SUMMARYFas induces apoptosis in lymphocytes via a poorly defined intracellular signalling cascade. Previously, we have demonstrated the involvement and significance of a signalling cascade from the Fas receptor via sphingomyelinases and ceramide to Ras in Fas-induced apoptosis. Here we demonstrate rapid and transient synthesis of reactive oxygen intermediates (ROI) via activation of Ras after Fas. Genetic inhibition of Ras by transfection of transdominant inhibitory N17Ras blocked Fas-mediated ROI synthesis and programmed cell death. Likewise, the antioxidants N-acetyl-cysteine and N-t-butylphenylnitrone abolished Fas-induced cell death, pointing to an important role for Ras-triggered ROI synthesis in Fas-mediated programmed cell death.

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Challenge with low-dose apomorphine causes a rise in growth hormone (GH) in patients with Parkinson's disease (PD). We studied 18 patients with early PD, who showed an increase of GH in the low-dose apomorphine test, by means of [(123)I] FP-CIT-SPECT. The mean specific dopamine transporter binding of the 18 patients was 1.50 +/- 0.56 in the striatum, 1.20 +/- 0.59 in the putamen, and 1.76 +/- 0.59 in the caudate nucleus. The increase of GH (1.05 +/- 1.01 ng/ml at baseline to 9.46 +/- 6.36 ng/ml 45 min after apomorphine injection; p < 0.001) was significant. There was a significant negative correlation of the increase of GH with the mean specific dopamine transporter binding in all three regions (r between -0.490 and -0.587; p between 0.04 and 0.01). Challenge with low-dose apomorphine may therefore be used as an indirect tool to measure the extent of nigrostriatal neurodegeneration in early PD.

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