Human thymic epithelial (TE) cells produce interleukin 1 alpha (IL-1 alpha), IL-1 beta, and IL-6, cytokines that are important for thymocyte proliferation. The mRNAs for these cytokines are short-lived and are inducible by multiple stimuli. Thus, the steady-state levels for IL-1 and IL-6 mRNAs are critical in establishing the final cytokine protein levels. In this study we have evaluated the effect of epidermal growth factor (EGF), a growth factor for TE cells, and its homologue transforming growth factor alpha (TGF-alpha), on primary cultures of normal human TE cells for the levels of IL-1 alpha, IL-1 beta, IL-6, and TGF-alpha mRNA. We showed that TE cells expressed EGF receptors (EGF-R) in vitro and in vivo, and that treatment of TE cells with EGF or TGF-alpha increased IL-1 and IL-6 biological activity and mRNA levels for IL-1 alpha, IL-1 beta, and IL-6. Neither EGF nor TGF-alpha increased transcription rates of IL-1 alpha, IL-1 beta, and IL-6 genes, but rather both EGF and TGF-alpha increased cytokine mRNA stability. By indirect immunofluorescence assay, TGF-alpha was localized in medullary TE cells and thymic Hassall's bodies while EGF-R was localized to TE cells throughout the thymus. Thus, TGF-alpha and EGF are critical regulatory molecules for production of TE cell-derived cytokines within the thymus and may function as key modulators of human T cell development in vivo.

The development of conditions for culturing normal human thymic epithelial (TE) cells free from contaminating stromal cells has allowed us to characterize a number of cytokines produced by TE cells. Using cDNA probes for human IL-6, granulocyte-monocyte-CSF, and leukemia inhibitory factor (LIF), we identified mRNA for these cytokines by RNA blot analysis of total RNA preparations derived from TE cells. We demonstrated that TE cells produced IL-6 transcripts and that TE cell culture supernatants contained IL-6 biologic activity, as determined by the ability to support proliferation of the T1165 plasmacytoma line. The 1.0-kilobase (kb) transcript of granulocyte-monocyte-CSF was also detected in TE cell-derived total RNA. TE cell culture supernatants contained LIF activity, as determined by proliferation of the murine cell line DA-1a, and a 4.0-kb LIF transcript was detected in TE cell-derived total RNA preparations. The 4.0-kb LIF transcript from TE cell-derived total RNA corresponded in size to the LIF transcripts in PMA-activated T lymphocytes. Thus, using biologic assays and RNA blot analysis, we demonstrated that cultured normal human TE cells produced both immunoregulatory cytokines and cytokines that drive various differentiation stages of human hematopoiesis. Our findings support the hypothesis that TE cells may play a role in providing cytokines that are important for the proliferation and differentiation of hematopoietic precursor cells that migrate to the thymus during fetal and postnatal human thymic development.

Objective: To examine associations between various measures of the food environment and BMI percentile among youth.Design: Cross-sectional, observational.Setting: Pitt County, eastern North Carolina.Subjects: We extracted the electronic medical records for youth receiving well child check-ups from January 2007 to June 2008. We obtained addresses for food venues from two secondary sources and ground-truthing. A geographic information systems database was constructed by geocoding home addresses of 744 youth and food venues. We quantified participants’ accessibility to food venues by calculating ‘coverage’, number of food venues in buffers of 0·25, 0·5, 1 and 5 miles (0·4, 0·8, 1·6 and 8·0 km) and by calculating ‘proximity’ or distance to the closest food venue. We examined associations between BMI percentile and food venue accessibility using correlation and regression analyses.Results: There were negative associations between BMI percentile and coverage of farmers’ markets/produce markets in 0·25 and 0·5 mile Euclidean and 0·25, 0·5 and 1 mile road network buffers. There were positive associations between BMI percentile and coverage of fast-food and pizza places in the 0·25 mile Euclidean and network buffers. In multivariate analyses adjusted for race, insurance status and rural/urban residence, proximity (network distance) to convenience stores was negatively associated with BMI percentile and proximity to farmers’ markets was positively associated with BMI percentile.Conclusions: Accessibility to various types of food venues is associated with BMI percentile in eastern North Carolina youth. Future longitudinal work should examine correlations between accessibility to and use of traditional and non-traditional food venues.

OBJECTIVES: Standardized quantitative methods are needed to study occurrence and timing of violence in relation to pregnancy and to study the context in which pregnancy-related violence occurs. METHODS: Data from three published studies of prevalence of violence during pregnancy are used to illustrate ways to measure the association of violence in relation to pregnancy. RESULTS: Four patterns of violence in relation to pregnancy are identified, and related research issues are discussed. Also, 2 population-based surveys that address the suggestions presented here are discussed. CONCLUSIONS: Better measurement of the association between violence and pregnancy will facilitate development of data-based prevention and intervention programs.