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521.
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Gale P 《Journal of applied microbiology》2006,101(2):261-274
The issue of whether the mechanism of infection is independent or co-operative for low doses of transmissible spongiform encephalopathy (TSE) agent is critical for risk assessment. The susceptibility (and hence ID(50)) of individuals with the same prion protein (PrP) genotype may vary considerably with a small proportion being very susceptible. Assuming independent action, the incubation period (IP) would continue to increase until the dose is below the ID(50) of the most susceptible individuals in the experiment, at which point it would become constant. This may explain the observed increase in IP with decreasing dose below the apparent ID(50) in experiments with untreated TSE agent. In contrast, IPs for autoclaved or NaOH-treated TSE agent increase greatly at doses 相似文献
524.
While the conversion of the normal form of prion protein to a conformationally distinct pathogenic form is recognized to be the primary cause of prion disease, it is not clear how this leads to spongiform change, neuronal dysfunction and death. Mahogunin ring finger-1 (Mgrn1) and Attractin (Atrn) null mutant mice accumulate vacuoles throughout the brain that appear very similar to those associated with prion disease, but they do not accumulate the protease-resistant scrapie form of the prion protein or become sick. A study demonstrating an interaction between cytosolically-exposed prion protein and MGRN1 suggested that disruption of MGRN1 function may contribute to prion disease pathogenesis, but we recently showed that neither loss of MGRN1 nor MGRN1 overexpression influences the onset or progression of prion disease following intracerebral inoculation with Rocky Mountain Laboratory prions. Here, we show that loss of ATRN also has no effect on prion disease onset or progression and discuss possible mechanisms that could cause vacuolation of the central nervous system in Mgrn1 and Atrn null mutant mice and whether the same pathways might contribute to this intriguing phenotype in prion disease. 相似文献
525.
D.W. Fairbairn R.N. Thwaits G.R. Holyoak K.L. O'Neill 《FEMS microbiology letters》1994,123(3):233-239
Abstract The etiology of spongiform encephalopathies has been sharply contested for decades. At the heart of the issue is the question of disease origin: Are prion diseases representative of primary neurodegenerative genetic disorders, or are they bona fide infectious diseases? This article provides a brief outline of the progress made in the elucidation of prion disease mechanisms in the context of pathological support of the 'protein only' hypothesis. The answer to the above question appears to be that spongiform encephalopathies are uniquely both infectious and genetic neurodegenerative diseases. 相似文献
526.
Chronic thiamine deprivation in the rat leads to ataxia, loss of righting reflex and neuropathological damage to lateral vestibular nucleus. Before onset of neurological symptoms, transketolase (TK) activities were found to be selectively reduced by 25% in lateral vestibular nucleus and surrounding pons. Further progression of thiamine deprivation resulted in a generalized reduction in TK activity. Measurement of enzyme activity in the presence of added TPP cofactor in vitro did not lead to normalisation of enzyme activities suggesting loss of apoenzyme. Administration of thiamine to symptomatic thiamine-deprived rats resulted in reversal of neurological symptoms and to normalisation of defective TK activities in less vulnerable structures such as cerebral cortex striatum and hippocampus; reduction of TK activity, however, persisted in brainstem and cerebellar regions. Pyrithiamine treatment results, within 3 weeks, in loss of righting reflex, convulsions and more widespread neuropathological damage compared to that observed following thiamine deprivation. TK activity was found to be significantly decreased before the onset of neurological symptoms in all brain regions and appearance of symptoms was accompanied by more severe reductions of TK. In contrast to chronic thiamine deprivation, TK activities following pyrithiamine treatment were: (i) equally reduced in magnitude in vulnerable and non-vulnerable brain structures, (ii) unchanged following reversal of neurological abnormalities by thiamine administration. 相似文献
527.
Early SIV encephalopathy 总被引:5,自引:0,他引:5
B Hurtrel L Chakrabarti M Hurtrel M A Maire D Dormont L Montagnier 《Journal of medical primatology》1991,20(4):159-166
SIV encephalopathy was studied in rhesus macaques early after intracerebral (IC) or intravenous (IV) inoculation. Although SIV was detected in the brain of all IC-inoculated animals, the CNS showed moderate neuropathological changes. IV-inoculated animals presented a spectrum of brain changes ranging from perivascular infiltrates to multinucleated giant cells. CNS infection was detected as early as seven days post-IV-inoculation, mostly in a perivascular localization. Using combined immunohistochemistry and in situ hybridization, infected cells were shown to express macrophage markers. 相似文献
528.
Transforming data sets to bring out expected model features can be valuable within limits and misleading outside them. Here we establish such limits for the widely used Gjedde-Patlak representation of dynamic PET data, with an application to hepatic encephalopathy. 相似文献
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530.
The variation of the exon 2 of the major histo-compatibility complex (MHC) class Ⅱ gene DRB locus in three feline species were examined on clouded leopard (Neofelis nebulosa), leopard (Panthera pardus) and Amur tiger (Panthera tigris altaica). A pair of degenerated primers was used to amplify DRB locus covering almost the whole exon 2. Exon 2 encodes the β1 domain which is the most vari-able fragments of the MHC class Ⅱ molecule. Single-strand conformational polymorphism (SSCP) analysis was applied to detect different MHC class Ⅱ DRB haplotypes. Fifteen recombinant plasmids for each individual were screened out, isolated, purified and sequenced finally. Totally eight distinct haplotypes of exon 2 were obtained in four individuals. With-in 237 bp nucleotide sequences from four samples, 30 vari-able positions were found, and 21 putative peptide-binding positions were disclosed in 79 amino acid residues. The ratio of nonsynonymous substitutions (dN) was much higher than that of synonymous substitutions (dS), which indicated that balancing selection probably maintain the variation ofexon 2. MEGA neighbor joining (N J) and PAUP maximum parsimo-ny (MP) methods were used to reconstruct phylogenetic trees among species, respectively. Results displayed a more close relationship between leopard and tiger; however, clouded leopard has a comparatively distant relationship form the other two. 相似文献