1,721,014 research outputs found
Analysis of the IGF axis in preneoplastic hepatic foci and hepatocellular neoplasms developing after low-number pancreatic islet transplantation into the livers of streptozotocin diabetic rats
No full textPreneoplastic hepatic foci have been demonstrated in liver acini, which drain the blood from intraportally transplanted pancreatic islets in streptozotocin-induced diabetic rats with mild persisting diabetes. In long-term studies of this animal model, hepatocellular adenomas and carcinomas (HCC) developed after a sequence of characteristic preneoplastic hepatic fool. In this experimental model, the local hyperinsulinism is thought to have a causative role. Because insulin and the insulin-like growth factor (IGF) axis are closely linked, an altered gene expression of the IGF axis components is likely. Therefore, preneoplastic hepatic foci and HCC were studied for the expression of IGF axis components. Glycogen-storing "early" preneoplastic hepatic fool were detectable several days after pancreatic islet transplantation. Northern blot analysis, in-situ hybridization, and immunohistochemical studies of these "early" lesions demonstrated increased expressions of IGF-I and IGF binding protein-4 (IGFBP-4) in altered parenchymal cells, and a decreased expression of IGFBP-1. IGF-II was not detected in these preneoplastic fool. HCC arising in this model had decreased expressions of IGF-I and IGFBP-4 but IGFBP-1 expression was not significantly altered. Some HCC showed a more than 100-fold overexpression of IGF-II, whereas other tumors were completely negative for IGF-II expression. Low IGF-I receptor expression was detected in preneoplastic foci and adjacent nonaltered liver tissue. However, HCC tissue consistently showed an increased IGF-I receptor expression, rendering these tissues susceptible to the mitogenic effects of IGF. The altered gene expression in glycogen-storing preneoplastic hepatic foci, especially the up-regulation of IGF-I and IGFBP-4 with the down-regulation of IGFBP-1, resemble the insulin-dependent regulation of these components in normal rat hepatocytes. These data agree with previous studies demonstrating a correspondence of the focal character, morphology, and enzyme pattern of preneoplastic hepatic foci with insulin effects on hepatocytes. The development from preneoplastic foci to HCC may be driven by insulin itself and/or an altered IGF axis component or yet unidentified factors
The IGF axis and hepatocarcinogenesis
No full textDeregulation of the insulin-like growth factor (IGF) axis, including the autocrine production of IGFs, IGF binding proteins (IGFBPs), IGFBP proteases, and the expression of the IGF receptors, has been identified in the development of hepatocellular carcinoma (HCC). Characteristic alterations detected in HCC and hepatoma cell Lines comprise the creased expression of IGF-II an IGF-I receptor (IGIF-IR), which nave emerged as crucial events in malignant transformation and the growth of tumours. Alterations of IGFBP production and the proteolytic degradation of IGFBPs resulting in an excess of bioactive IGFs, as well as the defective function of the IGF degrading IGF-II/mannose 6-phosphate receptor may further potentiate effects of IGFs in the HCC
Hepatocarcinogenesis following pancreatic islet transplantation in streptozotocin- and autoimmune-diabetic rats
No full textNuclear ErbB2 expression in hepatocytes in liver disease
Full text linkErbB2 is a prominent representative of the epidermal growth factor receptors that mainly attract attention as oncogenic drivers and therapeutic targets in cancer. Besides transmembrane signaling, ErbB2 may also translocate into the nucleus and mediate distinct nuclear signaling effects including DNA repair and cell cycle arrest. Unexpectedly, we found nuclear ErbB2 expression in human hepatocytes in various liver diseases so we aimed to investigate the characteristics of liver disease leading to nuclear ErbB2 translocation. The immunohistochemical pattern of ErbB2 staining was analyzed in 1125 liver biopsy samples from patients with hepatic dysfunction. Further signaling and metabolic markers were analyzed by immunohistochemistry in selected liver biopsy samples. We found a cytoplasmic and nuclear ErbB2 expression in hepatocytes from different disease conditions with the strongest expression detected in alcoholic steatohepatitis. Nuclear ErbB2 positivity significantly correlated with histologic parameters of hepatocellular damage including inflammatory activity in steatohepatitis, hepatocellular ballooning, and cholestasis. ErbB2 overexpressing hepatocytes revealed an increase of phospho-STAT3, a downstream effector of nuclear ErbB2 signaling. Notably, we observed in nuclear ErbB2-positive hepatocytes a downregulation of estrogen receptor expression. In alcoholic steatohepatitis and other toxic liver diseases, hepatocytes revealed a nuclear ErbB2 expression implying a so far unknown mechanism in hepatocytes upon cellular stress that might lead to resistance to cell death. Nuclear ErbB2-positive hepatocytes showed downregulation of estrogen receptor expression and increased levels of pSTAT3, which are signs of functionality of nuclear ErbB2 signaling. Furthermore, analysis of hepatocellular ErbB2 expression could serve as helpful tool for diagnosis of liver disease
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
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
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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