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Biomedical subjects

R Harrison

Publications and source records attributed to R Harrison.

At least 181 records · Page 10Linked to original sources
PubMed1987

Immunological factors in neuronal degeneration with particular reference to motor neurone disease.

Cellular and humoral immunoreactivity to neuronal antigens was investigated in patients with motor neurone disease (MND). Lymphocytes from patients with MND and normal healthy controls were cultured with a membrane fraction prepared from cultured spinal cord neurones. 4 out of 14 patients with MND and 0 out of 9 normal controls showed a significantly increased stimulation index. An enzyme-linked immunoabsorbent assay (ELISA) was established to detect antibodies to synaptic membrane fraction prepared from human motor cortex. Sera from MND patients showed a significantly increased immunoglobulin binding with respect to normal control sera. Antineuronal antibody production by MND lymphocytes was studied by using Epstein-Barr virus transformation followed by fusion with a mouse myeloma cell line. Antibody-producing clones were isolated. This procedure would allow a more detailed analysis of the antineuronal antibody production in MND.

Cell Transformation, Viral↗
PubMed1987

Fulminant hepatic failure after occupational exposure to 2-nitropropane.

Two construction workers became ill after applying an epoxy resin coating containing 2-nitropropane in the confined space of an underground concrete vault. One man died 10 days later from fulminant hepatic failure. The second man recovered but has had persistently elevated serum aminotransferase activity. The serum concentration of 2-nitropropane on admission of the man who died was 13 mg/L, and was 8.5 mg/L in his coworker. The acute toxicity of 2-nitropropane has not been widely appreciated despite previous reports of death due to hepatic failure after exposure to the compound in confined spaces. These cases show the importance of effective education and protective work practices.

Adult↗
PubMed1986

Subcellular fractionation and distribution of cholinergic binding sites in fetal human brain.

Conventional subcellular fractionation techniques have been applied to human fetal brain (13-15 weeks gestation) and the fractions have been characterized by assaying for marker enzymes, cholinergic binding sites and electron microscopy. Fractionation of the homogenate resulted in a nuclear pellet (P1), a crude mitochondrial pellet (P2) and a supernatant (S2). Further resolution of the P2 fraction by density gradient centrifugation resulted in two bands at the gradient interfaces and a pellet. The P2 and subsequently the P2B fraction contained intact plasma membrane profiles as judged by the predominance of adenylate cyclase activity and the presence of occluded lactate dehydrogenase which constituted over 70% of the total activity in these fractions. Morphological examination of the gradient fractions revealed that the P2B fraction contains membrane bound structures which resemble synaptosomes prepared from neonatal rat brain. These structures have a granular matrix in which mitochondria and frequently, neurofilaments were observed. Very few synaptic vesicles were present and there was no evidence for post synaptic attachments. The cholinergic markers choline acetyltransferase, acetylcholinesterase and receptor sites defined by quinuclidinyl benzilate and alpha-bungarotoxin binding were enriched in fractions P2 and P2B which contained the bulk of nerve ending particles. This enriched preparation of fetal synaptosomes may be valuable for functional studies on pre-synaptic terminals in developing brain.

Brain↗
PubMed1986

Cross-reactivity of a monoclonal antiglucocorticoid receptor antibody BuGR1 with glucocorticoid and mineralocorticoid receptors of various species.

The reactivity of a monoclonal antibody BuGR1, raised against glucocorticoid receptors of rat liver, with glucocorticoid and mineralocorticoid receptors of mammalian (rabbit) and amphibian (A6 cells) origin was examined. The glucocorticoid receptors of rabbit kidney and liver and of A6 cells were labeled with tritiated dexamethasone. The mineralocorticoid receptors were labeled with tritiated aldosterone in the presence or absence of RU26988, depending on whether aldosterone was bound to glucocorticoid receptors (A6 cells) or not (rabbit kidney), in addition to its binding to mineralocorticoid receptors. BuGR1 did not recognize mineralocorticoid receptors of A6 cells and rabbit kidney. BuGR1 cross-reacted with glucocorticoid receptors of rabbit liver and kidney but not of A6 cells, suggesting that the domain of glucocorticoid receptors recognized by BuRG1 could be present only in the mammalian species. The findings indicate that BuGR1 shows species differences as well as receptor class specificity.

Aldosterone↗
PubMed1986

Partial protection of baboons against Schistosoma mansoni using radiation-attenuated cryopreserved schistosomula.

Three groups of five baboons were vaccinated in Kenya using three doses of 10,000 viable cryopreserved schistosomula attenuated with either 10, 20 or 60 krad 60Co-irradiation prepared in England. Animals were vaccinated at four-week intervals, challenged after a further six weeks with 2,000 cercariae and perfused at 10 weeks after challenge. High antibody titres to schistosomula mediating in vitro cytoadherence with P 388D1 macrophage-like cells were demonstrated in all vaccinated animals but not in controls. Significant titres to soluble egg antigen (SEA) were also demonstrated by ELISA in the 10 and 20 krad vaccinated groups following the first vaccination. The subsequent vaccinations and the challenge boosted this response considerably. Mean anti-SEA titres were only elevated above background in the 60-krad group six weeks after the third vaccination and in the challenge controls six weeks after challenge. Peripheral eosinophil counts were slightly reduced and neutrophil counts slightly elevated before challenge while eosinophil and erythrocyte counts were elevated and neutrophil counts depressed after challenge. PCV values were erratic in all groups. Eggs appeared in the faeces from six weeks after challenge and excretion rates were higher in all three vaccinated groups than in the challenge controls by necropsy 10 weeks after challenge. Body-weights were depressed in all groups after challenge but subsequently rose in the 10 and 20 krad groups. The 60 krad and challenge control groups lost 12.4% and 7.9% of body-weight respectively after challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Stimulation by mitogens and neuronal membranes of lymphocytes from patients with motor neurone disease.

Stimulation of lymphocytes from motor neurone disease patients by either concanavalin A or PHA was shown to be significantly depressed relative to that from normal controls, as assayed by incorporation of [3H]thymidine or [3H]leucine or by glucose uptake. Corresponding significant differences were not shown by assays based upon incorporation of [3H]uridine or of lactate release. Lymphocytes from 4 out of 14 motor neurone disease patients showed a blastogenic response to membranes from rat spinal cord cells, compared with those from 0 out of 9 normal controls. These results not only suggest the possibility of an impaired cellular immune control in MND patients but also indicate the presence of lymphocytes sensitised specifically to neuronal membrane components.

Adult↗
PubMed1986

Decreased autologous mixed lymphocyte reaction in myasthenia gravis.

Myasthenia gravis is an autoimmune disease in which the autoantigen, the acetylcholine receptor at the neuromuscular junction, is well characterized. As with many other autoimmune diseases, however, the basic cause of immune malfunction is unknown. The autologous mixed lymphocyte reaction (AMLR) involves the proliferation of T lymphocytes when co-cultured with autologous non-T cells and may reflect in vivo mechanisms of immune control. We have measured the AMLR in 22 patients with myasthenia gravis and found the magnitudes of the peak responses to be significantly depressed compared to those of 41 normal healthy controls. Proliferative responses of T cells from myasthenic patients to the mitogens, Concanavalin A and Phytohaemagglutinin-P, were also found to be significantly depressed relative to controls. These abnormal immune cell responses can be, in part, interpreted in terms of defective suppressor cell functions in myasthenia gravis.

Acetylcholinesterase↗
PubMed1985

Cultured rat spinal cord neurons: interaction with motor neuron disease immunoglobulins.

Conditions have been developed for the culture of rat spinal cord neurons in serum-free media supplemented with hormones and growth factors. Neurons were identified by immunofluorescence-labeled anti-neurofilament antibody, and their growth was monitored by assay of choline acetyltransferase and cholinesterase activities. Activities of these enzymes were considerably higher than those of comparable cultures in serum supplemented media in which there were visibly many more nonneuronal cells. Serum immunoglobulins from patients with motor neuron disease showed enhanced binding to rat spinal cord cells maintained in both serum-supplemented and serum-free media, as compared with those from normal healthy individuals. Enhanced binding was more marked with the latter cells, presumably because of the higher proportion of neuronal cells in these cultures. Serum immunoglobulins from patients with other neurologic disorders showed a similar binding to that of the normal controls. The results demonstrate the presence of an immune response to spinal cord cell membrane components in patients with motor neuron disease, although whether the response is primary or secondary in the disease process remains unclear.

Animals↗
PubMed1985

In vivo distribution studies of radioactively labelled platinum complexes; cis-dichlorodiammine platinum(II), cis-trans-dichlorodihydroxy-bis-(isopropylamine) platinum(IV), cis-dichloro-bis-cyclopropylamine platinum(II), and cis-diammine 1,1-cyclobutanedicarboxylate platinum(II) in patients with malignant disease, using a gamma camera.

The in vivo distribution in man of the four platinum derivatives cis-dichlorodiammine platinum(II) (DDP), cis-trans-dichlorodihydroxy-bis-(isopropylamine) platinum (IV) (CHIP), cis-dichloro-bis-cyclopropylamine platinum(II) (CP), and cis-diammine 1, 1-cyclobutanedicarboxylate platinum(II) (CBDCA) has been observed. The availability of these compounds labelled with the radioactive isotope of platinum, platinum-191, has made serial in vivo imaging of their distribution possible. Injection of 17-35 MBq (5-28 mg) of the labelled compound IV was followed by imaging, using a gamma camera, with particular reference to the kidneys, liver, and tumour site. Hepatic and renal clearances were observed in all nine patients, but no unequivocal evidence of tumour uptake was found. The left kidney uptake was estimated at times up to 7 days after injection. Mathematical analysis of some of the uptake curves failed to show any significant difference between the clearance times observed. However, the two patients who received CBDCA did show a higher initial renal uptake, falling within the 1st day to levels comparable with those of the other compounds, and the three patients who received DDP showed consistently liver uptake.

Adult↗