1,720,984 research outputs found
Cathepsin D in the malignant progression of neoplastic diseases
No full textRecent studies suggest that aspartic proteinase Cathepsin D may be implicated in the process of tumor invasion and metastasis. In fact several in vitro observations showed that this proteinase may facilitate the spread of neoplastic cells through different mechanisms related to its proteolytic activity by acting at different levels of the metastatic cascade. Cathepsin D may promote tumor cell proliferation by acting as an autocrine mitogen through the activation of latent forms of growth factors or by interacting with growth factor receptors. The enzyme was also shown to be able to degrade in vitro extracellular matrix and to activate latent precursors forms of other proteinases involved in the invasive steps of the metastatic process. Although unequivocal proof of its active role in promoting these processes also in vivo has not been obtained so far recent clinical observations which showed a positive correlation between level of expression of Cathepsin D activity and malignant progression of some human neoplasms further support this hypothesis. These findings warrant extensive experimental and clinical studies to better assess the pathophysiological role of this acid proteinase in the spread of neoplastic diseases and suggest new and more selective therapeutic approaches to the treatment of human neoplasms
Kinetics of in vivo inhibition of tissue cathepsin d by pepstatin A
No full text1. 1. We have investigated the kinetics of inhibition of cathepsin D in heart, liver and skeletal muscle of CD-1 mice following administration of 25, 50, 100 and 200 mg/kg i.p. of pepstatin A, a specific inhibitor of this protease. 2. 2. In the liver, a significant inhibition of cathepsin D occurred up to at least 15 days, whereas, in heart and skeletal muscle, this inhibition lasted for a much shorter period of time. 3. 3. These results show that the recovery of enzyme activity to normal values is dose-dependent and that, at the same dose level, marked differences occur in the recovery of enzyme activity in these organ tissues, the liver being the most sensitive one. © 1988
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
Cathepsin D: A possible biochemical marker for anthracycline cardiomyopathy
No full textThis study was carried out in an attempt to assess the pattern of cathepsin D variations induced by Doxorubicin (DXR) and to clarify the role possibly played by this endopeptidase in the onset of anthracyclines-induced cardiotoxicity. We evaluated the variations in both total and 'sedimentable' enzyme activity of cathepsin D in the heart of mice treated once a week for up to 8 weeks with DXR (4 mg/kg i.v.b.wt.) and sacrificed 12h, 3 and 6 days after 1, 4, 5 and 8 administrations. Our results show that significant but transitory changes in both total and sedimentable activity of cathepsin D occur after each administration and decline after prolonged treatments. These data do not suggest, but do not exclude, a direct involvement of cathepsin D in the onset of DXR-induced cardiotoxicity: these phenomena might in fact be merely secondary to an increased catabolic activity of cathepsin D following an enhanced metabolic turnover of mitochondrial and myofibrillar protein damaged by DXR. This finding seems however quite interesting because cathepsin D variations might represent one of the long looked for biochemical marker of anthracyclines cardiotoxicity
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
Acute myocardial effects of mitoxantrone in the rabbit
No full textSome clinical studies that were performed for the purpose of assessing the potential cardiotoxicity of mitoxantrone (DHAD) have shown that repeated administrations of the drug in some patients cause a mild impairment of cardiac functions and morphological changes in the myocardial cells qualitatively similar to those elicited by anthracyclines. Since doxorubicin has been reported to cause acute cardiac effects, probably related to its chronic cardiotoxicity, experiments were carried out on the rabbit heart to investigate whether DHAD is also able to induce acute cardiac effects. Our results show that this drug caused a reversible dose-related impairment of cardiac contractility on the isolated and perfused rabbit heart while it was not able to induce ECG alterations in normal rabbits. These findings demonstrate that in the rabbit DHAD induces an acute cardiac activity qualitatively similar to that of doxorubicin and suggest that this animal model could be a useful tool to study the cardiac actions and related pathogenetic mechanism(s) of this antitumor drug
Lysosomal alterations in heart and liver of mice treated with doxorubicin
No full textThis study was carried out to evaluate the influence of long-term treatment with doxorubicin (DXR) (4mg/kg IV for 5 weeks) on heart and liver lysosomes of mice. We evaluated the variations in both total and "sedimentable" enzyme activity of cathepsin D, which is the major endopeptidase of myocites and probably involved in physiologic and pathologic degradation of actomyosin and mitochondria, and that of acid phosphatase, which is more prominent in interstitial cells. Our results show that marked changes occur in both total and sedimentable enzyme activity of cathepsin D in the heart of treated animals and to a lesser extent in the liver. In contrast, no modification of either total or sedimentable acid phosphatase was seen in either organ. The effects we observed are much more marked for cardiac cathepsin D; this is in good agreement with the cardiac specificity of DXR-induced cardiotoxicity with long-term administration and suggests that lysosomes could play a role in the pathogenesis of this phenomenon. © 1985 Springer-Verlag
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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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