Biomedical subjects

James C Vickers

Publications and source records attributed to James C Vickers.

21 records · Page 2Linked to original sources

PubMed2002

Sheep have an unusual variant of the brain-specific metallothionein, metallothionein-III.

Sheep metallothionein-III (MT-III) cDNA was isolated from a brain cDNA library and characterized. In contrast with MT-III from other species, sheep MT-III cDNA is predicted to encode a protein with significantly different metal-binding properties, owing to the loss of three of its cysteine residues. RT-PCR from other sheep confirmed that this aberrant structure is ubiquitous in this species. MT-III was successfully isolated from sheep brain, demonstrating that the cDNA does give rise to a protein product of the predicted structure. Sheep MT-III is similar to other mammalian MT-IIIs in that it retains the Cys-Pro-Cys-Pro motif which is thought to encode growth-inhibitory activity, and we show that it is likewise able to inhibit neuron survival in vitro. This is the first naturally occurring variant of MT-III (or any other major mammalian MT gene) which gives rise to a protein product. These findings are discussed in light of proposed roles of MT in the mammalian brain.

Amino Acid Sequence↗

PubMed2002

A vaccine against Alzheimer's disease: developments to date.

There are no significantly effective therapeutic or prophylactic agents for Alzheimer's disease (AD), the leading cause of age-related dementia. AD is characterised pathologically by plaque-like deposits of beta-amyloid in the brain as well as cytoskeletal ("neurofibrillary") alterations within nerve cells. A novel immunisation strategy directed at the beta-amyloid abnormalities underlying plaque pathology has recently been proposed for AD. This approach is supported by experimental studies utilising beta-amyloid as an immunogen, or antibodies to beta-amyloid, in transgenic experimental models that develop plaque pathology but not neurofibrillary alterations or severe neurodegeneration. Behavioural abnormalities in these mice related to deficits in spatial working memory were also ameliorated by immunisation with beta-amyloid. The promise of this novel approach to AD treatment and/or prevention has led to initial human trials utilising beta-amyloid as an immunogen.

Alzheimer Disease↗

PubMed2001

Morphologically distinct plaque types differentially affect dendritic structure and organisation in the early and late stages of Alzheimer's disease.

We have investigated the effects of the deposition of insoluble beta-amyloid plaques on dendritic morphology within the neocortex. Labelling for beta-amyloid identified three morphologically distinct plaque types present both within the brains of preclinical Alzheimer's disease (AD) and end-stage AD cases. In both preclinical and end-stage AD, the percentage area occupied by diffuse plaques contained a greater density of labelling for microtubule-associated protein-2 (MAP2) relative to the surrounding neuropil (case type, ratio of MAP2 labelling in plaque to MAP2 labelling in surrounding neuropil +/- SEM: preclinical, 1.27+/-0.04; end-stage, 1.32+/-0.05). In contrast, there was a greater density of MAP2-labelled processes surrounding dense-cored plaques compared to that found within the plaque area (preclinical, 0.73+/-0.05; end-stage, 0.62+/-0.07). Fibrillar plaques demonstrated a transition from the early to late stages of AD, with a substantial decrease in the density of MAP2 labelling within the plaque area in end-stage AD cases relative to preclinical AD cases (preclinical, 1.01+/-0.1; end-stage, 0.72+/-0.05). The morphology of dendrites associated with dense-core or fibrillar plaques suggest physical disruption of the neuropil by beta-amyloid plaque formation. These data demonstrate that plaque isoforms differentially affect dendritic morphology in both the early and late stages of AD, with progression to clinical AD associated with evolving dendritic damage localised to fibrillar and dense-core plaques.

Aged↗