Analyses of food chains supporting isolated clusters of sporadic TSEs (CWD in N Colorado, scrapie in Iceland, CJD in Slovakia) demonstrate a consistent 2 1/2+ fold greater concentration of the pro-oxidant divalent cat...
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Analyses of food chains supporting isolated clusters of sporadic TSEs (CWD in N Colorado, scrapie in Iceland, CJD in Slovakia) demonstrate a consistent 2 1/2+ fold greater concentration of the pro-oxidant divalent cation, manganese (Mn), in relation to normal levels recorded in adjoining TSE-free localities. Deficiencies of the antioxidant co factors Cu/Se/Zn/Fe and Mg, P and Na were also consistently recorded in TSE foodchains. Similarities between the clinical/pathological profile of TSEs and Mn delayed psycho-neurotoxicity in miners are cited, and a novel theory generated which suggests that sporadic TSE results from early life dependence of TSE susceptible genotypes on ecosytems characterised by this specific pattern of mineral imbalance. Low Cu/Fe induces an excessive absorption of Mn in ruminants and an increased oxidation of Mn2+ into its pro oxidant species, Mn3+, which accumulates in mitochondria of CNS astrocytes in Mn SOD deficient genotypes. Deficiencies of scavenger co factors Cu/Zn/Se/Fe in the CNS permits Mn3+ initiated chain reactions of auto-oxidant mediated neuronal degeneration to proliferate, which, in turn, up-regulates the expression of the Cu-metalloprotein, prion protein (PrP). Once the rate of PrP turnover and its demand for Cu exceeds the already depleted supply of Cu within the CNS, PrP can no longer bind sufficient Cu to maintain its conformation. Mn3+ substitutes at the vacated Gu domain on PrP, thus priming up a latent capacity for lethal auto-oxidative activity to be carried along with PrP like a 'trojan horse';where Mn3+ serves as the integral 'infectious' transmissible component of the misfolded PrP-cation complex. The Mn overactivation of concanavalin A binding to glycoprotein and Mn-initiated autoxidation results in a diverse pathological profile involving receptor capping, aggregation/modification of CNS membrane/cytoskeletal proteins. TSE ensues. The BSE/nv CJD strain entails a 'synthetic' induction of the same CNS mineral distur
A randomised sample of 2809 apparently healthy sheep, 55 per cent of them less than 15 months of age, which were slaughtered for human consumption at abattoirs in Great Britain in 1997/98, was taken to establish the p...
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A randomised sample of 2809 apparently healthy sheep, 55 per cent of them less than 15 months of age, which were slaughtered for human consumption at abattoirs in Great Britain in 1997/98, was taken to establish the prevalence of scrapie infection. The medulla oblongata of each sheep was examined histopathologically at the level of the obex, and fresh brain tissue was examined for scrapie-associated fibrils (SAF) to establish whether there was evidence of scrapie. In addition, histological sections of the medulla from 500 of the sheep were immunostained with an antiserum to PIP, and the same technique was also applied to any animal found positive or inconclusive by the histological or SAF examinations. Any sheep which was positive by any of these diagnostic methods was also examined by Western immunoblotting, for the detection of the disease-specific protein PrPSc. a total of 2798 sheep (99.6 per cent) were negative by all the methods applied. Ten animals were SAF-positive but negative by all the other methods, and in one animal there was immunohistochemical staining which could not be interpreted unequivocally as disease-specific. A mathematical model was used to estimate the prevalence of scrapie infection in the national slaughtered sheep population which would be consistent with these results. By this model, the absence of unequivocally substantiated cases of scrapie in the sample was consistent with a prevalence of infection in the slaughter population of up to 11 per cent.
In 1998, a questionnaire was sent to 11,554 British sheep farmers to determine how many believed that scrapie cases had occurred in their flock;61-4 per cent of them responded anonymously. The results indicated that 1...
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In 1998, a questionnaire was sent to 11,554 British sheep farmers to determine how many believed that scrapie cases had occurred in their flock;61-4 per cent of them responded anonymously. The results indicated that 14.9 per cent of farmers with more than 30 breeding ewes thought that they had ever experienced scrapie in their flock and 2.7 per cent thought that they had had cases in the past 12 months. A comparison of these results with the number of farmers reporting suspect scrapie cases to MAFF, in accordance with the statutory requirement, suggests that only 13 per cent of farmers who suspect that they may have cases of scrapie are currently reporting them. Scrapie occurred in all regions of the country but there was an apparent regional variation. Larger farms and those with purebred sheep appeared to be at greater risk of having cases. Other differences between affected and unaffected farms included lambing practices and sheep purchasing policy. On the majority of farms the first case occurred in a purchased animal. The survey also revealed a need for the provision of further information about scrapie to farmers.
Information from a scrapie epidemic in a closed INRA Romanov flock is presented. Performances, pedigree, histopathological diagnoses and PrP genotypes were recorded from the beginning of the outbreak (in 1993). Betwee...
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Information from a scrapie epidemic in a closed INRA Romanov flock is presented. Performances, pedigree, histopathological diagnoses and PrP genotypes were recorded from the beginning of the outbreak (in 1993). Between I st of April, 1993 and I st of May, 1997, 1015 animals were exposed to scrapie, and 304 died from this disease. A major influence of the polymorphisms at codons 136, 154 and 171 is shown, A(136)H(153)Q(171) allele carriers proving to be nearly as resistant as A(136)R(154)R(171) carriers. A possible relationship between gastrointestinal parasitism and scrapie is discussed. There is evidence of maternal transmission, with a risk;ratio for artificially fed lambs of 67 percent of the risk of lambs fed by their mother. Our results strongly suggest that resistant animals were not healthy carriers or at least were less infectious when comparing risk for lambs born to healthy dams either of resistant (risk = 0.431) or of susceptible (risk = 1.000) genotype.
Though considerable circumstantial evidence suggests that the pathogen of prion disease is proteinaceous, it has not yet been conclusively identified. Epidemiological observations indicate that a microbial vector is r...
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Though considerable circumstantial evidence suggests that the pathogen of prion disease is proteinaceous, it has not yet been conclusively identified. Epidemiological observations indicate that a microbial vector is responsible for the transmission of natural prion disease in sheep and goats and that the real causative agent may correspond to a structural protein of that microorganism. The microbial protein should resemble prion protein (PrP) and may replicate itself in the host by using mammalian DNA. A similar phenomenon was already described with a protein antigen of the ameba Naegleria gruberi (1-4). The various serotypes of the microbial protein may account for the existence of scrapie strains. It is proposed that many microbial proteins may be capable of replicating themselves in mammalian cells eliciting and sustaining thereby degenerative and/or autoimmune reactions subsequent to infections with microorganisms.
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