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Biomedical subjects

E D Bird

Publications and source records attributed to E D Bird.

At least 109 records · Page 6Linked to original sources
PubMed1983

Maternal transmission in Huntington's disease.

The effect of maternal transmission on age at onset of Huntington's disease (HD) was examined in 100 unrelated pedigrees. The age at which abnormal movement disorder first appeared could be estimated in 238 patients. More than twice as many of the late-onset cases (age 50 or later) inherited the HD gene from an affected mother than from an affected father. Affected offspring of late-onset females also had late-onset disease while those of late-onset males had significantly earlier ages of onset. This pattern of maternal inheritance suggests a model where the late-onset form of HD is related to a maternally transmitted factor such as the mitochondrion and its genome.

Adult↗
PubMed1983

Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain.

The activity of the pyruvate dehydrogenase complex (PDHC) was reduced in affected areas of brain from patients with Huntington disease (caudate, putamen) and Alzheimer disease (frontal cortex) where choline acetyltransferase (CAT) activity was low. PDHC was also deficient in an area (Huntington hippocampus) where CAT was not significantly reduced. The activity of fumarase, an inner mitochondrial marker, was normal in all areas examined. The activities of PDHC and CAT correlated well in caudate, putamen, and amygdala but not in hippocampus or frontal cortex. Both total activity and activation of PDHC were below normal in fibroblasts from 4 patients with C-21 trisomy Down syndrome, who are at very high risk to develop Alzheimer disease. However, no abnormality of PDHC was detected in Huntington or Alzheimer fibroblasts. Deficiency of PDHC may play a role in the pathophysiology of Huntington and Alzheimer diseases, although it does not appear to be a primary defect. Loss of tissue oxidative capacity may relate to the reduction in cerebral metabolic rate and blood flow which are characteristic of many dementing illnesses.

Alzheimer Disease↗
PubMed1983

Somatostatin is increased in the basal ganglia in Huntington disease.

Huntington disease (HD) is an autosomal dominant hereditary disorder characterized by premature cell death, predominantly in the neostriatum. Decreased concentrations of several neurotransmitters and neuropeptides have been reported in the basal ganglia in Huntington disease. We now report that concentrations of radioimmunoassayable somatostatin are increased in extracts of the caudate (mean +/- standard error of the mean, ng/gm net weight; 247 +/- 24 versus 85 +/- 11), putamen (275 +/- 48 versus 74 +/- 11), external globus pallidus (100 +/- 10 versus 27 +/- 6), and internal globus pallidus (108 +/- 21 versus 21 +/- 8) in the disease. The concentrations of immunoreactive substance P measured in the same extracts were markedly reduced in caudate (mean +/- standard error of the mean, pmol/gm wet weight; 25 +/- 3 versus 109 +/- 20), putamen (28 +/- 7 versus 88 +/- 28), external globus pallidus (39 +/- 9 versus 196 +/- 62), and internal globus pallidus (60 +/- 17 versus 263 +/- 39), as well as in both subdivisions of the substantia nigra. Gel permeation chromatography and high-performance liquid chromatography showed radioimmunoassayable somatostatin to include peptides with physicochemical properties of the tetradecapeptide somatostatin and larger substances, including somatostatin-28-like material. A single peak of immunoreactive substance P corresponding to synthetic substance P was found by high performance liquid chromatography. These results suggest that immunoassayable somatostatin-containing neuronal elements in the neostriatum and globus pallidus in Huntington disease are affected differentially by the disease process from neurons that contain immunoreactive substance P.

Adolescent↗
PubMed1983

A post-mortem comparison of the cortical cholinergic system in Alzheimer's disease and Pick's disease.

Assessment of neurochemical markers in the frontal cortex indicates that choline acetyltransferase is significantly decreased in Alzheimer's and Gerstmann-Straussler dementias but not in Pick's dementia. It therefore appears that the cholinergic innervation of the cortex from the basal forebrain is intact in Pick's disease. Cortical somatostatin was decreased only in Alzheimer's disease (AD), indicating that loss of somatostatin is not a constant feature in different forms of dementia. Muscarinic binding sites were unaltered in Pick's disease and Gerstmann-Straussler syndrome but were decreased in a subpopulation of AD patients. These data suggest that in some cases of AD a significant loss of cholinoceptive neurones in the cortex is evident.

Adult↗
PubMed1983

Lack of cholinergic deficit in the neocortex in Pick's disease.

Choline acetyltransferase activity was decreased in the frontal cortex in Alzheimer's and Gerstmann-Straussler dementias but not in Pick's disease. Cortical somatostatin was only decreased in Alzheimer's dementia. Postsynaptic muscarinic binding sites appeared to be decreased in a subpopulation of Alzheimer's patients. Our data indicate that a loss of cholinergic innervation of the cortex is not common to all dementias.

Choline O-Acetyltransferase↗
PubMed1982

Stability of monoamine metabolites in human cerebrospinal fluid.

Concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in human lumbar cerebrospinal fluid following storage at room temperature and 4 degrees C for intervals up to 72 hours. These monoamine metabolites were quantitated using a high-performance liquid chromatographic-electrochemical detector technique. No significant difference could be detected in any of the three metabolites stored at room temperature for up to 48 hours. Addition of ascorbic acid to CSF had no measurable effect on the levels of HVA and 5-HIAA. Repeated thawing and freezing produced no detectable change in metabolite levels. The results indicate that these monoamine metabolites are stable at room temperature for up to 48 hours after lumbar puncture and that the addition of an antioxidant, such as ascorbic acid, is not necessary. The data also demonstrate that immediate refrigeration or freezing of samples is not required for maintenance of metabolite levels.

Chromatography, High Pressure Liquid↗
PubMed1982

Dopamine and homovanillic acid concentrations in striatal and limbic regions of human brain.

In an attempt to further define the dopaminergic nature of the limbic nucleus accumbens from the morphologically similar striatal caudate and putamen, the levels of dopamine (DA), homovanillic acid (HVA), and HVA/DA ratios, an index of dopamine turnover, were measured in these three structures of human brain. The levels of dopamine in the accumbens (2.49 ng/mg), caudate (2.39 ng/mg), and putamen (3.00 ng/mg) were similar. The homovanillic acid concentration in the accumbens (7.44 ng/mg) and putamen (6.54 ng/mg) were comparable, while its concentration was considerably lower in the caudate (3.61 ng/mg). The most striking difference between the limbic accumbens and the striatum was observed in the HVA/DA ratio. This index of turnover was significantly higher in the accumbens (3.64) when compared to the caudate (1.80), and was 59% higher than that found in the putamen (2.53). The data provide evidence for differences in dopamine activity in the mesolimbic versus the nigrostriatal pathways.

Adult↗
PubMed1982

Phenothiazine biphasic effect on dopamine concentrations in the basal ganglia of subhuman primates.

Interpretation of data on the possible relationship between changes in endogenous putative transmitters and neuropsychiatric disorders may be altered by the use of neuroleptic agents. As one approach to this problem, we attempted to simulate the situation in man by measuring the changes in dopamine in basal ganglia of monkeys during the chronic (20 months) administration of an antipsychotic phenothiazine. Unexpectedly, a biphasic response was obtained: dopamine increased after 2 months but was markedly reduced after 20 months. Perhaps, dyskinesia is related to this biphasic effect of the antipsychotic phenothiazines.

Animals↗
PubMed1982

Huntington chorea is not associated with hyperactivity of nigrostriatal dopaminergic neurons: studies in postmortem tissues and in rats with kainic acid lesions.

We estimated dopamine release postmortem in the neostriatum of patients with Huntington disease (HD) and in controls. In HD, dopamine levels were unchanged in caudate and elevated in putamen, but homovanillic acid (HVA) and the ratio HVA:dopamine were unaltered in both nuclei. When rats were injected with kainic acid (an experimental model of HD), dopamine levels in striatum remained unchanged 2 to 30 days postoperatively; HVA and 3,4-dihydroxyphenylacetic acid (DOPAC) increased significantly from 2 to 18 days after injections but returned to normal levels later. These findings suggest that the nigrostriatal projection adapts to loss of striatal neurons that normally influence dopamine release and is not hyperactive in HD chorea.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

In vitro synthesis of human brain proteins including tubulin and actin by purified postmortem polysomes.

Polysomes were prepared from human brain tissue 2-6 h postmortem; the polysomes were active in a cell-free protein synthesis system containing rabbit reticulocyte factors. Protein synthesis was totally dependent upon added MgCl2, ATP, the reticulocyte factor fraction, and the human polysome fraction. Human brain proteins synthesized in the presence of L-[35S]methionine were analyzed by one- and two-dimensional polyacrylamide gel electrophoresis. Over 250 proteins were synthesized and they extended in size up to 250,000 d; many of the most abundant native human brain proteins were synthesized, including tubulin and actin. It was shown that human brain alpha and beta tubulin and actin isomers synthesized in vitro from human postmortem polysomes have the same apparent molecular weights and isoelectric points as the corresponding proteins synthesized by rat polysomes from fresh cortices. The corresponding tubulin and actin synthesized by human and rat brain polysomes also yield the same radioactive methionine-containing peptides after digestion with Staphylococcus aureus V8 protease. These analyses indicate that postmortem polysomes contain active messenger RNA which can direct the partial and/or complete synthesis of actin and tubulin subunits and other human brain proteins.

Actins↗
PubMed1981

The preparation of biologically active messenger RNA from human postmortem brain tissue.

Messenger RNA (mRNA) was extracted from human postmortem brain tissue by alkaline phenol extraction of polysomes followed by oligo (dT)-cellulose chromatography. The mRNA preparations stimulated protein synthesis in a cell-free system containing wheat germ homogenate. The products of protein synthesis were analyzed by one- and two-dimensional gel electrophoresis. These analyses indicated that numerous polypeptides, including tubulin subunits and actin isomers, were synthesized by the human mRNA. The molecular weight range of polypeptides synthesized by human mRNA fractions from two brain specimens were identical, and analysis by two-dimensional gel electrophoresis indicated qualitatively similar products. The yield of mRNA extracted per gram of human tissue was less than the yield obtained with rat forebrains from animals sacrificed immediately before brain removal and mRNA purification. A decrease in the amount of polysomes isolated from human tissue relative to rat brain tissue was a major factor contributing to the low yield. The molecular weight distribution of polypeptides synthesized by human and rat brain mRNA fractions in wheat germ homogenate was similar; thus, there was no indication for selective breakdown or inactivation of high molecular weight mRNA species in the human tissue. Our studies indicate that it is possible to utilize postmortem tissue for molecular biological investigations of human brain mRNA.

Animals↗
PubMed1981

Decreased receptor-binding sites for kainic acid in brains of patients with Huntington's disease.

The specific binding of (3H)kainic acid (KA) to high- and low-affinity receptor sites was assayed in postmortem samples from the brains of patients affected with Huntington's disease (HD) and age-matched controls. Treatment of rat brain with conditions that closely mimic the temperature gradient occurring in postmortem human brain only slightly but not significantly decreased receptor binding by 12 hr after death. In HD brains, total specific binding of (3H)KA was reduced in the caudate nucleus by 51%, putamen by 77%, and frontal cortex by 47%. Specific binding to the high-affinity site was virtually undetectable in the caudate nucleus and was reduced by 90% in the putamen from HD brains. No significant alterations in specific binding of (3H)KA were noted in the insular or temporal cortex, hippocampus, or cerebellum. Thus, losses of KA receptor binding were mainly localized to those regions of the HD brain that are most severely affected by neuronal degeneration, and the high-affinity receptor site appeared more affected.

Adult↗