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Biomedical subjects

R Somerville

Publications and source records attributed to R Somerville.

12 recordsLinked to original sources
PubMed1999

A single amino acid alteration (101L) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy.

A mutation equivalent to P102L in the human PrP gene, associated with Gerstmann-Straussler syndrome (GSS), has been introduced into the murine PrP gene by gene targeting. Mice homozygous for this mutation (101LL) showed no spontaneous transmissible spongiform encephalopathy (TSE) disease, but had incubation times dramatically different from wild-type mice following inoculation with different TSE sources. Inoculation with GSS produced disease in 101LL mice in 288 days. Disease was transmitted from these mice to both wild-type (226 days) and 101LL mice (148 days). In contrast, 101LL mice infected with ME7 had prolonged incubation times (338 days) compared with wild-type mice (161 days). The 101L mutation does not, therefore, produce any spontaneous genetic disease in mice but significantly alters the incubation time of TSE infection. Additionally, a rapid TSE transmission was demonstrated despite extremely low levels of disease-associated PrP.

Alleles↗
PubMed1999

Immunolocalization of the prion protein in scrapie affected rodent retinas.

Some mouse and hamster scrapie models are known to replicate infectivity in the retina, and this can be associated with photoreceptor atrophy. We used immuno-labelling to identify the cellular localization of the prion protein (PrP) in the retina and correlated this with infectivity titre. It is only with the 263K scrapie strain in hamsters that disease-associated PrP (PrP(Sc)) staining was always easily detectable. Very little PrP(Sc) immunolabelling was observed in any of the mouse models, even in those demonstrating scrapie-induced retinopathy in which high titres of infective agent are known to occur in the retina.

Animals↗
PubMed1999

Mechanism(s) of attenuation of Theileria annulata vaccine cell lines.

Attenuated vaccines are an important means of controlling Theileria annulata infection of cattle. Production is by prolonged cultivation of macroschizont-infected cells. The mechanism of attenuation remains unclear. There are three general nonmutually exclusive possibilities: Selection of avirulent subpopulations, genome rearrangements and alterations in gene expression. Several groups, including ours, have provided evidence that the population structure usually tends to simplify during attenuation. Our data on the T. annulata (Ta) Ankara cell line show that attenuation is not necessarily accompanied by the population becoming clonal. We have been unable to detect large DNA rearrangements. Evidence for alterations in host and parasite gene expression during attenuation is available. With respect to the host we have shown that attenuation is accompanied by loss of expression of parasite induced matrix metalloproteinases (MMPs). However, in different lines different protease activities are involved. In the T. annulata Ode line we have shown that 8 activities (including MMP9) are downregulated and that this correlates with a loss of metastatic behaviour. This has previously been shown in vitro using reconstituted basement membrane (Matrigel) and is demonstrated in vivo using scid mice in this study. Thus part of the pathology, namely the ability to disseminate, mediated by host MMPs, is lost upon attenuation. Re-isolation experiments have shown that the reduction/loss of MMP is a stable transferable trait. A logical extension is that loss of MMP activity (and virulence in general) must be at the most fundamental level a genetic trait of the parasite. Evidence for loss of parasite gene expression is implied by the loss of the ability to differentiate into merozoites on attenuation. Specific evidence for loss of parasite gene expression has been obtained using differential RNA display. We view virulence as a multifactorial phenomenon involving interacting subpopulations of cells and attenuation is a threshold effect whereby the number of virulence factors is reduced below a critical level. On this basis there will be many different ways to achieve attenuation.

Animals↗
PubMed1989

Bovine spongiform encephalopathy: a scrapie-like disease of British cattle.

Scrapie is a CNS degenerative infection of sheep and goats, which is invariably fatal after incubation periods of several months to years. Related disorders are found naturally in man and other species. There is a impairment of protein catabolism in scrapie and related diseases which leads to the accumulation of sparingly-soluble protein deposits in brain. These protein aggregates may share with the amyloid of Alzheimer's disease (AD) some common stage in the biochemical pathways of their formation, although different proteins are affected in scrapie (the PrP protein) and AD (the A4-precursor protein). Recently, cattle with the clinical signs and brain pathology of a neurodegenerative disease have been reported, and this cattle disorder has been called bovine spongiform encephalopathy (BSE). BSE-affected brains contain abnormal forms of the bovine homologue of PrP. This provides biochemical evidence that BSE is cattle scrapie rather than cattle AD.

Animals↗
PubMed1983

Trp repressor protein is capable of intruding into other amino acid biosynthetic systems.

Escherichia coli strains with elevated intracellular levels of Trp repressor protein displayed complete growth inhibition on minimal media which contained high levels of tryptophan. The inhibition was attributable to the acquisition of a compound nutritional requirement, which could be satisfied by a combination of isoleucine, leucine, valine, threonine, serine, phenylalanine, and tyrosine. It is proposed that Trp repressor protein, at elevated levels, represses the transcription of those genes which encode enzymes for the biosynthesis of these particular amino acids. Data which support this model are presented, together with a discussion of its regulatory implications.

Amino Acids↗
PubMed1980

Tertiary trisomy (22q11q),47,+der(22),t(11;22).

We describe a case of tertiary trisomy (22q11q) 47,XX,+der(22),(22pter = to 22q13 :: 11q25 = to 11qter) in a child with mental retardation, cleft palate, and congenital heart disease resulting from 3 : 1 meiotic nondisjunction in a maternal (11;22) translocation carrier. The clinical findings in previously reported cases are reviewed and compared with the features of reported patients with "partial trisomy 11q" and "trisomy 22" syndromes. Half of the ten reported families had additional balanced translocation carriers who may have an increased risk of having a liveborn child with an MCA/MR syndrome, although none have been reported to date.

Adolescent↗
PubMedDate not supplied

Oral care in the intensive care setting: a case study.

Oral care is discussed as an important part of total patient care. The aetiology of periodontitis, and the formation and control of plaque, are outlined. Principles of mouth care are illustrated through the use of a case study. Results of a small pilot study suggest there is a need for evidence-based teaching on oral care. Conclusions identify that oral care is an important component of promoting comfort.

Aged↗