To test whether community health workers are able to reach low-income parents of African American children hospitalized for asthma and to reduce rehospitalization among them.Design: A randomized controlled evaluation of usual care vs 2-year asthma coach intervention.Setting: An urban children's hospital and the surrounding community.
To evaluate the possible role for receptor-based tyrosine phosphorylation in growth signaling induced by interleukin-2 (IL-2), a series of substitution tyrosine mutants of the IL-2 receptor  and ␥ c chains was prepared and analyzed. Concurrent mutation of all six of the cytoplasmic tyrosines present in the  chain markedly inhibited IL-2-induced growth signaling in both pro-B and T cell lines. Growth signaling in a pro-B cell line was substantially reconstituted when either of the two distal tyrosines (Tyr-392, Tyr-510) was selectively restored in the tyrosine-negative  mutant, whereas reconstitution of the proximal tyrosines (Tyr-338, Tyr-355, Tyr-358, Tyr-361) did not restore this signaling function. Furthermore, at least one of the two cytoplasmic tyrosines that is required for  chain function was found to serve as a phosphate acceptor site upon induction with IL-2. Studies employing a chimeric receptor system revealed that tyrosine residues of the  chain likewise were important for growth signaling in T cells. In contrast, although the ␥ c subunit is a target for tyrosine phosphorylation in vivo, concurrent substitution of all four cytoplasmic tyrosines of this chain produced no significant effect on growth signaling by chimeric IL-2 receptors. However, deletion of either the Box 1, Box 2, or intervening (VBox) regions of ␥ c abrogated receptor function. Therefore, tyrosine residues of  but not of ␥ c appear to play a pivotal role in regulating growth signal transduction through the IL-2 receptor, either by influencing cytoplasmic domain folding or by serving as sites for phosphorylation and subsequent association with signaling intermediates. These findings thus highlight a fundamental difference in the structural requirements for IL-2R and ␥ c in receptor-mediated signal transduction.
Interleukin-2 (IL-2)1 is a helical cytokine that induces the proliferation of T and B lymphocytes as well as the expression of a number of immune effector functions by binding to the heterotrimeric IL-2 receptor complex (IL-2R). The 70 -75-kDa  (IL-2R) and 64-kDa ␥ (␥ c ) subunits of the IL-2R share structural homology with other members of a cytokine receptor superfamily (1) and together form a receptor complex that is competent to bind IL-2 with intermediate affinity and to transduce growth and differentiation signals (reviewed in Ref.2). As in other receptor systems, evidence has accumulated indicating that signal transduction is initiated upon ligand-induced heterodimerization of the  and ␥ c cytoplasmic tails (3, 4). Interestingly, IL-2R is also employed in the receptor for IL-15 (5, 6), whereas ␥ c participates in the formation of the receptors for IL-4 (7), IL-7 (8, 9), IL-9 (10), and IL-15 (6). Among the earliest biochemical changes induced by ligation of the IL-2 receptor is activation of cytoplasmic tyrosine kinases resulting in the phosphorylation of certain recognized and unrecognized cellular substrates. The biologic relevance of IL-2-induced tyrosine kinase activity is supported by the finding that sel...
The enhancement of tumor development following acute stress has been demonstrated in some animal studies. This study was designed to explore mechanisms that would account in part for the relationship between stress and tumor development at the level of DNA repair, using a rat model. Forty-four rats were given the carcinogen dimethylnitrosamine in their drinking water, and half were randomly assigned to a rotational stress condition. The levels of methyltransferase, a DNA repair enzyme induced in response to carcinogen damage, were significantly lower in spleens from the stressed animals. These data suggest that stress may impair DNA repair. Exposure to low-level carcinogens is a commonplace daily event. For example, nitrates are chemical carcinogens found in many processed meats, some American beers, and spinach. The benzopyrenes, another group of chemical Requests for reprints should be sent to
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