1,720,963 research outputs found

    Insights into gene therapy for critical limb ischemia: The devil is in the details

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    Patients with critical limb ischemia (CLI) without potential for revascularization are currently without alternate therapies. Several gene therapy trials have tested angiogenesis factors, hepatic growth factor, vascular endothelial growth factor, and basic fibroblast growth factor, in rescuing CLI patients from amputation and mortality, and for improved quality of life including decreased pain, improved healing, and blood flow. Trial results have been variable, with HGF gene therapy being the most successful. New studies examining each of these angiogenic factors provide insights that will be useful for the design of effective therapeutic strategies. © 2012 Elsevier Inc

    Hepatocyte growth factor/met gene transfer in cardiac stem cells-potential for cardiac repair

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    The adult heart has been recently recognized as a self-renewing organ that contains a pool of committed resident cardiac stem cells (CSCs) and cardiac progenitor cells (CPCs). These adult CSCs and CPCs can be induced by cytokines and growth factors to migrate, differentiate, and proliferate in situ and potentially replace lost cardiomyocytes. Ligand-receptor systems, such as the tyrosine kinase receptor mesenchymal-epithelial transition factor (Met) and its ligand hepatocyte growth factor (HGF), are potential candidates for boosting migration, engraftment and commitment of CSCs. Here, we discuss the possible application of HGF/Met gene therapy to enhance the ability of CSCs to promote myocardial regeneration. © Springer-Verlag 2010

    Long-term engraftment and angiogenic properties of lentivirally transduced adipose tissue-derived stromal cells

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    Human adipose tissue-derived stromal cells (ADSCs) are being evaluated for cardiovascular repair. We developed an ex vivo method for producing angiogenic ADSCs transduced with a self-inactivating lentiviral vector (LV) expressing the enhanced green fluorescence protein (EGFP) from an internal cytomegalovirus (CMV) promoter to track these cells after in vivo engraftment. ADSCs from visceral adipose tissue were transduced using a LV incorporating the Rous Sarcoma Virus (RSV) long terminal repeat (LTR) sequences and the Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) to enhance EGFP gene expression. We compared infection protocols with non-concentrated lentiviral supernatant or pellet fractions after ultracentrifugation, testing transduction efficiency, and reporter gene expression by quantitative flow cytometry at 5 and 28 days. Transduction of ADSCs with pellet after ultracentrifugation provided the highest transduction rate [flow cytometry titers: 6.5 ± 0.3 × 105 transduction units (TU)/mL and 20 ± 1.2 × 106 TU/mL at day 5 with non-concentrated lentiviral supernatant and pellet, respectively, with titer in the supernatant after ultracentrifugation remaining undetectable]. Reporter gene expression did not affect cell viability, morphology, proliferation, differentiation, self-renewal, or angiogenic activity. Furthermore, reporter gene expression did not significantly affect Fas/CD95-induced apoptosis. The in vivo implantation of transduced ADSCs into a mouse ischemic leg model resulted in efficient engraftment and angiogenesis. ADSC gene labeling using LVs is feasible and efficient, without impairment of stem cell characteristics, cell engraftment, and angiogenic activity. Such transduced ADSCs can be efficiently tracked in vitro and in vivo and may serve as vehicle for therapeutic genes. © 2012 Springer Science+Business Media, LLC

    Targeting phosphatidylinositol 3-kinase-Akt through hepatocyte growth factor for cardioprotection

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    Several growth factors have been shown to protect the cardiomyocyte from the detrimental effects of acute ischemia-reperfusion injury, through the activation of a variety of cell-surface receptors and the subsequent recruitment of a number of intracellular signal transduction pathways. Among these growth factors, hepatocyte growth factor (HGF), also named as scatter factor, acts by recruiting the phosphatidylinositol 3-kinase (PI3K)-Akt signal transduction pathway, linked to cardioprotection, at the time of myocardial infarction and myocardial reperfusion. HGF has been reported to increase in the early phase of myocardial infarction, and has been shown to have mitogenic, angiogenic, antiapoptotic and antifibrotic activities in cardiac myocytes and endothelial cells. Also, endogenous HGF may play an important role in the regeneration of endothelial cells and cardiomyocytes by promoting angiogenesis and inhibiting apoptosis during remodeling of the ischemic myocardium. Thus, HGF has the potential to emerge as a cardioprotective agent for the treatment of several pathological cardiac conditions. Here we review the role of HGF with respect to its ability to confer direct myocardial protection in the setting of ischemia-reperfusion injury, focusing on the main underlying signaling pathway involved. © 2013 Italian Federation of Cardiology

    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

    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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