Measles-virus antibody and antigen in subacute sclerosing panencephalitis.
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Biomedical subjects
Publications and source records attributed to I V Allen.
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Heterozygous dystrophic mice (strain 129 ReJ dy/+) were studied to determine the morphological changes that are characteristic of the heterozygote state. The morphology of the muscle in 35 heterozygotes (+/?) was compared with that of 35 homozygotes (dy/dy) and 20 normal controls (+/+). Muscle was examined with light microscopy, standard histochemical techniques, and electron microscopy. Few abnormalities were detected with light microscopy or with histochemistry. With electron microscopy, some slight nonspecific evidence of muscle damage in the form of focal myofibrillar degeneration was seen in all of the heterozygotes. The striking abnormality, however, was the presence of tubular aggregates in type 2 fibers in 60% of the heterozygotes. Tubular aggregates were not found in homozygous dystrophic mice or in normal controls. The significance of this finding is discussed and it is suggested that tubular aggregates may represent lateral sac dilatation and infolding.
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The general pathology in 120 necropsy-proven cases of multiple sclerosis has been compared with that of matched neurological and general controls. There was no significant difference in the incidence of coronary thrombosis, myocardial infarction, cerebral haemorrhage, thyroid atrophy and splenic haemosiderosis. There was also no significant difference in malignancy in the three groups. The implications of these findings with particular reference to immunopathology are discussed. 74% of patients with multiple sclerosis died from complications of the disease; 26% died from apparently unrelated diseases.
Using a combined biochemical and histological approach certain conclusions can be drawn as to the origin of the increase in lysosomal enzymes in white matter from MS brains. Firstly, there is a gradient of lysosomal enzyme activity, plaque greater than periplaque greater than macroscopically normal white matter, which appears to be independent of the stage of evolution of the plaque. The most consistent change in cellular composition within and around all plaques is a marked astrocytosis. It thus appears that the increases in lysosomal enzymes can be mainly attributed to reactive astrocytes; macrophages and the cells of the perivascular infiltrate making only a limited contribution. Secondly, only one of the enzymes tested was significantly elevated in histologically normal white matter, i.e. n-acetyl-beta-D-glucosaminidase. Since this enzyme appears to be a particularly sensitive marker for astrocytes this may be indicative of proliferation of astrocytes in so-called normal white matter.
Existing techniques have been adapted and it has been possible to demonstrate acid phosphatase (APP) and myelin, lipid or astrocytic fibres in the same histological section. In normal controls APP was demonstrated in neurons, astrocytes, ependyma including choroid plexus epithelium and in pericytes, but not in oligodendrocytes. In multiple sclerosis (MS), APP positive cells were found in the plaque, plaque edge and macroscopically normal white matter. Contrary to some previous reports, not only macrophages, but also astrocytes in the MS plaque were found to be APP positive, although the distribution of enzyme in these cells was predominantly diffuse, unlike the particulate distribution in normal astrocytes and other APP positive cells: the significance of this finding is discussed. It is concluded that astrocytes and macrophages are the main source of the elevated levels of APP found biochemically in MS and that in old plaques astrocytes make the major contribution.
The possibility that cerebral lysosomes in the white matter from patients with multiple sclerosis (MS) are more fragile than in normal controls was investigated in tissue obtained at necropsy. In the MS cases no differences were found in results from samples obtained from histologically distinct areas of white matter, i.e. plaque, periplaque and macroscopically normal white matter. However, in comparison to white matter from a group of controls, certain differences were found. Firstly, the cerebral lysosomes in MS white matter appeared to be more fragile than those in the control cases. Secondly, the remaining intact lysosomes in MS cases showed different characteristics from those obtained in control cases. These results, in the light of earlier experiments in rat brain, were interpreted as further evidence of a greater fragility in the cerebral lysosomes from MS cases. The implications of these results in relation to current thinking on the aetiology of MS are discussed.
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The relationship between neuropathological abnormalities, antibody response and neurovirulence of plaque isolates has been studied in an experimental model of canine distemper in the hamster. Genetic virus variance influenced neurovirulence and the experimental evidence supports the hypothesis that the mechanism of this effect may be through the modulating effect of circulating antibody. Large plaque virus (LPV) produced severe encephalitis with little early antibody response and a high degree of pathological abnormality. Small plaque virus (SPV) produced mild chronic encephalitis and early antibody response. Microscopically, histological abnormalities in this group were qualitatively similar to those seen with LPV but generally of lesser degree. Immunosuppression in SPV infected animals increased the severity of the encephalitis, reflected by the increase in inflammation and inclusion formation. Combined SPV and LPV infection produced high antibody levels and less severe disease than LPV infection alone with an intermediate pattern of histological abnormality.
A case of primary malignant melanoma of the meninges is described in which the clinical presentation is that of visual loss and limb weakness. Clinically a diagnosis of carcinomatous meningitis was made and subsequently malignant cells were found in the cerebrospinal fluid (CSF). At autopsy the diagnosis of primary malignant melanoma of the meninges was made.
Neurofibrillary tangle (NFT) formation is a feature of postencephalitic Parkinsonism (PEP) and Alzheimer's disease (AD). Tangle formation has been compared immunohistochemically in these 2 conditions. Staining patterns for tau protein, ubiquitin and beta/A4 amyloid protein were studied in frontal lobe, hippocampus, and midbrain in 2 classical cases of PEP, 2 cases of AD and 2 controls matched for age and sex. NFTs were present in all cases, but with varying frequency: all tangles were tau-positive and many were ubiquitinated. In the frontal cortex and hippocampus, irrespective of the case category, tangle formation was associated with beta/A4 amyloid deposition. A similar association was present in the 2 AD cases in the midbrain. However, in PEP tangle formation in the midbrain was not associated with adjacent beta/A4 amyloid deposition. This finding raises the possibility that the pathogenetic mechanism of tangle formation in PEP is different from that of AD, although the final cellular morphological expression of abnormality in both conditions is similar.