1,720,957 research outputs found

    HIV-1 gp 120 increases the permeability of rat brain endothelium cultures by a mechanism involving substance p

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    OBJECTIVE: To analyse whether an HIV-1 envelope protein might play a role in damaging the blood-brain barrier as a fundamental step in the early invasion of the central nervous system by HIV-1. DESIGN: Analysis of permeability of rat brain endothelium cultures to albumin, to assess the functional integrity of the vascular component of the blood-brain barrier. METHODS: Rat brain endothelium cultures prepared by cerebral microvessels were exposed to recombinant gp120IIIB on microporous membranes and passage of biotin-labelled albumin was analysed. Scanning electron microscopy was used to analyse cell culture morphology. Some cultures were preincubated with N-nitro-L-arginine methyl ester (L-NAME), a selective inhibitor of nitric oxide synthase, or with spantide, a selective substance P antagonist. RESULTS: HIV-1 gp120 increased the permeability of rat brain endothelial cells to albumin in a dose-dependent manner. Scanning electron microscopy revealed profound gp120-induced alterations in cell morphology accounting for the increased permeability to macromolecules. These alterations were neutralized by anti-gp120 monoclonal antibody but not by isotype control antibody or L-NAME. By contrast, spantide and anti-substance P polyclonal antibody completely blocked the gp120-induced increase in albumin permeability. Control cultures exposed to measles virus nucleoprotein showed an increase in permeability that was not blocked by spantide. Brain endothelial cells, exposed to gp120, displayed cell surface immunoreactivity for substance P, suggesting that substance P is secreted by brain endothelium in response to gp120 stimulation and binds to brain endothelial cells through a receptor-mediated mechanism. CONCLUSIONS: These findings suggest a role for substance P in the gp120-induced increase in permeability of brain endothelium

    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

    Optimal conditions for detection of human immunodeficiency virus type 1 DNA by polymerase chain reaction with nested primers

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    An assessment of optimal conditions for nested primer amplification of low copy number target DNA sequences was made using a human immunodeficiency virus type 1 (HIV-1) model. In this polymerase chain reaction (PCR) strategy, an outer primer pair is first used to amplify the target sequence and a fraction of the amplification product is further amplified with a pair of inner (nested) primers. Several methodological parameters were evaluated, including number of cycles in the first and second step of the reaction, proportion of preamplified material to be used as the template for the second amplification, concentrations of primers, deoxynucleotides, and Taq DNA polymerase in the outer and inner PCR. The two-step PCR required minimal amounts of reaction components and was shown to be highly flexible, resulting in exquisite and specificity over a wide range of technical conditions. Potential drawbacks of this practical and effective amplification procedure are also 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

    Serum fractions from amyotrophic lateral sclerosis patients depress voltage-activated Ca2+ of rat cerebellar granule cells in culture

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    Whole-cell patch clamp recording from rat cerebellar granule cells in culture was used to study the effect of immune protein fractions extracted from the serum of amyotrophic lateral sclerosis (ALS) patients on voltage-activated Ca2+ currents. The inward currents, carried by Ba2+, were induced by depolarizing step commands positive to -50 mV and showed typical voltage-dependent inactivation. Application of immunoprotein fractions obtained from the serum of ALS patients produced a strong depression of the inward current amplitude without changing its threshold potential at which the maximum was attained, or its time course. These data support the hypothesis that the serum of ALS patients contains an immunoprotein capable of interacting with high threshold Ca2+ channels of central neurones

    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

    Evidence of blood-brain barrier alteration and activation in HIV-1 gp120 transgenic mice

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    OBJECTIVE: To verify whether HIV envelope protein gp120 changes the blood-brain barrier in vivo, as a fundamental mechanism of early central nervous system damage by HIV-1. DESIGN: Analysis of the functional integrity and immune activation of the blood-brain barrier in brains of HIV-1 gp120 transgenic mice secreting circulating gp120 at levels similar to those detected in AIDS patients. METHODS: Number of vessels/mm2 section area with perivascular albumin and percentage of vessels expressing adhesion molecules (ICAM-1 and VCAM-1) were determined by immunohistochemistry in frozen brains from autopsied transgenic and non-transgenic mice. The percentage of vessels showing substance P immunoreactivity was also calculated, as this neuropeptide is known to mediate the increase in permeability of the rat brain endothelium in vitro caused by HIV-1 gp120. RESULTS: The number of vessels with albumin extravasation was significantly higher in transgenic than non-transgenic mice brains (P = 0.0003). A greater percentage of ICAM-1- and VCAM-1-positive brain vessels in transgenic than non-transgenic mice was shown (P = 0.0017 and P = 0.0008 respectively). Significant immunoreactivity for substance P was detected in brain vessels in transgenic mice and a significant correlation was found between the percentage of substance P-positive and ICAM-1-positive brain vessels (P < 0.0001) in transgenic mice. CONCLUSIONS: These findings demonstrate that HIV-1 gp120 is capable of changing and activating in vivo the vascular component of the blood-brain barrier

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods
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