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Articles by R Thomas
Total Records ( 3 ) for R Thomas
  H. R Glazer , M. D Clark , R Thomas and H. Haxton

The death of a spouse is a complicated experience in a family. Understanding the circumstances of the loss is part of the family’s healing process. The current qualitative phenomenological study builds on the existing studies by focusing on the lived experience of parents as they transition to single parenthood. Six individuals participated in this study. Data analysis revealed 5 themes related to the change to single parenting after the loss of the spouse including the need to revision the parenting role and the role of support. The study has implications for the design of interventions and groups following the death of a spouse.

  C. M Grafer , R Thomas , L Lambrakos , I Montoya , S White and L. M. Halvorson

Recent studies have demonstrated a clear role for pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of gonadotropin biosynthesis and secretion, both alone and in conjunction with GnRH. First defined as a hypothalamic releasing factor, PACAP subsequently has been identified in the gonadotrope subpopulation of the anterior pituitary gland, suggesting that PACAP may act as an autocrine-paracrine factor in this tissue. In initial studies, we determined that GnRH markedly stimulated endogenous PACAP mRNA levels and promoter-reporter activity in the mature gonadotrope cell line, LβT2. GnRH-stimulated rat PACAP promoter activity was blunted with deletion from position –915 to –402 and eliminated with further truncation to position –77 relative to the transcriptional start site. Site-directed mutagenesis demonstrated a functional requirement for a cAMP response element (CRE)-like site at position –205 and an activating protein-1 (AP-1)-like site at position –275, both of which bound CRE binding protein and AP-1 family members on EMSA. Treatment with pharmacological activators or inhibitors of second messenger signaling pathways implicated the protein kinase A, protein kinase C, and MAPK pathways in the GnRH response. In support of these in vitro data, we demonstrate that JunB binds to the rat PACAP gene promoter by chromatin immunoprecipitation assay and that small interfering RNA knockdown of JunB, cFos, and CRE binding protein factors blunts PACAP expression. In summary, these results further elucidate the complex functional interactions between PACAP and GnRH in the anterior pituitary. Specifically, these studies demonstrate that GnRH-stimulated PACAP gene expression is mediated via multiple signaling pathways acting on CRE/AP-1 sites in the proximal gene promoter. Because both PACAP and GnRH regulate gonadotropin biosynthesis and secretion, these results provide important insight into the critical fine tuning of gonadotrope function and, thereby, the maintenance of normal reproductive function.

  I Isomura , S Palmer , R. J Grumont , K Bunting , G Hoyne , N Wilkinson , A Banerjee , A Proietto , R Gugasyan , W Li , A McNally , R. J Steptoe , R Thomas , M. F Shannon and S. Gerondakis

During thymopoiesis, a unique program of gene expression promotes the development of CD4 regulatory T (T reg) cells. Although Foxp3 maintains a pattern of gene expression necessary for T reg cell function, other transcription factors are emerging as important determinants of T reg cell development. We show that the NF-B transcription factor c-Rel is highly expressed in thymic T reg cells and that in c-rel–/– mice, thymic T reg cell numbers are markedly reduced as a result of a T cell–intrinsic defect that is manifest during thymocyte development. Although c-Rel is not essential for TGF-β conversion of peripheral CD4+CD25 T cells into CD4+Foxp3+ cells, it is required for optimal homeostatic expansion of peripheral T reg cells. Despite a lower number of peripheral T reg cells in c-rel–/– mice, the residual peripheral c-rel–/– T reg cells express normal levels of Foxp3, display a pattern of cell surface markers and gene expression similar to those of wild-type T reg cells, and effectively suppress effector T cell function in culture and in vivo. Collectively, our results indicate that c-Rel is important for both the thymic development and peripheral homeostatic proliferation of T reg cells.

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