Foundation for Life Sciences.
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Biomedical subjects
Publications and source records attributed to A D Kidman.
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An in vitro tissue slice technique has been developed and used to compare radioisotope precurosr incorporation into RNA and protein in normal and dystrophic mouse gastrophic muscle. Significant differences are observed with both RNA and protein when incorporation is measured on a fresh weight of muscle basis. Specific activity comparisons show significantly increased incorporation with protein but not with RNA. A comparison of the results with in vivo studies has been made. The in vitro system developed is applicable to the study of macromolecular metabolism in normal and diseased human muscle tissue.
Chicken sciatic nerves undergo demyelination following intraneural injection of diphtheria toxin and subsequent atrophy of some muscular cells. Paresis occurs after one week and lasts approximately three weeks; at the height of the lesion C14-leucine was injected into the ventral horn cells of the spinal cord. The axonal transport of fast flowing labelled proteins was followed down the sciatic nerve axons and flow rates at two different times were measured. Muscle cells were stained for succinic dehydrogenase and ATPase; fibre diameters, total protein, and total radioactivity associated with the nerves were also measured. The results showed that the fast flowing labelled proteins accumulated at the demyelination site while the muscle cells supplied by these nerves showed reduction of fibre diameter and evidence of degeneration. Further studies are in progress on slow moving proteins and muscle cells.
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The validity of reproduction of the controlled contusion injury to the spinal cord in the experimental animal is questioned. The dynamic pathology involving the microvasculature within the first two hours is illustrated using light microscopy. After 15-30 minutes swelling of axons and disruption of myelin sheaths become evident in most areas of white matter. After four hours microcysts have formed in the columns of white matter and are evidence of irreversible damage. Swelling of the cord following injury results from congestion, extravasation and intracellular swelling of neurones, rather than from any demonstrable increase in extracellular fluid. Oedema was only demonstrated with perfusion fixation. Isotope and contrast myelography were compared in the identification of the degree and extent of spinal cord swelling. Significant improvement in motor power was found in a group of paraplegic sheep treated with alpha-methyl paratyrosine. There was no significant improvement in the degree of recovery of motor power or sensation in those animals treated with intrathecal methyl prednisolone (Depo-Medrol). The histopathology in the crushed spinal cord tissue of the treated and untreated animals at various intervals of time was compared. Some possible explanations for the different patterns of clinical recovery in the treated animals are discussed.
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Diphtheria toxin administered by direct intraneural injection procedures demyelination in the mouse sciatic nerve. A dose in the order of 2 million times greater on an equal weight of nerve basis to required to produce the lesion compared with the dose required in the chicken.