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904.
T C Johnson R J Kinders J E McGee 《Biochemical and biophysical research communications》1981,102(1):328-334
The possible relationship between a newly isolated glycoprotein virus inhibitor and interferon was assessed. Comparisons of the cell surface glycopeptide, obtained from mouse cerebral cortex, and interferon included antiviral activity, radioimmune assays, and the ability of antibodies raised against the brain cell surface glycoprotein (BCSG) and against mouse L cell interferon to precipitate the biological activity. BCSG was able to inhibit virus replication but only in a transient fashion. Although anti-BCSG precipitated a major portion of the radiolabelled inhibitor in a double antibody assay, anti-mouse interferon did not. Over 90% of the inhibitory activity was removed with anti-BCSG and protein A while anti-mouse interferon removed little, or none, of the activity under similar reaction conditions. Other properties of the BCSG that distinguish it from interferon are presented. 相似文献
905.
Direct anesthetic-like effects of forskolin on the nicotinic acetylcholine receptors of PC12 cells 总被引:6,自引:0,他引:6
Forskolin is thought to be a highly specific activator of adenyl cyclase. However, when applied to rat pheochromocytoma (PC12) cells at concentrations of 1 microM or higher it caused an immediate, concentration-dependent inhibition of carbachol-stimulated uptake of 86Rb+ through the nicotinic receptors, which did not appear to be related to activation of adenyl cyclase. The inhibition of receptor activation occurred instantaneously whereas cellular cAMP content did not increase for a measureable period of time. Normal receptor function was recovered rapidly upon removal of forskolin. Additional evidence that this effect of forskolin was not related to cAMP was obtained when 1,9-dideoxyforskolin (an analog of forskolin which does not activate adenyl cyclase) also caused a rapid, concentration-dependent, rapidly reversible inhibition of receptor-mediated influx of 86Rb+ into the cells. An examination of the effect of forskolin on 86Rb+ uptake at various concentrations of carbachol showed that forskolin was not acting by competing with carbachol for the receptor activation site. Given the lipophilic nature of forskolin, it probably acts like a general anesthetic to perturb the plasma membrane lipid structure and alter the function of the nicotinic acetylcholine receptors, possibly by increasing the rate of closure of open channels. 相似文献
906.
Haley S. Ruther Kalyn Phillips Dolores Ross Alyssa Crawford M. Payton Weidner Osama Sammra Christoph L?mmler David J. McGee 《PloS one》2015,10(9)
Arcanobacterium haemolyticum is a Gram-positive, β-hemolytic emerging human pathogen that is classified into smooth or rough biotypes. This bacterial species is also a rare pathogen of animals. Smooth biotypes possess smooth colony edges, are moderate to strong in β-hemolysis, and predominately cause wound infections. In contrast, rough biotypes possess rough and irregular colony edges, have weak to no β-hemolytic activity, and predominately cause pharyngitis. Using horse erythrocytes we confirmed that smooth isolates are generally more hemolytic than rough isolates. A hemolysin from A. haemolyticum, arcanolysin (aln/ALN), was recently discovered and is a member of the cholesterol-dependent cytolysin (CDC) family. PCR amplification of aln from all 36 smooth A. haemolyticum isolates yielded the expected 2.0 kb product. While 21 rough isolates yielded the 2.0 kb product, 16 isolates had a 3.2 kb product. The extra 1.2 kb segment was 99% identical to IS911 (insertion sequence) from Corynebacterium diphtheriae. PCR amplification and sequence analysis of the upstream region of aln revealed ~40 nucleotide polymorphisms among 73 clinical isolates from Finland, Denmark, Germany and United States (Nebraska). Remarkably, multi-sequence alignments of the aln upstream region demonstrated that ~90% of the isolates phylogenetically clustered as either smooths or roughs. Differential restriction enzyme analysis of the aln upstream region also demonstrated that the aln upstream region of most (~75%) smooth isolates was cleaved with ClaI while this region in most (~86%) rough isolates was cleaved with XcmI. We conclude that the aln upstream region can be used to genetically distinguish between smooth and rough biotypes of this important emerging pathogen. 相似文献
907.
Seyoung Lee Megan A. Evans Hannah X. Chu Hyun Ah Kim Robert E. Widdop Grant R. Drummond Christopher G. Sobey 《PloS one》2015,10(11)
Functional modulation of the non-AT1R arm of the renin-angiotensin system, such as via AT2R activation, is known to improve stroke outcome. However, the relevance of the Mas receptor, which along with the AT2R forms the protective arm of the renin-angiotensin system, as a target in stroke is unclear. Here we tested the efficacy of a selective MasR agonist, AVE0991, in in vitro and in vivo models of ischemic stroke. Primary cortical neurons were cultured from E15-17 mouse embryos for 7–9 d, subjected to glucose deprivation for 24 h alone or with test drugs, and percentage cell death was determined using trypan blue exclusion assay. Additionally, adult male mice were subjected to 1 h middle cerebral artery occlusion and were administered either vehicle or AVE0991 (20 mg/kg i.p.) at the commencement of 23 h reperfusion. Some animals were also treated with the MasR antagonist, A779 (80 mg/kg i.p.) 1 h prior to surgery. Twenty-four h after MCAo, neurological deficits, locomotor activity and motor coordination were assessed in vivo, and infarct and edema volumes estimated from brain sections. Following glucose deprivation, application of AVE0991 (10−8 M to 10−6 M) reduced neuronal cell death by ~60% (P<0.05), an effect prevented by the MasR antagonist. By contrast, AVE0991 administration in vivo had no effect on functional or histological outcomes at 24 h following stroke. These findings indicate that the classical MasR agonist, AVE0991, can directly protect neurons from injury following glucose-deprivation. However, this effect does not translate into an improved outcome in vivo when administered systemically following stroke. 相似文献
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909.
Hannah E. Rockwell Victoria J. McCurdy Samuel C. Eaton Diane U. Wilson Aime K. Johnson Ashley N. Randle Allison M. Bradbury Heather L. Gray-Edwards Henry J. Baker Judith A. Hudson Nancy R. Cox Miguel Sena-Esteves Thomas N. Seyfried Douglas R. Martin 《ASN neuro》2015,7(2)
Sandhoff disease (SD) is an autosomal recessive neurodegenerative disease caused by a mutation in the gene for the β-subunit of β-N-acetylhexosaminidase (Hex), resulting in the inability to catabolize ganglioside GM2 within the lysosomes. SD presents with an accumulation of GM2 and its asialo derivative GA2, primarily in the central nervous system. Myelin-enriched glycolipids, cerebrosides and sulfatides, are also decreased in SD corresponding with dysmyelination. At present, no treatment exists for SD. Previous studies have shown the therapeutic benefit of adeno-associated virus (AAV) vector-mediated gene therapy in the treatment of SD in murine and feline models. In this study, we treated presymptomatic SD cats with AAVrh8 vectors expressing feline Hex in the thalamus combined with intracerebroventricular (Thal/ICV) injections. Treated animals showed clearly improved neurologic function and quality of life, manifested in part by prevention or attenuation of whole-body tremors characteristic of untreated animals. Hex activity was significantly elevated, whereas storage of GM2 and GA2 was significantly decreased in tissue samples taken from the cortex, cerebellum, thalamus, and cervical spinal cord. Treatment also increased levels of myelin-enriched cerebrosides and sulfatides in the cortex and thalamus. This study demonstrates the therapeutic potential of AAV for feline SD and suggests a similar potential for human SD patients. 相似文献
910.