We describe several families of African origin with SCA3/Machado-Joseph disease gene expansions. In these cases, the phenotype ranges from ataxia with parkinsonian signs to a syndrome clinically almost indistinguishable from idiopathic, L-dopa-responsive Parkinson's disease. In contrast, these parkinsonian phenotypes are rare in those of European descent. Haplotype analysis shows that these African families do not share a common founder, thus a cis-acting element in the promoter is unlikely to be responsible these unusual presentations. We suggest that trans-acting factors are responsible for the variable phenotype and discuss the implications of diseases showing racially different expressivities.

In a recent study, antioxidant therapy at the time of renal transplantation in humans was associated with fewer rejection episodes and extended graft survival. A hypothesis generated by such studies and based on the response-to-injury model is that reducing the oxidative injury during transplantation may dampen certain cellular responses to injury that are important in triggering allograft rejection. To test whether ablation of oxidative injury would limit such responses, kidneys were transplanted between Wistar-Furth rats, with and without antioxidant 21-aminosteroid. 21-Aminosteroid was administered before kidney harvest and, again, before transplant reperfusion. The recipient's left kidneys, removed to accommodate the donor kidneys, were used as normal control. The removal of the right kidneys contralateral to the transplant were delayed to day 4 to provide interim renal support. The transplanted kidneys were harvested on day 7. Administration of 21-aminosteroid was associated with better graft function and reduced lipid peroxidation. Compared with the normal control kidneys, the kidneys transplanted with vehicle had higher cytokine mRNA levels (measured by reverse transcriptase-polymerase chain reaction) for interleukin 2, interleukin 6, tumor necrosis factor-alpha, and interferon-gamma. The levels for these cytokines were reduced in kidneys transplanted with 21-aminosteroid. An increase in inducible nitric oxide synthase mRNA in the transplanted kidney was inhibited by 21-aminosteroid, as were the increase in class I and II MHC antigens. The new finding, that a reduction in transplantation-related oxidative injury in a syngeneic model is accompanied by a reduction in the expression of cytokines, MHC antigens, and inducible nitric oxide synthase, provides partial support for the response-to-injury hypothesis in the setting of renal transplantation. The data also demonstrate for the first time the efficacy of 21-aminosteroid to reduce lipid peroxidation and renal injury in kidneys transplanted after cold preservation.

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