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Biomedical subjects

D R Crapper

Publications and source records attributed to D R Crapper.

At least 19 recordsLinked to original sources
PubMed1980

Interaction of aluminum species with deoxyribonucleic acid.

Interactions of aluminum with deoxyribonucleic acid (DNA) have been studied by thermal denaturation, circular dichroism, and fluorescent dye binding; a pH- and concentration-dependent alteration in the interaction of aluminum with DNA was observed. Three distinguishable complexes are produced when DNA is denaturated at pH 5.0-7.5 and in aluminum to DNA mole ratios of 0-0.7. Complex I appears at neutral pH and stabilizes a portion of DNA. Complex II is observed at acidic pH, destabilizes a fraction of the DNA double-helical molecule, and produces intrastrand cross-links. Complex III occurs at all pHs, is maximal at intermediate pH values, and is characterized by a noncooperative melting profile and cross-linking at low pH (less than 6.0). The DNA in complexes II and III can be renatured by treatment with either ethylenediaminetetraacetic acid (EDTA) or a high concentration of sodium chloride. The properties of complexes I and II are consistent with what could be expected for DNA complexes of Al(OH)2+ and Al3+, respectively. Complex III has intermediate properties that are consistent with a structure in which both ions bind the DNA simultaneously. The characteristics of complex III depend on the ratio of Al3+/Al(OH)2+ in solution. Aluminum-DNA complexes differ from other metal-DNA complexes in that melting profiles under many conditions are biphasic. Apparently more than one form of DNA can exist at any time in the presence of aluminum. The different DNA-aluminum complexes, which arise from the multiple species of aluminum in aqueous solution, lead to a variety of reactions with DNA.

Aluminum↗
PubMed1980

Intranuclear aluminum content in Alzheimer's disease, dialysis encephalopathy, and experimental aluminum encephalopathy.

Nuclear and chromatin fractions were prepared from cerebral cortex of 34 human and 37 animal brains. Chromatin was separated into a heavy heterochromatin fraction and two euchromatin fractions: intermediate euchromatin and light euchromatin. Compared to age-matched controls, aluminum content expressed per gram of DNA was significantly increased in nuclear and heterochromatin fractions in pre-senile Alzheimer's disease. In contrast nuclear preparations from brains of patients who had died with dialysis encephalopathy contained less aluminum than controls, although whole tissue concentrations were elevated ten to fifteen times above the control concentrations. Direct injection of aluminum into the cerebrospinal fluid of cats resulted in a progressive encephalopathy with neurofibrillary degeneration and increased intranuclear aluminum content. It is speculated that in Alzheimer's disease the normal blood-brain and cytoplasmic barriers for this neurotoxic metal are defective permitting aluminum to gain access to DNA-containing constitutents of the nuclei.

Adolescent↗
PubMed1979

Altered chromatin conformation in Alzheimer's disease.

Chromatin samples were prepared from forty human brains. Chromatin was separated into a heavy heterochromatin fraction and two euchromatin fractions: intermediate euchromatin and light euchromatin. Employing a bacterial RNA polymerase as probe, only the euchromatin fractions were capable of RNA synthesis. In Control human brains, in brains of patients with dialysis dementia and in brains of elderly individuals without or with dementia of a type other than Alzheimer's disease, the euchromatin fractions accounted for about 75 per cent of the total DNA. In contrast, in brains of patients with advanced senile dementia or presenile dementia of the Alzheimer type, a wide range of euchromatin content was encountered with an average value of 55 per cent. Heterochromatization occurred in both neuron and glia enriched fractions suggesting that a major alteration in protein metabolism occurs in Alzheimer's disease.

Aged↗
PubMed1978

Brain aging and Alzheimer's disease.

The most common cause of senile dementia appears to be a pathological process indistinguishable from that found in presenile dementia of the Alzheimer type. Consideration of the neuropathological changes suggest that this disease may involve in interaction of at least three processes: a viral-like infection, a disorder in the immune system and the neurotoxic effect of an environmental agent. The evidence in support of this hypothesis is reviewed.

Aging↗
PubMed1976

Neurofibrillary degeneration induced by systemic aluminum.

Neurofibrillary degeneration was induced in brain of rabbits by repeated, subcutaneous administration of soluble aluminum salts. Atomic absorption spectroscopy showed brain aluminum levels to increase from 1.1+/0.3mug/g (dry weight) in uninjected animals to concentrations ranging from 2.5 to 47.9 mug/g (dry weight). The Bielschowski silver stain revealed intracellular, argentophilic deposits, which were birefringent when stained with Congo red and viewed in polarized light. The histochemical stain morin revealed aluminum to be concentrated on nuclear chromatin. Analysis by electron microscopy showed the intra-neuronal deposits to be composed of accumulations of 100 A diameter filaments. These observations indicate that systemic aluminum crosses an apparently intact blood-brain barrier and induces neurofibrillary degeneration identical to that following direct brain injection.

Aluminum↗
PubMed1976

Neuron culture from adult goldfish.

Neurons and glia from the central nervous system of the adult teleost Carassius auratus have been grown as explant cultures of minced brain tissue and as trypsin dissociated cells. These cultures exhibit extensive neurite growth from two neuronal types, have organotypic ultrastructure, and contain electrically active cells. Autoradiographic data indicate that these neurons do not divide in culture, and histological evidence suggests that some mature neurons survive explantation and regenerate processes. However, explantation of brain fragments not containing undifferentiated cells, localized in the ventricular and subventricular zones in the brains of fish, resulted in mesenchymal and glial cell cultures only. Therefore, a contribution to the population of cells in culture by undifferentiated cells must be considered. The cultured neurons remained viable for at least 19 weeks and ultrastructural and electrophysiological data indicate synaptic interaction between cells in explant cultures.

Action Potentials↗
PubMed1976

Aluminium, neurofibrillary degeneration and Alzheimer's disease.

Aluminium is neurotoxic and results in the proliferation of 100 A diameter filaments in the cytoplasm of certain neurons. The aluminium concentration for 7 normal human brains was 1-9 +/- 0-7 SD mug/g dry weight (n = 208 samples). The aluminium content of 585 areas sampled in 10 post-mortem cases of Alzheimer's disease ranging in age from 50 to 88 years, in which the diagnosis was based on the specific histological appearances, revealed an elevated aluminium content in some regions. A range of 0-4 - 107-0 mug/g was encountered and 28 per cent of all regions sampled had concentrations in excess of 4 mug/g. Five of 6 cerebral biopsies from patients with Alzheimer's disease also had elevated aluminium content. In 2 additional Alzheimer's brains with neurofibrillary degeneration restricted to certain anatomical areas, elevated aluminium content was found to be associated with neurofibrillary degeneration and not with senile plaques. Furthermore, elevated aluminium content in multiple cortical regions was not found in 2 vascular dementias of the elderly. While the cytotoxic concentration for human neurons is unknown, the cytotoxic concentration for cat's cerebral neurons appears to lie between 4 and 6 mug/g dry weight.

Adolescent↗
PubMed1975

Neuronal correlates of an encephalopathy associated with aluminum neurofibrillary degeneration.

A previous study reported that the intracranial injection of a soluble aluminum salt induced an encephalopathy which may serve as a useful animal model of dementia. An early sign of the encephalopathy in cats was a progressive decrement in both the performance of a short-term visual retention task and acquisition of a conditioned avoidance response in the presence of normal visual discrimination. This study reports that 10 days following the application of aluminum (AlCl3) there was an absence in cat visual cortex of neurons with spontaneous frequencies between 7 and 12 spikes/sec. The loss was associated with neurofibrillary degeneration and aluminum concentrations in lateral gyrus between 4 and 6 mug/g dry weight. The remaining neurons decreased their variability of response to identical visual stimuli and increased their probability of response and frequency of discharge.

Aluminum↗
PubMed1975

Alzheimer degeneration in Down syndrome. Electrophysiologic alterations and histopathologic findings.

Progressive electroencephalographic disorganization and decreased voltage amplitude in the late components of the averaged visual evoked potentials were recorded in the last two years of life of a patient with Down disease and Alzheimer degeneration. Taken together with quantitative histopathologic findings, the electrophysiologic alterations are interpreted in terms of recent evidence from an experimental animal model of dementia. Neurons with neurofibrillary degeneration become electrically inactive and contribute to the loss of voltage generators associated with neuron death in Alzheimer disease. Loss of voltage generators may result in disfacillitation and disinhibition of surviving neurons, thus causing the loss of normal rhythms.

Adult↗