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D Araneda

Publications and source records attributed to D Araneda.

At least 37 records · Page 2Linked to original sources
PubMed1991

Improved xenograft survival with continuous infusion deoxyspergualin and RATG.

The critical shortage of available donor organs is the major limit to current allogeneic transplantation. Xenografting has the potential to overcome this difficult problem. Suppressing the vigorous rejection response remains a major obstacle to the clinical application of xenografting, 15-Deoxyspergualin (DOSP), a potent new immunosuppressive agent has been shown to be effective in allogeneic and xenogeneic experimental models. This study tests DOSP in combination with rabbit antithymocyte globulin (RATG) in the hamster-to-rat cardiac xenograft. Results show that combination therapy with DOSP/RATG was superior to treatment with either agent alone (p less than .05). Optimal graft prolongation (20.9 days versus control of 3.1 days, p less than .05) was achieved with combination therapy of RATG and DOSP 2.5 mg/kg day-1 by continuous infusion.

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PubMed1991

Immunobiology of the xenograft response: xenograft rejection in immunodeficient animals.

These studies provide insight into the immunobiology of xenograft rejection. They suggest that xenograft rejection involves T-cell phenomena, although the ability of the nude rat (functionally known to be T-cell deficient) to reject the vascularized xenograft normally is striking and clearly indicates a need for future studies of this phenomenon. These studies strongly suggest a role for NK and K cell-type activity in xenograft rejection, although they also indicate this immune function is only an ancillary one and that xenograft rejection will eventually occur despite deficiencies in these systems. These studies are most provocative in showing a failure of efficiency of skin graft rejection in the purest model of B-cell deficiency, the XID model. Since these results are obtained with the so-called secondarily vascularized xenograft (skin grafts) it is not possible to exclude the role of B-cell and B-cell-associated phenomena in vascularized organ grafts without further studies.

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PubMed1988

Anti-interleukin 2 receptor monoclonal antibodies spare phenotypically distinct T suppressor cells in vivo and exert synergistic biological effects.

The therapeutic efficacies of ART-18, ART-65, and OX-39, mouse antibodies of IgG1 isotype recognizing distinct epitopes of the p55 beta chain of the rat IL-2-R molecule, were probed in LEW rat recipients of (LEW X BN)F1 heterotopic cardiac allografts (acute rejection in untreated hosts occurs within 8 d). A 10-d course with ART-18 prolongs graft survival to approximately 21 d (p less than 0.001). Therapy with ART-65, but not with OX-39, was effective (graft survival approximately 16 and 8 d, respectively). Anti-IL-2-R mAb treatment selectively spared T cells with donor-specific suppressor functions; the CD8+ (OX8+ W3/25-) fraction from ART-18-modified recipients, and primarily the CD4+ (W3/25+ OX8-) subset from ART-65-treated hosts conferred unresponsiveness to naive syngeneic rats after adoptive transfer, increasing test graft survival to approximately 16 and 45 d, respectively. Concomitant administration of ART-18 and ART-65 to recipient animals in relatively low doses exerted a strikingly synergistic effect, with 30% of the transplants surviving indefinitely and 50% undergoing late rejection over 50 d. These studies provide evidence that anti-IL-2-R mAbs selectively spare phenotypically distinct T cells with suppressor functions. The data also suggest that in vivo targeting of functionally different IL-2-R epitopes may produce synergistic biological effects.

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PubMed1988

Synergy between subtherapeutic doses of cyclosporine and immunologic enhancement in rat recipients of cardiac allografts.

We have analyzed the adjunctive effect of subtherapeutic doses of cyclosporine (CsA, 1.5 mg/kg/day x 7 or 14 days) on cardiac allograft survival in actively and passively enhanced rats. This CsA dose, one tenth of the effective dose, when administered after, but not before, transplantation into enhanced hosts produced permanent graft acceptance; cardiac allografts survive c. 25 days in recipients enhanced only and 1 week in untreated animals. Adoptive transfer of spleen T cells of OX8+ or W3/25+ phenotype from long-term (greater than 200 days) graft recipients prolonged donor-specific test graft survival in naive rats (c. 16 days and c. 14 days, respectively, P less than 0.001) and delayed rejection in reconstituted B rats from 7 days to 21-23 days (P less than 0.001). Indeed, both T subsets were separately equally potent and with no overlap responsible for the suppressor activity. The phenotypic profile of the immune cells in the maintenance phase of enhanced or enhanced + CsA-treated recipients was comparable to naive or isografted controls as demonstrated by flow cytometry and immunohistologic studies. Furthermore, the activation status of the graft infiltrate in long-term survivors was similar regardless of the initial immunosuppressive protocol. CsA contributed selectively to the enhancing regimen in the induction phase of unresponsiveness, diminishing the cellularity of graft infiltrate and preventing intragraft T cell activation. These studies stress synergy between subtherapeutic doses of CsA and immunologic active/passive enhancement, 2 immunosuppressive modalities that spare T cells with suppressor capabilities but differ in the inhibition of T helper cell activation.

Animals↗
PubMed1988

Synergy between subtherapeutic doses of cyclosporine and immunobiological manipulations in rat heart graft recipients.

Cyclosporine in combination with other chemical or biological immunosuppressive modalities has been useful in clinical and experimental organ transplantation. In these studies, the efficacy of adjunctive subtherapeutic doses of CsA given to immunologically enhanced heart graft recipients or to animals treated with an anti-IL-2 receptor monoclonal antibody (ART18) are described. Individually, the treatment entities are only partially effective. In rats undergoing active and passive enhancement alone, heart allograft survival was increased to 25 +/- 12 days in two-thirds, indefinitely in one-third. After ART18 treatment, grafts survive 21 +/- 1 days. Grafts are accepted permanently in animals receiving full-dose CsA (15 mg/kg X 7), but are rejected acutely (c. 7 days) when subtherapeutic doses (1.5 mg/kg X 7) are used. However, when subtherapeutic doses of CsA are given in combination with immunological enhancement or with interleukin-2-receptor-targeted therapy, graft survival increases dramatically, with permanent or markedly prolonged engraftment occurring in all instances. In the early phases of host unresponsiveness, both enhancement and IL-2R-targeted therapy, graft survival increases dramatically, with permanent or markedly prolonged engraftment occurring in all instances. In the early phases of host unresponsiveness, both enhancement and IL-2R-targeted therapy spare selectively T cells with suppressor activity in vivo; in enhanced animals, the W3/25+ subset is responsible for prolonged graft survival, the OX8+ fraction is responsible in ART18-treated animals and in CsA-treated animals. Both subpopulations show suppressor activity in the later stages of combination treatment. IL-3 production is increased significantly in these states of unresponsiveness, an observation also noted during maintenance CsA treatment; this seems to correlate with suppressor activity. Immunoperoxidase studies of the graft infiltrates emphasize the synergistic effects of combination treatments. Thus, subtherapeutic doses of CsA plus biologic host manipulations produce greatly increased graft survival by affecting selectively different host immune mechanisms.

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