Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Graft failure in recipients of lymphocyte-depleted allogeneic bone marrow transplants is a major limitation to the success of this approach for preventing acute graft-versus-host disease. In a rat BMT model, we evaluated the effect of cyclosporine dose and schedule of administration on the engraftment of MHC-mismatched bone marrow. Lewis Brown-Norway rat recipients were prepared with myeloablative doses of busulfan (day -2) and cyclophosphamide (day -1) and then transplanted with MHC-mismatched ACI rat BM (day 0) that had been depleted of lymphocytes by counterflow centrifugal elutriation. Beginning on day -1, LBN rats received variable doses of CsA (i.e., 12.5, 10.0, 7.5, 5.0, 2.5, 0.0 mg/kg/day) for various lengths of time after BMT (i.e., 7, 14, 21, or 28 days). While all rats receiving high-dose CsA (i.e., 12.5 or 10.0 mg/kg/day) for 28 days had stable donor-derived hematopoietic reconstitution, rats receiving a daily dose of CsA less than or equal to 5.0 mg/kg/day or CsA for less than or equal to 21 days had a high incidence of graft failure. The data argue that (1) graft resistance can be suppressed by CsA and (2) the effectiveness of CsA for securing engraftment is dependent upon both dose and duration of treatment.
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PMID:Prevention of graft failure by cyclosporine in rats receiving lymphocyte-depleted MHC-mismatched bone marrow. 154 56

UV-B irradiation (700 J/m2) of bone marrow cells (BMC) before transplantation into lethally irradiated (1050R) allogeneic rats prevents graft-versus-host disease (GVHD) and results in stable chimerism. This study examined whether UV-B modulation of BMT is useful in the subsequent induction of tolerance to small bowel transplant (SBT) and avoids the danger of GVHD, which remains the major obstacle to successful SBT. Lethally irradiated Lewis recipients of UV-B irradiated (700 J/m2) BMT (10(8) BMC admixed with 5 x 10(6) splenic leukocytes) either from ACI or Wistar-Furth (WF) rats developed stable chimerism without any evidence of GVHD for > 360 days. Lewis recipients of UV-B ACI BMC expressed 95 +/- 6% ACI lymphoid cells at 50 and 150 days after BMT using complement-dependent cytotoxicity assay. Unmodified Lewis recipients of orthotopic ACI SBT rejected their grafts and died in 7-9 days, whereas Lewis chimeras accepted permanently (> 200 days) bone marrow donor (ACI) SBT without any evidence of GVHD when the SBT was performed at 60 or 150 days after BMT. In contrast, when SBT was performed, only 30 days after induction of chimerism with UV-B ACI BMT, the recipients developed severe GVHD and died between 17 and 21 days. The Lewis chimeras rejected third part (WF) SBT acutely and died in 7-9 days, thus demonstrating the specificity of the induction of tolerance in this model. That this immunologic unresponsiveness is not restricted by the recipient-donor rat strain combination was shown by the permanent acceptance of WF SBT without GVHD by Lewis/WF chimeric recipients. Furthermore, the Lewis chimeras that were made diabetic with STZ 28 days after BMT permanently accepted (> 300 days) BM donor-type (WF) and recipient-type (Lewis) islet cells and became normoglycemic, thus indicating tolerance to both donor and recipient Ags. The diabetic Lewis chimeras that became normoglycemic permanently accepted (> 200 days) WF SBT without any evidence of GVHD after donor-type SBT 110 days after WF islet transplantation. The apparent lack of organ-specific unresponsiveness in this model confirmed our previous observation with combined islet and heart transplants. In vitro MLR studies showed that the chimeric animals were specifically unreactive to donor- and recipient-type alloantigens. Our results demonstrate that UV-B irradiation of BMT is a promising approach to the induction of tolerance to SBT.
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PMID:Prevention of graft-versus-host disease in rat small bowel transplantation by recipient pretreatment with UV-B-modulated bone marrow cells. 851 7

We compared the effects of intraosseous BMT with those of standard i.v. BMT on the efficacy on donor-cell engraftment into the BM and lymphoid organs across an MHC barrier in rats. Twenty-four intraosseous and 24 i.v. BMTs were performed from 48 ACI (RT1(a)) donors to 48 Lewis (RT1(l)) recipients. Each transplant group received either intraosseous or i.v. BMT. Groups I and II served as controls without immunosuppression (n=16); groups III and IV received cyclosporine monotherapy (n=16); and V and VI received alphabeta-TCR monoclonal antibody and cyclosporine A (alphabeta-TCR/CsA) for 7 days (n=16). In each group, four rats received 35 x 10(6) transplanted bone marrow cells (BMCs) and four received 70 x 10(6) cells. All animals survived without GVHD. Mean (+/-s.d.) donor-cell engraftment into BM of recipients after intraosseous BMT was 7.9% (+/-1.3%) in recipients receiving alphabeta-TCR-CsA and 70 x 10(6) BMCs, and 4.2% (+/-1.4%) in recipients after i.v. transplantation. The seeding efficacy of donor cells into lymphoid tissue was greater after intraosseous BMT and alphabeta-TCR-CsA than after standard i.v. transplantation. In our model, intraosseous BMT facilitated donor-cell engraftment under short-term immunodepletive alphabeta-TCR/CsA protocol, which resulted in a temporary state of immune unresponsiveness.
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PMID:Donor-origin cell engraftment after intraosseous or intravenous bone marrow transplantation in a rat model. 1757 7