A point mutation at tyrosine-809 in the human colony-stimulating factor 1 receptor impairs mitogenesis without abrogating tyrosine kinase activity, association with phosphatidylinositol 3-kinase, or induction of c-fos and junB genes.

Substitution of phenylalanine for tyrosine-809 in the human colony-stimulating factor 1 receptor (CSF-1R) inhibited its ability to transduce ligand-dependent mitogenic signals in mouse NIH 3T3 cells. When combined with an "activating" mutation at codon 301 that induces constitutive CSF-1R tyrosine kinase activity, the codon 809 mutation suppressed ligand-independent cell transformation. Comparative mapping of tryptic phosphopeptides from mutant and wild-type CSF-1R indicated that tyrosine-809 is a site of ligand-dependent receptor phosphorylation in vivo. The mutant receptor was active as a tyrosine kinase in vitro and in vivo, underwent CSF-1-dependent association with a phosphatidylinositol 3-kinase, and induced expression of the protooncogenes c-fos and junB, underscoring its ability to trigger some of the known cellular responses to CSF-1. The mutant receptor is likely to be impaired in its ability to interact with critical cellular effectors whose activity is required for mitogenesis.     

Effects of a treatment adherence enhancement program on health literacy, patient-provider relationships, and adherence to HAART among low-income HIV-positive Spanish-speaking Latinos

The impact of an adherence enhancement program for low income HIV-infected Spanish-speaking Latinos on health literacy, patient-provider relationships, and adherence to HAART was examined. Evaluations were conducted at baseline, 6 weeks, and 6 months for participants (n = 85) randomly assigned to either the intervention group or a comparison group; 69 (81%) remained in the study for the entire 6-month duration. The intervention group scored significantly better than the comparison group on 3 of 5 measures of HIV health literacy at 6 weeks and on 2 of 5 measures, at 6 months. While there was a weak trend for the intervention group to report an increase in self-efficacy of medication adherence management, baseline to 6 weeks, no other changes were significant. Perceptions of the quality of relationship and communications with their HIV-treating physicians improved both at 6 weeks (p = 0.04) and at 6 months (p < 0.001). The comparison group showed little change baseline to 6 weeks and baseline to 6 months. While there was a trend for the pilot group to report better medication adherence, these differences were not statistically significant. Further evaluation of the impact of this adherence enhancement program is needed.     

Associations between obesity and asthma in a low-income,urban, minority population

BackgroundCommunity-based studies of obesity, asthma, biomarkers of oxidative stress, and adipokines among low-income, urban, minority populations are lacking. Oxidative stress, perhaps modulated by adipokines, may increase airway inflammation in obese individuals.ObjectivesTo characterize associations between obesity and asthma in a low-income, urban, minority community and evaluate adipokines, biomarkers of inflammation, and oxidant-antioxidant balance in association with asthma and obesity.MethodsA door-to-door evaluation of asthma and obesity prevalence was performed in a low-income housing development. Nonsmoking adults and children underwent additional evaluation, including allergy skin testing, and measures of serum adipokines, and indicators of oxidative stress in blood and exhaled breath.ResultsThe prevalences of current asthma and a body mass index in the 85th percentile or higher were 15.8% and 35.3%, respectively, among 350 nonsmokers older than 4 years. Asthma and obesity were not associated with one another (odds ratio, 1.0; 95% confidence interval, 0.55-1.84). Among 116 nonsmoking participants who underwent biomarker evaluation, obesity was not associated with exhaled nitric oxide. In multivariate logistic models that adjusted for age category, sex, and a body mass index in 85th percentile or higher, leptin concentrations in the highest quartile were associated with asthma (odds ratio, 8.34; 95% confidence interval, 1.29-50.2) but not with atopy. Adiponectin was associated with total antioxidant capacity in exhaled breath.ConclusionAsthma and obesity, although both common in a low-income, minority community, were not associated with one another. Nevertheless, adipokines were associated with asthma status and with markers of oxidative stress in the lungs, providing some support for an adipokine-inflammatory mechanistic link between the two conditions.     

Amplification of genes encoding human myeloid membrane antigens after DNA-mediated gene transfer

Spontaneous amplification of genes encoding two different human myeloid surface antigens was observed after DNA-mediated gene transfer of cellular DNA from the human myeloid cell line HL-60 into NIH-3T3 mouse fibroblasts. Transformed recipient cells with highly amplified expression of either of two donor membrane polypeptides, gp150 or p67, were isolated with a fluorescence-activated cell sorter (FACS), using monoclonal antibodies specific for human myeloid cells. Immunoprecipitation of enzymatically radioiodinated polypeptides from the surface of transformed NIH-3T3 cells confirmed that expression of these proteins was amplified tenfold to 20-fold in comparison to their expression on human myeloid cell lines. The cellular DNA of cloned secondary and tertiary transformants expressing high levels of gp150 and p67 contained amplified sets of DNA restriction fragments that hybridized with human repetitive DNA sequences. Cytogenetic analysis of subclones overexpressing gp150 revealed extrachromosomal double minutes (DMs), whose presence correlated with the unstable expression of the membrane polypeptide. Human sequences in gp150-positive clones did not localize to chromosomes, consistent with their association with extrachromosomal DMs. By contrast, p67-positive subclones stably expressed the antigen, and in situ hybridization to metaphase spreads demonstrated that amplified human DNA sequences were integrated into a specific marker chromosome. Cytogenetic analysis of the parental NIH- 3T3 subclone used in these studies disclosed DMs in a low percentage of metaphases, suggesting that the recipient cells have a propensity for amplifying donor DNA.