Homeodomain proteins function in determination of mating type in yeast, segmentation in fruit flies and cell-type specific gene expression in mammals. In Drosophila, expression of homeobox genes is controlled by cell-autonomous interactions between regulatory proteins and environmental clues. Similar controls may operate during mammalian limb development and frog embryogenesis. But, the exact way in which expression of homeodomain proteins is regulated in these systems is not clear and requires biochemical analysis of homeobox gene transcription. We now describe such an analysis of the GHF1 gene, which encodes a mammalian homeodomain protein specifying expression of the growth hormone (GH) gene in anterior pituitary somatotrophs. GHF1 is transcribed in a highly restricted manner and the presence of GHF1 protein is correlated both temporally and spatially with activation of the GH gene during pituitary development. Analysis of the GHF1 promoter indicates that transcription is also controlled by cell-autonomous interactions involving positive autoregulation by GHF1, and environmental cues that modulate the intracellular level of cyclic AMP and thereby the activity of cAMP response element binding protein (CREB), a ubiquitous transactivator that binds to the GHF1 promoter.

During pituitary development, the homeo domain protein GHF-1 is required for generation of somatotropes and lactotropes and for growth hormone (GH) and prolactin (PRL) gene expression. GHF-1 mRNA is detectable several days before the emergence of GH-or PRL-expressing cells, suggesting the existence of a somatotropic progenitor cell in which GHF-1 transcription is first activated. We have immortalized this cell type by using the GHF-1 regulatory region to target SV40 T-antigen (Tag) tumorigenesis in transgenic mice. The GHF-Tag transgene caused developmental entrapment of somatotropic progenitor cells that express GHF-I but not GH or PRL, resulting in dwarfism. Immortalized cell lines derived from a transgenic pituitary tumor maintain the characteristics of the somato/lactotropic progenitor in that they express GHF-1 mRNA and protein yet fail to activate GH or PRL transcription. Using these cells, we identified an enhancer that activates GHF-1 transcription at this early stage of development yet is inactive in cells representing later developmental stages of the somatotropic lineage or in other cell types. These experiments not only demonstrate the potential for immortalization of developmental progenitor cells using the regulatory regions from cell type-specific transcription factor genes but illustrate the power of such model systems in the study of developmental control.

A144Eur J Hosp Pharm 2013;20(Suppl 1):A1-A238 pharmacy service claims. Demographic data, C-reactive protein (CRP), HLA-B27, axial or mixed AS subtypes, disease activity (BAS-DAI, BASFI) and concomitant and previous AS treatments were analysed. Associated costs were estimated based on public ex-factory prices including tax (2011 Euros Background Compliance is sometimes difficult for patients treated with temozolomide, because of the inconvenience due to the high daily number of capsules needed. Studies with other drugs showed that pillboxes increased patient satisfaction. Purpose To determine if pharmaceutical information and the use of pillboxes may improve satisfaction of patients treated with temozolomide. Materials and MethodsThis prospective and interventional study included adult patients who picked temozolomide up in our Hospital Pharmacy (01/03/2012 to 31/08/2012). In the first visit, patients previously treated with temozolomide completed a satisfaction questionnaire, which was adapted from the ESTAR questionnaire (ARPAS study). It consisted of 9 questions to be answered from 0 (very unsatisfied) to 6 (very satisfied), and another two items about temozolomide information. In addition, pharmaceutical information and pillboxes were provided to all patients.At their next visit, patients received another questionnaire, with 6 of the previous satisfaction questions and 5 new questions about usefulness of the pillbox and of the received information. Results 35 patients were evaluated with the first questionnaire (50.69 ± 13.38 years old; 77.14% were treated with ≥3 capsules per dose) and 28 of them filled in the second questionnaire (50.32 ± 12.45

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