1,721,117 research outputs found

    Suramin induces deoligomerization of human tumor necrosis factor alpha

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    : Suramin inhibits the biological activity of human tumor necrosis factor alpha (TNF) through a direct action on the ligand rather than on its receptors (Grazioli, L., Alzani, R., Ciomei, M., Mariani, M., Restivo, A., Cozzi, E., and Marcucci, F. (1992) Int. J. Immunopharmacol. 14, 637-642). In order to clarify the mechanism whereby suramin leads to inhibition of TNF, we investigated the possibility that suramin might modify the quaternary structure of TNF which is biologically active as a trimer. For this purpose we used a new assay (double streptavidin sandwich assay) designed for the rapid detection of oligomer-monomer conversion of proteins. Taking advantage of this assay we observed, upon incubation with suramin, dissociation of TNF. Suramin-induced dissociation of TNF was confirmed by gel filtration chromatography. Under conditions of partial dissociation, two molecular species were separated. One of higher molecular weight, corresponding to trimeric TNF, was biologically active, whereas the other, corresponding to monomeric TNF, was inactive. These results are at variance with others recently reported, where suramin has been shown to induce microaggregation of several polypeptides (Middaugh, C. R., Mach, H., Burke, C. J., Volkin, D. B., Dabora, J. M., Tsai, P. K., Bruner, M. W., Ryan, J. A., and Marfia, K. E. (1992) Biochemistry 31, 9016-9024). This suggests that suramin inhibits the bioactivity of different protein molecules through opposite effects on their quaternary structure. The present results are, to our knowledge, the first demonstration of a drug inhibiting a target molecule through dissociation of its quaternary structure

    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

    Accurate differentiation of focal nodular hyperplasia from hepatic adenoma at gadobenate dimeglumine-enhanced MR imaging: prospective study

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    PURPOSE: To prospectively determine the accuracy of differentiating benign focal nodular hyperplasia (FNH) from hepatic adenoma (HA) and liver adenomatosis (LA) by using gadobenate dimeglumine-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: The ethics committee at each center approved the study, and all patients provided informed consent. Seventy-three patients with confirmed FNH and 35 patients with confirmed HA (n = 27) or LA (n = 8) underwent MR imaging before (T2-weighted half-Fourier rapid acquisition with relaxation enhancement or T2-weighted fast spin-echo and T1-weighted gradient-echo [GRE] sequences) and at 25-30 seconds (arterial phase), 70-90 seconds (portal venous phase), 3-5 minutes (equilibrium phase), and 1-3 hours (delayed phase) after (T1-weighted GRE sequences only, with or without fat suppression) bolus administration of 0.1 mmol per kilogram of body weight gadobenate dimeglumine. The enhancement of 235 lesions (128 FNH, 32 HA, and 75 LA lesions) relative to the normal liver parenchyma was assessed. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy for the differentiation of FNH from HA and LA were determined. RESULTS: Hyper- and isointensity on T2-weighted and iso- and hypointensity on T1-weighted GRE images were noted for 177 (88.9%) of 199 lesions visible on unenhanced images. On dynamic phase images after contrast material administration, 231 (98.3%) of 235 lesions showed rapid strong enhancement during the arterial phase and appeared hyper- to isointense during portal venous and equilibrium phases. Accurate differentiation of FNH from HA and LA was not possible on the basis of precontrast or dynamic phase images alone. At 1-3 hours after contrast material enhancement, 124 (96.9%) of 128 FNHs appeared hyper- or isointense, while 107 (100%) HA and LA lesions appeared hypointense. The sensitivity, specificity, PPV, NPV, and overall accuracy for the differentiation of FNH from HA and LA were 96.9%, 100%, 100%, 96.4%, and 98.3%, respectively. CONCLUSION: Accurate differentiation of FNH from HA and LA is achievable on delayed T1-weighted GRE images after administration of gadobenat
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