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Biomedical subjects

J B Cavanagh

Publications and source records attributed to J B Cavanagh.

At least 73 records · Page 4Linked to original sources
PubMed1982

Recovery from 2,5-hexanediol intoxication of the retinotectal tract of the rat. An ultrastructural study.

Rats were given 2,5-hexanediol, a metabolite of n-hexane, in the drinking water until they developed a marked degree of paresis over about 7 weeks and were then allowed to recover naturally. The time course and the manner of removal of the neurofilamentous masses accumulated within axons caused by the intoxication were followed by electron microscopy over the subsequent 8 weeks. The neurofilamentous masses slowly disappeared completely from the axons of this tract, without there being any degeneration, over 6-7 weeks. They disappeared first from the fibres in the brachium of the superior colliculus, perhaps by transport towards the terminals, and later from the axons within the superior colliculus itself. Particularly in preterminal fibres in the superior colliculus the filamentous accumulations became permeated by a network of smooth endoplasmic reticulum which may have played a part in the removal of the filaments. Accumulations of mitochondria and dense bodies in preterminal regions, presumed to be caused by obstruction to retrograde transport, disappeared pari passu with loss of the filaments. The significance of these events in relation to neurofilament metabolism is discussed.

Animals↗
PubMed1982

Selective loss of Purkinje cells from the rat cerebellum caused by acrylamide and the responses of beta-glucuronidase and beta-galactosidase.

Acrylamide (30 mg/kg) given daily to rats five times each week for 3 weeks leads to progressive loss of Purkinje cells. The necrotic cells begin to be visible from the third day and their numbers reach a peak at the time when the dosing ceases at 18 days. They are less frequent thereafter, but are still visible almost 3 weeks later in small numbers. The density of Purkinje cells per millimeter falls to about 70% of normal at the 7th day, and a similar degree of reduction of the neuronal marker enzyme, beta-galactosidase, is found over the same time scale. By contrast, while there is a brisk macrophage/microglial response in the molecular layer to the loss of the Purkinje cell dendrites, the increase in beta-glucuronidase activity is relatively minor and is not significantly different from normal until after the 21st day. These responses are discussed in the context of the use of lysosomal enzyme activities in the assay of certain neurotoxic lesions.

Acrylamides↗
PubMed1981

Enhancement of sensitivity to acrylamide after nerve ligature.

Acrylamide given to rats after damage to the posterior tibial nerve by a tight ligature causes retrograde degeneration of axons. The number of fibres affected and the extent of degeneration towards the cell body are dose dependent. The effect is the same whether the acrylamide is given immediately after ligature or one week later. The degeneration is delayed several days after giving acrylamide. Before axonal disintegration occurs, focal accumulations of SER, vesicle and multivesicular bodies are seen beneath the axon membrane. Associated with these changes larger vacuoles occur, either in the axon or external to it. It is suggested that these early changes are a response by the axon and perikaryon to the local metabolic damage caused by the toxic chemical. Somewhat similar changes also occur in early predegenerative INH intoxication, and before the axon degeneration in O-P neurotoxicity.

Acrylamides↗
PubMed1980

"Dying back" above a nerve ligature produced by acrylamide.

The application of a tight ligature around a nerve before daily administration of acrylamide (40 or 50 mg/kg) for 4 or 5 days leads to ascending degeneration of the injured nerves, the number of affected fibres and the degree of "dying back" being dependent on the dose of acrylamide given. The same response occurs whether acrylamide is given immediately after nerve ligation or 1 week later. Centripetal degeneration follows after a short delay period and is maximal at about 10 days after beginning acrylamide injections. The response is not found with INH, with misonidazole or with 2,5-hexanedione.

Acrylamides↗
PubMed1980

Automated measurement of peripheral nerve fibres in transverse section.

Transverse sections of rat tibial nerve were scanned with an automated flying-spot microscope and the pictures examined in a one bit (black-and-white) form. Computer programs have been developed, and are described briefly, to isolate individual nerve fibres in the field of view, and to measure axon area and myelin area, from which it is trivial to calculate average axon diameter and average myelin thickness if the axon is assumed to be circular in cross-section. At the magnification used, it was possible to measure 40-50 fibres per field and the time required to do this was 5-7 minutes. For each specimen, 7-8 fields were measured, providing data on 300-400 fibres. Measurements, made on nerves from rats between 3 and 38 weeks of age, show the rate at which nerve fibres grow and also show that the ratio between axon diameter and fibre diameter remains constant, within experimental error, over this period and is close to the predicted value.

Age Factors↗
PubMed1979

Studies on the early changes in acute isoniazid neuropathy in the rat.

Large single doses if isoniazid by mouth (1--2g/kg) have been shown to produce in rats Wallerian degeneration visible with the light microscope from the third day onwards. By contrast, changes in axons are seen from 24 h onwards by electron microscopy. The earliest ultrastructural changes are associated with vacuoles appearing between axon and Schwann cells. These are large and focal, and often compress the axon. The adjacent axon may show changes in smooth ER, and in microtubular arrangement. Alterations in smooth membranes and in mitochondria are visible in Schwann cell cytoplasm, not necessarily related to the vacuole formation and axonal features. It is suggested that INH neuropathy is essentially a multifocal axonal lesion.

Acute Disease↗
PubMed1979

The distribution of degenerative changes in INH neuropathy. Further evidence for focal axonal lesions.

Rats were given isoniazid either in a single large dose or continuously in drinking water and killed 5--105 days later. The distribution of degenerating fibres in various nerves (sensory and mixed) and in various sites along nerves and spinal roots was studied by light and electron microscopy. It was found that sensory nerves tended to be less affected than motor, and degeneration was more proximal in the latter. It was concluded that the pattern of degeneration and regeneration supported the view that the initial metabolic lesion is in the axon, rather than in the cell body.

Animals↗
PubMed1979

The 'dying back' process. A common denominator in many naturally occurring and toxic neuropathies.

The "dying back" process can be defined as a pathological changes affecting certain neurons in a number of systematized degenerative conditions. Examples exist to illustrate the nature of this process, which is unique to nervous tissue, and there is an association of this process with certain chronic vitamin-deficiency syndromes and some important neurotoxic chemicals. Albeit largely speculative, one can attempt to group the conditions showing the dying back process in terms of putative metabolic lesions. Although this attempt is admittedly only a first approximation, it enables us to look ahead to a future understanding of the metabolic problems of long neurons and how their selective degeneration comes about.

Acrylamides↗
PubMed1979

Organophosphorous neuropathy. I. A teased-fiber study of the spatio-temporal spread of axonal degeneraion.

The spatio-temporal spread of axonal degeneration in organophosphorous neuropathy has been studied by means of the teased-fiber technique. Young adult cats were given a single intraperitoneal injection of di-isopropylfluorophosphate (DFP) and were killed 14, 18, 20, 21, and 28 days later by intracardiac perfusion with aldehydes. The cats developed clinical signs of delayed neurotoxicity 16 to 18 days after DFP injection. A histologic survey of the central and peripheral nervous systems revealed that the topographic distribution of axonal degeneration was characteristic of a dying-back neuropathy. In teased-fiber preparations from the left recurrent laryngeal nerve, we found that the axonal degeneration was initially focal and nonterminal but that the axonal degeneration subsequently spread in a somatofugal direction to involve the entire distal axon. Nerve fibre varicosities and paranodal demyelination preceded the axonal degeneration. It is concluded that neurotoxic organophosphates induce a focal, distal but not terminal axonal degeneration. This "chemical transection" of the axon then precipitates wallerian degeneration of the more distal axon. Thus, the traditional hypothesis that dying-back neuropathies evolve from a retrograde axonal degeneration is not valid for organophosphorous neuropathy.

Animals↗
PubMed1979

Organophosphorous neuropathy. II. A fine-structural study of the early stages of axonal degeneration.

The early stages in the evolution of axonal degeneration in organophosphorous neuropathy have been studied by electron microscopy of single nerve fibers. Two young adult cats were given a single, intraperitoneal injection of di-isopropylfluorophosphate (DFP). Eighteen and 20 days later, respectively, after intracardiac perfusion with glutaraldehyde, single nerve fibers were teased from the cats' left recurrent laryngeal nerves. Four nerve fibers in progressive stages of axonal degeneration, were subserially sectioned and studied in the electron microscope. Unique, mid-internodal nerve fiber varicosities preceded an axonal degeneration which was initially focal and nonterminal. The varicosities were associated ultrastructurally with intra-axonal and/or intramyelinic vacuoles. Accumulations of axonal agranular reticulum were found in all four fibers but were associated with less than one half the varicosities. It appeared, both by light and electron microscopy, that the nerve fiber varicosities progressed to the focal, nonterminal axonal degeneration.

Animals↗
PubMed1978

Some effects of a thallium salt on the proliferation of hair follicle cells.

Thallium sulphate has been given to young rats at 4 and 7 days of age and the mitotic activity of the hair follicles has been assessed quantitatively. It has been found that there is a marked decline in mitotic rate over 48 hr in the thallium-treated animals, which is followed by variable amounts of cell death in the matrix zone. No specific mitotic lesion was found or change in cell cycle indices. A failure of energy metabolism is suggested as a possible cause of the inhibition of hair follicle mitosis by thallium.

Animals↗
PubMed1977

Sensory neuropathy produced in the cat with thallous acetate.

A method of poisoning cats with thallium is described. The chief functional disturbances in the nervous system are hypotonia and ataxia. The pathological changes are confined to the central and peripheral axons of primary sensory neurones and are of the 'dying back' type. No motor nerve fibre degeneration was found in this species. While extensive degeneration of sensory nerves was found, those in muscle were apparently unaffected. The significance of this anomalous finding is discussed in relation to the mechanism of the 'dying back' process.

Animals↗
PubMed1976

Autoradiographic localisation of 3H-uridine in spinal ganglion neurones of the rat and the effects of methyl mercury poisoning.

The uptake of 3H-uridine into rat spinal ganglion neurones has been followed by autoradiography for up to 48 h after its intravenous injection. Labelling of nucleoli and of nuclei reached a peak within 1 h and then declined. Nuclear labelling returned to background levels by 24 h, but nucleolar labelling was still significant after 48 h. Animals dosed with methyl mercury chloride (7.5 mg/kg daily) showed no change in labelling rate in nucleolus or nucleus after 1, 2, or 4 doses. After 8 doses there was severe reduction in labelling in both nucleolus and nucleus; this amount causes extensive loss of axons, loss of some cell bodies and a marked reduction in amino acid incorporation into proteins. On recovery after a further 8 days, labelling levels returned to normal. It is concluded that at the time when loss of ribosomes occurs from the cytoplasm methyl mercury is more likely to be directly disturbing ribosomal structure than RNA synthesis, for methyl mercury causes marked changes in ribosomal organisation after 4 doses, but disturbances to RNA synthesis do not occur until the 8th dose.

Animals↗