Biomedical subjects

I A Gray

Publications and source records attributed to I A Gray.

12 recordsLinked to original sources

PubMed2004

A controlled investigation of the cause of chronic idiopathic axonal polyneuropathy.

To investigate the aetiology of chronic idiopathic axonal polyneuropathy (CIAP), 50 consecutive patients were compared with 50 control subjects from the same region. There were 22 patients with painful neuropathy and 28 without pain, 26 with sensory neuropathy and 24 with sensory and motor neuropathy. The typical picture was a gradually progressive sensory or sensory and motor neuropathy. It caused mild or sometimes moderate disability, and reduced the quality of life. There was no evidence that alcohol, venous insufficiency, arterial disease or antibodies to peripheral nerve antigens played a significant part. There was a possible history of peripheral neuropathy in the first or second-degree relatives of six patients and no controls (P = 0.01), and claw toes were present in 12 patients and four controls (P = 0.03). Thirty-two per cent of the patients and 14% of the controls had impaired glucose tolerance or fasting hyperglycaemia but, after adjusting for age and sex, the difference was not significant (P = 0.45), even in the painful neuropathy subgroup. The mean (SD) fasting insulin concentrations were significantly (P = 0.01) higher in the patients [75.9 (44.4) mmol/l] than the controls [47.3 (37.9) mmol/l], and the mean was higher still in the painful neuropathy subgroup [92.2 (37.1) mmol/l] (P < 0.0001). However, insulin resistance as assessed using the homeostasis model assessment formula was not significantly greater in the patients, even in those with pain, than the controls. After adjustment for body mass index as well as age and sex, there was no significant difference in the serum cholesterol concentrations, but there were significantly higher triglyceride concentrations in the patients [mean 1.90 (1.41) mmol/l] than the controls [mean 1.25 (0.79] mmol/l) (P = 0.02). In the patients with painful peripheral neuropathy, the mean triglyceride concentration was 2.37 (1.72), which was even more significantly greater compared with the controls (P = 0.003). In conclusion, CIAP is a heterogeneous condition. A logistic regression analysis identified environmental toxin exposure and hypertriglyceridaemia, but not glucose intolerance or alcohol overuse as significant risk factors that deserve further investigation as possible causes of CIAP.

Aged↗

PubMed2003

A randomized controlled trial of recombinant interferon-beta 1a in Guillain-Barré syndrome.

The authors recruited 19 nonambulant patients with Guillain-Barré syndrome into a pilot, double-blind, randomized, placebo-controlled safety trial of interferon beta 1a (IFN[beta]-1a) (Rebif). Participants received IFN[beta]-1a or placebo subcutaneously three times weekly, 22 microg for the first week and then 44 microg for up to 24 weeks, in addition to IV immunoglobulin (IVIg). IFN[beta] did not have any unexpected interaction with IVIg and there was no significant difference in rate of improvement.

Cytokines↗

PubMed1997

Immunological investigation of chronic inflammatory demyelinating polyradiculoneuropathy.

In order to investigate the hypothesis that chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease related to the acute inflammatory form of Guillain-Barre Syndrome (GBS), we studied 40 patients, 40 age and sex matched controls with other forms of peripheral neuropathy (ONP) and 37 controls from the same family or household (FC). We sought antibodies to gangliosides GM1 and LM1 by enzyme linked immunoassay (ELISA) confirmed by immuno-overlay. Only 6 (15%) CIDP patients had IgM antibodies to ganglioside GM1 (GM1) and none had IgG antibodies. We found IgM antibodies to ganglioside LM1 in 2 (5%) and IgG antibodies in 4 (10%) CIDP patients. Antibodies of IgG or IgM class were detected by ELISA to chondroitin sulphate C or sulfatide in up to 7.5% of CIDP patients. There were IgM antibodies in 3 (7.5%) and IgG in 4 (10%) patients against 25, 28 or 36 kD myelin proteins identified by immunoblot. Antibodies to any of these candidate myelin autoantigens were not significantly more frequent in CIDP than FC or ONP controls. Sera from 5 CIDP patients with active disease which subsequently responded to plasma exchange did not induce more demyelination upon intraneural injection into rat sciatic nerve than ONP sera. Serum tumor necrosis factor alpha (TNFalpha) concentrations were not increased in any of the CIDP patients. Serological evidence of Campylobacter jejuni (Cj) infection was present in 4 (10%) CIDP patients. IgM antibodies to cytomegalovirus (CMV) were not detected in any sera. CIDP is not commonly associated with either of these infections or with an antibody-mediated response to any of these glycolipid or myelin autoantigens.

Adult↗

PubMed1997

Comparison of the effects of oral versus intravenous methylprednisolone regimens on peripheral blood T lymphocyte adhesion molecule expression, T cell subsets distribution and TNF alpha concentrations in multiple sclerosis.

We investigated in multiple sclerosis the difference between two commonly used oral and intravenous steroid regimens on the level of adhesion molecule expression on blood T lymphocytes, the distribution of circulating T cell subsets, and the concentration of serum tumour necrosis factor alpha. Venous blood samples were collected from a cohort of 22 patients with acute relapses who were participating in a randomised trial comparing intravenous methylprednisolone 1000 mg daily for 3 days with oral methylprednisolone 48 mg daily for one week, 24 mg daily for one week, and finally 12 mg daily for one week. There was a similar significant reduction of T cell LFA-1 surface expression and serum TNF alpha concentrations after 4 days of treatment with each regimen. There was no change in other lymphocyte adhesion molecules expression (ICAM-1, LFA-3 or CD2) at day 4, although LFA-3 and CD2 expression was moderately decreased at day 28 and day 90 respectively; nor was there any change in the distribution of lymphocyte subsets (CD4, CD8, and CD45RA, CD45RO), although a small decrease in CD45RO circulatory T cells was noted at day 28. This study suggests that some of the beneficial effects of glucocorticosteroids may be related to the inhibition of lymphocyte adhesion as well as the modulation of proinflammatory cytokines.

Administration, Oral↗

PubMed1990

Major histocompatibility complex class I and class II polymorphism in chronic idiopathic demyelinating polyradiculoneuropathy.

Thirty-one chronic idiopathic demyelinating polyradiculoneuropathy (CIDP) patients have been typed for HLA-A, -B and -C antigens serologically and for HLA-DR, -DQ and -DP class II genes by RFLP analysis. Our results confirm a previously reported slight association with HLA-B8 and identify a stronger association with HLA-Cw7.

Adult↗

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↗

PubMed1987

Major histocompatibility antigens and lymphocyte subsets during experimental allergic neuritis in the Lewis rat.

Major histocompatibility antigens were identified in frozen sections of normal Lewis rat peripheral nerve tissue with monoclonal antibodies and an avidin-biotin-peroxidase complex system. Class I antigen is normally required for cytotoxic/suppressor T lymphocyte function and class II antigen for activation of helper T lymphocytes. In the sciatic nerves class I antigen was expressed diffusely by most endoneurial and perineurial cells but class II antigen only by a minority. In the cauda equina class I antigen was expressed by all arachnoid and some endoneurial cells, while class II antigen was expressed by a smaller proportion of arachnoid cells in the endoneurium of spinal roots and interstitial cells surrounding dorsal root ganglion neurons. The endothelium of endoneurial, perineurial and meningeal vessels uniformly expressed class I but not class II antigen. Experimental allergic neuritis was induced in Lewis rats by immunisation with bovine intradural root myelin. Early lesions consisted of multifocal infiltration of the nerve roots by cells expressing leucocyte common antigen. Surrounding endoneurial cells showed markedly increased expression of major histocompatibility antigens. In inflammatory lesions about 10% of the cells were stained with pan T cell antibodies. T lymphocyte subsets were identified with antibody W3/25 for helper cells and MRC OX-8 for cytotoxic/suppressor cells. The W3/25 positive cells were usually slightly in excess of OX-8 positive cells and their relative proportions did not alter during the disease. The presence of class I antigen on normal endothelium and its increased expression on endoneurial cells in the early phase of inflammation suggest an important role for class I restricted lymphocytes in the pathogenesis of the early stages of experimental allergic neuritis.

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↗

PubMed1983

Lymphocyte subpopulations and suppressor cell activity in acute polyradiculoneuritis (Guillain-Barré syndrome).

Ficoll-Triosil separated peripheral blood mononuclear (PBM) cells were analysed by fluorescent microscopy with Ortho monoclonal antisera to T cells (OKT3+) helper cells (OKT4+) and suppressor cytotoxic cells (OKT8+) and with polyclonal antiserum to surface immunoglobulin. Twenty-five normal subjects, 16 patients with acute polyradiculoneuritis (Guillain-Barré syndrome, AP) and 10 patients with other neurological diseases were studied. The percentages of OKT3+, OKT4+ and immunoglobulin bearing cells were similar in the three patient groups but the percentage of OKT8+ cells was reduced to 13.5 +/- 4.1 (mean +/- s.d.) compared with 19.4 +/- 4.9 in the normal subjects and 18.5 +/- 3.1 in the patients with other neurological diseases. The ratio of OKT4+/OKT8+ cells was correspondingly increased to 3.5 +/- 2.1 compared with 2.1 +/- 0.5 in the normal subjects and 2.1 +/- 0.4 in the patients with other neurological diseases. In one test of suppressor cell function Con A incubated mitomycin treated PBM cells were added to autologous PBM cells stimulated with Con A to compare the degree of suppression with that produced by control incubated mitomycin treated cells (Con A suppression test). In a second test of suppressor cell function short lived suppressor cell (SLS) activity was assayed by comparing PBM stimulation by Con A added at the start of culture with that produced by Con A added after 24 hr. Neither test revealed any significant differences between AP patients and control subjects.

Acute Disease↗

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↗

PubMed1981

Immune responses in experimental allergic neuritis.

The antibody and cell mediated immune responses were investigated in inbred Lewis rats with experimental allergic neuritis (EAN) induced by either P2, a protein purified from the bovine cauda equina nerve roots, or whole bovine nerve root myelin. In the P2 immunised animals both antibodies to P2 detected by radioimmunoassay and cell-mediated immunity to P2 assayed by skin testing appeared before the onset of EAN and persisted during and after the disease. In the myelin immunised animals the antibody titres were lower and somewhat delayed and the skin tests became negative at the height of the disease. Complement-fixing antibodies to galactocerebroside, which have been implicated in the production of demyelination under some circumstances, could not be detected in the serum after immunisation with either P2 or myelin. EAN was transferred passively with lymph node cells from rats immunised with either P2 or myelin although anti-P2 antibodies could not be detected in the serum of recipients with EAN. The results favour a cell-mediated immune response to P2 as the most important pathogenetic mechanism in EAN induced wtih whole myelin in the rat.

Animals↗

PubMed1979

Lymphocyte transformation in the presence of myelin basic protein in multiple sclerosis and control subjects.

The transformation of lymphocytes in vitro in the presence of human myelin basic protein has been investigated in normal people, patients with multiple sclerosis (MS) and controls with other neurological diseases. There was little or no response at low concentrations (1--10 microgram/ml) but significant transformation at higher concentrations (100--1000 microgram/ml) in all three groups. There was no significant difference among the groups as a whole, but those MS patients who had had disease for more than 10 years did show greater responses than normal subjects (P less than 0.05). Increased responses could not be correlated with any other aspect of disease activity: in particular they were not increased in patients with acute relapses. The use of autologous serum instead of homologous AB Rhesus positive serum did not significantly alter lymphocyte responsiveness. The absence of any response in the presence of purified calf thymus histone suggests that the response to myelin basic protein indicates a low level of lymphocyte sensitization to this antigen even in normal subjects. The present evidence does not support a primary pathogenetic role for such a reaction in MS. The increased response in patients with a long duration of disease might merely be an effect of white matter damage or might represent an amplification of the normal immune response contributing to myelin breakdown and leading to the emergence of the progressive stage of the disease. The study of lymphocyte responsiveness over a wide range of concentrations of myelin basic protein is considered to resolve some of the controversy surrounding this subject in the literature.

Adolescent↗