Biomedical subjects

E J Thompson

Publications and source records attributed to E J Thompson.

At least 127 records · Page 7Linked to original sources

PubMed1992

In vivo relationship of tumor necrosis factor-alpha to blood-brain barrier damage in patients with active multiple sclerosis.

Tumor necrosis factor-alpha (TNF-alpha) has well recognized effects on cerebral endothelial cells and, therefore, may mediate disruption of blood-brain barrier in patients with multiple sclerosis (MS). To evaluate the in vivo relationship of TNF-alpha to blood-brain barrier impairment in MS, levels of this cytokine in cerebrospinal fluid (CSF) and serum samples from 38 patients with active MS and 48 controls were correlated with CSF to serum albumin ratios. TNF-alpha was detected in the serum of 74% and the CSF of 66% of patients with active MS. CSF levels of TNF-alpha were significantly higher in active MS compared to stable MS or other controls, and were significantly higher than corresponding serum levels. In patients with active MS, only those with detectable TNF-alpha showed signs of blood-brain barrier damage. Moreover, intrathecal levels of TNF-alpha in active MS correlated with albumin ratios and with the degree of barrier damage. Our findings are important in understanding some of the pathological changes in active multiple sclerosis.

Adult↗

PubMed1992

Blood-brain barrier damage in patients with bacterial meningitis: association with tumor necrosis factor-alpha but not interleukin-1 beta.

Brain damage after meningeal infection could result from impairment of cerebral endothelial cell functions and disruption of blood-brain barriers. Tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) produce many of their effects by acting on endothelial cells. This study correlates levels of TNF alpha and IL-1 beta in paired cerebrospinal fluid (CSF) and serum samples with the degree of blood-brain barrier damage, as manifested by CSF to serum albumin quotient, in 48 patients with bacterial meningitis and 66 controls. CSF levels of TNF alpha and IL-1 beta in bacterial meningitis were significantly higher than in controls. Intrathecal levels of TNF alpha, but not IL-1 beta, correlated with albumin quotient (P less than .001), with degree of blood-brain barrier disruption (P less than .001), and with disease severity and indices of meningeal inflammation. Sequential CSF samples demonstrated that IL-1 beta and TNF alpha disappear from the CSF within 24 h of antibiotic treatment. Data presented here suggest that TNF alpha is related to blood-brain barrier damage in bacterial meningitis and that its effect could be dissociated from that of IL-1 beta.

Adolescent↗

PubMed1992

IgG paraproteins in neurological diseases: lack of association with neurotropic viral/bacterial antigens.

In this study we tested the hypothesis that IgG paraproteins in neurological diseases might be regarded as an anti-idiotypic response raised by a nervous system antigen associated with certain neurotropic agents. After initial ELISA screen, positive samples from 34 neurological patients who had paraproteins in their CSF and serum on routine IEF investigation, were tested by immunoblot technique for the presence of specific monoclonal immunoglobulin G (IgG) against eight different neurotropic antigens. Only one patient had specific monoclonal IgG against herpes simplex virus. The results of this study did not confirm our hypothesis. Further study of IgM/IgA paraproteins is indicated.

Adolescent↗

PubMed1992

Immunoblotting of transferrin in the identification of cerebrospinal fluid otorrhoea and rhinorrhoea.

Cerebrospinal rhinorrhoea is potentially serious due to the risk from infection. In patients presenting with a nasal discharge of clear fluid it is important to identify the nature of the fluid. Cerebrospinal fluid is readily identified by the presence of asialo-transferrin (tau protein). A method is presented for the identification of tau protein based upon agarose electrophoresis, followed by transfer onto cellulose nitrate membrane and immunochemical detection of transferrin. The method is reliable, sensitive and simple, and requires only basic electrophoresis apparatus.

Asialoglycoproteins↗

PubMed1992

Oligoclonal immunoglobulin D in the cerebrospinal fluid of neurologic patients.

Oligoclonal immunoglobulin D (IgD) bands were observed in 20 of 110 CSF samples investigated by our method for isoelectric focusing (IEF) of IgD in unconcentrated CSF. These were mostly from demyelinating disorders, viral CNS infections, and CNS tumors. The patterns of expression of IgD were similar to that of IgG, except in cases with tumors where oligoclonal IgD may occur independently of IgG. The study shows for the first time the presence of oligoclonal IgD in CSF from neurologic patients.

Humans↗

PubMed1991

A new qualitative method for detecting IgD in unconcentrated cerebrospinal fluid.

We report a method which is capable of demonstrating the isoelectric focusing (IEF) pattern of immunoglobulin D in unconcentrated cerebrospinal fluid (CSF) samples containing as little as 0.1-0.5 ng of total IgD. The method used was an immuno-sandwich technique, with alkaline phosphatase enzyme amplification. Oligoclonal and polyclonal IgD patterns were seen in CSF samples. No cross-reactivity with other immunoglobulins (IgG, IgA and IgM) was detected.

Humans↗

PubMed1991

The predictive value of intrathecal immunoglobulin synthesis and magnetic resonance imaging in acute isolated syndromes for subsequent development of multiple sclerosis.

The intrathecal synthesis of IgM in patients presenting with acute monosymptomatic syndromes may be relevant in predicting eventual progression to multiple sclerosis but has not been previously evaluated. We undertook a prospective 18-month combined clinical, cerebrospinal fluid, and magnetic resonance imaging study of 45 patients who had presented with acute isolated lesions of brainstem and spinal cord to evaluate the predictive value of intrathecal synthesis of IgM and IgG (through the detection of cerebrospinal fluid oligoclonal bands) and magnetic resonance imaging brain lesions at presentation, for the subsequent progression to multiple sclerosis. Results indicate that the highest risk of developing multiple sclerosis is seen in patients who are positive for oligoclonal IgM and IgG bands and who have disseminated cerebral white matter magnetic resonance imaging lesions at the initial presentation. Oligoclonal IgM bands predict progression to multiple sclerosis more frequently than oligoclonal IgG or magnetic resonance imaging alone. Our results confirm and further extend previous reports, and indicate that detection of cerebrospinal fluid oligoclonal IgM bands at presentation is a valuable prognostic indicator in patients presenting with acute isolated brainstem or spinal cord syndromes.

Acute Disease↗

PubMed1991

Age-related changes in cerebrospinal fluid protein concentrations.

The blood-brain barrier (BBB) has a key role in CSF homeostasis and preservation of normal neuronal function. There has been little investigation of changes in barrier function in elderly subjects without evidence of neurological disease. The ageing brain demonstrates increased vulnerability to a variety of insults, which may reflect a deterioration in barrier performance. Direct measurement of BBB function is difficult but the CSF/serum quotients of individual proteins is the most widely used parameter. The present study sought age related changes in the CSF/serum quotients of prealbumin, albumin, immunoglobulin G and alpha 2-macroglobulin in adults with no neurological deficit. A prospective study was established, and 107 subjects (aged 18-89 yrs) were recruited from patients undergoing spinal anaesthesia or diagnostic myelography. A weak but significant positive correlation was found between the CSF/serum quotients and age for all the proteins studied, but with the exception of alpha 2-macroglobulin, these changes probably reflect age related falls in serum protein concentrations found in this study. alpha 2-Macroglobulin appears to be a sensitive indicator of barrier function for large populations, suggesting a subtle decline of BBB integrity with increasing age. This may be a true age-related change or could reflect an increased incidence of subclinical disease in an ageing population.

Adolescent↗

PubMed1991

The relationship of interleukin-2 and soluble interleukin-2 receptors to intrathecal immunoglobulin synthesis in patients with multiple sclerosis.

The in vivo relationship of interleukin-2 (IL-2) to the local humoral immune response within the central nervous system (CNS) in patients with multiple sclerosis (MS) is hitherto largely unknown. Intrathecal levels of IL-2 and soluble IL-2 receptors (sIL-2R) were correlated to the local CNS synthesis of immunoglobulin G, A, D, and M isotypes in 70 patients with clinically definite MS. Levels were also determined in 19 normal control subjects to establish normal reference limits. High cerebrospinal fluid levels of IL-2 and sIL-2R were detected mainly in patients with acute relapsing-remitting MS and were significantly higher than corresponding serum levels. Intrathecal levels of IL-2 significantly correlated with local CNS synthesis of IgD and IgM, while no correlation was found with either IgG or IgA. Similarly, intrathecal sIL-2R levels significantly correlated with local CNS production of IgD and IgM, but not IgG or IgA. These findings further extend previous reports and also suggest that IL-2 and sIL-2R are involved in the early intrathecal humoral immune response in MS.

Female↗

PubMed1991

Neospora abortion in New Zealand cattle.

Protozoal abortion in cattle was retrospectively studied by examining material submitted to the Batchelar Animal Health Laboratory in the years 1987-90. Only cases in which foetal brain had been submitted were examined. Histologically, protozoal lesions were seen in the brains of 28% of 320 aborted foetuses. Lesions were also seen in 10% of the hearts and 34% of the placentas examined, but these were not as characteristic as those in the brains. Protozoa, confirmed immunohistochemically as being Neospora caninum-like in two brains, were seen in 5% of aborted foetuses with lesions. No protozoa or associated lesions were seen in 57 late term foetuses or neonatal controls. A farm survey supported the hypothesis that Neospora is an important cause of multiple abortions in cattle. Laboratory and farm data suggested that protozoal abortion was more common in early gestation. No predisposing causes of abortion were found and there was no evidence of point infection of affected herds.

Journal Article↗

PubMed1991

Intrathecal immunoglobulin M synthesis in multiple sclerosis. Relationship with clinical and cerebrospinal fluid parameters.

Intrathecal IgM synthesis was assessed through the detection of oligoclonal bands in cerebrospinal fluid (CSF) and through calculation of IgM index values and total CSF IgM amounts. Intrathecal production of IgM was then evaluated along with other CSF parameters and clinical variables in 150 patients with multiple sclerosis (MS). Intrathecal production of IgM was detected in 55% of patients and was found to correlate with disease activity, manifesting as a recent relapse, as well as the total number of relapses. An inverse correlation was found between CSF oligoclonal IgM and both the time interval between the last relapse and lumbar puncture, and duration of the disease process. It also correlated with the number of leucocytes, free kappa and lambda light chain bands in CSF. No correlation was found between intrathecal IgM synthesis and degree of disability (Kurtzke scale), disease progression index (Poser scale), or total cerebral plaque burden (detected by enhanced CT and MRI scans). Oligoclonal IgM bands were found to be more specific for active disease process than either IgM index or total CSF IgM amount. It is concluded that intrathecal synthesis of IgM, as detected by CSF oligoclonal bands, is a useful parameter in monitoring disease relapse activity in MS.

Adult↗

PubMed1990

Affinity distributions of antigen-specific IgG in patients with multiple sclerosis and in patients with viral encephalitis.

We report a method for displaying the affinity distribution of a polyclonal antibody population using sodium thiocyanate elution followed by an ELISA detection technique. We have used this method to study the affinity distribution of antibodies in samples of CSF and serum from patients with MS, and compared the results to those obtained from patients with viral encephalitis. Patients with MS had predominantly low affinity antibody against a particular antigen whilst patients with a primary viral infection had predominantly high affinity antibody against the causative organism.

Antibody Affinity↗

PubMed1990

A sensitive ELISA system for the rapid detection of virus specific IgM antibodies in the cerebrospinal fluid.

The intrathecal production of IgM antibodies to different viral antigens was measured by a modification of ELISA that was both sensitive and specific. Suitably diluted CSF and homologous serum samples containing similar amount of IgM were examined, and a comparison of the photometric signals permitted the detection of specific antibodies secreted from activated lymphocytes into the CSF compartment during the course of viral infections of the central nervous system. Polyvinyl chloride (PVC) microtitre plates were activated by glutaraldehyde and then coated with different viral antigens. Test samples were incubated on these solid-phase antigens and virus-specific IgM antibodies were detected using a peroxidase-conjugated F (ab')2 fragment of anti-human IgM antibody to avoid interference from rheumatoid factors.

Antibodies, Viral↗

PubMed1990

Isoelectric focusing versus quantitative measurements in the detection of intrathecal local synthesis of IgG.

Specimens from 1007 patients with suspected neurological disturbances had quantitative and qualitative measurements made of cerebrospinal fluid and serum to investigate the presence of locally synthesised IgG. Qualitative measurement was recorded as the presence or absence of oligoclonal banding, and the quantitative measurement was derived by the use of the IgG index, the log index and the Reiber, Schuller and Tourtellotte formulae. The patients were divided into two categories, on the basis of banding: those with local synthesis and those without. The sensitivity, specificity and efficiency for each of the quantitative measurements were then calculated. Receiver-operator curves were also constructed for each of the quantitative measurements. 282 samples showed local synthesis of IgG by isoelectric focusing, whereas the best quantitative assay (log index) could only detect 198. Therefore, we conclude that oligoclonal banding should be adopted as the standard laboratory measurement of local synthesis of IgG in the diagnosis of neurological disorders, and that the diagnostic use of quantitative measurements should be abandoned for routine purposes. Furthermore, we suggest that quantitative analysis, at its current level, is misleading and has little value in the understanding of neurological disorders, but may be of use in serially monitoring individual patients as part of their therapeutic trials.

Humans↗

PubMed1990

Intrathecal synthesis of IgM in neurological diseases: a comparison between detection of oligoclonal bands and quantitative estimation.

Immunoglobulin (Ig) M concentration in cerebrospinal fluid (CSF) was measured in 30 reference subjects to determine reference ranges which were up to 0.41 mg/l for CSF IgM, 0.06 for IgM index, and 9 x 10(-4) mg/l for the Reiber empirical formula. Intrathecal IgM synthesis was then studied in 159 patients with different neurological diseases both by detecting CSF oligoclonal IgM bands and by determining the IgM index and Reiber's intrathecal IgM production values. At the same time, the state of blood-CSF barrier was evaluated in all patients by CSF polyacrylamide gel electrophoresis and by CSF/serum albumin ratio. Oligoclonal IgM bands were present mainly in patients with intrathecal humoral immune response, e.g. multiple sclerosis, other inflammatory nervous diseases, and infections of the central nervous system. Quantitative IgM ratios were, however, elevated in conditions not associated with local humoral immune response. Furthermore, quantitative ratios were elevated in patients with damaged blood-CSF barriers. Oligoclonal IgM bands are thus considered to be the most useful tool in detecting intrathecal synthesis of IgM.

Adolescent↗

PubMed1990

Local synthesis of specific IgG in the cerebrospinal fluid of patients with neurosarcoidosis detected by antigen immunoblotting using Kveim material.

The technique of antigen immunoblotting for detection of specific immunoglobulin G (IgG), using Kveim material as antigen, was applied to paired sera and cerebrospinal fluid from 11 patients with definite neurosarcoidosis, 9 patients with definite sarcoidosis and suspected neurosarcoidosis, 22 patients with possible neurosarcoidosis and 16 patients with other neurological disorders, including multiple sclerosis and optic neuritis. Six of the 11 (55%) patients with neurosarcoidosis, none of the 9 patients with definite sarcoidosis and suspected neurosarcoidosis, 5 of the 22 (23%) with possible neurosarcoidosis, and none of the control patients had local synthesis of specific IgG reacting with Kveim material at some stage in the disease. Six of the 8 (75%) patients with definite neurosarcoidosis who had never received steroids or immunosuppressants had local synthesis of Kveim-specific IgG. Local synthesis of Kveim-specific IgG was not found in patients who had received in the past, or were still receiving, immunomodulating agents, and local synthesis was abolished when such treatment was introduced to those patients who had been positive. Those patients whose cerebrospinal fluid showed local synthesis of oligoclonal total IgG were more likely to have local synthesis of Kveim-specific IgG, but not necessarily in an oligoclonal fashion. Immunoblotting, using Kveim material, may thus be a useful adjunct for the investigation of suspected neurosarcoidosis.

Central Nervous System Diseases↗

PubMed1990

A study of immunoglobulin G in the cerebrospinal fluid of 1007 patients with suspected neurological disease using isoelectric focusing and the Log IgG-Index. A comparison and diagnostic applications.

Cerebrospinal fluid and serum immunoglobulin G from 1007 patients with suspected neurological disease were analysed by 2 methods: isoelectric focusing for the detection of oligoclonal banding, and quantitative measurement of IgG and albumin for the formulation of a Log IgG-Index. A comparison of the 2 methods in the detection of local synthesis of IgG showed that isoelectric focusing not only gave a much higher yield overall, with 282 patients showing local synthesis versus 225 for the Log IgG-Index, but also a higher specificity, with a false positive rate of 0% versus 3.5%. In addition, of the 282 patients positive by isoelectric focusing only 163 (58%) were positive by the Log IgG-Index. Of the 1007 patients studied, 206 had multiple sclerosis (MS), and isoelectric focusing showed local synthesis in 95% of clinically definite cases, with a 90% detection rate overall. The Log IgG-Index was positive in only 67% of clinically definite cases, with an overall 59% detection rate. Thus with the exceptions noted above, local synthesis of IgG as defined by isoelectric focusing is confined to demyelinating, inflammatory, infectious and postinfectious disorders. Our results compare very favourably with the published sensitivities of magnetic resonance imaging in the detection of abnormalities in multiple sclerosis, and better than those for evoked potentials. Where both these investigations are readily available isoelectric focusing provides a useful adjunct. For the majority of physicians and neurologists who do not have ready access to magnetic resonance imaging, isoelectric focusing is an excellent alternative. We would also recommend that it become the standard for the measurement of IgG abnormalities in the cerebrospinal fluid and that the use of quantitative data be abandoned for routine purposes.

Demyelinating Diseases↗

PubMed1990

Spleen versus CNS immunoglobulin G in multiple sclerosis: an isoelectric focusing study.

Immunoglobulin G (IgG) band patterns were investigated in a peripheral immune compartment, the spleen, and the central nervous system (CNS) compartment in 6 multiple sclerosis (MS) subjects and 3 controls in a search for systemic humoral immune response that may be related to the localized immune response seen in MS. Using the isoelectric focusing (IEF) technique with immunoperoxidase staining of proteins transferred to nitrocellulose membranes, we were not able to demonstrate any qualitative abnormalities of spleen or serum IgG in the MS cases, whilst all matched CNS tissues and CSF specimens were clearly positive for oligoclonal IgG bands. Our results suggest that there is no systemic oligoclonal IgG secretion in MS. This further supports the presence of a compartmentalized IgG intrathecal immune response in MS and emphasizes the organ specificity of MS.

Central Nervous System↗