SummaryMechanisms of tumor development were studied in SCID mice injected with human lymphoid cells from Epstein-Barr virus-positive (EBV +) donors. About 80% of peripheral blood mononuclear cell (PBMC)-injected animals developed a lymphoproliferative disease associated with oligoclonal EBV + tumors of human B cell origin. No change in tumor development rate occurred when monocyte-depleted PBMC were inoculated. No tumors developed when purified B cells were injected. B cell lymphoproliferative disease was also prevented in most cases when PBMC-injected animals were treated with agents that prevent T cell activation, such as cyclosporin A. Both CD4 § and CD8 + T cell subpopulations were able to provide putative factor(s) necessary for EBV + B cell expansion and progression to tumors. These data suggest that the transfer alone of potentially tumorigenic human cells into an immunodeficient environment, such as the SCID mouse, might not be sufficient for cell progression to tumor, and raise the possibility that chronic activation events could play a major role in the pathogenesis of some EBV + lymphomas in the immunocompromised host.

The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.

MLR3 molecule is a membrane glycoprotein (mol. mass range 28-34 kDa) present on activated, but not resting human peripheral T cells, B cells and thymocytes. Its kinetics of appearance on the cell surface (3 h after the addition of the inductive signal to the cells) suggests that it is an early activation antigen. The proliferative response of cultured T and B lymphocytes and thymocytes to different activation signals is inhibited by the addition of MLR3 monoclonal antibody. Moreover the antibody in combination with non-mitogenic doses of phorbol myristate acetate leads to proliferation of thymocytes and resting B and T lymphocytes. In the latter, synthesis of interleukin 2 is also induced. Biochemical analysis of MLR3 antigen indicates that it is a phosphorylated protein with N-linked sugar moieties. Together these data suggest a role for MLR3 antigen in the signal transduction process during activation, both for mature lymphocytes and for T cell precursors.

Canavan's disease is an autosomal recessive disorder characterized by a deficiency of aspartoacylase and accumulation of N‐acetylaspartic acid (NAA), leading to a severe leukodystrophy and spongy degeneration of the brain. N‐Acetylaspartylglutamate (NAAG), the presumed product of NAA, also accumulates in this disease. The endogenous dipeptide NAAG has been suggested to have low potency at NMDA receptors. Here we have tested the actions of NAAG and NAA on NMDA‐evoked responses in cultured cerebellar granule cells. In differentiating granule cells grown in low‐K+ medium, NAAG negated the survival‐promoting effects of NMDA but not K+ depolarization. Neither NAAG nor NAA alone promoted cell survival in low‐K+ medium. The modest trophic action of 50 µM kainic acid in low‐K+ medium was reinforced by the NMDA receptor antagonist dizocilpine maleate and by NAAG. In K+‐differentiated granule cells, NAAG raised the threshold of NMDA neurotoxicity but not that of kainate. The observed activities of NAAG were overcome by excess NMDA and were not mimicked by NAA. These data raise the possibility that disruption of NMDA receptor processes by NAAG may be of pathophysiological relevance.

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