Search PubMed⌕ Search

Biomedical subjects

R H Kimberlin

Publications and source records attributed to R H Kimberlin.

At least 55 records · Page 3Linked to original sources
PubMed1982

Pathogenesis of mouse scrapie: patterns of agent replication in different parts of the CNS following intraperitoneal infection.

The dynamics of agent replication were studied at 8 levels of spinal cord and in 9 areas of brain of mice infected intraperitoneally with the 139A strain of scrapie agent. Replication in the CNS was first detectable at 2 levels of spinal cord between thoracic vertebrae 4 and 9. The onset of replication was progressively delayed by up to 4 weeks at increasingly lower levels of spinal cord. A similar trend was seen at higher levels of spinal cord and in brain. In brain, agent replication occurred first in medulla, then in the pons and midbrain, thalamus and hypothalamus and, finally, striatum, septum, hippocampus and cerebral cortex. These results are highly suggestive of spread of infection from peripheral sites of agent replication along autonomic fibres to midthoracic cord, followed by an ascending and descending spread of agent at an apparent rate of 0.5 to 1.0 mm/day until the whole CNS is infected. However, experiments involving sympathectomy gave inconclusive results and the evidence for neural spread of scrapie in the peripheral nervous system is circumstantial.

Animals↗
PubMed1981

Scrapie.

Explore the source record for details and available documents.

Animals↗
PubMed1980

Pathogenesis of mouse scrapie: evidence for neural spread of infection to the CNS.

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 thoracic cord after about 35% of the total incubation period had elapsed (range 25 to 42%). This was followed by the simultaneous onset of replication in brain and lumbar cord which occurred 2 to 4 weeks later. It is difficult to explain these results on the basis of haematogenous spread of infection from peripheral sites of replication (e.g. in spleen) to the CNS. However, the data are consistent with spread of infection along peripheral nerves and, in particular, along nerves of the sympathetic nervous system. It is suggested, therefore, that this may be the major route by which scrapie agent invades the CNS.

Adrenergic Fibers↗
PubMed1980

Sensitivity of scrapie infectivity to detergents and 2-mercaptoethanol.

Exposure of fractions obtained from scrapie-infected mouse brain to Triton X-100 resulted in no change in its infectivity except after sedimentation. Infectivity was reduced after exposure to 2-mercaptoethanol but only in the presence of SDS. These results support the view that protein is an important component of the scrapie agent and that disulfide bonds may play a part in maintaining the structural integrity of the infectious agent.

Animals↗
PubMed1979

Pathogenesis of scrapie: agent multiplication in brain at the first and second passage of hamster scrapie in mice.

The intracerebral (i.c.) injection of mice with a particular source of hamster passaged scrapie produced disease after an incubation period of 325 +/- 6 days (mean +/- s.e.). The incubation period at the second i.e. passage in mice was reduced to 149 +/- 2 days. Studies were made of the dynamics of agent replication at 1st and 2nd passages in mice. At first passage, there was a 'zero phase' lasting about 175 days, when no infectious agent was detected in brain (or spleen), followed by a period of agent replication which lasted 150 days. At second passage, there was no significant 'zero phase' and agent replication occupied the whole of the incubation period. The occurrence of a 'zero phase' on interspecies passage of scrapie is discussed in relation to other reports of a 'zero phase' in mouse passaged scrapie.

Animals↗
PubMed1978

Evidence that the transmission of one source of scrapie agent to hamsters involves separation of agent strains from a mixture.

A previous paper (Kimberlin & Walker, 1977) described an experimental model of scrapie in hamsters in which the incubation period decreased progressively over the first 4 passages before becoming stable at the 5th and subsequent passes. Studies have been made of some of the agent strains present in brains taken from the 2nd, 3rd, 4th and 6th hamster passes. The results indicate the presence of at least two strains of agent at the 3rd passage level. One of these (431K) is highly pathogenic for mice and the other (263K) has an extremely low pathogenicity for mice. However only one of these strains (263K) is present in hamster brain after the 6th serial passage. It is suggested that the 'adaptation' of scrapie to hamsters may involve the selection, from a mixture, of a single strain which is highly pathogenic for hamsters. The possibility of modification of the properties of agent strains on passage discussed.

Animals↗
PubMed1977

Characteristics of a short incubation model of scrapie in the golden hamster.

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 higher (greater than 8-0 -log10 LD50 i.c. units/0-05 g) than those found in mouse scrapie. The biological characteristics of this model of hamster scrapie are reported, including the effects on incubation period of route of inoculation, dose of agent, sex of hamster, ambient temperature (hibernation) and splenectomy. Some general and specific applications of this experimental model of scrapie are discussed.

Age Factors↗
PubMed1977

Genetic markers in Herdwick sheep: no correlation with succeptibility or resistance to experimental scrapie.

Genetic markers were studied in Herdwick sheep, bred at Compton, with special reference to genetically selected lines which differ in susceptibility or resistance to experimentally produced scrapie. There were no correlations between susceptibility to the disease and albumin, pre-albumin, esterase and haemoglobin phenotypes, and between reduced glutathione levels and alpha-mannosidase isoenzymes, the latter possibly representing a previously undescribed genetic marker in sheep.

Animals↗