Gene/Protein Disease Symptom Drug Enzyme Compound
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The study was designed to determine the effect on bovine spongiform encephalopathy (BSE) and scrapie agents of the solvent extraction processes used in the past by British renderers. The raw material was mouse spleen infected with either the 22A strain of scrapie agent or the 301V strain of BSE agent. Samples were exposed to hexane, heptane, petroleum spirit or perchlorethylene at the relevant temperatures for the appropriate times. Control samples were exposed to the same range of temperatures for the same range of times in saline. Other samples were exposed to the hot solvents, followed by treatment with dry heat at 100 degrees C for 30 minutes and steam at 100 degrees C for 30 minutes. Further samples were exposed only to the dry heat and steam cycles. No single complete process was significantly more effective than any of the others, and they all produced only slight inactivation, less than one log on average for both strains of agent. The average degree of inactivation produced by exposure to hot saline was generally comparable to that produced by exposure to the hot solvents. This was also true for the samples exposed only to dry heat and steam compared with those exposed to hot solvent before treatment with dry heat and steam, and suggests that the slight inactivation was caused by the heat rather than by the solvents. It is concluded that the solvent extraction processes used by renderers in Britain had little capacity to inactivate BSE and scrapie agents.
Vet Rec 1998 Jul 04
PMID:Solvent extraction as an adjunct to rendering: the effect on BSE and scrapie agents of hot solvents followed by dry heat and steam. 969 25

Natural scrapie is associated with polymorphisms in the prion protein (PrP) gene. In Suffolks, codon 171 is the codon at which most variation is found; RR171 is thought to be associated with resistance to developing the clinical signs of the disease and QQ171 is associated with susceptibility to the disease. The objectives of this study were first to determine the PrP genotypes of Suffolk stock rams in Ireland, and secondly to compare the genotype profiles of ram lambs from flocks where a breeding programme based on the genotype AA136RR154RR171 had been initiated and from flocks where there was no breeding programme based on PrP genotype. Approximately 13 per cent of the stock rams genotyped in the Irish population were genetically susceptible to showing the clinical signs of the disease. However, lambs from farms that had initiated a selective breeding strategy for RR171 over the past year had a larger proportion of RR171 and a smaller proportion of QQ171 than the stock rams or ram lambs from farms not applying a breeding strategy.
Vet Rec 2000 Mar 18
PMID:Detection of polymorphisms in the prion protein gene in a population of Irish Suffolk sheep. 1077 39

A randomised sample of 2,809 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 PrP, 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 PrP(Sc). A total of 2,798 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.
Vet Rec 2000 Apr 01
PMID:Scrapie surveillance in Great Britain: results of an abattoir survey, 1997/98. 1088 3

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.
Vet Rec 2000 Apr 15
PMID:Descriptive epidemiology of scrapie in Great Britain: results of a postal survey. 1081 30

To determine the levels of background scrapie-like pathology in the brains of clinically normal adult sheep, the brains of 1106 sheep from 28 known scrapie-infected flocks and nine apparently uninfected flocks were examined during 1998 and 1999. One per cent of the brains had vacuolar pathology and disease-specific accumulations of prion protein consistent with a diagnosis of scrapie. All the positive animals had at least one allele of the prion protein gene encoding valine at codon 136, and originated from flocks in which cases of clinical scrapie had been confirmed within the last four years. The parasympathetic nucleus of the vagal nerve was the most consistently and severely affected nucleus in the medulla oblongata, suggesting that the infection enters the brain via ascending fibres of the vagus nerve.
Vet Rec 2000 Oct 14
PMID:Prevalence of vacuolar lesions consistent with scrapie in the brains of healthy cull sheep of the Shetland Islands. 1107 39

Sections of the medulla oblongata from the brains of sheep were examined for prion protein (PrP) by immunohistochemistry. On the basis of the morphology and neuroanatomical distribution of the deposits, distinct disease-associated patterns of PrP deposition were identified in scrapie-affected sheep, suggesting at least four distinct phenotypes of scrapie. In addition, clearly defined patterns of PrP deposition, readily distinguished from the disease-associated PrP deposits, were identified in some normal sheep from scrapie-free flocks. In five sheep, believed to be preclinically affected by scrapie, PrP deposition of a disease-specific type but of restricted distribution was identified, demonstrating the sensitivity of the technique for the diagnosis of scrapie. The neuroanatomical distribution of these early PrP deposits suggest that the route of entry of the scrapie agent into the brain is via parasympathetic motor neurons in the vagus nerve which innervate the gastrointestinal tract.
Vet Rec 2001 Jan 06
PMID:Immunohistochemical detection of PrP in the medulla oblongata of sheep: the spectrum of staining in normal and scrapie-affected sheep. 1120 Apr 10

This paper compares the dinical signs, histopathology, detection of PrPSc protein and PrP genetics of the transmission of BSE to sheep and goats, with the effects of the transmission of natural scrapie from a brain homogenate from a single sheep. After intracerebral and oral inoculations there were similarities in the clinical signs due to the two sources of infection, but there were differences in pathology at the end stage of disease and in the genotypes of the sheep which succumbed to the challenges. The incubation period of BSE was associated with the sheep PrP codon 171 genotype, but the natural scrapie source, despite inducing disease only in known susceptible genotypes, showed no clear association with PrP genotype.
Vet Rec 2001 Feb 10
PMID:Clinical signs, histopathology and genetics of experimental transmission of BSE and natural scrapie to sheep and goats. 1125 21

An accidental infection from a vaccine was suggested as the explanation for the sudden increase in outbreaks of scrapie in Italy in 1997 and 1998. This paper describes a recent outbreak of scrapie in sheep and goats which were exposed to the same vaccine. No ewes or goats had been imported into the herd since 1992, but a vaccine against Mycoplasma agalactiae had been administered twice, in 1995 and 1997. High rates of crude mortality and scrapie incidence were experienced by both species, all birth cohorts were involved and a large proportion of aged animals was affected. A pattern of brain lesions was observed, with slight differences between the sheep and goats, which was very similar to the pattern observed in animals previously exposed to the same vaccine but clearly different from that observed in the brains of sheep with scrapie in a flock not exposed to the vaccine. Regardless of their exposure status, genotype analysis of the sheep showed the presence of polymorphism only at codon 171. The patterns of both incidence and brain lesions provide evidence that the epidemic of scrapie was due to the use of the vaccine.
Vet Rec 2001 Apr 28
PMID:Evidence for the transmission of scrapie to sheep and goats from a vaccine against Mycoplasma agalactiae. 1135 46

Genetic susceptibility to scrapie is associated with polymorphisms in three different codons of the ovine prion protein (PrP) gene (136, 154, 171). Studies of PrP genotypes linked to scrapie have revealed the resistance of homozygous PrPARR/PrPARR animals and the high risk of PrPVRQ/PrPVRQ and PrPvRQ/PrPARQ animals in scrapie-affected flocks. The selection of PrPARR/PrPARR genotypes may therefore provide a strategy for controlling clinical scrapie. The genotypes of 1361 German breeding sheep from 15 different breeds in northern Germany were determined. Apart from the wildtype allele PrPARQ, at least four mutually exclusive allelic variants were found. The greatest variability within the PrP gene was encountered in texel sheep, in which 14 PrP genotypes were found. In the important meat breeds, Suffolk, German whiteheaded mutton and German blackheaded mutton, the PrPARR allele was predominant, and in these breeds the breeding of scrapie-resistant pedigree flocks within four generations seems to be a feasible option. In the texel sheep, the German merino, the German milk and the German land sheep breeds, the frequency of the PrPARR allele was much lower, and in several breeds no homozygous rams were available for breeding purposes. In these breeds the breeding strategy would depend on the number of heterozygous rams available, but resistant pedigree flocks could be achieved within nine generations.
Vet Rec 2001 Sep 22
PMID:PrP genotype frequencies in German breeding sheep and the potential to breed for resistance to scrapie. 1159 80

Semen from 13 bulls, eight with clinical bovine spongiform encephalopathy (BSE), was used to artificially inseminate (AI) 167 cows with clinical BSE, and their resultant embryos were collected non-surgically seven days after AI. The viable and non-viable embryos with intact zonae pellucidae were washed 10 times (as recommended by the International Embryo Transfer Society) then frozen. Later, 587 of the viable embryos were transferred singly into 347 recipient heifers imported from New Zealand, and 266 live offspring were born of which 54.1 per cent had a BSE-positive sire and a BSE-positive dam. The recipients were monitored for clinical signs of BSE for seven years after the transfer, and the offspring were monitored for seven years after birth. Twenty-seven of the recipients and 20 offspring died while being monitored but none showed signs of BSE. Their brains, and the brains of the recipients and offspring killed after seven years, were examined for BSE by histopathology, PrP immunohistochemistry, and by electron microscopy for scrapie-associated fibrils. They were all negative. In addition, 1020 non-viable embryos were sonicated and injected intracerebrally into susceptible mice (20 embryos per mouse) which were monitored for up to 700 days, after which their brains were examined for spongiform lesions. They were all negative. It is concluded that embryos are unlikely to carry BSE infectivity even if they have been collected at the end-stage of the disease, when the risk of maternal transmission is believed to be highest.
Vet Rec 2002 Mar 23
PMID:Studies of embryo transfer from cattle clinically affected by bovine spongiform encephalopathy (BSE). 1193 10


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