Richard H Kimberlin

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Previous studies of peripherally injected mouse scrapie suggested that invasion of the CNS occurs initially in mid-thoracic cord by neural spread of infection from spleen and other visceral sites of extraneural replication. We now show that infection of the left sciatic nerve leads to direct spread of infection to brain (at a rate of approximately 1.0-2.0(More)
The interspecies transmission of scrapie is frequently associated with exceptionally long incubation periods at first passage in the new host compared to later passages (the species barrier effect). The basis of this was investigated using the 139A strain of scrapie which had been cloned by three serial passages in mice at limiting infectious doses. Cloned(More)
The pathogenesis of 139A scrapie has been studied in CW mice infected intraperitoneally (i.p.), intravenously (i.v.) or subcutaneously (s.c.). In mice splenectomised before i.p. infection, the evidence points to a neuroinvasive pathway from visceral lymph nodes (and other sites of scrapie replication in the peritoneum) to the thoracic spinal cord. However,(More)
Repeated passage of the "Chandler" strain of scrapie in female golden hamsters using the intracerebral route of inoculation reduces the minimum incubation period to 60 days, about half of the minimum incubation period so far found in any of the mouse models of scrapie. The infectivity titres in brain in the clinical stage of the disease are considerably(More)
The replication of infectious agent has been studied in brain, thoracic cord, and lumbar cord of Compton white mice (Sinc87) infected with the 139A strain of scrapie. Nine experiments were carried out using four different peripheral routes of injection. A highly consistent pattern of results was obtained in which replication in the CNS started in the(More)
Infection via the gastrointestinal tract is likely to be a natural route of scrapie infection in sheep. This paper describes the pathogenesis of the 139A strain of scrapie introduced intragastrically (i.g.) into CW mice. There was an almost immediate uptake of infectivity and onset of replication in Peyer's patches which preceded replication in spleen.(More)
After intracerebral (i.c.) infection of hamsters, the 263K strain of scrapie replicated at a nearly constant exponential rate until clinical disease developed when titres in brain averaged 9.8 log10 LD50 i.c. units/g. After intraperitoneal infection, scrapie replication was first detected in spleen, then in thoracic spinal cord and finally in lumbar cord(More)
A variety of disinfection procedures were tested on two strains of scrapie agent, treated either as brain macerates (autoclaving) or as 10% homogenates (chemical treatments). It is suggested that a given treatment should produce a titre loss, of both strains of scrapie, of at least 10(4) units before it be regarded as useful for the disinfection of the(More)
The development of a short incubation model of scrapie (strain 263K), in golden hamsters has added impetus to the purification of the infectious agent. Our own attempts have been based on methods pioneered by Millson and developed by Prusiner. We present here results indicating that a purification factor of up to 10(4) with respect to protein may now be(More)