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M J Stack,
S J Moore,
A Davis, P R Webb,
J M Bradshaw,
Y H Lee,
M Chaplin,
R Focosi-Snyman,
L Thurston,
Y I Spencer,
S A C Hawkins,
M E Arnold,
M M Simmons,
G A H Wells
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[hide abstract]
ABSTRACT: Bovine spongiform encephalopathy (BSE) is a prion disease of domesticated cattle, first identified in Great Britain (GB) in 1986. The disease has been characterized by histopathological, immunohistochemical, biochemical and biological properties, which have shown a consistent disease phenotype among cases obtained by passive surveillance. With the advent of active surveillance in 2001, immunological tests for detection of the prion protein revealed some cases with different biochemical characteristics and, in certain instances, differences in pathology that have indicated variant phenotypes and the possibility of agent strain variation. This study examines a case set of 523 bovine brains derived from archived material identified through passive surveillance in GB. All cases conformed to the phenotype of classical BSE (BSE-C) by histopathological, immunohistochemical and biochemical approaches. The analyses consolidated an understanding of BSE-C and, by western blotting, confirmed differentiation from the known atypical BSE cases which exhibit higher or lower molecular masses than BSE-C (BSE-H and BSE-L respectively).
Journal of comparative pathology 12/2010; 144(4):277-88. · 1.73 Impact Factor
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M M Simmons,
J Spiropoulos, P R Webb,
Y I Spencer,
S Czub,
R Mueller,
A Davis,
M E Arnold,
S Marsh,
S A C Hawkins,
J A Cooper,
T Konold,
G A H Wells
[show abstract]
[hide abstract]
ABSTRACT: Tissues from sequential-kill time course studies of bovine spongiform encephalopathy (BSE) were examined to define PrP immunohistochemical labeling forms and map disease-specific labeling over the disease course after oral exposure to the BSE agent at two dose levels. Study was confined to brainstem, spinal cord, and certain peripheral nervous system ganglia-tissues implicated in pathogenesis and diagnosis or disease control strategies. Disease-specific labeling in the brainstem in 39 of 220 test animals showed the forms and patterns observed in natural disease and invariably preceded spongiform changes. A precise temporal pattern of increase in labeling was not apparent, but labeling was generally most widespread in clinical cases, and it always involved neuroanatomic locations in the medulla oblongata. In two cases, sparse labeling was confined to one or more neuroanatomic nuclei of the medulla oblongata. When involved, the spinal cord was affected at all levels, providing no indication of temporal spread within the cord axis or relative to the brainstem. Where minimal PrP labeling occurred in the thoracic spinal cord, it was consistent with initial involvement of general visceral efferent neurons. Labeling of ganglia involved only sensory ganglia and only when PrP was present in the brainstem and spinal cord. These experimental transmissions mimicked the neuropathologic findings in BSE-C field cases, independent of dose of agent or stage of disease. The model supports current diagnostic sampling approaches and control measures for the removal and destruction of nervous system tissues in slaughtered cattle.
Veterinary Pathology 11/2010; 48(5):948-63. · 1.95 Impact Factor
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M E Arnold,
J B M Ryan,
T Konold,
M M Simmons,
Y I Spencer,
A Wear,
M Chaplin,
M Stack,
S Czub,
R Mueller, P R Webb,
A Davis,
J Spiropoulos,
J Holdaway,
S A C Hawkins,
A R Austin,
G A H Wells
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[hide abstract]
ABSTRACT: This study examines tissues from sequential-kill, time-course pathogenesis studies to refine estimates of the age at which disease-specific PrP (PrP(Sc)) can first be detected in the central nervous system (CNS) and related peripheral nervous system ganglia of cattle incubating bovine spongiform encephalopathy (BSE). Such estimates are important for risk assessments of the age at which these tissues should be removed from cattle at slaughter to prevent human and animal exposure to BSE infection. Tissues were examined from cattle dosed orally with 100 or 1 g BSE-infected brain. Incubation period data for the doses were obtained from attack rate and the sequential-kill studies. A statistical model, fitted by maximum likelihood, accounted for the differences in the lognormal incubation period and the logistic probability of infection between different dose groups. Initial detection of PrP(Sc) during incubation was invariably in the brainstem and the earliest was at 30 and 44 months post-exposure for the 100 g- and 1 g-dosed sequential-kill study groups, respectively. The point at which PrP(Sc) in 50 % of the animals would be detected by immunohistochemistry applied to medulla-obex was estimated at 9.6 and 1.7 months before clinical onset for the 100 g- and 1 g-dosed cattle, respectively, with a low probability of detection in any of the tissues examined at more than 12 months before clinical onset. PrP(Sc) was detected inconsistently in dorsal root ganglia, concurrent with or after detection in CNS, and not at all in certain sympathetic nervous system ganglia.
Journal of General Virology 12/2007; 88(Pt 11):3198-208. · 3.36 Impact Factor
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M.J. Stack,
S.J. Moore,
A. Davis, P.R. Webb,
J.M. Bradshaw,
Y.H. Lee,
M. Chaplin,
R. Focosi-Snyman,
L. Thurston,
Y.I. Spencer,
S.A.C. Hawkins,
M.E. Arnold,
M.M. Simmons,
G.A.H. Wells
[show abstract]
[hide abstract]
ABSTRACT: Bovine spongiform encephalopathy (BSE) is a prion disease of domesticated cattle, first identified in Great Britain (GB) in 1986. The disease has been characterized by histopathological, immunohistochemical, biochemical and biological properties, which have shown a consistent disease phenotype among cases obtained by passive surveillance. With the advent of active surveillance in 2001, immunological tests for detection of the prion protein revealed some cases with different biochemical characteristics and, in certain instances, differences in pathology that have indicated variant phenotypes and the possibility of agent strain variation. This study examines a case set of 523 bovine brains derived from archived material identified through passive surveillance in GB. All cases conformed to the phenotype of classical BSE (BSE-C) by histopathological, immunohistochemical and biochemical approaches. The analyses consolidated an understanding of BSE-C and, by western blotting, confirmed differentiation from the known atypical BSE cases which exhibit higher or lower molecular masses than BSE-C (BSE-H and BSE-L respectively).
Journal of Comparative Pathology.
