Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2.

The maintenance of peripheral naive T lymphocytes in humans is dependent on their homeostatic division, not continuing emigration from the thymus, which undergoes involution with age. However, postthymic maintenance of naive T cells is still poorly understood. Previously we reported that recent thymic emigrants (RTEs) are contained in CD31+CD25- naive T cells as defined by their levels of signal joint T cell receptor rearrangement excision circles (sjTRECs). Here, by differential gene expression analysis followed by protein expression and functional studies, we define that the naive T cells having divided the least since thymic emigration express complement receptors (CR1 and CR2) known to bind complement C3b- and C3d-decorated microbial products and, following activation, produce IL-8 (CXCL8), a major chemoattractant for neutrophils in bacterial defense. We also observed an IL-8-producing memory T cell subpopulation coexpressing CR1 and CR2 and with a gene expression signature resembling that of RTEs. The functions of CR1 and CR2 on T cells remain to be determined, but we note that CR2 is the receptor for Epstein-Barr virus, which is a cause of T cell lymphomas and a candidate environmental factor in autoimmune disease.

Human embryonic lung epithelial tips are multipotent progenitors that can be expanded in vitro as long-term self-renewing organoids.

The embryonic mouse lung is a widely used substitute for human lung development. For example, attempts to differentiate human pluripotent stem cells to lung epithelium rely on passing through progenitor states that have only been described in mouse. The tip epithelium of the branching mouse lung is a multipotent progenitor pool that self-renews and produces differentiating descendants. We hypothesized that the human distal tip epithelium is an analogous progenitor population and tested this by examining morphology, gene expression and in vitro self-renewal and differentiation capacity of human tips. These experiments confirm that human and mouse tips are analogous and identify signalling pathways that are sufficient for long-term self-renewal of human tips as differentiation-competent organoids. Moreover, we identify mouse-human differences, including markers that define progenitor states and signalling requirements for long-term self-renewal. Our organoid system provides a genetically-tractable tool that will allow these human-specific features of lung development to be investigated.

Lung epithelial tip progenitors integrate glucocorticoid- and STAT3-mediated signals to control progeny fate.

Insufficient alveolar gas exchange capacity is a major contributor to lung disease. During lung development, a population of distal epithelial progenitors first produce bronchiolar-fated and subsequently alveolar-fated progeny. The mechanisms controlling this bronchiolar-to-alveolar developmental transition remain largely unknown. We developed a novel grafting assay to test if lung epithelial progenitors are intrinsically programmed or if alveolar cell identity is determined by environmental factors. These experiments revealed that embryonic lung epithelial identity is extrinsically determined. We show that both glucocorticoid and STAT3 signalling can control the timing of alveolar initiation, but that neither pathway is absolutely required for alveolar fate specification; rather, glucocorticoid receptor and STAT3 work in parallel to promote alveolar differentiation. Thus, developmental acquisition of lung alveolar fate is a robust process controlled by at least two independent extrinsic signalling inputs. Further elucidation of these pathways might provide therapeutic opportunities for restoring alveolar capacity.

Standardized audiotape versus recorded consultation to enhance informed consent to a clinical trial in breast oncology.

BACKGROUND: The purpose of this study was to systematically compare two audiotape formats for the delivery of information relevant to informed consent to participate in a clinical trial in breast oncology, and to establish the feasibility of adding a consultation recording protocol to a clinical treatment trial. METHOD: Participants were 69 women with newly diagnosed breast cancer and 21 oncologists from 5 Canadian cancer centers. Patients were block randomized to one of three groups: 1. standardized audiotape; 2. consultation audiotape; or 3. both audiotapes. Patients received their tapes immediately following the clinical trial consultation. Patient outcomes included perception of being informed about clinical trials, knowledge of information relevant to providing informed consent to a clinical trial, and satisfaction with communication during the consultation. RESULTS: The consultation audiotapes contained less trial-related information than the standardized audiotape but there were no differences in clinical trial knowledge or perception of being informed across the intervention groups. Patients expressed a marginally significant preference for consultation audiotapes over standardized audiotapes. CONCLUSIONS: Patients tended to prefer receiving an audiotape of their own consultation over a standardized audiotape. The majority of oncologists considered the audiotape intervention feasible but were less enthusiastic about being involved in a larger study given the accrual challenges that arose when trying to "piggy-back" one randomized controlled trial on an existing clinical trial.

Use of home visit and developmental clinic services by high risk Mexican-American and white non-Hispanic infants.

OBJECTIVE: To investigate whether US-born infants of mothers of Mexican descent who were enrolled in Arizona's Newborn Intensive Care Program (NICP) received follow-up services (developmental clinic and community health nurse [(CHN)] home visits) at the rates similar to White non-Hispanic (WNH) infants. Socio-economic and health status characteristics were controlled using stepped regressions in order to assess the impact of each on service use. METHODS: This population-based study used retrospective data from the NICP administrative database that were linked to birth certificates for years 1994-1998. The study population was limited to Arizona-born infants; it included 7442 infants of WNH mothers, 2612 infants of US-born Mexican American (MA) mothers and 2872 infants of Mexico-born mothers. Four service use indicators were used in the analysis. RESULTS: Both Hispanic infant subgroups were less likely to have a CHN visit by 6 months and by 1 year, and to average fewer CHN visits. A smaller percent attended the developmental clinic by age one. After controlling for language, demographics, health status, socio-economic characteristics, and mothers' prenatal care use, infants of US-born MA mothers had rates of use similar to WNH. However, even after controlling for the study variables, infants of Mexico-born mothers were less likely (OR = .83) to use the developmental clinic. Hispanics continued to lag behind in the use of services compared with WNHs. The disparity is not a function of ethnicity, but appears attributable to demographic and socio-economic characteristics. Infants who had a CHN visit were significantly more likely (OR = 2.51) to use the developmental clinic than those without a nurse visit. Infants whose mothers had inadequate prenatal care were less likely to use these follow-up services even after controlling for study variables. CONCLUSIONS: Infants whose mothers had inadequate prenatal care should be targeted for more intense CHN visits. Infants of mothers born in Mexico may need additional support/assistance in using the developmental clinic.

Infant heel nodules. Calcification of epidermal cysts.

Calcified nodules of the heel have been reported in high-risk neonates following multiple needle sticks to draw blood. Previous reports suggest that the needle stick trauma causes dystrophic calcification. A case of multiple discrete firm heel lesions, which began shortly after birth in an immature-birth weight neonate who had sustained multiple needle sticks of the heel, is presented. Histologically, these lesions demonstrated foci of calcification and fragments of keratin surrounded by an epithelial lining, suggesting that calcified nodules may also arise from epidermal implantation cysts that secondarily calcify.