Linda Davis
Veterinary Laboratories Agency
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Veterinary Record | 2006
L. González; Mark P. Dagleish; Susan J Bellworthy; Sílvia Sisó; M.J. Stack; Melanie J. Chaplin; Linda Davis; S. A. C. Hawkins; J. Hughes; Martin Jeffrey
Samples of tissue from the central nervous system (CNS), the lymphoreticular system (LRS) and the rectal mucosa of a large number of scrapie-exposed sheep, with and without signs of clinical disease, were examined immunohistochemically for evidence of disease-associated prion protein (PrPd). The rectal mucosa has received almost no attention so far in scrapie diagnosis, despite its abundant rectoanal mucosa-associated lymphoid tissue, and its accessibility. The scrapie-confirmed cases included 244 with clinical disease, of which 237 (97·1 per cent) were positive in the rectal mucosa, and 121 apparently healthy sheep, of which 104 (86 per cent) were positive in the rectal mucosa. PrPd was detected in 86·4 to 91·5 per cent of the other LRS tissues of the healthy sheep examined and in 77·7 per cent of their CNS tissues. The stage of infection, therefore, affected the probability of a positive result in the rectal mucosa, whereas the breed, PrP genotype, age and sex had little or no independent effect. Accumulations of PrPd were observed in the rectal mucosa and other LRS tissues of VRQ/ARR sheep with preclinical and clinical scrapie, albeit with a lower frequency and magnitude than in sheep of other PrP genotypes. Western immunoblotting analyses of samples of rectal mucosa gave the characteristic PrP glycoprofile, with a sensitivity similar to that of immunohistochemistry.
Journal of General Virology | 2009
M.J. Stack; Lorenzo González; Martin Jeffrey; Stuart Martin; Colin Macaldowie; Melanie J. Chaplin; Jemma Thorne; Robin Sayers; Linda Davis; Jason Bramwell; Steve Grimmer; Sue J. Bellworthy
During the 1980s, bovine spongiform encephalopathy (BSE)-contaminated meat and bonemeal were probably fed to sheep, raising concerns that BSE may have been transmitted to sheep in the UK. The human disease, variant Creutzfeldt-Jakob disease, arose during the BSE epidemic, and oral exposure of humans to BSE-infected tissues has been implicated in its aetiology. The concern is that sheep BSE could provide another source of BSE exposure to humans via sheep products. Two immunological techniques, Western immunoblotting (WB) and immunohistochemistry (IHC), have been developed to distinguish scrapie from cases of experimental sheep BSE by the characteristics of their respective abnormal, disease-associated prion proteins (PrP(d)). This study compares the WB and IHC characteristics of PrP(d) from brains of primary, secondary and tertiary experimental ovine BSE cases with those of cattle BSE and natural sheep scrapie. Discrimination between experimental sheep BSE and scrapie remained possible by both methods, regardless of the route of challenge.
Journal of Mass Spectrometry | 2009
Adriana Gielbert; Linda Davis; A. Robin Sayers; James Hope; Andrew C. Gill; Maurice J. Sauer
New forms of transmissible spongiform encephalopathy (TSE) continue to be identified, and consequently sensitive differential diagnosis is increasingly important both for the management of disease in humans and livestock and in providing confidence in the safety of the food chain. TSE diseases are associated with accumulation of protease-resistant prion protein (PrP(Sc)) and detection of this marker protein is central to diagnosis. Proteolysis by proteinase K (PK) generates protease-resistant products (PrP(res)) with partially variable N-termini. The conformation(s) of PrP(Sc) and thus the points of PK cleavage are thought to be dependent on the strain of prion disease. Western blot (WB) analysis of PrP(res) gives characteristic migration patterns that can be used to diagnose TSEs, but the relatively low resolution of this technique limits its ability to differentiate certain disease strains. Mass spectrometry (MS) has the capability to resolve these various PK cleavage sites to the level of individual amino acid residues. In the present study multiple selected reaction monitoring (mSRM) was used to detect and quantify PrP(res) N-terminal tryptic peptides by MS and thus to define the N-terminal amino acid profiles (N-TAAPs) of PrP(res) characteristic for various TSEs in sheep. The fragmentation behaviour of the N-terminal tryptic peptides was studied to allow selection of the transitions specific for each peptide. Different PrP(res) preparation methods were evaluated and the most effective approach applied to differentiate the N-TAAPs corresponding to various sheep TSE isolates. Marked differences were identified between the N-TAAPs of bovine spongiform encephalopathy (BSE) and classical scrapie, and between classical scrapie and the experimental strains SSBP/1 and CH1641, thereby validating this approach as a means of TSE-strain specific diagnosis.
Veterinary Record | 2007
Linda A. Terry; R. Jenkins; Leigh Thorne; Sally J. Everest; Melanie J. Chaplin; Linda Davis; M.J. Stack
have been recognised that differ in their PrPres profiles from those typically found. These cases have been detected in Europe (Biacabe and others 2004, Casalone and others 2004, Buschmann and others 2006), Japan (Yamakawa and others 2003) and the USA (Richt and others 2007). Colloquially referred to as ‘atypical BSE’, these cases fall into two types based on the molecular mass of the unglycosylated PrPres band relative to that of classical BSE, one of higher molecular mass (H-type) and the other lower molecular mass (L-type). A transmission study of an H-type BSE agent of French origin to mice has shown that it has biological characteristics distinct from those of the classical BSE agent (Beringue and others 2006). This short communication describes the first case of BSE in Great Britain showing an H-type molecular profile that was indistinguishable from a case previously identified in France. Frozen brainstem from five cases of BSE in cattle and one sheep scrapie case were tested by immunoblotting (TeSeE Western blot kit; Bio-Rad Laboratories) (Arsac and others 2007) according to the manufacturer’s instructions. The samples were diluted, in order to balance the PrPres in each lane, before loading on to a 12 per cent Bis-Tris SDS gel (Bio-Rad
Zoonoses and Public Health | 2009
M.J. Stack; R. Focosi-Snyman; Saira Cawthraw; Linda Davis; R. Jenkins; Leigh Thorne; Melanie J. Chaplin; Sharon Everitt; G. Saunders; Linda A. Terry
Bovine spongiform encephalopathy (BSE) was first identified in Great Britain (GB) in 1986 and was subsequently detected in many other countries, world‐wide. A decade after the start of the bovine epidemic, the first cases of new variant Creutzfeldt‐Jakob disease (vCJD) in humans were linked to probable ingestion of BSE infected tissue, highlighting a new zoonotic disease. An abnormal protease‐resistant protein (PrPres) in a diseased subject, derived from a post‐translational change of a normal host cellular membrane protein (PrPc), is a reliable disease marker for the whole group of neurodegenerative transmissible spongiform encepalopathies (TSEs). Immunology‐based techniques, such as Western immunoblotting, have previously indicated that BSE cases all give a uniform molecular profile for PrPres. Periodic lesion profiling of the spongiform change throughout different brain regions of infected mice and cattle has also indicated a single agent for BSE. However, in 2001 rapid testing for PrPres was introduced for the active surveillance of ruminants within Europe, and approximately 40 BSE cases have now been recognized that differ in their molecular profiles from those typically found. These unusual BSE cases have been detected in several European countries, and in Japan and the USA. At present, the cases appear as two distinct types based on the molecular mass (Mm) of the unglycosylated PrPres protein band relative to that of classical BSE. One type is of a higher Mm (H‐type) and the other shows a lower Mm (L‐type). Transmission studies in mice have shown that both H‐type and L‐type BSE have biological characteristics that are different from those of the classical BSE agent. This study describes the prion protein (PRNP) genotype and molecular profiles of the first two cases of H‐type BSE detected in GB in comparison with those obtained for classical BSE, scrapie in sheep from GB and a control H‐type BSE case from France.
Analytical Biochemistry | 2013
Adriana Gielbert; Linda Davis; A. Robin Sayers; Yue Tang; James Hope; Maurice J. Sauer
Prions are proteins that can exist in two (or more) folding states, a normal or cellular form and a series of infectious or prion forms, which are prone to aggregate. The prion form can induce conversion of the cellular form and so transmit phenotypic effects of this structural rearrangement within and between cells and organisms. The conversion of PrP(C), the mammalian prion glycoprotein, to its prion form, PrP(Sc), in the brain is a precursor to progressive neurological degeneration, and the various folded forms of PrP(Sc) (defined by the size and glycosylation of protease-resistant core peptides of the PrP aggregates, PrP(res)) are characteristic of a particular neurodegenerative phenotype or prion disease. Here, quantitative multiplex mass spectrometry was used for N-terminal amino acid profiling (N-TAAP) of PrP(res) from sheep affected by scrapie, the prion disease of small ruminants, to rapidly assess the diversity of prions within particular flocks. In 29 cases, PrP(res) concentrations varied from below the limit of detection (350 fmol/g) to 15 pmol/g wet brain. Although most had a single N-TAAP profile, two novel variants were identified: one common to the ARH/ARQ animals in this study and one in an animal of the wild-type sheep PrP genotype (ARQ/ARQ).
Research in Veterinary Science | 1998
M.J. Stack; Melanie J. Chaplin; A.M. Aldrich; Linda Davis
The distribution of scrapie-associated fibrils (SAFs) throughout four brain regions, the pituitary gland, along the whole length of the spinal cord and in the sciatic nerve was assessed in 10 sheep terminally affected by scrapie and in four control sheep. Tonsils, retropharyngeal, broncho-mediastinal and mesenteric lymph nodes, the distal ileum, proximal colon and spleen were also examined for fibrils in all 14 sheep. Fibrils were detected in all four brain regions and throughout the length of the spinal cord in nine of the scrapie affected sheep. SAFs were not detectable in any of the sciatic nerve samples tested. In one of the 10 clinically affected sheep only minimal lesions were found by histopathology and fibrils were detected only from the cerebrum and one spinal cord region (taken at the C1 C2 vertebrae). Fibrils were not detected in the tonsils or retropharyngeal lymph nodes but were detected in other non-neural tissues of some of the scrapie-affected sheep. These tissues included pituitary gland, broncho-mediastinal and mesenteric portal lymph nodes, distal ileum, proximal colon and spleen. Fibrils could not be detected in any of the tissues taken from the four control sheep.
Veterinary Record | 2013
M.J. Stack; Melanie J. Chaplin; Linda Davis; Sharon Everitt; M. M. Simmons; Otto Windl; James Hope; P. J. Burke
Bovine spongiform encephalopathy (BSE) is a prion disease of cattle which was first observed in Great Britain (GB) in 1986. Throughout the subsequent BSE epidemic, cases identified by passive surveillance have shown consistent histopathological, immunohistochemical, biochemical and biological properties. However, since the start of active surveillance in 2001, across Europe and elsewhere, approximately 67 cases with different biochemical characteristics have been identified by Western blotting (WB). These cases fall into two categories; ‘H-type’ (H-BSE) or ‘L-type’ (L-BSE), based on the relatively heavy (H-BSE) or light (L-BSE) mass of the unglycosylated band of the prion protein, as compared with WB against that obtained from classical BSE (C-BSE) cases. Here we report the detection and confirmation of the first four L-BSE cases by active surveillance in GB, two of which were born after the reinforced feed ban of 1996 (BARB cases). These four L-BSE cases were found in relatively old cattle (age range; 11–21 years old) and the carcases did not enter the human food chain or animal feed chains.
Veterinary Record | 2005
Lorenzo González; Martin Jeffrey; Sílvia Sisó; Stuart Martin; Sue J. Bellworthy; Mick J. Stack; Melanie J. Chaplin; Linda Davis; Mark P. Dagleish; Hugh W. Reid
Veterinary Record | 2009
M.J. Stack; R. Focosi-Snyman; Saira Cawthraw; Linda Davis; Melanie J. Chaplin; P. J. Burke