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Biomedical subjects

M L Cuzner

Publications and source records attributed to M L Cuzner.

At least 109 records · Page 6Linked to original sources

Cerebrospinal fluid complement proteins in neurological disease.

CSF levels of C3 and C4 were similar in patients with no neurological disease, minor non-inflammatory conditions, degenerative disease and MS during relapse, but slightly lower in MS during remission and higher in patients with inflammation. All MS patients had low CSF levels of alpha 1-antitrypsin and high levels of IgG. The roles of local production and consumption of complement protein and damage to the blood-brain barrier are discussed.

Cerebrospinal Fluid Proteins↗

On the role of sensitised T-lymphocytes in the pathogenesis of multiple sclerosis.

Peripheral blood lymphocytes from 24 out of 26 patients with clinically well-defined multiple sclerosis in remission showed sensitisation to multiple sclerosis brain extracts as assayed by enhancement of the early erythrocyte rosette test. Such an increase in the number of early rosettes was not found when the lymphocytes of multiple sclerosis patients were exposed to extracts of control brains. In contrast the sensitised cells were found in the circulation in only two of 11 patients with multiple sclerosis in acute relapse. The percentage of circulating T-lymphocytes which formed early rosettes was lower in the group of patients suffering a relapse than in patients in remission. A longitudinal study of one patient who was tested before, during and after a relapse revealed the disappearance from the blood of the sensitised T-cells during the relapse and their subsequent reappearance after recovery. Of 36 patients with other neurological diseases, two responded solely to multiple sclerosis brain, two responded to both multiple sclerosis and control brain, and three responded only to control brain. No healthy controls showed sensitisation to any brain extract.

Adult↗

Proteinase inhibitors in cerebrospinal fluid in multiple sclerosis.

Levels of the proteinase inhibitors alpha 2-macroglobulin (alpha 2-m) and alpha 1-antitrypsin (alpha 1-at), and total protein, IgG and transferrin were measured in cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) and other neurological diseases. All groups except that termed "meningitis" had similar alpha 2-m levels, but alpha 1-at and transferrin were significantly depressed in MS. Total protein levels were normal and IgG levels were elevated in MS. Serum levels of alpha 1-at were normal so the decreases observed in the CSF in MS were not due to impaired systemic production. In view of previous reports that proteinase activity is high in MS plaques and CSF, the inhibitory capacity of alpha 2-m and alpha 1-at in CSF was measured. As any decreases in inhibitory capacity noted in MS were slight, they could only be important in the local environment of a plaque where enzyme levels may be critically high.

Cerebrospinal Fluid Proteins↗

Proteolytic enzyme activity of blood leukocytes and cerebrospinal fluid in multiple sclerosis.

Upon stimulation by immune complexes, the polymorphonuclear (PMN) blood secretes lysosomal hydrolases, including neutral proteinase, which is concentrated in the PMN cell. Neutral and acid proteinase activity were increased and decreased, respectively, in the circulating white cells of patients with multiple sclerosis during an exacerbation of the disease, but there was no correlation with serum immune complex levels. Neutral proteolytic activity in the cellular fraction of the cerebrospinal fluid was also found to be elevated in acute multiple sclerosis, as monitored by digestion of myelin basic protein.

Antigen-Antibody Complex↗

Proteolytic activity in CSF.

Proteolytic enzyme activity, present at both acid and neutral pH values, in cerebrospinal fluid, can be measured by a sensitive assay, which monitors the rate of 125I-basic protein breakdown on polyacrylamide gel electrophoresis. CSF cellular neutral proteinase and supernatant acid proteinase are increased in acute multiple sclerosis and in CNS infections.

Acute Disease↗

Myelin composition in acute and chronic multiple sclerosis in relation to cerebral lysosomal activity.

The neuropathology of 3 cases of acute multiple sclerosis was correlated with biochemical analyses. Astrocytosis was a characteristic feature of the diffuse demyelinating lesions in one case and lymphocytic cuffing characterized the well-defined plaques present in the white matter of the other two cases. No abnormalities were found in the protein or lipid composition of isolated myelin, despite a wide range of recovery. Nevertheless, the gel electrophoretic protein pattern of white matter adjacent to plaque areas showed selective loss of myelin basic protein. Lysosomal acid proteinase and beta-glucuronidase levels were very significantly increased in all white matter samples in which astrocytosis was a major neuropathological feature. Levels were less markedly raised in samples containing discrete active plaques. Enzyme changes were also found in the apparently normal white matter of 2 of the cases. Acid proteinase activity was in the normal range but the activities of beta-glucuronidase and acetylcholine esterase were elevated. The significance of these results in relation to glial cell activity in the early stages of demyelination is discussed.

Adolescent↗

Neurochemical findings in a perinatal sudanophilic leukodystrophy rich in steryl ester.

Neurochemical and neuropathological studies have been made of a 10-day-old child who suffered from a sudanophilic leukodystrophy. The brain white matter contained abundant sudanophilic material. The patient's grey matter total cholesterol content was 30% higher than whole brain tissue derived from a comparable control. White matter cholesterol content was more than double the control value. Nearly 80% of the white matter cholesterol was esterified. Subcellular fractionation of the white matter resulted in a "floating fraction" rich in cholesteryl ester. The steryl ester fatty acid composition was not typical of control tissue or demyelinating tissue. Patient phospholipid fatty acid composition patterns differed from control, but white matter galactolipid fatty acid composition appeared normal. Cholesteryl ester hydrolase activity appeared normal. Myelin and myelin-like fractions, isolated from diseased and normal brain tissue, were of a primitive developing nature but appeared to be comparable. The findings indicate a neonatal sudanophilic leukodystrophy which doubtless began in prenatal life and which was rich in cholesteryl ester. The aetiology of the leukodystrophy is unknown.

Brain↗

Leucocyte proteinase activity and acute multiple sclerosis.

Increased leucocyte neutral proteinase activity is associated with an attack of multiple sclerosis. Raised neutral proteinase is found in other diseases with rapid destruction of neural tissues. Increased enzyme activity may be responsible for removing antigenic protein from the blood.

Humans↗

The lipid composition of rat brain myelin and subcellular fractions during development.

1. The lipids of whole brain and subcellular fractions of the rat were analysed during development. 2. The deposition of cholesterol occurred in two phases, one related to increasing wet weight of the brain and the second to myelination. Cerebroside accumulation was related only to myelination. 3. The composition of myelin isolated from 12-day-old rat brain was different in some respects from that of the adult. In the former there was an increase of phospholipid in relation to cholesterol and a marked deficiency in cerebroside. 4. It is suggested that early myelin is extruded glial plasma membrane, which only later becomes mature myelin.

Aging↗