TNF-alpha receptors simultaneously activate Ca2+ mobilisation and stress kinases in cultured sensory neurones.

The cytokine tumour necrosis factor-alpha (TNF) has been implicated in autoimmune diseases and may play an indirect role in activation of pain pathways. In this study we have investigated the possibility that TNF directly activates cultured neonatal rat dorsal root ganglion (DRG) neurones and provides a signalling pathway from cells in the immune system such as macrophages to sensory neurones. Expression of TNF receptor subtypes (TNFR1 and TNFR2) on sensory neurones was identified using immunohistochemistry, fluorescence-activated cell sorting analysis and RT-PCR. Biochemical and immunocytochemical analysis showed that TNF activated p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) but not p42/p44 MAPK. TNF treatment evoked transient Ca2+-dependent inward currents in 70% of DRG neurones. These TNF-evoked currents were significantly attenuated by ryanodine or thapsigargin or by inclusion of BAPTA in the patch pipette solution. Responses were also evoked in subpopulations of cultured DRG neurones by human mutant TNFs that cross-reacted with rat receptors and selectively activated TNFR1 or TNFR2 subtypes. TNF-evoked transient increases in [Ca2+]i were also detected in 34% of fura-2-loaded DRG neurones. The link between TNF receptor activation and Ca2+ release from stores remains to be elucidated. However, responses to TNF were mimicked by sphingolipids, including sphingosine-1-phosphate, which evoked a transient rises in [Ca2+]i in a pertussis toxin-insensitive manner in fura-2-loaded DRG neurones. We conclude that distinct receptors TNFR1 and TNFR2 are expressed on cultured DRG neurones and that they are functionally linked to intracellular Ca2+ mobilisation, a response that may involve sphingolipid signalling.

Programming generalization of in-class transition skills: teaching preschoolers with developmental delays to self-assess and recruit contingent teacher praise.

We investigated a self-management intervention package that taught preschoolers with developmental delays to self-assess performance of targeted skills and to recruit teacher praise. Self-assessment alone resulted in increases in active engagement across all participants during the training sessions, but generalization to classrooms was sporadic and short-lived. When recruitment of contingent praise was added to the training package, treatment effects generalized to the participants' classrooms and teachers' rates of contingent praise increased. The implications of combining self-assessment and recruitment of contingent teacher praise are discussed.

Sun exposure and sun-protection behaviors and attitudes among U.S. youth, 11 to 18 years of age.

BACKGROUND: Adolescence is a high-risk period for the development of melanoma and nonmelanocytic skin cancers later in life. This study examines the prevalence and correlates of sun-protection practices among U.S. youth. METHODS: During July-October, 1998, a national, population-based telephone survey was conducted (N = 1,192 paired interviews of youth and their parents). Weighted prevalence and adjusted prevalence odds ratios and 95% confidence intervals were estimated. Multiple logistic regression analyses examined associations between sociodemographics, attitudes, and other modifiable correlates to specific behaviors. RESULTS: Routinely practiced sun-protection behaviors among youth on sunny days were wearing sunglasses (32%) or long pants (21%), staying in the shade (22%), and applying sunscreen (31%). Fifty-eight percent used a sunscreen with SPF > or =15 when at the beach or pool. Age, sex, and sun sensitivity were associated with substantial variation in some sun-protection behaviors. Factors associated with specific sun-protection behaviors included a lower appeal to tanning, a higher perceived benefit of sun protection, and information from family and friends about sun protection. CONCLUSION: Effective sun protection is practiced by less than one-third of U.S. youth. This baseline survey will help to monitor progress in skin cancer prevention in this critical age group in the future.