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T Tierney

Publications and source records attributed to T Tierney.

7 recordsLinked to original sources
PubMed2006

Post-translational modification plays an essential role in the translocation of annexin A1 from the cytoplasm to the cell surface.

Annexin A1 (ANXA1) has an important role in cell-cell communication in the host defense and neuroendocrine systems. In both systems, its actions are exerted extracellularly via membrane-bound receptors on adjacent sites after translocation of the protein from the cytoplasm to the cell surface of adjacent cells. This study used molecular, microscopic, and pharmacological approaches to explore the mechanisms underlying the cellular exportation of ANXA1 in TtT/GF (pituitary folliculo-stellate) cells. LPS caused serine-phosphorylation of ANXA1 (ANXA1-S27-PO4) and translocation of the phosphorylated protein to the cell membrane. The fundamental requirement of phosphorylation for membrane translocation was confirmed by immunofluorescence microscopy on cells transfected with wild-type or mutated (S27/A) ANXA1 constructs tagged with enhanced green fluorescence protein. The trafficking of ANXA1-S27-PO4 to the cell surface was dependent on PI3-kinase and MAP-kinase. It also required HMG-coenzyme A and myristoylation. The effects of HMG-coenzyme A blockade were overcome by mevalonic acid (the product of HMG-coenzyme A) and farnesyl-pyrophosphate but not by geranyl-geranylpyrophosphate or cholesterol. Together, these results suggest that serine-27 phosphorylation is essential for the translocation of ANXA1 across the cell membrane and also identify a role for isoprenyl lipids. Such lipids could target consensus sequences in ANXA1. Alternatively, they may target other proteins in the signal transduction cascade (e.g., transporters).

Animals↗
PubMed2003

Evidence from studies on co-cultures of TtT/GF and AtT20 cells that Annexin 1 acts as a paracrine or juxtacrine mediator of the early inhibitory effects of glucocorticoids on ACTH release.

Annexin 1 (ANXA1) is a key mediator of the inhibitory effects of glucocorticoids on adrenocorticotropic hormone (ACTH) release, which develop within 1-2 h of a steroid challenge. Our previous studies, which showed that (i) ANXA1 is expressed principally by the nonsecretory folliculo-stellate cells in the pituitary gland; (ii) glucocorticoids cause the exportation of ANXA1 from these cells; and (iii) corticotrophs express specific ANXA1 binding sites, led us to propose that ANXA1 serves as a paracrine or juxtacrine mediator of glucocorticoids. To address this hypothesis, we examined ANXA1-dependent glucocorticoid actions in co-cultures of murine corticotroph (AtT20 clone D1) and folliculo-stellate (TtT/GF) cell lines. ANXA1 mRNA and protein were found in abundance in TtT/GF cells but neither was detectable in the AtT20 cells. AtT20 cells (alone and in co-culture with TtT/GF cells) responded to corticotropin-releasing hormone (CRH) (0.1-1 micro m) with increased ACTH release. The CRH-stimulated release of ACTH from AtT20 cells cultured alone was unaffected by preincubation with dexamethasone (Dex, 100 nm); by contrast, in co-cultures of AtT20 and TtT/GF cells, the steroid readily inhibited the secretory response to CRH. The effects of Dex on ACTH release were mimicked by N-terminal ANXA1 fragments (ANXA1Ac2-26, 2 micro g/ml and ANXA11-188, 0.1 ng/ml) and reversed by mifepristone (1 micro m) and by an antisense oligodeoxynucleotide (ODN) to ANXA1 (50 nm) but not by control ODNs. The antisense ODN also specifically blocked the Dex-induced externalization of ANXA1 from TtT/GF cells. Immunofluorescence imaging of the co-cultures localized the exported protein to the vicinity of the AtT20 cells and identified ANXA1 binding sites on these cells. These results provide functional and histological evidence to support our premise that the early inhibitory effects of glucocorticoids on ACTH release are dependent upon paracrine/juxtacrine actions of ANXA1 derived from folliculo-stellate cells.

Adrenocorticotropic Hormone↗
PubMed2002

Increased lactotrophs despite decreased somatotrophs in the dwarf (dw/dw) rat: a defect in the regulation of lactotroph/somatotroph cell fate?

The dwarf (dw/dw) rat differs from all other rodent models of GH deficiency in that its pituitary prolactin (PRL) content is normal or even increased. We have now studied this throughout postnatal development, using a combination of immunocytochemistry, RIA and fluorescence-activated cell sorting (FACS) and analysis. Compared with normal Albino Swiss (AS) rats, adult dw/dw rats showed a profound reduction in pituitary GH content accompanied by increased PRL content, significantly so in females (AS vs dw/dw; P<0.01). Somatotroph hypoplasia was evident in the adult dw/dw rats, with most GH(+ve) cells showing weak immunostaining, whereas many more strongly stained PRL cells were evident in pituitary sections from dw/dw rats. Facs analysis confirmed both somatotroph hypoplasia and relative lactotroph hyperplasia in dw/dw rats at all ages studied (9-144 days); the difference in somatotrophs increased with age whereas the difference in lactotrophs declined with age. At 9 days, the percentage of lactotrophs was 10-fold higher in dw/dw rats than in AS rats. Young dw/dw rats also had a higher proportion of mammosomatotrophs than AS rats, although this difference disappeared as the mammosomatotroph proportions increased with age in both strains. GHRH released GH from both dw/dw and as cells maintained in culture for 5 days. The sensitivity to GHRH and the amount of GH released was lower in the dw/dw cultures, mostly explained by their fewer GH cells and lower initial GH content. GHRH increased cAMP in as but not in dw/dw cultures, even when these were greatly enriched for dw/dw somatotrophs by FACS sorting prior to culture. These results suggest that GHRH-induced cAMP stimulation is required for trophic effects on GH synthesis and somatotroph proliferation, but is not required for GHRH-stimulated GH release. The inverse changes in somatotroph and lactotroph numbers suggest that the dw/dw mutation disturbs the mechanism that specifies and retains appropriate numbers of somatotrophs in their differentiated state, and results in a higher proportion of the remaining cells progressing to lactotrophs. The dw/dw phenotype is thus not confined to somatotrophs.

Animals↗
PubMed1997

Who's the patient here? Inpatient psychiatric rehabilitation in a state hospital setting.

1. The primary focus of psychiatric rehabilitation is on improving the competencies of persons with psychiatric disabilities. 2. Both patients and staff must change their ideas about themselves and each other before the work of rehabilitation could move forward. 3. Institutional rigidity works against psychiatric rehabilitation, with its value on individual growth and self-sufficiency.

Activities of Daily Living↗
PubMedDate not supplied

What's your strategy for managing knowledge?

The rise of the computer and the increasing importance of intellectual assets have compelled executives to examine the knowledge underlying their businesses and how it is used. Because knowledge management as a conscious practice is so young, however, executives have lacked models to use as guides. To help fill that gap, the authors recently studied knowledge management practices at management consulting firms, health care providers, and computer manufacturers. They found two very different knowledge management strategies in place. In companies that sell relatively standardized products that fill common needs, knowledge is carefully codified and stored in databases, where it can be accessed and used--over and over again--by anyone in the organization. The authors call this the codification strategy. In companies that provide highly customized solutions to unique problems, knowledge is shared mainly through person-to-person contacts; the chief purpose of computers is to help people communicate. They call this the personalization strategy. A company's choice of knowledge management strategy is not arbitrary--it must be driven by the company's competitive strategy. Emphasizing the wrong approach or trying to pursue both can quickly undermine a business. The authors warn that knowledge management should not be isolated in a functional department like HR or IT. They emphasize that the benefits are greatest--to both the company and its customers--when a CEO and other general managers actively choose one of the approaches as a primary strategy.

Commerce↗