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Biomedical subjects

A M Gibson

Publications and source records attributed to A M Gibson.

At least 19 recordsLinked to original sources
PubMed2005

A new quantitative analysis of significant timing differences between externally cued and self-initiated motor tasks in an fMRI study.

It is generally accepted that the temporal resolution of blood oxygenation level dependent functional MRI is limited due to the inherent latency and longevity of the haemodynamic response. However, in this study we introduce a technique for measurement of timing differences from within the same brain region in two (or more) separate tasks that allows accurate determination of cortical timing differences 200 ms. Our technique, based on a novel use of linear regression analysis, is shown to yield accurate results both in simulated and experimental data. We show that cortical timing differences measured using fMRI are consistent with published electrophysiological results. Measurement of timing differences using this technique could prove a useful strategy for identifying neural network components in a wide range of cognitive paradigms.

Algorithms↗
PubMed2005

Choosing life support for suddenly severely ill elderly relatives.

OBJECTIVE: To determine whether relatives are more likely to request intensive treatment for elderly relatives than the elderly parents would wish for themselves, and to explore the reasons which drive this behaviour. METHODS: A potential end-of-life scenario was presented to 30 elderly people and also to their next generation relative who could be required to be a surrogate decision-maker for their elderly relative in the future. A semi-structured interview (which was designed to avoid the use of leading questions) was undertaken by a trained psychology researcher to ascertain the views of the subjects with regard to treatment choices and the motivation underlying these views. RESULTS: Of the potential patients, 83% reported that they would not want intensive treatment in the hypothetical situation. However, while 76% of surrogates also stated that they believed that treatment was inappropriate, all of the surrogates elected to initiate treatment. The need for time to get the family together, the need to reach family consensus and the need to be more certain of prognosis, were major influences which led the surrogates to request initiation of intensive treatment. CONCLUSIONS: Better understanding of the factors which motivate surrogate decision-makers may help the development of measures to avoid the inappropriate use of high technology treatment at the end of life and to achieve outcomes which better match the wishes of the patients whom we treat. Measures which encourage elderly, chronically ill patients to determine their treatment (e.g. by advance directives), rather than delegating the responsibility to relatives, are likely to result in less demand for inappropriate intensive care treatment.

Journal Article↗
PubMed2004

Influence of the amyloid precursor protein locus on dementia in Down syndrome.

BACKGROUND: The amyloid precursor protein (APP) locus on chromosome 21 influences the development of Alzheimer disease. METHOD: The authors investigated the relationship between a tetranucleotide repeat on intron 7 of the APP gene and the age at onset of dementia in Down syndrome (DS). RESULTS: There was a 13-year difference in the age at onset of dementia in DS associated with the number of tetranucleotide repeat alleles in APP. CONCLUSION: APP is an important locus predicting the age at onset of dementia in people with Down syndrome.

Adult↗
PubMed2001

Nitric oxide synthase gene polymorphisms in Alzheimer's disease and dementia with Lewy bodies.

Evidence suggests that vascular and inflammatory components may be important in the aetiology of dementia and genetic risk factors affecting these processes may therefore influence disease development. Recently, polymorphisms in the endothelial constitutive nitric oxide synthase 3 (NOS3) and also the inducible nitric oxide synthase gene (NOS2A) have been suggested to lead to increased risk of Alzheimer's disease (AD) or dementia with Lewy bodies. We have studied the relationship of both these NOS gene polymorphisms to development of AD and dementia with Lewy bodies and find no evidence for association with either condition. We conclude that NOS gene polymorphisms do not alter disease risk in the majority of late-onset dementia cases.

Aged↗
PubMed2000

The effect of 100% CO2 on the growth of nonproteolytic Clostridium botulinum at chill temperatures.

The growth of a cocktail of spores from six nonproteolytic Clostridium botulinum type B and E isolates at 5 and 10 degrees C was used to assess the combined effect of NaCl (0.5-4.5% w/v), pH (5.5-6.5) and atmosphere (10% H2:90% N2, 5% CO2:10% H2:85% N2, or 100% CO2) in buffered peptone, yeast, glucose, starch broth with an Eh of approximately -350 mV. Under all atmospheres growth tended to be slower as the concentration of NaCl increased and with NaCl combined with pH levels below 6.0. Of the atmospheres tested, growth occurred at a slower rate and over a narrower range of conditions when C. botulinum was exposed to 100% CO2. This effect was enhanced when the incubation temperature was 5 degrees C. The results indicate that while CO2 decreased C. botulinum growth at chill temperatures, prevention of growth also depended on the NaCl concentration and the pH of the medium.

Carbon Dioxide↗
PubMed2000

Lack of association of the alpha2-macroglobulin locus on chromosome 12 in AD.

OBJECTIVE: Analysis of AD has revealed that the apolipoprotein E locus (APOE) cannot account for all of the genetic risk associated with AD. Whole genome scanning in AD families suggests that a chromosome 12 locus may contribute significantly to disease development. The alpha2-macroglobulin gene (A2M) has been suggested as a candidate locus for AD based on analysis of familial AD. METHOD: We determined, in 195 neuropathologically verified AD cases and 107 age-matched control subjects, the association of two common polymorphisms in A2M (a pentanucleotide deletion 5' to the bait domain exon, and a valine-1000-isoleucine polymorphism in the thiolester site of the protein). RESULTS: Evidence was observed for linkage disequilibrium between the deletion and Ile1000 polymorphisms. No evidence was observed for an association between the thiolester polymorphism and AD alone or when accounting for the APOE-epsilon4 allele. No alteration in the frequency of the bait domain deletion was observed, although a small excess (4%) of deletion homozygotes was found in the AD group, which were absent in the control population. CONCLUSIONS: The A2M deletion polymorphism at most accounts for a small fraction of the genetic contribution toward AD, and this is small compared with APOE. Furthermore, reverse transcriptase PCR of A2M RNA from the brains of patients homozygous for the deletion polymorphism showed that the bait domain exon still is present in the RNA. This suggests that the A2M deletion polymorphism may be nonfunctional and that the chromosome 12 AD locus is situated elsewhere.

Aged↗
PubMed1999

Alpha2-macroglobulin polymorphisms in Alzheimer's disease and dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is the second most common cause of dementia in the elderly after Alzheimer's disease (AD). The apolipoprotein E gene (APOE) is a major risk factor, but can only account for approximately 50% of AD cases. Whole genome scanning in late-onset AD families has suggested that a locus on chromosome 12 may contribute significantly to disease development. Recently the alpha2-macroglobulin gene (A2M) on chromosome 12 has been suggested as a candidate locus for AD. We therefore determined the influence of two polymorphisms in A2M, a pentanucleotide deletion 5' to the bait domain exon, and a valine to isoleucine polymorphism in the thiolester site of the protein, in AD and DLB cohorts. No evidence was observed for an association between the thiolester or deletion polymorphisms and AD or DLB alone or when accounting for the APOE epsilon4 allele. We did, however, identify a non-significant excess of deletion homozygotes in the AD and DLB groups. This genotype accounted for 4% of disease cases but was absent in the control population. Given that the A2M deletion polymorphism is non-functional, the chromosome 12 AD/DLB locus may be situated elsewhere and not with these A2M polymorphisms.

Aged↗
PubMed1998

No association between the K variant of the butyrylcholinesterase gene and pathologically confirmed Alzheimer's disease.

The polymorphic K variant of the butyrylcholinesterase ( BCHE-K ) gene recently has been demonstrated to have an elevated frequency in Alzheimer's disease (AD) patients carrying the epsilon4 allele of the apolipoprotein (APO E) gene when compared with a control population. We therefore genotyped a large series of pathologically confirmed AD patients and controls to confirm this association. We found no change in the frequency of this genetic variant, either in the AD group as a whole or in early- or late-onset patients when compared with age-matched controls. Stratification of these groups with reference to the APO E epsilon4 allele also showed no difference between AD and control groups. To determine if a biological effect were present, we also looked at senile plaque and neurofibrillary tangle densities in the frontal, temporal, parietal and occipital cortices in AD patients either carrying or not carrying a copy of the K variant. We found no difference in plaque or tangle load between these two groups in either the total, late-onset or early-onset AD subjects. Stratification of the total AD group in terms of APO E epsilon4 allele possession, and further comparison of plaque and tangle load between carriers and non-carriers of BCHE-K still failed to disclose a relationship between BCHE-K and AD. We conclude that in the population studied here there is no association between BCHE-K and AD, or that if such a relationship exists it is precluded by another, as yet unknown factor.

Age of Onset↗
PubMed1997

Degradation of Alzheimer's beta-amyloid protein by human and rat brain peptidases: involvement of insulin-degrading enzyme.

We examined the degradation of Alzheimer's beta-amyloid protein (1-40) by soluble and synaptic membrane fractions from post mortem human and fresh rat brain using HPLC. Most of the activity at neutral pH was in the soluble fraction. The activity was thiol and metal dependent, with a similar inhibition profile to insulin-degrading enzyme. Immunoprecipitation of insulin-degrading enzyme from the human soluble fraction using a monoclonal antibody removed over 85% of the beta-amyloid protein degrading activity. Thus insulin-degrading enzyme is the main soluble beta-amyloid degrading enzyme at neutral pH in human brain. The highest beta-amyloid protein degrading activity in the soluble fractions occurred between pH 4-5, and this activity was inhibited by pepstatin, implicating an aspartyl protease. Synaptic membranes had much lower beta-amyloid protein degrading activity than the soluble fraction. EDTA (2mM) caused over 85% inhibition of the degrading activity but inhibitors of endopeptidases -24.11, -24.15, -24.16, angiotensin converting enzyme, aminopeptidases, and carboxypeptidases had little or no effect.

Alzheimer Disease↗
PubMed1996

Degradation of Alzheimer's beta-amyloid protein by human cathepsin D.

The aim of the study was to identify and characterize human brain peptidases capable of degrading Alzheimer's beta-amyloid protein. Synthetic beta-amyloid protein (1-40) was rapidly degraded by a human brain soluble fraction, optimum activity occurring at around pH4. Pepstatin totally inhibited the activity showing that an aspartyl protease was responsible. HPLC separation and identification of the degradation products showed that the L34-M35 bond was the primary site of cleavage followed by hydrolysis of the F19-F20 and F20-A21 bonds. The major lysosomal aspartyl protease, cathepsin D, hydrolysed beta-amyloid protein with the same pH profile, inhibitor sensitivity and bond specificity as the activity present in human brain soluble fraction. We suggest that cathepsin D may play an important role in regulating brain concentrations of beta-amyloid protein (1-40).

Amino Acid Sequence↗
PubMed1994

Predicting fungal growth: the effect of water activity on Aspergillus flavus and related species.

Growth of four species belonging to Aspergillus Section Flavi (A. flavus, A. oryzae, A. parasiticus and A. nomius) was studied at 30 degrees C at ten water activities (aw) between 0.995 and 0.810 adjusted with equal mixtures of glucose and fructose. Colony diameters were measured at intervals and plotted against time. A flexible growth model describing the change in colony diameter (mm) with respect to time was first fitted to the measured growth data and from the fitted curves the maximum colony growth rates were calculated. These values were then fitted with respect to aw to predict colony growth rates at any aw within the range tested. The optimum aw for each species and time to reach a colony diameter of 3 mm were also calculated.

Aspergillus flavus↗
PubMed1994

Polymerase chain reaction for detection of Clostridium botulinum types A, B and E in food, soil and infant faeces.

The application of the polymerase chain reaction (PCR) for detection of Clostridium botulinum types A, B and E in foods, environmental and clinical samples was evaluated and compared to the mouse bioassay. Samples inoculated with 10, 100 and 1000 spores of Cl. botulinum types A and B included pasteurized milk, UHT milk, infant formula, infant faeces, meat juice, canned tuna, mushrooms, blood sausage and soil. Clostridium botulinum type E spores were inoculated into fish eggs, canned tuna, picked herring, raw fish and soil at similar levels. Spores were added to 2.5 g of each sample with the exception of soil which was inoculated in 10 g samples. The presence of Cl. botulinum in sample enrichments was determined by both PCR and the bioassay. An overall correlation of 95.6% was observed between PCR results and the mouse bioassay. Of the total of 114 samples tested there was disparity between the mouse bioassay and the PCR in three samples of soil inoculated with 100 type A or E spores and 10 type B spores per 10 g, respectively, and two samples of infant faeces inoculated with 10 type A or B spores per 2.5 g. All of these samples gave negative animal results and positive PCR results.

Animals↗
PubMed1994

Application of PCR to a clinical and environmental investigation of a case of equine botulism.

PCR for the detection of botulinum neurotoxin gene types A to E was used in the investigation of a case of equine botulism. Samples from a foal diagnosed with toxicoinfectious botulism in 1985 were reanalyzed by PCR and the mouse bioassay in conjunction with an environmental survey. Neurotoxin B was detected by mouse bioassay in culture enrichments of serum, spleen, feces, and intestinal contents. PCR results compared well with mouse bioassay results, detecting type B neurotoxin genes in these samples and also in a liver sample. Other neurotoxin types were not detected by either test. Clostridium botulinum type B was shown to be prevalent in soils collected from the area in which the foal was raised. Four methods were used to test for the presence of botulinum neurotoxin-producing organisms in 66 soil samples taken within a 5-km radius: PCR and agarose gel electrophoresis (types A to E), PCR and an enzyme-linked assay (type B), hybridization of crude alkaline cell lysates with a type B-specific probe, and the mouse bioassay (all types). Fewer soil samples were positive for C. botulinum type B by the mouse bioassay (15%) than by any of the DNA-based detection systems. Hybridization of a type B-specific probe to DNA dot blots (26% of the samples were positive) and PCR-enzyme-linked assay (77% of the samples were positive) were used for the rapid analysis of large numbers of samples, with sensitivity limits of 3 x 10(6) and 3,000 cells, respectively. Conventional detection of PCR products by gel electrophoresis was the most sensitive method (300-cell limit), and in the present environmental survey, neurotoxin B genes only were detected in 94% of the samples.

Animals↗