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Biomedical subjects

B McDonald

Publications and source records attributed to B McDonald.

At least 19 recordsLinked to original sources
PubMed1992

Nitric oxide-induced S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase inhibits enzymatic activity and increases endogenous ADP-ribosylation.

Using conditions that produced chronic inflammation in rat liver, we were able to find a correlation between induction of nitric oxide production and inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12). This enzyme is a tetramer composed of identical M(r) 37,000 subunits. The tetramer contains 16 thiol groups, four of which are essential for enzymatic activity. Our information indicates that four thiol groups are S-nitrosylated by exposure to authentic nitric oxide (NO) gas. Furthermore, NO decreased GAPDH activity while increasing its auto-ADP-ribosylation. Reduced nicotinamide adenine dinucleotide and dithiothreitol are required for the S-nitrosylation of GAPDH caused by the NO-generating compound sodium nitroprusside. Our results suggests that a new and important action of nitric oxide on cells is the S-nitrosylation and inactivation of GAPDH. S-Nitrosylation of GAPDH may be a key covalent modification of multiple regulatory consequences in chronic liver inflammation.

Adenosine Diphosphate Ribose↗
PubMed1992

Detection in life of confirmed Alzheimer's disease using a simple measurement of medial temporal lobe atrophy by computed tomography.

The medial temporal lobe of the brain is important for normal cognitive function, notably for memory, and is the region with the most extensive pathological change in Alzheimer's disease (AD). We wanted to find out if atrophy of the medial temporal lobe could be detected in life in patients in whom a diagnosis of AD was subsequently established histopathologically. The minimum width of the medial temporal lobe, measured by temporal-lobe-oriented computed tomography (CT) about one year before death, in 44 patients with a histopathological diagnosis of AD (cases) was nearly half (0.56 of the median) that in 75 controls of the same age with no clinical evidence of dementia (95% confidence interval 0.51-0.61). There was little overlap between the distributions of measurements in cases and controls. A cut-off (< 0.79 MoM) selected to yield a 5% false-positive rate gave an expected detection rate of 92%. A cut-off selected to yield a false-positive rate of 1% (< 0.70 MoM) yielded a 79% detection rate. 20 of the 44 patients with histopathologically diagnosed AD had been scanned more than once before death, and the test (cut-off < 0.79 MoM) was positive in all 20 more than a year before and in 9/10 more than 2 years before death. In 10 subjects with dementia but with histopathology excluding AD, the mean minimum width of the medial temporal lobe was significantly greater than that in the cases with AD, but was not significantly different from that in controls. Medial temporal lobe CT is a non-invasive, rapid, simple and effective test for AD which could have immediate application firstly in improving the accuracy of prevalence and incidence studies and, secondly, for the identification of groups of high-risk patients in the evaluation of novel treatments for AD. In the future, it could be applied as a screening test.

Aged↗
PubMed1992

Absence of aluminium in neuritic plaque cores in Alzheimer's disease.

Controversy exists over whether aluminium has a role in the aetiology of Alzheimer's disease. Alzheimer's disease is neuropathologically characterized by the occurrence of a minimum density of neurofibrillary tangles and neuritic plaques in the hippocampus and the association cortex of the brain. The purported association of aluminium with Alzheimer's disease is based on: (1) the experimental induction of fibrillary changes in the neurons of animals by the injection of aluminium salts into brain tissue; (2) reported detection of aluminium in neuritic plaques and tangle-bearing neurons; (3) epidemiological studies linking aluminium levels in the environment, notably water supplies, with an increased prevalence of dementia; and (4) a reported decrease in the rate of disease progression following the administration of desferroxamine, an aluminium chelator, to clinically diagnosed sufferers of Alzheimer's disease. Here we use nuclear microscopy, a new analytical technique involving million-volt nuclear particles, to identify and analyse plaques in postmortem tissue from patients with Alzheimer's disease without using chemical staining techniques and fail to demonstrate the presence of aluminium in plaque cores in untreated tissue.

Aluminum↗
PubMed1992

Group A streptococcal infection in an aboriginal community.

OBJECTIVE: To determine whether group A streptococcal infection and poststreptococcal sequelae are still a significant health issue for Aboriginal communities. DESIGN: A cross-sectional survey of streptococcal carriage, infection and antibody levels. SETTING: A north Queensland Aboriginal community. PARTICIPANTS: One hundred and twenty preschool and school-aged children (2 to 12 years of age) living in the Lockhart River Community on Cape York Peninsula. RESULTS: Pyoderma was present in 43% of the children and in 76% of these culture of skin lesions grew group A streptococci. Group A streptococci also grew from 13% of throat swabs, making a total of 36% of children culture positive. Anti-streptolysin O and anti-DNAase B levels were remarkably high and increased with age. CONCLUSIONS: The evidence presented confirms a high level of group A streptococcal carriage and infection in children of the Lockhart River Community. Further investigation of this problem is warranted in other Aboriginal communities with a view to instituting appropriate control programs.

Antistreptolysin↗
PubMed1992

Acetylcholinesterase and butyrylcholinesterase activities in cerebrospinal fluid from different levels of the neuraxis of patients with dementia of the Alzheimer type.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities of cerebrospinal fluid (CSF) collected post mortem from the lateral ventricles, cisterna magna, and lumbar regions of the spinal cord of patients with a histologically confirmed diagnosis of Alzheimer's disease were compared with those of normal, age matched control patients, patients with dementia of non-Alzheimer aetiology, and patients with non-dementing neurological disorders. The AChE activity of the ventricular CSF of patients with Alzheimer's disease was 48% lower (p < 0.005) than that of age matched controls or patients with other types of dementia, and the AChE activity of CSF sampled from the basal cistern was 40% lower (p < 0.005) in patients with Alzheimer's disease. There were no significant differences between the AChE activity in Alzheimer's disease and control patients in CSF collected from the lumbar cistern. AChE activity was lower in CSF sampled from the basal and lumbar cistern of patients with dementia of non-Alzheimer aetiology, while ventricular activity was in the normal range. BuChE activity in ventricular CSF of Alzheimer's disease patients was 41% lower than normal (p < 0.05) and in the normal range in all other samples. The secretion of AChE from forebrain and hindbrain regions is reduced in Alzheimer's disease patients, leading to decreased ventricular and cisternal levels of the enzyme. Secretion from more caudal regions of the central nervous system seems to be unaffected by the disease, resulting in AChE in the lumbar CSF of patients with Alzheimer's disease being in the control range. Such altered secretion of AChE in the brain could have profound implications not only for cholinergic transmission in these patients but also for the proposed noncholinergic modulatory actions of AChE.

Acetylcholinesterase↗
PubMed1992

Dietary fats and inflammatory bowel disease in Asians.

Chemically processed, hydrogenated fats, such as margarine, have been implicated in the aetiology of inflammatory bowel disease. Toxic by-products may occur in their production or during frying and cooking. A survey of dietary oil usage was conducted among Asians in Leicester, comparing inflammatory bowel disease patients with healthy controls. Two groups were comparable for age, sex, religion, place of birth, number of years spent in Britain and vegetarian status. There were no significant differences in actual oils used between healthy controls and patients with ulcerative colitis or Crohn's disease (chi 2 = 0.142 and 1.803 respectively, p greater than 0.50). However patients with Crohn's disease were found to recycle their cooking oil significantly more often than age and sex-matched colitics (p less than 0.05) and particularly age and sex-matched controls (p less than 0.01). A similar study needs to be conducted in India where the incidence of inflammatory bowel disease is low. If this difference is confirmed a programme of health education in cooking habits could lower the incidence of Crohn's disease.

Dietary Fats↗
PubMed1991

Anomalous molecular form of acetylcholinesterase in cerebrospinal fluid in histologically diagnosed Alzheimer's disease.

The possibility that the different molecular forms of acetylcholinesterase (AChE) in cerebrospinal fluid (CSF) which can be revealed by isoelectric focusing may reflect changes in AChE in pathologically affected neurons in Alzheimer's disease was tested in a retrospective study. CSF samples obtained at necropsy from 33 patients with clinically diagnosed dementia, 9 with possible dementia, and 19 without a diagnosis of dementia were examined by isoelectric focusing. An additional band indicating an anomalous molecular form of AChE was present in CSF from 19 of 23 patients with a histological diagnosis of Alzheimer's disease and no other central nervous system disorder but in none of the 19 non-demented patients (without a histological diagnosis of Alzheimer's disease). The band was also present in 2 of 8 patients with histologically defined Alzheimer's disease plus other neurological disorders and in 4 of 8 patients with possible dementia who did not meet histopathological criteria for Alzheimer's disease. The absence of the anomalous form of AChE from the CSF of non-demented patients and its presence in the CSF of the majority of patients with Alzheimer's disease has implications for our understanding of the biological basis of the disease and might form the basis of an antemortem diagnostic test.

Acetylcholinesterase↗
PubMed1991

Alzheimer's disease: specific increases in a G protein subunit (Gs alpha) mRNA in hippocampal and cortical neurons.

The GTP binding protein, Gs, activates adenyl cyclase in direct response to stimulation of several neurotransmitter receptors. In situ hybridization histochemistry (ISHH) with a 35S-labelled oligonucleotide has been used to detect the mRNA encoding the alpha subunit of Gs (Gs alpha) in human hippocampus, temporal and visual cortices and cerebellum, and its level has been compared between Alzheimer's disease (AD) and control brains. A marked regional increase was found in the hippocampus of AD cases. Analysis of levels of Gs alpha mRNA in individual constituent pyramidal cells confirmed this increase (3 to 4-fold in densitometric units) in hippocampal fields CA1, CA3 and CA4, as well as in temporal cortex. Levels of Gs alpha mRNA were also determined relative to total poly(A)+ mRNA in the same cell populations in each case. Gene-specific elevation of Gs alpha mRNA was thereby confirmed in hippocampal fields, and also in temporal cortex. No changes were seen in visual cortex. The increase in Gs alpha mRNA may represent a response by AD neurons in affected areas to receptor alterations, or to an abnormality in receptor-G protein coupling. Alternatively, altered G protein gene expression might be a pathogenic event underlying changes in linked receptor populations.

Aged↗
PubMed1991

Increased muscarinic receptor messenger RNA in Alzheimer's disease temporal cortex demonstrated by in situ hybridization histochemistry.

A 35S-labelled synthetic oligonucleotide directed against part of the mRNA coding for the M1 subtype muscarinic receptor was used for in situ hybridization histochemistry in sections of human temporal cortex. M1 receptor mRNA was found in cell populations throughout the grey matter, especially in pyramidal cells. Quantitative densitometric analysis of autoradiograms was used to compare levels of this mRNA between Alzheimer's disease and controls. A significant (2.7-fold) increase in hybridization signal was found in Alzheimer's disease cases, both in absolute terms and relative to total polyadenylated mRNA as determined by hybridization with an oligodeoxythymidine probe. Elevated levels of muscarinic receptor mRNA may reflect up-regulation of transcription of this gene in response to the cholinergic deficits occurring in the disease.

Alzheimer Disease↗
PubMed1991

Metastatic meningioma in the neck.

Although meningiomas represent 15 per cent of tumours of the central nervous system, they rarely metastasize. A case is presented in which metastasis to a cervical lymph node occurred, together with local recurrence, nine years after initial diagnosis and treatment. This case serves to illustrate that malignant meningioma is a rare cause of a neck mass.

Head and Neck Neoplasms↗
PubMed1991

Regional and neuronal reductions of polyadenylated messenger RNA in Alzheimer's disease.

Messenger RNA (mRNA) is the key intermediate in the gene expression pathway. The amount of mRNA in Alzheimer's disease (AD) brains has been determined using in situ hybridization histochemistry (ISHH) to detect the poly(A) tails of polyadenylated mRNA (poly(A) + mRNA). On a regional basis, AD cases had significantly less poly(A) + mRNA than controls in hippocampus (field CA3) and cerebellum (granule cell layer). Analysis of constituent pyramidal neurons showed mean reductions per cell within AD hippocampus (field CA3) and temporal cortex, but not in visual cortex. Similar changes were seen in a small group of non-AD dementias. The finding of reduced poly(A) + mRNA content is another indication of the altered brain gene expression occurring in AD. It is proposed that measurement of poly(A) + mRNA may be valuable in identifying functionally impaired neuronal populations. The methodology also provides a means by which changes in the quantitative distribution of individual mRNAs can be determined relative to that of poly(A) + mRNA as a whole.

Adult↗
PubMed1991

A monoclonal antibody that reacts immunohistochemically with amyloid deposits in the brain tissue of Alzheimer patients binds to an epitope present on complement factor 4.

The mouse monoclonal antibody SMP has previously been demonstrated to react immunohistochemically with neurofibrillary tangles, argyrophilic plaques, and leptomeningeal vascular amyloid deposits in the brain tissue of individuals dying from pathologically diagnosed Alzheimer's disease. In preliminary studies the antibody was shown, by size exclusion chromatography, to bind to a protein with an apparent molecular mass of 260 kDa present in the CSF and serum of demented individuals. Chromatographic separation of a 40% ammonium sulphate precipitate of CSF and serum yielded immunoreactive fractions that were subjected to 9% sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by western blotting. Probing the nitrocellulose blot with the antibody revealed that the antibody selectively binds to a protein chain with an apparent molecular mass of 100 kDa. By using a combination of affinity chromatography and sodium dodecyl sulphate-polyacrylamide gel electrophoresis, coupled with western blotting, the serum component with which the antibody reacts has been identified as complement factor 4. In addition, the antibody has been shown to react specifically with an epitope on the alpha-chain of this protein.

Alzheimer Disease↗
PubMed1991

Presence of a soluble form of acetylcholinesterase in human ocular fluids.

Samples of ocular fluid obtained from normal persons at necropsy and during eye surgery have been assayed for the presence of acetylcholinesterase. Measurable levels could be detected in all samples examined, but levels of acetylcholinesterase in vitreous humour were consistently higher than those in aqueous humour, indicating a possible retinal origin. Polyacrylamide gel electrophoresis revealed that the enzyme of ocular fluid had the same mobility as that of acetylcholinesterase from cerebrospinal fluid. It is probable that acetylcholinesterase is secreted from neuronal structures in the retina into the ocular fluid in an analogous manner to the secretion of acetylcholinesterase from brain neurones into cerebrospinal fluid.

Acetylcholinesterase↗