1,721,017 research outputs found

    Circulating gp120 alters the blood-brain barrier permeability in HIV-1 gp120 transgenic mice

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    The mechanism underlying invasion of the central nervous system by HIV-1 is unclear. We recently demonstrated blood-brain barrier changes in a model of HIV-1 gp120 transgenic mice. To test whether this alteration was intrinsic to the brain endothelium of transgenic mice or depended on circulating gp120, we used brain endothelial cultures from gp120 transgenic and non-transgenic mice and exposed them to serum from gp120 transgenic or non-transgenic mice. We measured permeability to albumin as a marker of functional endothelial integrity. A significant increase in permeability (up to 47%) was observed in transgenic and non-transgenic cultures exposed to serum samples from transgenic but not to those from non-transgenic mice. This permeability was neutralized after immunoabsorption of sera with anti-gp120 monoclonal antibody. These findings demonstrate that the blood-brain barrier alteration in HIV-1 gp120 transgenic mice is due to circulating gp12

    Expression of preprotachykinin-A mRNA isoforms and substance P production in T lymphocytes of human healthy subjects

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    The influence of sex and age on the expression pattern of preprotachykinin-A (PPT-A) mRNA isoforms encoding substance P and other tackykinins such as neurokinin A (NKA), neuropeptide K (NPK) and neuropeptide gamma (NPgamma) in human immunocompetent cells and the role of this pattern on SP production are unknown. To investigate these questions, we assessed PPT-A isoform expression and SP production in CD3+ lymphocytes of normal healthy subjects. There were no significant differences in PPT-A isoforms in relation to sex or age. The most frequently expressed isoforms were beta and gamma: after lymphocyte stimulation with phytohemagglutinin (PHA), there was a significant increase in their frequency (p<0.0001). Significantly higher SP levels were found in subjects expressing beta and gamma PPT-A than in those with beta PPT-A only (p=0.001). These findings provide evidence of a heterogeneous expression of PPT-A isoforms in CD3+ lymphocytes of normal healthy subjects

    Association of circulating anti-CD64 IgM levels with favourable long-term clinical outcomes in multiple sclerosis patients

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    Circulating levels of IgM anti-CD64, an immunosuppressive antibody recently identified in long-term stable multiple sclerosis (MS) patients, were found to fluctuate over time in MS patients. Antibody-positive patients showed a significantly lower annualized relapse rate value as well as reached sustained disability worsening and had a relapse in a significantly longer median time than those without antibody. Disease-modifying therapies (DMTs) only were the covariate influencing both the relapse occurrence and the disability accrual. Serum IgM anti-CD64 levels are associated with maintenance of clinical stability in MS and may be tested as a candidate biomarker predictive of benign course and favourable long-term response to DMTs treatment

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    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

    Variations on the Author

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    “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

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    We 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

    Enhanced secretion of substance P by cytokine-stimulated rat brain endothelium cultures

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    Substance P (SP) was analyzed in rat brain endothelium cultures after cytokine stimulation. SP secretion was found after stimulation with high doses of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). High doses of interferon-gamma (INF-gamma) had no effect on this secretion. Elevated SP release was found to be associated with mRNA expression of beta-preprotachykinin (beta-PPT), precursor of SP, in the cells. Under cytokine stimulation, part of SP was bound to brain endothelial cell surface, suggesting the existence of an autocrine network for this neuropeptide. These findings suggest that SP may have an immunomodulatory action at the blood-brain barrier during inflammatory and autoimmune processes in the central nervous system
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