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Biomedical subjects

N A Gregson

Publications and source records attributed to N A Gregson.

At least 73 records · Page 4Linked to original sources
PubMed1988

A prospective study of acute idiopathic neuropathy. III. Immunological studies.

The immune responses of 100 patients who presented with an acute idiopathic neuropathy were compared with those of age and sex matched controls. Blood lymphocytes and their subsets were counted with a fluorescent activated cell sorter. CD8+ (putative suppressor) lymphocytes were significantly reduced in the first week of the disease but total lymphocytes, total T and CD4+ (putative helper) cells were not altered. This reduction depended on the nature of the preceding infection. Serum complement C3 and C4 concentrations remained normal and immune complexes were rarely detected with a C1q binding assay. Complement-fixing antibodies to human peripheral nerve antigens were discovered in the serum of 7% of patients but only 1% of controls. Complement-fixing antibodies to galactocerebroside were not discovered in any sera. Enzyme-linked immunoassays detected increased antibody responses to galactocerebroside but none at all to human P2 myelin protein in the patient sera. Forty microliter of serum from five patients injected into the sciatic nerves of rats did not induce significantly more demyelination than the serum from control patients. It is concluded that auto-immune responses can only be detected by these techniques in a small minority of patients with acute idiopathic neuropathy.

Adolescent↗
PubMed1985

Identification and partial purification of fibroblast growth factor from the brains of developing rats and leucodystrophic mutant mice.

High titres of fibroblast growth factor activity (assessed by mitogenicity for Balb/c 3T3 fibroblast cells in vitro) have been extracted from the brains of foetal and neonatal rats long before myelinogenesis commences, from the brains of hypomyelinated, leucodystrophic, murine mutants and from normal adult rats. Partial purification, by ion-exchange chromatography and gel filtration, indicates that the brain fibroblast growth factor activity from these sources is associated with very similar basic protein fractions. These results, together with the observation that none of the samples of partially purified basic fibroblast growth factor elicits the experimental allergic encephalomyelitis response attributed to myelin basic protein in the rat, suggest that basic fibroblast growth factor is not a degradation product of myelin basic protein.

Aging↗
PubMed1984

The binding of human IgM paraprotein from cases of polyneuropathy associated with benign monoclonal gammopathy to specific neurons of the rodent brain.

Human sera from patients with IgM paraproteinaemia were screened for IgM binding to frozen sections of the rat cerebellum by the indirect immunoperoxidase procedure. Out of 18 patients with a benign IgM gammopathy and associated demyelinating polyneuropathy (PPN), 17 showed binding to the surface of specific neurons, i.e. those of the deep cerebellar nuclei and the intermediate cell of Lugaro. Examination of other regions of the mouse brain suggests that the reactivity is restricted to cells of certain nuclei of the sensory-motor system. The use of F(ab)2 and monoclonal anti-idiotype antibodies demonstrate that the binding involves the antigen binding sites of the paraprotein. This reactivity indicates that some neurons have on their surface an antigen having an hapten in common with human myelin-associated glycoprotein (MAG) and the pi granules of human Schwann cells and furthermore is an additional serological characteristic of this group of patients. In addition 3 sera from the PPN group stained a particulate component in the cytoplasm of all medium-sized and large neurons. A similar staining was found with 7 out of 52 other unselected IgM paraproteinaemias.

Animals↗
PubMed1984

Immune responses to myelin antigens in Guillain-Barré syndrome.

Antibodies to nerve antigens were sought in the sera of 17 patients with acute Guillain-Barré syndrome (GBS), 11 with chronic relapsing demyelinating poly-radiculoneuropathy (CRP), 20 with other neuropathies (ON), 15 with other neurological diseases (OND) and 19 normal subjects. Complement-fixing antibodies to a suspension of human peripheral nerve tissue were identified in only 2 patients with GBS and 1 with chronic progressive neuropathy. Five GBS sera gave complement fixation reactions with rabbit sciatic nerve. The sera were also tested for galactocerebroside (Gal-C) binding activity using a solid phase assay. The range of values in all groups was the same, although the mean values for patients with GBS, ON and OND were higher than those of normal subjects. In a radioimmunoassay for antibodies to bovine P2 slightly more radiolabelled antigen was precipitated by the GBS group of sera than by sera from the other groups, but only one serum from the GBS and another from the CRP patients precipitated more than 10% of the label. Addition of bovine P2 to cultures of peripheral blood mononuclear cells from 11 patients with GBS did not cause significant stimulation. Immunoassay for antibody to myelin basic protein (MBP) showed an increased proportion of sera with low binding activity in the GBS and CRP groups. The results suggest that humoral immune responses to potentially neuritogenic antigens are found with marginally increased frequency in patients with GBS and CRP.

Adolescent↗
PubMed1984

Spontaneous and experimental neuritis and the distribution of the myelin protein P2 in the nervous system.

The P2 contents of nervous tissues from the human, rabbit, guinea pig, and Lewis rat were measured by radioimmunoassay. The ventral spinal roots contained more P2 than any other tissue. Human dorsal roots and peripheral nerves contained 41-65% of the amount in human ventral roots. Human olfactory and optic nerves and brain contained 1.1-2.7%, spinal cord, 2.8%, cranial nerve VIII, 11%, and cerebral grey matter, 0%. The relative amounts in the rabbit nervous system were similar except that the spinal cord contained 20% of the amount in the ventral roots. Qualitative estimates in the guinea pig showed that the spinal roots and peripheral nerves contained more P2 than the spinal cord, and that none was present in the brain. In the Lewis rat, P2 could be detected in the spinal roots and peripheral nerves but not in the CNS. The distribution of P2 in the human nervous system parallels the incidence and severity of lesions in acute polyradiculoneuritis. It also explains the absence of any lesions in the CNS when experimental allergic neuritis is induced in the Lewis rat.

Animals↗
PubMed1984

Investigation of the idiotypic determinants of IgM monoclonal proteins associated with neuropathy.

Occasionally IgM monoclonal proteins (MP) from benign gammopathies bind neural antigens and have been associated with demyelinating peripheral neuropathy. A monoclonal antibody (McAb) has been raised against a cross-reactive idiotypic determinant expressed by three out of 12 MP with specificity for neural antigens. The determinant recognised by this MoAb is only expressed when both H and L chain are properly associated. The idiotypic determinant was not expressed by 130 MP randomly selected from patients without neuropathy nor in polyclonal immunoglobulin preparations obtained from healthy individuals.

Antibodies, Monoclonal↗
PubMed1983

IgM paraproteins with immunological specificity for a Schwann cell component and peripheral nerve myelin in patients with polyneuropathy.

The sera of 9 patients with benign IgM paraproteinaemia and chronic sensorimotor neuropathy were tested for reactivity to human peripheral nerves by the indirect immunoperoxidase method. They reacted in very high titre (10(-3)-10(-6) with a cytoplasmic Schwann cell component, and to lesser degree, with peripheral nerve myelin (10(0)-10(-3). The Schwann cell staining was in the form of perinuclear cytoplasmic granules and was only seen with adult nerve. The distribution of the antigen was similar to that of the metachromatically staining Pi-granules of Reich, which accumulate in the peripheral nerves with age. Specific activity was present in the IgM and F(ab)2 fractions and could be absorbed out with peripheral nerve tissue, but not with liver. Reactivity is not a simple function of the IgM level, since many IgM paraproteins do not react. The antibody is species specific and binds to human, but not to any component of rabbit, rat or guinea pig sciatic nerves. Antigenicity is removed by pretreatment of the nerve with chloroform-methanol or periodate, but not protease or trypsin. Reactivity is restored, after periodate treatment, by exposure to sodium borohydride. It is suggested that some IgM paraproteins have a specificity for a myelin glycolipid or glycoprotein, which normally accumulates in the Pi-granules of the Schwann cell cytoplasm as a function of age.

Humans↗
PubMed1983

A paralytic disease in nude mice associated with polyoma virus infection.

Nude mice (nu/nu), heterotransplanted with human tumours and kept in isolators, were found to suffer from wasting and posterior paralysis. Electron microscopy of spinal cord tissue revealed virus particles in the oligodendrocytes consistent in size (35 to 40 nm), morphology and distribution with those of the polyoma--SV40 sub-group of papovaviruses. Serology and restriction enzyme analysis of the virus genome showed that the virus was the murine polyoma A2 strain. Inoculation of uninfected nude mice with 10(7) TCID50 of polyoma A2 strain virus produced a similar disease in these mice with wasting and, after 10 to 23 weeks, paralysis of the hind legs of all surviving mice. Extensive myelin disruption was seen throughout the brain stem and sacral region of the spinal cord and high titres of polyoma virus were found in the whole brain (10(8.8) TCID50/brain) and in the spinal cord (10(6.8) TCID50/spinal cord).

Animals↗
PubMed1982

The cell surface of Plasmodium gallinaceum sporozoites: microelectrophoretic and lectin-binding characteristics.

The cell surface properties of Plasmodium gallinaceum sporozoites have been investigated by means of microelectrophoretic and lectin-binding studies. Their electrophoretic mobility has been measured as a function of pH, the results suggesting qualitative and quantitative differences in the surface ionogenic groups between sporozoites from mature oocysts and those from salivary glands. Reaction of sporozoites with citraconic anhydride produced a small but significant increase in mobility, whereas 5,5-dithio-bis-(2-nitrobenzoic) acid had no effect on mobility; thus there appear to be amino groups but not -SH groups at the surface of sporozoites. Treatment of sporozoites with trypsin considerably reduced their mobility and suggests that a significant proportion of the cell surface charge is associated with protein. Incubation with neuraminidase, however, had no effect on sporozoite mobility and indicates that sialic acid residues, responsible for much of the negative charge associated with mammalian cells, are probably not present on the cell surface of sporozoites. Evidence for the presence of carbohydrates on the cell surface membrane of sporozoites was sought using fluorescein isothiocyanate-Concanavalin A. Results demonstrated that ligands similar to alpha-D-glucose and alpha-D-mannose are not present in an exposed or reactive form on the cell surface membrane of P. gallinaceum sporozoites.

Animals↗
PubMed1982

The effects of 2,5-hexane dione on remyelination in the peripheral nervous system of the mouse.

We compared the development and resolution of a demyelinating lesion (produced by the intraneural injection of lysophosphatidyl choline) in mice exposed to a known neurotoxic agent (2,5-hexane dione) with similar events in control animals. A prolongation of the pro-myelin stage was observed in the hexane dione-treated animals: the suppression of remyelination became progressively more marked with the length of exposure to hexane dione. Prolongation of the pro-myelin stage is an indication of a disturbance in some component of the complex interaction between Schwann cell and axon, and presumably reflects the neurotoxicity of 2,5-hexane dione.

Animals↗
PubMed1982

Multiple sclerosis-lymphocyte transformation with multiple sclerosis and normal brain myelin basic protein and subcellular fractions.

Possible sensitisation of peripheral blood mononuclear cells from multiple sclerosis (MS) patients was studied in the presence of both normal and MS brain subcellular fractions. Myelin, synaptosomal and microsomal fractions and myelin basic protein were prepared by sucrose density gradient centrifugation from normal and MS brain. These preparations were added to mononuclear cell microcultures from the peripheral blood of nine acute and six chronic MS patients, 10 patients with other neurological diseases and 10 normal subjects. There was no significant increment in the peripheral blood mononuclear cell transformation of any of the acute MS patients with any of the fractions. Therefore there is no evidence that immunity to antigens in any of the fractions of MS or normal brain is of primary pathogenetic importance. A small increment in peripheral blood mononuclear cell transformation in the presence of several fractions was observed in two of six chronic MS patients, which might indicate the development of a secondary immune response after prolonged disease.

Acute Disease↗
PubMed1980

Experimental allergic neuritis in the Lewis rat: characterization of the activity of peripheral myelin and its major basic protein,P2.

Experimental allergic neuritis has been produced in the inbred Lewis rat in the absence of experimental allergic encephalomyelitis (EAE) using bovine intradural root myelin. The lack of EAE is probably because P1 is only weakly encephalitogenic in the rat. One of the basic proteins of bovine peripheral myelin, P2, was isolated and demonstrated to be pure by amino acid analysis and SDS PAGE. It was found to have a molecular weight of 15,400 and contained 4 mol 1/2-cystine/mol. This P2 was found to be highly neuritogenic and is probably the sole neuritogenic antigen in this system. The successful demonstration of its neuritogenicity must be due in large part to the use of the inbred Lewis rat and bovine P2, but an explanation could also involve the omission of denaturing organic solvents, the prevention of oxidative denaturation and presumably the fact that any changes which may occur are not sufficient to prevent recognition of the active site by the immune system of the inbred Lewis rat. P2 was neuritogenic down to 5 micrograms/animal. Its activity was enhanced by but not dependent on the presence of Mycobacterium in the adjuvant. This suggested that release of P2 could possibly break tolerance and produce an auto-immune disease such as the Guillain--Barre syndrome.

Amino Acids↗
PubMed1980

Antibodies against defined nerve cell components: gangliosides.

Antisera have been raised in rabbits against the purified brain gangliosides GM(1), GD(1a) and GT(1b). The reactivity of these sera with a range of purified gangliosides has been examined by complement fixation and their specificities partially defined by absorptions with purified gangliosides.

Animals↗