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Biomedical subjects

J Coates

Publications and source records attributed to J Coates.

At least 19 recordsLinked to original sources

The effect of the apolipoprotein E gene polymorphisms and haplotypes on behavioural and psychological symptoms in probable Alzheimer's disease.

BACKGROUND: Patients with Alzheimer's disease and dementia commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in Alzheimer's disease has been demonstrated. Several studies have investigated whether the exon 4 epsilon2/epsilon3/epsilon4 haplotype of the apolipoprotein E (APOE) gene is associated with BPSD, with variable results. OBJECTIVE: We investigated the exon 4 polymorphisms and extended this study to include promoter polymorphisms and the resultant haplotypes across the gene. METHODS: Our large independent cohort of 388 patients with longitudinal measures of BPSD assessed by the Neuropsychiatric Inventory was used to analyse whether any of these variants were associated with the presence of BPSD. RESULTS: We revealed several significant relationships before correction for multiple testing. The exon 4 haplotype was associated with hallucinations and anxiety, A-491T with irritability, T-427C with agitation/aggression and appetite disturbances, and T-219C with depression. Haplotype analyses of all variants did not reveal any statistically significant findings. CONCLUSIONS: Our data and a review of previous studies showed a diversity of relationships, suggesting that these findings might be due to chance and so collectively do not support a role for the APOE gene in BPSD.

Aged↗

How to reduce the stress of general dental practice: the need for research into the effectiveness of multifaceted interventions.

While the practice of dentistry has been demonstrated to be significantly stressful, there have been few published studies describing interventions to reduce the stress of dental practitioners. This article describes research into the prevention and alleviation of stress amongst a variety of healthcare professionals, including dental practitioners, and describes the findings from a small scale study of an intervention aimed at general dental practitioners who reported high levels of work related stress. It is argued that to be effective, interventions should be tailored to the individual needs of the practitioner, within a structured intervention framework. Further research into the effectiveness and cost-effectiveness of stress management for dental practitioners is required.

Burnout, Professional↗

Are the estrogen receptors involved in Alzheimer's disease?

Retrospective analysis shows that women who took estrogen replacement therapy may have less risk of cognitive decline and of developing Alzheimer's disease (AD). The greater risk associated with female gender and these observations suggest that estrogen may be implicated in the aetiology of AD. Estrogen is one of a family of sex steroids that exerts many of its genomic effects through the activation of the nuclear estrogen receptors, ERalpha and ERbeta. Previously, increased risk for AD has been reported for polymorphisms in the ERalpha gene in a Japanese cohort, however, this association has not been systematically replicated. We have further investigated polymorphisms in the ERalpha and have extended this to investigate an association with a polymorphism within the ERbeta gene in an independent UK Caucasian population. We found no independent association of these polymorphisms with the risk of developing AD in the total sample nor within either gender. However, we did detect a significant interaction between the ERalpha and ERbeta polymorphisms and the risk for AD (OR=0.22 95% CI (0.05-0.88), P=0.02). If this finding can be supported in other independent studies, it may suggest that the risk for AD may be modulated only when both ERalpha and ERbeta have particular variations in their expression and/or biological activities.

Aged↗

The -48 C/T polymorphism in the presenilin 1 promoter is associated with an increased risk of developing Alzheimer's disease and an increased Abeta load in brain.

Mutations in the presenilin 1 gene (PS1) account for the majority of early onset, familial, autosomal dominant forms of Alzheimer's disease (AD), whereas its role in other late onset forms of AD remains unclear. A -48 C/T polymorphism in the PS1 promoter has been associated with an increased genetic risk in early onset complex AD and moreover has been shown to influence the expression of the PS1 gene. This raises the possibility that previous conflicting findings from association studies with homozygosity for the PS1 intron 8 polymorphism might be the result of linkage disequilibrium with the -48 CC genotype. Here we provide further evidence of increased risk of AD associated with homozygosity for the -48 CC genotype (odds ratio=1.6). We also report a phenotypic correlation with Abeta(40), Abeta(42(43)), and total Abeta load in AD brains. The -48 CC genotype was associated with 47% greater total Abeta load (p<0.003) compared to CT + TT genotype bearers. These results suggest that the -48 C/T polymorphism in the PS1 promoter may increase the risk of AD, perhaps by altering PS1 gene expression and thereby influencing Abeta load.

Age of Onset↗

Incursion of epizootic hemorrhagic disease into the Okanagan Valley, British Columbia in 1999.

In September 1999, unusually high mortality rates in white-tailed deer and California bighorn sheep occurred in the southern Okanagan Valley. Necropsy and histopathologic findings were compatible with epizootic hemorrhagic disease (EHD); the presence of virus was not demonstrated. Subsequent serologic and polymerase chain reaction assays on sentinel cattle suggested an EHD virus incursion.

Animals↗

Dose response studies of acute feline immunodeficiency virus PPR strain infection in cats.

The effects of virus dose on host response were evaluated for the PPR strain of feline immunodeficiency virus (FIV-PPR). Specific pathogen-free cats were inoculated intravenously with 50, 250 or 1250 TCID(50) of FIV-PPR. Two weeks after inoculation, virus was detected in 10(6) peripheral blood mononuclear cells (PBMCs) of all infected animals, and the CD4(+):CD8(+) T lymphocyte ratios fell from greater than 2 to approximately 1 in all infected animals within the first 8 weeks after infection. Provirus detected in all groups using PCR and 10(3) PBMC was biphasic. Nine of 15 animals were positive between weeks 2 and 4 p.i. and 14 of 15 were positive by week 8 p.i. Transient lymphadenopathy was detected in most cats receiving 1250 TCID(50) and the 250 TCID(50) of virus, whereas no lymphadenopathy was detected in the 50 TCID(50) group or the five uninfected cats. Animals that had received the largest dose seroconverted earliest (on average at week 4.0) and those receiving the least seroconverted last (on average at week 5.6). Neither neutropenia nor lymphopenia were detected. FIV-specific CTL responses of memory effector cells could be detected in animals receiving all three doses but was highly variable among individual animals. Neurological manifestations determined after 15 weeks p.i. were observed in most infected cats, including two of the three that had received 50 TCID(50) of virus. However, the observed neurologic abnormalities were markedly less severe in the animals receiving the least amount of virus. Therefore, lymphadenopathy and neurologic signs of illness were less severe and seroconversion was slower in the animals that received the lowest dose compared with those receiving the 250 and 1250 TCID(50) doses of the FIV-PPR strain.

Animals↗