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221.
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Long-lasting adenovirus transgene expression in mice through neonatal intrathymic tolerance induction without the use of immunosuppression. 总被引:6,自引:0,他引:6
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The major barrier to the clinical application of adenovirus gene therapy for diseases that require stable transgene expression is the immunogenicity of recombinant adenovirus, which ordinarily limits the duration of its effects to a period of about 2 weeks. We postulated that tolerance to adenovirus could be induced and transgene expression could be prolonged if T lymphocytes underwent thymic selection in the presence of adenovirus antigens. Mice were inoculated in the thymus with a recombinant adenovirus containing the lacZ marker gene during the neonatal period at a time before T-cell maturation had occurred. When the virus was administered intravenously to these mice in adulthood, they were found to have an impaired adenovirus-specific cytotoxic T-lymphocyte response which allowed prolonged hepatic lacZ expression, for up to 260 days. The ability to achieve unresponsiveness to a recombinant adenovirus after inoculation of the thymus in neonates extends the paradigm of intrathymic tolerance induction. Furthermore, this model will enable the study of stable adenovirus transgene expression in vivo without the use of immunosuppression and ultimately may have clinical utility. 相似文献
223.
A temperature increase from 35° to 40–42°C enhances the rise of cytoplasmic serine proteinase (ISP1) activity in Bacillus megaterium incubated in a sporulation medium. A temperature shift from 27°C in the growth medium to 35°C in the sporulation medium has the same effect. Elevated temperature stimulates the increase of ISP1 level when applied immediately after the transfer of cells from the growth to the sporulation medium (at T0) or at T3, when sporulation becomes irreversible. The cytoplasmic PMSF-resistant activity or the proteolytic activity associated with the membrane fraction is stimulated only slightly or not at all. A temperature increase to 45–47°C suppresses the rise of proteolytic activities in all cell fractions. In addition to the elevation of the ISP1 activity by an upward temperature shift, the rise of this enzyme in nongrowing cells is also stimulated by osmotic stress. In growing populations, in contrast to the rise of the ISP1 activity caused by elevated temperature in nongrowing cells, this proteinase is induced by low temperatures (24–27°C). The ISP1 activity roughly correlates with the enzyme protein concentration determined by immunoblotting. 相似文献
224.
Thérèse M. Delahunty Ji Y. Jiang Raiford T. Black Bruce G. Lyeth 《Neurochemical research》1995,20(4):405-411
In the fluid percussion model of traumatic brain injury (TBI), we examined muscarinic and metabotropic glutamate receptor-stimulated polyphosphoinositide (PPI) turnover in rat hippocampus. Moderate injury was obtained by displacement and deformation of the brain within the closed cranial cavity using a fluid percussion device. Carbachol and (±)-1-Aminocyclopentane-trans-1,3.-dicarboxylic acid (trans-ACPD)-stimulated PPI hydrolysis was assayed in hippocampus from injured and sham-injured controls at both 1 hour and 15 days following injury. At 1 hour after TBI, the response to carbachol was enhanced in injured rats by up to 200% but the response to trans-ACPD was diminished by as much as 28%. By contrast, at 15 days after TBI, the response to carbachol was enhanced by 25% and the response to trans-ACPD was enhanced by 73%. The ionotropic glutamate agonists N-methyl-D-aspartate (NMDA), and -amino-3 hydroxy-5-methyl-4-isoxazolepropionate (AMPA), did not increase PPI hydrolysis in either sham or injured rats and injury did not alter basal hydrolysis. Thus, hippocampal muscarinic and metabotropic receptors linked to phospholipase C are differentially altered by TBI.Abbreviations used TBI
traumatic brain injury
- EAA
excitatory amino acids
- PPI
polyphosphoinositides
- IP
inositol phosphates
- NMDA
N-methyl-D-aspartate
- AMPA
-amino-3-hydroxy-5-methylisoxazole-4-propionate
- trans-ACPD
(±)-1-Aminocyclopentanetrans-1,3-dicarboxylic acid
- LTP
long term potentiation 相似文献
225.
Oxidative stress during exercise: Implication of antioxidant nutrients 总被引:17,自引:0,他引:17
LiLi Ji 《Free radical biology & medicine》1995,18(6):1079-1086
Research evidence has accumulated in the past decade that strenuous aerobic exercise is associated with oxidative stress and tissue damage in the body. There is indication that generation of oxygen free radicals and other reactive oxygen species may be the underlying mechanism for exercise-induced oxidative damage, but a causal relationship remains to be established. Enzymatic and nonenzymatic antioxidants play a vital role in protecting tissues from excessive oxidative damage during exercise. Depletion of each of the antioxidant systems increases the vulnerability of various tissues and cellular components to reactive oxygen species. Because acute strenuous exercise and chronic exercise training increase the consumption of various antioxidants, it is conceivable that dietary supplementation of specific antioxidants would be beneficial. 相似文献
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海马内生长抑素与γ-氨基丁酸在大鼠穿梭箱主动回避反应中的作用 总被引:1,自引:0,他引:1
本实验以大鼠穿梭箱主动回避反应(AAR)的习得和消退为学习记忆的指标,研究了海马内生长抑素(SS)和γ-氨基丁酸(GABA)在学习记忆中的作用。结果如下:(1)经训练而建立了AAR的大鼠,其海马内SS较对照组显著增高,而海马内GABA含量却明显降低;(2)海马内注入SS的耗竭剂半胱胺(Cys,20g/L)使大鼠AAR的习得受到明显损害,AAR的消退显著加速,海马内SS明显降低,而GABA含量却显著升高;(3)海马内注入GABA(200g/L)使大鼠AAR的消退显著加速的同时,其海马内SS含量亦显著降低。由此表明,海马内SS可能有促进学习记忆的作用,而海马内GABA升高则有相反的效应;二者在海马调控学习记忆过程中具有重要作用。 相似文献
228.
229.
Three enzymes which catalyze the hydrolysis of L-asparagine have been identified in extracts of Citrobacter freundii. One of these (asparaginase-glutaminase (EC 3.5.1.1) also shows substantial glutaminase activity. This enzyme is extremely labile, is sensitive to inactivation by p-chloromercuribenzoate, and is not protected by dithiothreitol. A second enzyme (asparaginase B) is also sensitive to mercurials but is protected from inactivation by dithiothreitol. This enzyme has a relatively low affinity for L-asparagine (Km = 1.7-10(-3) M). The third enzyme (asparaginase A) is insensitive to inactivation by mercurials, is stable upon long term storage and has a relatively high affinity for L-asparagine (Km = 2.9-10(-5) M). This enzyme has been purified to homogeneity and has a molecular weight of approx. 140 000; the subunit weight being approx. 33 000. The C. freundii asparaginase A produced significant increases in the survival time of C3H/HE mice carrying the 6C3HED lymphoma tumor. 相似文献
230.