Indeed, the conversion of PrPc to PrPsc can occur at multiple cellular sites. If a predominant, neuronal site is required for the neuropathological impact of prion disease then accumulation at secondary sites, such as glia, could alter the neuropathology. The progressive increase in reactive gliosis observed in animals inoculated with PrPsc+RADA suggests an active disease process but may reflect a more robust neuro-protective response. Future experiments will determine binding of prion from different species and strains to RADA and the capability of RADA to disrupt in vitro PrPc to PrPsc conversion. The participation of an intrinsic rodent RGD-like motif in PrPc+ protein interaction might account for discrepancies in the efficacy of prion conversion between species, strains, and anti-prion compounds observed in assays based on the rodent PrP protein. A further evaluation of PrP interaction with synthetic peptides corresponding to RGD motifs may be useful in elucidating the molecular mechanism by which certain compounds exert their anti-prion activity and illuminate distinct biochemical properties inherent in the structural variability of prions. We conclude that RADA impedes the propagation of PrPsc from endogenous PrPc resulting in an altered rate of PrPsc accumulation that delays disease onset and extends survival. The choice between using cells of a single type and a BAY-60-7550 structure mixture of cells in microarray-based analysis of global gene expression is difficult. Analysing cells of one type, such as monocytes, necessitates an isolation step that may be technically difficult and which may induce non-specific changes in gene expression. Analysing a cell mixture, such as peripheral blood mononuclear cells , is simpler but gene expression changes in cells of a specific cell type, particularly if present in small numbers, may not be detected. Specifically, significant changes of gene expression in the cell type of interest may be undetectable as a result of the dilutional effect of a majority of non-responding cells or obscured by opposite responses in other cell types. In addition, it is impossible to attribute observed differential expression to individual cell types. This study compared gene expression in PBMC with expression in monocytes alone after stimulation with lipopolysaccharide as a paradigm for determining the extent to which changes in gene expression in a particular cell type can be detected in a cell mixture. A strategy was used that preserved the advantage of the cellular interactions of PBMC but which allowed detection of gene expression from an individual cell type by separating monocytes after stimulation of PBMC ex vivo. Analysis was undertaken in monocytes isolated by both positive and negative selection to control for possible gene expression induced by CD14-mediated pathways. Gene expression was also measured in the nonmonocyte cell fraction remaining after positive selection to provide information about the effect on gene expression in PBMC.