties of new oral prostaglandin E1 analogs.

Prostaglandins play an important role in cell-mediated immune responses. Their clinical use has been limited by poor oral bioavailability, short half-lives, and significant toxicity profiles. We studied the immunosuppressive properties of new, synthetic, prostaglandin E1 (PGE1) methyl ester analogs (misoprostol, enisoprost) with oral bioavailability using an allogeneic in vitro immunoassay. Our results show that the PGE1 analogs suppress alloproliferative responses and supplement the immunosuppressive activity of cyclosporine and methylprednisolone. Moreover, we demonstrate that addition of recombinant interleukin-2 to the PGE1 analogs restores alloimmune responsiveness and the expression of surface class II antigen and IL-2 receptors on responder lymphocytes. These studies, together with preliminary in vivo data in rodents and man, suggest that the new synthetic oral PGE1 analogs may provide therapeutic efficacy in clinical transplantation and a variety of immunologically mediated diseases.

Administration, Oral↗
PubMed1990

T suppressor cells induced by transfusions and cyclosporine. Studies in the murine cardiac allograft model.

Pregraft transfusion combined with immunosuppression at the time of grafting improves the survival of clinical and experimental allografts. The mechanisms responsible for this effect were investigated in the murine model of cardiac transplantation, combining transfusions 7 to 30 days prior to transplantation with cyclosporine 100 mg/kg, 7 to 20 days pregraft or on days 0, 4, and 6 after grafting. Pregraft DST, third-party blood, and CsA all improved graft survival in the BALB/c-to-CBA donor-recipient combination. In animals treated with DST at 14 days pregrafting, 4/9 grafts survived for greater than 100 days. In those given C57BL/6 blood, or CsA on days 0, 4, 6 postgraft, 1/9 grafts survived for greater than 100 days. When 10(7) spleen cells from DST-treated CBA mice with long-surviving BALB/c heart grafts were transferred to naive CBA mice that then received a BALB/c heart 24 hr later, the transferred cells prolonged graft survival, with all grafts functioning at greater than 40 days, and 4/7 at greater than 100 days. Selective removal of T cells from the spleen cell population prior to transfer showed that L3T4+ T cells, but not Ly-2+ T cells, were required to maintain BALB/c allografts. Combining a short course of CsA with DST was more effective than either treatment alone. The most effective combined treatment was DST at day -14 with 100 mg/kg CsA given on days 0, 4, and 6 postgrafting (8/10 grafts survived greater than 100 days). This treatment also induced splenic suppressor T cells of the L3T4+ Ly-2- phenotype. These results clearly show that L3T4+ splenic T suppressor cells are induced by donor-specific blood transfusion with or without CsA treatment, and that these cells play a role in maintaining long-term tolerance to allografts in the mouse heart transplant model.

Animals↗
PubMed1990

Model of orthotopic renal transplantation in the rabbit.

A microsurgical method of orthotopic renal allotransplantation in the rabbit is described, and the results of 179 consecutive procedures are presented. There were 10 (5.5%) deaths within 1 week of transplantation. Early complications included vascular thrombosis (4.4%), and obstruction (6.7%) and fistula formation (0.6%) at the uretero-ureteric anastomosis. This method of end-to-end vascular and ureteric anastomoses is straightforward and, in contrast to other models, does not require occlusion of the recipient inferior vena cava or aorta, use of a long segment of donor ureter, or operation on the recipient bladder.

Anastomosis, Surgical↗