1,720,979 research outputs found
The regulatory region of the human plasminogen activator inhibitor type-1 (PAI-1) gene
No full textThe human gene for plasminogen activator inhibitor type-1 (PAI-1) has been isolated and its promoter region characterized. PAI-1 regulation by glucocortiooids, transforming growth factor-β (TGF-β) and the phorbol ester PMA is shown to be exerted at the promoter level. A fragment spanning 805 nuclectides of the 5′ flanking and 72 of the 5′ untraslated region contain information enough to promote transcription and to respond to glucocorticoids when fused to a reporter gene and transfected into human fibrosarccma cells. A moderately repectitive DNA sequence, containing a TATA box, a GRE consensus, a Z-DNA forming sequence and two imperfect direct repeats at the extremities, is present a few nucleotides 5′ of the human PAI-1 gene transcription start site, raising the possiblity that this gene could have been activated by DNA insertion during evolution. © 1988 IRL Press Limited
TRANSFORMING GROWTH FACTOR-BETA-1-RESPONSIVE ELEMENT - CLOSELY ASSOCIATED BINDING-SITES FOR USF AND CCAAT-BINDING TRANSCRIPTION FACTOR-NUCLEAR FACTOR-I IN THE TYPE-1 PLASMINOGEN-ACTIVATOR INHIBITOR GENE
No full textTransforming growth factor β (TGF-β) is the name of a group of closely related polypeptides characterized by a multiplicity of effects, including regulation of extracellular proteolysis and turnover of the extracellular matrix. Its cellular mechanism of action is largely unknown. TGF-β1 is a strong and fast inducer of type 1 plasminogen activator inhibitor gene transcription. We have identified a TGF-β1-responsive element in the 5'- flanking region of the human type 1 plasminogen activator inhibitor gene and shown that it is functional both in its natural context and when fused to a heterologous nonresponsive promoter. Footprinting and gel retardation experiments showed that two different nuclear factors, present in extracts from both TGF-β1-treated and nontreated cells, bind to adjacent sequences contained in the responsive unit. A palindromic sequence binds a trans-acting factor(s) of the CCAAT-binding transcription factor-nuclear factor I family. A partially overlapping dyad symmetry interacts with a second protein that much evidence indicates to be USF. USF is a transactivator belonging to the basic helix-loop-helix family of transcription factors. Mutations which abolish the binding of either CCAAT-binding transcription factor-nuclear factor I or USF result in reduction of transcriptional activation upon exposure to TGF-β1, thus showing that both elements of the unit are necessary for the TGF-β1 response. We discuss the possible relationship of these findings to the complexity of the TGF-β action
Tumor necrosis factor-α regulates mRNA for urokinase-type plasminogen activator and type-1 plasminogen activator inhibitor in human neoplastic cell lines
No full textTumor necrosis factor-α (TNF-α) was found to induce type-1 plasminogen activator inhibitor (PAI-1) antigen in the human fibrosarcoma cell line HT-1080, and PAI-1 and urokinase-type plasminogen activator (u-PA) antigens in the human carcinoma cell line T-CAR1; tissue-type plasminogen activator (t-PA) antigen was not affected or slightly decreased. The effects in HT-1080 and T-CAR1 cells were preceded by increases in the cellular levels of the corresponding mRNAs. Cycloheximide caused an increase of PAI-1 mRNA in T-CAR1 cells, but not in HT-1080 cells; during this increase the relative abundance of the two PAI-1 mRNA species, of 2.3 kb and 3.4 kb, respectively, changed strongly in favor of the longer transcript. We conclude that TNF-α may affect proteolytic activity in the microenvironment of cells in malignant tumors by affecting gene expression of u-PA and PAI-1. © 1989
Urokinase receptor is up-regulated in endothelial cells and macrophages associated with fibrinoid deposits in the human placenta
No full textPlasminogen activator inhibitor type-1 protein, mRNA and gene transcription are increased by phorbol esters in human rhabdomyosarcoma cells
No full textBy use of an enzyme-linked immunosorbent assay, we have found that phorbol 12-myristate 13-acetate (PMA) causes an approximately 10-fold increase in the level of type-1 plasminogen activator inhibitor (PAI-1) accumulated in conditioned medium of the human rhabdomyosarcoma cell line. Half-maximal stimulation occurred at ≃15 nM PMA. The effect was only observed with phorbol esters that are tumor promoting. Maximal levels of secreted PAI-1 were observed 24 h after PMA addition. The increase in secreted PAI-I was preceded by a transient approximately 10-fold increase in intracellular PAI-1 content, maximal at 8 h after PMA addition. There was a 20-fold increase in the cellular level of two 2.3- and 3.4-kilobase PAI-1 mRNAs and a more than 5-fold increase in the PAI-1 gene transcription rate. The protein synthesis inhibitor cycloheximide (10 μg/ml) also increased the level of PAI-1 mRNA, and when both cycloheximide and PMA were used, an additive effect was observed. Cycloheximide changed the ratio between the two PAI-1 mRNAs in favor of the 3.4-kilobase species. Overall, the data show that transcriptional activation of the PAI-1 gene forms part of the pleiotropic responses to tumor-promoting phorbol esters
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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