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Biomedical subjects

E J Thompson

Publications and source records attributed to E J Thompson.

At least 145 records · Page 8Linked to original sources
PubMed1990

Oligoclonal immunoglobulin G in cerebrospinal fluid of myasthenia gravis patients.

Immunoglobulin G (IgG) band patterns were investigated in cerebrospinal fluid (CSF) from 19 patients with myasthenia gravis (MG) in a search for abnormalities indicating central nervous system (CNS) involvement in this disorder. Using the isoelectric focusing (IEF) technique and antiserum immunoblotting against IgG, we found no evidence of the presence of oligoclonal IgG in CSF from most of MG patients. In 2 cases, the positive findings of oligoclonal IgG in CSF may have reflected a manifestation of an associated disease, which has already been associated with immune abnormalities within the CNS. Further investigations with more sophisticated techniques are required to give additional insight into humoral immune events within the CNS in MG patients.

Adult↗
PubMed1990

Laboratory investigation of cerebrospinal fluid proteins.

Analysis of CSF proteins is useful in the diagnosis and management of neurological diseases in the following situations: 1. In inflammatory conditions when there is breakdown of blood-CSF barrier integrity. Meningitis is a medical emergency, with CSF total protein measurement being only a screening test. 2. In the detection of immune responses within the CNS. This is by far the most important application in a routine clinical setting, as it is now a firmly established criterion in the diagnosis of multiple sclerosis. Oligoclonal bands restricted to the CSF are the only reliable indicators of intrathecal immunoglobulin G synthesis and are practically always associated with inflammatory disease of the CNS. The method fo choice for detecting oligoclonal bands is isoelectric focusing with immunofixation. Quantitative measurement of IgG in the CSF is of no value in diagnostic pathology. 3. In destructive brain diseases when brain-specific proteins are released into the CSF, measurement of these proteins can give prognostic information.

Cerebrospinal Fluid Proteins↗
PubMed1990

The occurrence of oligoclonal IgG in tears from patients with MS and systemic immune disorders.

Using isoelectric focusing (IEF) and immunoperoxidase staining of proteins transferred to nitrocellulose membranes, we have examined the IgG band pattern in tears and matched serum and CSF specimens of 28 patients with MS, 4 patients with optic neuritis (ON), 30 individuals with systemic, inflammatory, or other neurologic diseases, and 5 patients with tension headache. We found no evidence of positive oligoclonal IgG in tears in any MS or ON patients, while 10 out of 16 cases with systemic immune disorders or infections of the CNS had positive tear oligoclonal bands. We are thus not able to support the hypothesis that tears from MS patients reveal abnormalities in their humoral immune response.

Adult↗
PubMed1989

Differential oligoclonal band patterns on polyvinyldifluoride membranes.

We report a novel observation which has been reproducibly noted whilst studying immunoglobulin G binding to antigen immobilized on polyvinyldifluoride membranes. In some samples we have observed a difference between the pattern of oligoclonal bands on the front surface when compared to the reverse side of the membrane. We postulate that this observation results from differing affinities of the specific antibody binding to the antigen immobilised on the membrane. High affinity antibody will bind to antigen on the surface of the membrane next to the gel, while lower affinity antibody appears to diffuse through to the reverse side of the membrane.

Antibody Affinity↗
PubMed1989

Viral specific IgG and IgM antibodies in the CSF of patients with tropical spastic paraparesis.

The cerebrospinal fluid (CSF) from seven West Indian migrants to the United Kingdom with tropical spastic paraparesis were studied by antigen immunoblotting for specific anti-HTLV1 oligoclonal IgG and IgM. Eight CSFs from five patients were positive for specific IgG and negative for IgM; three CSFs from two patients were positive for IgM and negative for IgG. No patient had both IgG- and IgM-positive CSF. Those patients with IgM only had disease of the shortest duration. When looking for evidence that neurological damage is caused by HTLV1, both IgM and IgG should be examined.

Adult↗
PubMed1989

Antibodies against the paramyxovirus SV5 are not specific for cerebrospinal fluid from multiple sclerosis patients.

An aetiological agent for multiple sclerosis has not yet been identified. The paramyxovirus SV5 (Simian virus 5) has been suggested as an important cause in some cases. Using antigen immunoblotting with SV5 virus, we confirmed the binding to SV5 of immunoglobulin G from the cerebrospinal fluid of 58% of multiple sclerosis patients, but also found binding in 70% of patients with a variety of neurological disorders where oligoclonal banding was present. This suggests that the antibodies present are not specific for multiple sclerosis and that the SV5 virus is thus unlikely to be of aetiological significance.

Antigens, Viral↗
PubMed1989

Glutaraldehyde-enhanced immunofixation: a sensitive new method for detecting oligoclonal immunoglobulin M.

A new, specific and economical method with enhanced sensitivity for rapid detection of IgM oligoclonal bands in unconcentrated cerebrospinal fluid (CSF) is presented. It is based on the use of glutaraldehyde during immunofixation of electrophoresed specimens and utilizes peroxidase-conjugated F(ab')2 fragment of anti-IgM antibody to avoid cross-reactivity with other CSF gamma globulins. It is able to detect 1 ng of IgM banded protein in electrophoresed CSF. Using this method, oligoclonal IgM was mainly detected in inflammatory and infectious conditions of the central nervous system.

Aldehydes↗
PubMed1989

Cyclosporin A curtails the progression of free light chain synthesis in the CSF of patients with multiple sclerosis.

Free light chains in the cerebrospinal fluid of patients with multiple sclerosis correlate closely with disease activity. As part of a double-blind placebo controlled trial of immunosuppression using cyclosporin A in patients with multiple sclerosis, light chain analysis was performed on pre- and post-treatment CSF samples in 19 patients, nine having received cyclosporin A and 10 placebo. The placebo treated patients showed continued immunological activity, as evidenced by an increase in both free kappa and lambda chains, but cyclosporin A treatment resulted in no change or an improvement in light chain response, indicative of suppression of continued activity. As cyclosporin A does not enter the CSF, this implies that systemic stimulation is at least partly responsible for continued disease activity in multiple sclerosis. Cyclosporin A may thus be effective in preventing the deterioration of patients with multiple sclerosis.

Adult↗
PubMed1989

Immunoglobulin M in the cerebrospinal fluid: an indicator of recent immunological stimulation.

Using a sensitive new method for detecting oligoclonal immunoglobulin M (IgM) in unconcentrated cerebrospinal fluid (CSF), the intrathecal synthesis of IgM was correlated with that of free light chains in patients with multiple sclerosis, infections of the central nervous system and other neurological conditions. A strong correlation was found between the presence of oligoclonal IgM and that of free light chains in the CSF from patients with multiple sclerosis and infections of the central nervous system. No oligoclonal IgM response was observed in patients with non-inflammatory or non-infectious neurological conditions. This implies that oligoclonal IgM has the same diagnostic significance as free light chains.

Central Nervous System Diseases↗
PubMed1989

A micro-method for measuring total protein in cerebrospinal fluid by using benzethonium chloride in microtiter plate wells.

By using a benzethonium chloride concentration 12-fold that described originally (Clin Chem 1979;25:1317-9), we developed a reliable method suitable for routine measurement of total protein in cerebrospinal fluid. Only 10 microL of sample is required. Reactivity to immunoglobulin G (IgG) and to albumin (Alb) is similar, as is necessary for specimens that can have very varied IgG/Alb ratios. The assay, performed in a microtiter plate for ease of use, has a between-batch coefficient of variation of 3.4% for a protein concentration of 450 mg/L. This contrasts with a dye-binding technique with Ponceau S, for which the CV was 9% at the same concentration.

Albumins↗
PubMed1987

B cell development and regulation after T cell-depleted marrow transplantation.

Antibody secreting B lymphocytes from immunized donors can be adoptively transferred after T cell-depleted marrow transplantation to produce protective levels of antibody in the recipient. We have investigated whether these transferred lymphocytes remain subject to continued clonal selection and subsequently became memory B cells even in the initial absence of T cells. Twenty-eight donor/recipient pairs were randomized pretransplant to be immunized or not with tetanus toxoid (TT). The recipients were then vaccinated with TT at 3, 6, and 12 mo posttransplant, and the anti-TT antibody response (IgG and IgM) was measured. Only when both donor and recipient were immunized pretransplant could the recipient respond to antigen challenge within the first year posttransplant. Examination of the spectrotype pattern of the recipient anti-TT antibody shows that selection of B cell clones continues, so that T cell depletion does not prevent the appearance of oligoclonal antibody responses. However, because the spectrotype pattern of the recipient did not match the donors, B cell regulatory mechanisms in donor and recipient are nonidentical. These data contrast with observations made in recipients of non-T cell-depleted marrow and serve to illustrate the role of T lymphocytes in the induction and regulation of secondary antibody responses in man. The results also suggest that optimal humoral responses to any antigen after T cell depletion can only occur when both donor and recipient are immunized pretransplant, a prediction borne out by studies on the influence of donor cytomegalovirus status on the severity of cytomegalovirus infection in the recipient.

B-Lymphocytes↗
PubMed1986

Proteins as parameters in the discrimination between different blood-CSF barriers.

Data on cerebrospinal fluid to serum concentration ratios for albumin, IgG and alpha 2-macroglobulin were analysed by groupings based on electrophoretic or clinical criteria. Statistically significant differences (P less than 0.01) were found for distinguishing up to three different blood-CSF barriers, when compared to normal barrier function.

Albumins↗
PubMed1985

Cerebrospinal fluid in multiple sclerosis: relationships between immunoglobulins, leucocytes and clinical features.

Cerebrospinal fluid (CSF) from 120 patients with multiple sclerosis was analyzed by polyacrylamide gel electrophoresis, as well as routine laboratory microscopy and assays of total protein and immunoglobulin G (IgG). Negative correlations were found between leucocyte counts and patient age, duration of disease and time from last clinical relapse. There was a positive correlation between the leucocyte count and amount of gammaglobulin. A correlation between gammaglobulin content and degree of disability was found. With increasing duration, the gammaglobulin concentration rose only if there was increasing disability. In terms of correlations with clinical features, differences existed depending on whether IgG was assayed immunologically or by electrophoresis and densitometry. Evidence of increased blood: CSF barrier permeability (transudation of high molecular weight proteins) was found in patients with progressive disease. The presence of oligoclonal bands was the CSF abnormality most frequently encountered.

Adolescent↗
PubMed1985

Free light chains in the cerebrospinal fluid: an indicator of recent immunological stimulation.

A group of 38 patients with immunoglobulin free light chains (kappa and/or lambda) in the cerebrospinal fluid was studied. Only five of them showed one band of kappa free light chains, 36 of them showed one or more bands of lambda free light chains. There were 33 multiple sclerosis patients among them and they were compared with 33 control multiple sclerosis patients who did not have free light chains but only showed an oligoclonal pattern of immunoglobulins in their CSF. Of several clinical and pathological parameters, only three were statistically significant: (A) for all patients, as well as for the multiple sclerosis patients alone, elevated numbers of free light chains of type lambda were associated with the elevated numbers of white blood cells in the CSF (p less than 0.003), (B) for multiple sclerosis patients, elevated numbers of free light chains of type lambda were associated with associated with shorter time intervals between the last relapse and the date of the lumbar puncture (p less than 0.004) and (C) also with shorter duration of the disease (p less than 0.01). The presence of lambda free light chains in the cerebrospinal fluid seems to indicate that recent antigenic stimulation has occurred within the central nervous system following exacerbation. The inverse association of the number of lambda free light chains with the duration of the disease is suggestive of a pathological expression of the "burning out" phenomenon of the multiple sclerosis process.

Electrophoresis, Polyacrylamide Gel↗
PubMed1985

High electroendosmotic agarose electrophoresis and nitrocellulose immobilisation for the detection of oligoclonal bands in unconcentrated cerebrospinal fluid.

A sensitive (1 microL of unconcentrated sample), specific (IgG Fc) and economical (10 p/test) method for the detection of oligoclonal bands in cerebrospinal fluid is presented. Using commonly available technology (agarose gel electrophoresis) and giving results within 6 h, the approach used here is a powerful tool in the investigation of immunoglobulin abnormalities in many biological fluids.

Collodion↗