Transplantation
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Comparative Study
HLA class I (ABC) upregulation on peripheral blood CD3+/CD8+ T lymphocyte surface is a potential predictor of acute rejection in renal transplantation.
Renal transplantation is currently the prevalent therapy for most patients with end-stage renal disease. No clinical markers for such rejection have been universally accepted. We aimed to investigate the possibility of use of human leukocyte antigen (HLA) class I (ABC) on peripheral blood CD3+/CD8+ T lymphocytes as a marker of acute rejection. ⋯ Upregulation of HLA class I (ABC) on peripheral-blood CD3+/CD8+ T lymphocytes could be used as an accurate and reliable predictor of AR after renal transplantation.
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Comparative Study
Induction of regulatory T cells and indefinite survival of fully allogeneic cardiac grafts by ursodeoxycholic acid in mice.
Ursodeoxycholic acid (UDCA) has been used to treat patients with cholestatic and autoimmune liver diseases. Several studies have addressed whether UDCA can inhibit graft rejection in experimental and clinical transplantation, but the results have varied. We investigated the effect of UDCA and the mechanism of its effect on alloimmune responses in a murine model of cardiac transplantation. ⋯ UDCA induced unresponsiveness to fully allogeneic cardiac allografts and generated CD4+ CD25+ regulatory cells in our model. FK506, but not CyA, was compatible with UDCA treatment.
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Multicenter Study
Phase I study of high-stringency CD8 depletion of donor leukocyte infusions after allogeneic hematopoietic stem cell transplantation.
Donor leukocyte infusions (DLI) are given after hematopoietic stem-cell transplantation to eradicate persistent tumor or correct mixed chimerism (MC). The drawback of DLI is the risk of graft-versus-host disease (GVHD). In this phase I study, we examined the potential of highly extensive CD8 depletion of DLI as a means of improving its safety profile. ⋯ Graft-versus-tumor effects can be observed after high-stringency CD8-depleted DLI, although the major toxicity remains GVHD in this high-risk patient group. The safety and efficacy profile of this approach will require testing in a randomized controlled study.
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In response to ischemic/hypoxic preconditioning, tissues/organs exhibit protective responses to subsequent and severe ischemic stress. We hypothesized that repetitive hypoxic preconditioning (RHP) may provide long-lasting protection than single preconditioning against ischemia/reperfusion injury in rat kidneys through hypoxia-induced factor (HIF)-1-dependent pathway. ⋯ RHP activates an HIF-1 alpha-dependent signaling cascade leading to an increase in Bcl-2 protein expression, an inhibition in cytosolic Bax and mitochondrial cytochrome c translocation, and a hypoxic/ischemia tolerance against renal ischemia/reperfusion injury.