1,721,039 research outputs found
Endothelial intercellular adhesion molecule-1 expression is suppressed in human malignancies: the role of angiogenic factors
Genetic and molecular determinants of atherosclerotic plaque instability
Arachidonic acid metabolism plays a key role in atherothrombotic events affecting the coronary or cerebrovascular territory, as reflected by experimental studies based on biochemical measurements of eicosanoid biosynthesis and the results of inhibitor trials in these settings. Two cyclooxygenase (COX)-isozymes exist, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression, tissue distribution, substrate specificity, and susceptibility to inhibition by drugs. Whereas the role of COX-1 expressed in platelets in acute coronary syndromes and ischemic stroke is definitely established through several large clinical studies with aspirin, the role of COX-2 activity in these settings is still unclear, because this enzyme was characterized only recently (1991) and its inhibitors (coxibs) only became available in 1998. In this review, we discuss the different expression profile of COX-2-related enzymes in the cells actively involved in atherothrombosis, the role of these enzymes as cause of plaque "instability", and the clinical consequences of their inhibition. Recent studies suggest that variable expression of transmembrane and downstream receptors, as well as genetic mutations represent important determinants of the functional consequences of COX-2 expression and inhibition in different clinical setting
The murine p202 protein, an IFN-Inducible modulator of transcription, is activated by the mitogen platelet-derived growth factor
p202 is a murine interferon (IFN)-inducible protein belonging to a cluster of IFN-inducible genes (the 200 family) located in a segment of chromosome I. It is a nuclear DNA-binding protein that is able to modulate transcription by interacting with a heterogeneous set of transcription factors, including NF-kappaB, (p50/p65), AP-1, c-fos, c-jun, and RB-1, The p202 protein is believed to attenuate cell growth/proliferation, mainly through the activation of IFN-stimulated of gene factor 3 (ISGF3), which binds IFN-stimulated response elements (ISRE) located in the promoters of type I IFN genes. In this report, we show that the p202 gene can also be induced by platelet-derived growth factor (PDGF), a mitogen known to drive G(o)-arrested cells toward reentry into the cell cycle, PDGF transiently enhances the steady-state mRNA level of p202 and increases the p202 protein level independently from IFN signaling, by acting at the transcriptional level on its promoter. The kinetics of p202 induction by PDGF are faster and more transient than those of IFN, These data identify p202 as a member of the IFN-inducible gene family that can be directly regulated by mitogenic stimuli
Molecular organization of oncogenes and potentially oncogenic regulatory genes in primary human brain tumors
Genomic organization and cytokine-mediated inducibility of the human TRIM-8/GERP gene.
Cytokine signaling is negatively regulated by a set of SH2 domain-containing proteins, the Suppressors of Cytokine Signaling (SOCS) acting as intracellular modulators. Experimental evidence indicates that SOCS gene expression is induced by cytokines and pro-inflammatory stimuli and is highly controlled both at transcription and translation level. Furthermore, SOCS proteins appears rapidly degraded inside the cells, mostly controlling their stability by interacting with specific molecules such as elongin B and C. It has been shown that SOCS-1/JAB, a member of the SOCS family interacts with TRIM-8/Gerp, a new ring protein specifically binding SOCS-1 recombinant polypeptide in vitro and in vivo. TRIM-8/Gerp, transcribes a 3.0Kb mRNA, spans 551 AA and is highly conserved during evolution. In addition, it can be induced by IFN-gamma in epithelial and lymphoid cells and is expressed mostly ubiquitously in murine and human tissues. Here in this report we present the genomic organization of this new SOCS-1 interactor and we add new tools for extending investigation of the complex mechanism that undergoes negatively regulation of cytokine signaling
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
Ocular clinical pictures disclosed by PCR molecular diagnosis of Chlamydia trachomatis infection performed following the appropriate sampling modality in ocular ecosystem.
Four clinical cases regarding the correct diagnosis of early ocular Chlamydia trachomatis (Ct) inflammation, performed by two different modalities on the ocular ecosystem, are discussed. The present study was carried out in parallel using a cotton flock ocular swab and the scraping of upper lid conjunctiva. The ocular samplings were carried out by a first ocular swab from inner canthus and fornix, while the second by a conjunctival scraping from upper the conjunctiva of four patients. In the first case, by ocular swab, all samples resulted negative to Ct-DNA research by PCR, while the cultural analyses showed a growth of saprophytic and opportunist germs in all patients. No growth micetes resulted. On the contrary, in the second case, by conjunctival scraping, three of four samples were positive to Ct-DNA research. No fungal growth was observed, while only the 3rd patient, negative to Ct-DNA research, showed microbial growth. Our study, carried out with two different modalities of sampling on different areas of the same ecosystem, showed different results, demonstrating the importance of sampling accuracy for chlamydial research by molecular analysis in PCR, during the slight phase of inflammation. These initial data indicate that laboratory diagnosis by PCR for precocious Ct infection, not revealed clinically, could represent the first step for a correct diagnostic procedure, eliminating one of the critical points, allowing an accurate, effective and precocious antibiotic therapy. We hypothesize that only by following these correct procedures of sampling during the early phase of chlamydial inflammation, in the future, will it be possible to reduce a pejorative evolution of this worsening disease in people genetically susceptible, building a more efficacious Public Health program of prevention against chronic conjunctivitis and to favour a major prevention of trachoma in endemic areas
Variations on the Author
“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
- …
