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  • 1
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims:  To evaluate the clinicopathological and immunohistochemical characteristics of Merkel cell carcinoma (MCC) in an attempt to find new, potentially significant, prognostic markers.Methods and results:  Clinical data and follow-up, histopathological features (pattern, cell size, thickness, mitoses, vascular invasion, lymphocytic infiltration) and immunohistochemical detection [CK20, thyroid transcription factor (TTF-1), chromogranin A, synaptophysin, p53, Ki67, Fli-1, CD99, c-Kit] were evaluated in 20 cases of MCC. Fli-1 and CD99 were detected in 90% and 55% of cases, respectively. Tumour size 〉 30 mm, stage II, ‘absent’ lymphocytic infiltration, and the presence of 〉 50% of Ki67+ tumour cells, were found to be prognostic indicators of disease-free interval (DFI), but only ‘absent’ lymphocytic infiltration constituted an independent prognostic factor of DFI after multivariate analysis. For overall survival, the same variables, together with local recurrence and lymph node involvement, had prognostic significance, with only local recurrence as an independent prognostic factor after multivariate analysis.Conclusions:  Absence of lymphocytic infiltration and Ki67 immunoreactivity in more than 50% of tumour cells should be evaluated in conjunction with other well-known prognostic markers in MCC. Furthermore, recognizing that Fli-1 and CD99 expression is commonly found in MCC by immunohistochemistry may avoid misinterpretation in the differential diagnosis of MCC with other small round cell tumours.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 The effect of WAY 405 ((R)-N-(2-methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexane carboxamide), a putative 5-HT1A receptor antagonist, on cardiovascular function was studied. 2 In anaesthetized rats, the i.v. injection of WAY 405 did not significantly modify basal heart rate nor blood pressure at doses of 1, 3, 10 and 30 μg kg−1; while the antagonist dose dependently antagonized the 5-HT1A receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin)-induced hypotension and bradycardia. 3 WAY 405 antagonized noradrenaline-induced contraction in isolated arteries, with pKB values of 6.6 ± 0.1, 6.5 ± 0.1 and 6.5 ± 0.1, for rat tail artery (α1A-adrenoceptors), rabbit aorta (α1B-adrenoceptors), and rat aorta (α1D-adrenoceptors) respectively. 4 The results show that in the control of blood pressure the new compound, WAY 405, behaves as a silent 5-HT1A receptor antagonist in the anaesthetized rat, also having low affinity for vascular α1-adrenoceptors.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 The pressor action of noradrenaline and its blockade by selective α1-adrenoceptor antagonists in the pithed mouse were evaluated. 2 Chloroethylclonidine (α1B/D-adrenoceptor alkylating agent) or BMY 7378 (α1D-adrenoceptor antagonist), both at 1 mg kg−1, did not block the increase in blood pressure induced by noradrenaline. 3 5-Methylurapidil (α1A-adrenoceptor antagonist), at 0.1 mg kg−1, displaced the dose–response curve approximately six-fold to the right. 4 The results support the idea that the pithed mouse vasculature express α1A-adrenoceptors and suggest that it is a good model to study the roles of α1-adrenoceptors in gene knockout or overexpression.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 The effect of WAY100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride), a 5-HT1A receptor antagonist, on cardiovascular function was studied. 2 The i.v. injection of WAY100635 dose-dependently decreased blood pressure in anaesthetized rats; while in pithed rats WAY100635 (1 mg  kg−1) displaced the phenylephrine pressor effect. 3 WAY100635 antagonized phenylephrine-induced contraction in rabbit and rat aorta (pA2 of 6.88 and 7.93 and Schild slopes of −0.83 and −1.21, respectively); while in rat caudal artery pKB was 7.45 and the Schild slope of −0.56, suggesting a complex interaction in this vessel. 4 The results show that WAY100635 induced hypotension in the anaesthetized rat and suggest that this effect could be partially explained by antagonism of vascular α1-adrenoceptors.
    Type of Medium: Electronic Resource
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  • 5
    Publication Date: 2018-04-28
    Description: Herpes simplex virus 1 (HSV-1) is a neurotropic pathogen that can infect many types of cells and establishes latent infections in the neurons of sensory ganglia. In some cases, the virus spreads into the central nervous system, causing encephalitis or meningitis. Cells infected with several different types of viruses may secrete microvesicles (MVs) containing viral proteins and RNAs. In some instances, extracellular microvesicles harboring infectious virus have been found. Here we describe the features of shedding microvesicles released by the human oligodendroglial HOG cell line infected with HSV-1 and their participation in the viral cycle. Using transmission electron microscopy, we detected for the first time microvesicles containing HSV-1 virions. Interestingly, the Chinese hamster ovary (CHO) cell line, which is resistant to infection by free HSV-1 virions, was susceptible to HSV-1 infection after being exposed to virus-containing microvesicles. Therefore, our results indicate for the first time that MVs released by infected cells contain virions, are endocytosed by naive cells, and lead to a productive infection. Furthermore, infection of CHO cells was not completely neutralized when virus-containing microvesicles were preincubated with neutralizing anti-HSV-1 antibodies. The lack of complete neutralization and the ability of MVs to infect nectin-1/HVEM-negative CHO-K1 cells suggest a novel way for HSV-1 to spread to and enter target cells. Taken together, our results suggest that HSV-1 could spread through microvesicles to expand its tropism and that microvesicles could shield the virus from neutralizing antibodies as a possible mechanism to escape the host immune response. IMPORTANCE Herpes simplex virus 1 (HSV-1) is a neurotropic pathogen that can infect many types of cells and establishes latent infections in neurons. Extracellular vesicles are a heterogeneous group of membrane vesicles secreted by most cell types. Microvesicles, which are extracellular vesicles which derive from the shedding of the plasma membrane, isolated from the supernatant of HSV-1-infected HOG cells were analyzed to find out whether they were involved in the viral cycle. The importance of our investigation lies in the detection, for the first time, of microvesicles containing HSV-1 virions. In addition, virus-containing microvesicles were endocytosed into CHO-K1 cells and were able to actively infect these otherwise nonpermissive cells. Finally, the infection of CHO cells with these virus-containing microvesicles was not completely neutralized by anti-HSV-1 antibodies, suggesting that these extracellular vesicles might shield the virus from neutralizing antibodies as a possible mechanism of immune evasion.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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