Biomedical subjects

Gillian Hamilton

Publications and source records attributed to Gillian Hamilton.

4 recordsLinked to original sources

PubMed2005

Nicastrin gene polymorphisms, cognitive ability level and cognitive ageing.

The hypothesis that polymorphisms in the gene for nicastrin (NCSTN) are associated with differences in cognitive level and ageing was tested in 462 relatively healthy surviving participants of the Scottish Mental Survey 1932. None had a history of dementia. They were tested on the Moray House Test of verbal reasoning at age 11 in 1932 and at age 79 between 1999 and 2001. At age 79 they also took tests of non-verbal reasoning, short- and long-term verbal declarative memory, Verbal Fluency, and a short screening test for dementia. Subjects who possessed at least one copy of the NCSTN B haplotype (Hap B) had higher scores on the Moray House Test (a test principally of verbal reasoning) at age 11 (p=0.036) and age 79 (p=0.027). The effect of Hap B on cognition at age 79 was non-significant after adjusting for the effect at age 11. Therefore, the effect of Hap B in this sample is on the life-long stable trait of cognitive ability, and not on age-related cognitive change. The possibility that this result might be a selection effect was not supported by the samples being in Hardy-Weinberg equilibrium with respect to the distribution of NCSTN genotypes.

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PubMed2005

Glycogen synthase kinase-3 is increased in white cells early in Alzheimer's disease.

Alzheimer's disease (AD) is a disorder without a molecular marker in peripheral tissues or a disease modifying treatment. As increasing evidence has suggested a role for glycogen synthase kinase-3 (GSK-3) in the pathogenesis of the condition we measured total GSK-3 protein (alpha and beta isoforms) and GSK-3 activity (serine 9 phosphorylation) in a group of healthy elderly people, in AD and in mild cognitive impairment (MCI). Total GSK-3 protein was increased in both AD and in MCI without a compensatory decrease in activity. These data suggest that GSK-3 assays might be a useful diagnostic marker in a readily available tissue and moreover that GSK-3 activity is increased in the prodromal phase of the disorder suggesting that inhibition of GSK-3 might be a useful therapeutic strategy.

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PubMed2004

Alpha-T-catenin is expressed in human brain and interacts with the Wnt signaling pathway but is not responsible for linkage to chromosome 10 in Alzheimer's disease.

The gene encoding alpha-T-catenin, CTNNA3, is positioned within a region on chromosome 10, showing strong evidence of linkage to Alzheimer's disease (AD), and is therefore a good positional candidate gene for this disorder. We have demonstrated that alpha-T-catenin is expressed in human brain, and like other alpha-catenins, it inhibits Wnt signaling and is therefore also a functional candidate. We initially genotyped two single-nucleotide polymorphisms (SNPs) in the gene, in four independent samples comprising over 1200 cases and controls but failed to detect an association with either SNP. Similarly, we found no evidence for association between CTNNA3 and AD in a sample of subjects showing linkage to chromosome 10, nor were these SNPs associated with Abeta deposition in brain. To comprehensively screen the gene, we genotyped 30 additional SNPs in a subset of the cases and controls (n > 700). None of these SNPs was associated with disease. Although an excellent candidate, we conclude that CTNNA3 is unlikely to account for the AD susceptibility locus on chromosome 10.

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PubMed2003

The PhoenixCare Program.

In response to a perceived need for patient access to palliative care and supportive services prior to hospice eligibility, Phoenix-based Hospice of the Valley (HOV) applied for and received a 3-year demonstration grant (1999-2001) from The Robert Wood Johnson (RWJ) Promoting Excellence in End-Of-Life Care Project. HOV established the PhoenixCare project as a demonstration of palliative and coordinated care (case management) services for seriously chronically ill individuals still undergoing active treatment of their disease within a managed care setting. The model emphasized patient/family self-empowerment and prevention. The goal was to demonstrate that it was possible to expand the scope of care for the seriously chronically ill, add palliative care, and improve patient quality of life at less (or no more) cost than that for a comparable group of managed care patients not receiving PhoenixCare services. The model proved most useful to patients willing and able to assume a degree of control over their own care. Physicians referred fewer than 5% of the patients enrolled while managed care plan case managers and hospital discharge planners referred 83%, suggesting that in organized systems of care physicians are not a primary source for patient referrals. The structure and content of the PhoenixCare model, its general acceptability to patients, physicians and managed care plans, and its applicability to other sites are discussed in this article. Outcomes from the study will be published in a subsequent paper.

Arizona↗