Development of the NADPH-diaphorase-positive neurons in the sympathetic ganglia

Changes in the distribution of NADPH-diaphorase (NADPH-d) were studied in neurons of the superior cervical ganglion (SCG), stellate ganglion (SG) and celiac ganglia (CG) in newborn, 10-, 20-day-old, 1-month-old, 2-month-old and 6-month-old rats, mice and kittens. NADPH-d-positive neurons were revealed in all sympathetic ganglia in kittens but not in rodents from birth onwards. In kittens, the largest population of NADPH-d-positive cells was found in the SG, the smallest in the SCG (<1%) and we observed only a few cells in the CG. The proportion of NADPH-d-positive cells in the SG increased from 3.1±0.15% in newborn kittens to 9.3±0.63% in 20-day-old animals and decreased further from 8.1±0.75% in 30-day-old kittens to 3.4±0.54% in 2-month-old animals. The content of NADPH-d-positive cells in the CG and SCG did not change during development. There were no differences in cross-sectional area between neurons located in different ganglia of animals from the same age group under study. We conclude that the development of NADPH-d-positive neurons in different sympathetic ganglia has its own time dynamics and is completed by the end of the second month of life.     

Age-dependent changes in the susceptibility to apoptosis of peripheral blood CD4+ and CD8+ T lymphocytes with virgin or memory phenotype

Susceptibility to apoptosis changes with age and most of the available data on lymphocytes refer to mitogen stimulated cells. We studied this susceptibility in quiescent, purified CD4+ or CD8+ T cells from a group of Italian old people compared with a group of young people. We found that an apoptotic agent such as 2-deoxy-D-ribose (dRib), which acts via glutathione depletion and oxidative stress, was more effective in CD4+ T cells from young donors, while no difference was found in CD8+ T cells. On the contrary, another agent such as TNF-alpha, which acts via receptor engagement, was more effective in CD8+ T cells from old subjects, and no difference was found in CD4+ T cells. When marker of activation-memory were investigated, no difference between young and old subjects was found when dRib was used. Differently, when TNF-alpha was used, memory and activated CD4+ T cells from old donors were less sensitive than younger counterparts, while memory CD8+ T cells from old donors were more sensitive than younger counterparts. This suggests that age-related changes in susceptibility to apoptosis of resting T cells largely depend on the type of the apoptotic stimulus which is used as well as on the memory phenotype of the cells. These results may also account, at least in part, for the deep remodelling of T cell repertoire that occurs during ageing.     

TNF revisited: TNF-independent antitumor activity in sera of mice sensitized with Propionibacterium acnes and challenged with lipopolysaccharide

Sera of mice sensitized with bacteria and subsequently challenged with lipopolysaccharide promote hemorrhagic necrosis of tumors in vivo and display cytotoxic activity against tumor cells in vitro, which has been attributed to the induction of tumor necrosis factor (TNF). Here, we describe the induction of a previously unrecognized antitumor activity in such sera, which is distinct from TNF but displays tumor-specific cytocidal activity in vitro as well as potent tumor-regressing activity in vivo. Biochemical analysis of this activity yielded a molecular mass of approximately 150 kDa, closely resembling a novel tumoricidal factor of murine macrophages (Mphi) termed MTC 170 (Mphi tumor cytotoxin, approximate molecular mass 170 kDa), which we have previously proposed to constitute a major effector pathway for the destruction of tumor cells by activated Mphi.     

Detection of apple chlorotic leaf spot virus using a 5' nuclease assay with a fluorescent 3' minor groove binder-DNA probe

The development of a real-time 5' nuclease RT-PCR assay for the detection of apple chlorotic leaf spot virus (ACLSV) from infected plant material is described. A short fluorogenic 3' minor groove binder-DNA hydrolysis probe was used to circumvent genome variability between isolates and target a short conserved sequence. The covalent attachment of the minor groove binder moiety at the 3' end of the probe increased the probe/target duplex stability and raised the melting temperature to a range suitable for real-time analysis. The method is rapid, sensitive and takes place within a single tube without post-PCR handling of the amplification products.     

Classical and alternative pathway complement activation are not required for reactive systemic AA amyloid deposition in mice

During induction of reactive systemic amyloid A protein (AA) amyloidosis in mice, either by chronic inflammation or by severe acute inflammation following injection of amyloid enhancing factor, the earliest deposits form in a perifollicular distribution in the spleen. Because the splenic follicular localization of immune complexes and of the scrapie agent are both complement dependent in mice, we investigated the possible complement dependence of AA amyloid deposition. In preliminary experiments, substantial depletion of circulating C3 by cobra venom factor had little effect on experimental amyloid deposition. More importantly, mice with targeted deletion of the genes for C1q or for both factor B and C2, and therefore unable to sustain activation, respectively, of either the classical complement pathway or both the classical and alternative pathways, showed amyloid deposition similar to wild type controls. Complement activation by either the classical or alternative pathways is thus not apparently necessary for the experimental induction of systemic AA amyloid in mice.     

Dendritic cells and autoimmunity

Dendritic cells (DC) are professional antigen-presenting cells that are specialized in the uptake of antigens and their transport from peripheral tissues to the lymphoid organs. Because of their capacity to stimulate naive T cells, DC have a central role in the initiation of primary immune responses and are considered promising tools and targets for immunotherapy. Emerging data suggest a role for DC in initiating autoimmune attacks. Direct analysis of DC phenotypes and DC-T-cell interactions in rodent and human autoimmune diseases should shed light on how pathogenesis occurs, and suggest novel avenues of treatment aimed at alleviating deviant DC function.     

Profilin-mediated food-induced allergic reactions are associated with oral epithelial remodeling

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