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Biomedical subjects

E J Thompson

Publications and source records attributed to E J Thompson.

At least 19 recordsLinked to original sources
PubMed1998

Antigen-dependent intrathecal antibody synthesis in the normal rat brain: tissue entry and local retention of antigen-specific B cells.

The intrathecal Ab response to Ag introduced into the normal brain has not been fully explored. Involvement of Ag-specific, peripheral B cells in an intrathecal response was studied using a normal rat model of Ag infusion through an indwelling cannula into defined brain sites, while maintaining a functionally intact blood-brain barrier. Specific Ab was detected in serum and cerebrospinal fluid. The intrathecal response is first detectable at day 14. Isoelectric focusing of cerebrospinal fluid reveals banding patterns consistent with local Ab production. To increase Ag-specific, circulating peripheral lymphocytes available for trafficking to Ag-stimulated brain and for enhancing intrathecal Ab synthesis, rats were preimmunized peripherally. Subsequently, Ag or saline (control) was infused through the cannula. Under this protocol, intrathecal synthesis is detectable earlier (day 5 postinfusion). Immunohistochemical studies at the infusion site assessed Ag-specific B cells, T cells, and activated APCs. Rats receiving peripheral preimmunization followed by Ag into caudate nucleus have far greater numbers of these cells, including plasma cells, within the infusion site compared with saline controls. Results confirm previous indirect evidence of intrathecal Ab synthesis in normal rat brain and provide the first direct evidence for B cell trafficking across normal brain barriers plus retention at the Ag deposition site. Our studies indicate that the normal brain microenvironment supports development of Ag-directed humoral immunity. We propose that immune privilege in normal brain is characterized by down-regulation of cell-mediated but not Ab immune responses within the central nervous system.

Animals↗
PubMed1998

Elevated cerebrospinal fluid and serum nitrate and nitrite levels in patients with central nervous system complications of HIV-1 infection: a correlation with blood-brain-barrier dysfunction.

As nitric oxide (.NO) is hypothesised to play a role in the immunopathogenesis of neurological complications associated with inflammation, we compared levels of cerebrospinal fluid (CSF) and serum .NO metabolites in 24 patients with HIV-1 infection, to those in 58 non-HIV infected patients with neurological disorders. Levels of .NO metabolites were correlated with blood-brain-barrier dysfunction. CSF and serum nitrate and nitrite levels were measured by the nitrate reductase and Griess reaction methods. The .NO metabolites, nitrate and nitrite, were raised in the CSF and serum of patients with AIDS and central nervous system complications, when compared to non-HIV infected patients with inflammatory and non-inflammatory neurological disorders (median nitrate and nitrite: CSF=18.3 microM vs. 11.1 microM vs. 7.0 microM, P<0.001, and serum=53.8 microM vs. 50.3 microM vs. 41.4 microM, P=0.04, respectively). CSF nitrate and nitrite levels correlated with the albumin quotient. This study supports the evidence that .NO is a potential mediator of blood-brain-barrier breakdown in inflammatory diseases of the central nervous system.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Protein adsorption to hydrocephalus shunt catheters: CSF protein adsorption.

OBJECTIVE: To assess the quantity and nature of the proteins that adsorb to hydrocephalus shunt catheters after implantation, and to determine whether sufficient could accumulate to obstruct the catheter. DESIGN: Elution of proteins from 102 explanted shunt catheters, with protein assay and electrophoresis of the eluate, and scanning electron microscopy (SEM) of the catheters. RESULTS: The amount of protein elutable was extremely low, and significant protein, apart from a thin film, was not found on SEM. Qualitative analysis disclosed that most of the adsorbed protein was albumin. CONCLUSIONS: Protein deposition on hydrocephalus catheters does not occur in sufficient quantities to cause catheter obstruction.

Adsorption↗
PubMed1998

Protein markers of brain damage.

Brain proteins are released into body fluids in a fashion which reflects the underlying pathogenetic mechanisms for individual diseases. It is therefore important to distinguish not only different protein markers (reflecting various brain cells from which they have been released), but also their metabolism at different sites within the body (e.g. reticulo-endothelial system vs renal clearance) which will have an important bearing on whether fragments of the protein are found in urine or blood. It is clear that different patterns of protein abnormalities would be helpful in differential diagnosis of the individual diseases which afflict the nervous system. It would also be useful to monitor these proteins either as surrogate markers of the natural history of the condition or in the various therapies for each disease.

Biomarkers↗
PubMed1997

Increased S100beta in the cerebrospinal fluid of patients with frontotemporal dementia.

Levels of S100beta, a calcium-binding protein found in astrocytes, were measured using a sandwich ELISA in the cerebrospinal fluid (CSF) of patients with frontotemporal dementia and Alzheimer's disease and compared with controls. Mean CSF S100beta concentrations were significantly raised in patients with frontotemporal dementia when compared with healthy controls (0.49 +/- 0.28 vs. 0.22 +/- 0.08 ng/ml, P < 0.001). There was no correlation between age at disease onset, disease severity or length of illness. The increased concentration of CSF S100beta seen in frontotemporal dementia may reflect the marked astrocytosis seen in this condition.

Adult↗
PubMed1997

A specific and sensitive ELISA for measuring S-100b in cerebrospinal fluid.

A sensitive, simple and specific sandwich ELISA for S-100b is described. This method involves the binding of a monoclonal anti-S-100b antibody to the wall of a microtitre plate. This capture antibody is subsequently incubated with S-100b standard, control or patient sample in the form of cerebrospinal fluid (CSF). After incubation, the microtitre plate is washed and horseradish peroxidase-labelled polyclonal anti-S-100b is added (detector antibody). The amount of detector antibody bound to the microtitre plate is proportional to the amount of S-100b in the sample. The assay has a lower limit of detection of 0.04 ng/ml and shows < 0.006% reactivity with the closely related polypeptide S-100a. The assay has a mean within-batch precision of 9.3 and 5.6% at S-100b concentrations of 0.38 and 0.8 ng/ml, respectively. The between batch precision is 8.9 and 8.1% at S-100b concentrations of 0.12 and 0.34 ng/ml, respectively. The recovery of S-100b from CSF spiked with 0.5 ng/ml was 94% with a CV of 8.5%. The assay may be completed in less than 5 h using precoated microtitre plates, thus lending itself to routine use in clinical laboratories. Using this ELISA, 154 CSF samples were analysed and 19% of samples were found to have elevated levels. The highest levels were found in patients with cerebral haemorrhage or central nervous system malignancy. S-100b concentrations from individuals without evidence of neurological disease were found to be less than 0.4 ng/ml. Only 5% of patients with multiple sclerosis were found to have elevated CSF S-100b concentrations. Serial CSF samples taken from a patient with an infected in-dwelling shunt showed a dramatic decline, suggesting that S-100b is rapidly cleared.

Enzyme-Linked Immunosorbent Assay↗
PubMed1997

An improved, ultrasensitive method for the detection of IgM oligoclonal bands in cerebrospinal fluid.

A new, 10-fold more sensitive method, based on an improved immunofixation technique, has been devised to detect oligoclonal IgM bands in unconcentrated cerebrospinal fluid (CSF). Using agarose gel electrophoresis, 5 microliters of an unconcentrated sample containing oligoclonal bands was separated and blotted on to a polyvinyldifluoride membrane. To visualise the pattern, a peroxidase-labelled double-antibody technique was used. No prior concentration of CSF was needed and the process required only 5 h. The technique may prove very useful in diagnosing an early intrathecal immune response.

Cross Reactions↗
PubMed1997

Raised serum nitrate and nitrite levels in patients with multiple sclerosis.

Nitric oxide and its highly reactive derivative peroxynitrite have been implicated as non-specific inflammatory mediators of neuronal and oligodendrocyte damage and death in multiple sclerosis. In a cross-sectional study we found levels of the nitric oxide metabolites nitrate and nitrite to be raised in the serum of patients with demyelinating disease (65.6 microM (SD 32.9)), acquired immune deficiency syndrome (57.9 microM (SD 34.9)) and inflammatory neurological disease (57.5 microM (SD 31.3)), compared with normal control subjects (32.8 microM (SD 12.2)) and patients with non-inflammatory neurological disease (41.1 microM (SD 12.3), p < 0.001). Nitric oxide metabolites were raised in all clinical subtypes of multiple sclerosis, as well as in clinically isolated syndromes compatible with demyelination, and were not related to progressive disease or disability. This study provides further evidence for a role of nitric oxide in the immunopathogenesis of inflammatory diseases of the central nervous system, including multiple sclerosis.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Daily urinary neopterin excretion as an immunological marker of disease activity in multiple sclerosis.

The aim of this study was to assess neopterin, a marker of interferon gamma (IFN-gamma) induced macrophage activity, as a possible surrogate marker of inflammation in patients with multiple sclerosis. Urinary neopterin to creatinine ratios (UNCRs) were measured daily in 10 primary progressive (PP). 10 relapsing remitting (RR) and 11 secondary progressive (SP) patients with multiple sclerosis, and 14 normal control (NC) subjects, for periods of up to 12 weeks. After excluding measurements related to infection, the median of the individuals' average UNCRs was significantly higher in patients than in controls (P < 0.001 for all patients and P < 0.01 for each of the three groups of patients); the median UNCRs (and interquartile ranges) were 187 (135-231), 187 (165-277), 218 (164-517) and 134 (97-152) mumol/mol for PP, RR, SP patients and controls, respectively. Similarly, patients had a greater median proportion of days with a UNCR above normal (P < 0.001 for all patients and P < 0.01 for each group); the median percentage (and interquartile ranges) were 16 (6-62), 28 (21-36), 49 (14-86) and 0 (0-6)% for PP, RR, SP patients and controls, respectively. They also had a greater number of peaks in their serial UNCR measurements than controls (P < 0.001 for all patients and P < 0.01 for each group); the means +/- SD peaks/subject/month were: 2.1 +/- 1.8; 3.0 +/- 1.7; 3.3 +/- 2.3 and 0.2 +/- 0.6 for PP, RR, SP patients and controls, respectively. Nine relapses occurred in nine patients during the study, and all were associated with increased neopterin excretion, which tended to be greater than that on days not associated with a relapse. Three of the nine relapses were preceded by an upper respiratory tract infection. In eight out of 13 patients who had infections during the study, increased neopterin excretion was noted for periods of up to 6 weeks post-infection, significantly longer than that which occurred after infections in controls. This confirms infection as a potent inducer of symptomatic and asymptomatic disease activity in mutiple sclerosis, and provides further support of a pivotal role for IFN-gamma in te pathogenesis of mutiple sclerosis. Urinary neopterin excretion is increased in patients with both progressive and relapsing mutiple sclerosis, and therefore has potential as a surrogate marker of the inflammatory component of mutiple sclerosis disease activity.

Adult↗
PubMed1997

Cerebrospinal fluid ferritin in HIV infected patients with acute neurological episodes.

OBJECTIVES: To measure cerebrospinal fluid (CSF) ferritin in HIV infected patients with acute neurological episodes and to correlate the findings with the type and severity of neurological disease. METHODS: CSF ferritin and the ratio of CSF to serum albumin (QAlb) were prospectively measured in 27 consecutive HIV infected patients admitted to a specialist unit for investigation of acute neurological episodes; the results were compared with their clinical diagnoses. RESULTS: Ten patients had HIV associated dementia complex, six had cryptococcal meningitis, two had primary CNS lymphoma and nine had miscellaneous conditions including herpes simplex virus encephalitis, cytomegalovirus encephalitis, cerebral toxoplasmosis and mononeuritis multiplex. Overall, 16 (59%) patients had raised CSF ferritin levels, ranging from 13.0 to 50.2 micrograms/l, (median = 16.1 micrograms/l: normal range = 1.0-12.0 micrograms/l). Thirteen of the 16 also had normal QAlb values, implying an intact CSF-blood barrier, and thus that local synthesis of ferritin had occurred. Elevated ferritin levels were not associated with particular neurological diagnoses. In those with HIV associated dementia complex there was no correlation between CSF ferritin levels and the severity of clinical cognitive deficit or the extent of magnetic resonance imaging abnormalities. CONCLUSIONS: An elevated CSF ferritin level is a non-specific finding in HIV infected patients presenting with acute neurological episodes.

AIDS Dementia Complex↗
PubMed1997

Adaptation of the nitrate reductase and Griess reaction methods for the measurement of serum nitrate plus nitrite levels.

Nitrite and nitrate determinations in biological fluids are increasingly being used as markers of nitric oxide production. We have modified a nitrate reductase and Griess reaction method for the measurement of serum nitrate and nitrite in ultrafiltrated samples using a microtitre plate. The recoveries of nitrate and nitrite were 95% (range = 86-113%) and 100% (range = 92-109%), respectively. The intra and inter assay coefficients of variation for nitrate plus nitrite in the concentration range 40-50 microM were 9.1% and 7.8%, and in the concentration range of 2.5-10 microM 23.4% and 25.5%, respectively. At its lower limit the assay is able to detect 125 pmoles of nitrate plus nitrite in 50 microL of sample (2.5 mumol/L). A mean serum nitrate plus nitrite level of 32.8 mumol/L (SD 12.3) was measured in 24 healthy adult volunteers (12 men and 12 women), no age or sex differences were noted.

Adult↗
PubMed1997

Longitudinal study of soluble adhesion molecules in multiple sclerosis: correlation with gadolinium enhanced magnetic resonance imaging.

OBJECTIVE: To assess whether serial serum levels of soluble forms of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) are useful as surrogate markers of disease activity in multiple sclerosis (MS). BACKGROUND: Increased levels of sICAM-1 and sVCAM-1 have been described in cross-sectional, but not longitudinal, studies of patients with MS. Although they appear to correlate with clinical and MRI markers of disease activity, their role as potential surrogate markers remains undefined. METHODS: Serial serum levels of sICAM-1 and sVCAM-1 were measured in patients with MS undergoing monthly gadolinium-enhanced MRI studies of the brain (462 gadolinium-enhanced MRI in 57 patients) and in 12 normal control subjects. Ten patients had primary progressive (PP), 22 relapsing remitting (RR), and 25 secondary progressive (SP) disease. RESULTS: Levels of sICAM-1 and sVCAM-1 were increased intermittently in patients with all subtypes of MS. Median levels of sICAM-1 were elevated in patients with MS compared with normal controls (normal controls median [interquartile range] = 176[119-209] compared with PP = 502[194-1768], RR = 419[158-481], and SP = 352[196-469] ng/mL; p = 0.04). After excluding patients with PP MS, patients with high sICAM-1 levels had a greater number of gadolinium-enhancing lesions per study (1.9[0.9-4.3]) than patients with normal levels (0.4[0-2.7], p = 0.03), and patients with MRI studies with no gadolinium-enhancing lesions had lower associated sICAM-1 levels (200 ng/mL[85-561]) than patients with only persistent (349 ng/mL[82-615]) or new enhancing lesions (497 ng/mL[108-667], p = 0.03). Patients with RR or SP disease that progressed clinically during the study had a greater number of gadolinium-enhancing lesions per MRI study (3.5[0.4-5.5]) than did patients in whom disease did not progress (1.2 [0.3-2.7], p = 0.03). The patients with progressive disease tended to have higher sICAM-1 levels (469 ng/mL [196-1019]) than patients in whom disease did not progress (353 ng/mL [171-469], p = 0.07). Although MS patients tended to have higher sVCAM-1 levels than did normal controls, this finding was not significant. No correlation could be found between levels of sVCAM-1 and gadolinium enhancement on MRI. CONCLUSIONS: Patients with MS have elevated levels of sICAM-1, which correlate with gadolinium enhancement on MRI and possibly short-term disease progression. Soluble ICAM-1, and not sVCAM-1, may therefore be suitable as a long-term surrogate marker of disease activity in MS.

Adult↗
PubMed1997

The potential risks to animal health from imported sheep and goat meat.

Alerted by outbreaks of foot and mouth disease and the swine fevers which have been attributed to international trade in meat, regulators have tended to adopt conservative policies with respect to the importation of meat. However, for disease introduction to occur as a result of meat importation, a number of criteria must be satisfied. A qualitative assessment of the risks posed by sheep and goat meat leads to the conclusion that, with the possible exception of foot and mouth disease there is little likelihood that Office International des Epizooties List A or List B diseases would be spread through trade in adequately matured meat obtained from animals which have passed veterinary ante-mortem and post-mortem inspections.

Animals↗
PubMed1996

Affinity of anti-GM1 antibodies in Guillain-Barré syndrome patients.

In this study, we investigated the affinity of anti-GM1 IgG antibodies as well as their IgG subclass distribution in a series of 38 patients with Guillain-Barré syndrome. In 7 sera elevated titres of IgG anti-GM1 antibodies could be detected. With respect to affinity there were two distinct groups of anti-GM1 antibodies: one group was of high affinity and did not cross-react with other glycolipids; the other group was of low affinity and cross-reacted with asialo-GM1. IgG1 was the predominant and almost exclusive subclass of high affinity anti-GM1 antibodies. Axonal degeneration occurred significantly more frequently in patients with high affinity anti-GM1 antibodies than in patients without anti-GM1 antibodies or in patients with low affinity anti-GM1 antibodies. The presence of anti-Campylobacter jejuni antibodies was not associated with a specific electrophysiological pattern. The prognosis was not dependent on the detection of any of the antibodies, whereas axonal loss and ventilation were associated with a poor prognosis.

Adult↗
PubMed1996

Serum oligoclonal IgG is a common and persistent finding in multiple sclerosis, and has a systemic source.

Synthesis of oligoclonal IgG within the central nervous system is a well established feature of multiple sclerosis. The occurrence of oligoclonal IgG in the serum of patients with multiple sclerosis has received little attention. We detected such a serum response in 20/45 consecutive patients (44%, 95% CI 30-59%) but in only 3/41 age- and sex-matched healthy controls (p < 0.01). We present qualitative and quantitative evidence that this oligoclonal IgG has a systemic origin. The plasma cell clones responsible for the serum response are often also represented in the intrathecal compartment. In a further study of the clinical significance of serum oligoclonal bands, in 80 patients, their presence was associated with elevated levels of intrathecal synthesis, increasing age, later disease onset and the presence of serum autoantibodies. These findings add to the evidence that there is a systemic immune disturbance in multiple sclerosis.

Adult↗
PubMed1996

Soluble E-selectin in multiple sclerosis: raised concentrations in patients with primary progressive disease.

OBJECTIVE: To determine whether concentrations of soluble E-selectin (sE-selectin), an immunological marker of endothelial activation, were correlated with gadolinium-DPTA enhancement on MRI in patients with multiple sclerosis. METHODS: Serial sE-selectin concentrations were measured in 28 patients with multiple sclerosis undergoing monthly gadolinium (Gd) enhanced MRI of the brain and spinal cord, and in 10 control subjects. C reactive protein (CRP), von Willebrand factor (vWF), and tumour necrosis factor-alpha (TNF alpha) were also determined. RESULTS: Primary progressive patients had significantly increased sE-selectin concentrations compared with the relapsing remitting and secondary progressive patients who had normal sE-selectin concentrations (22.2 (SD1 6.1) ng/ml v 9.8 (SD2.1) ng/ml and 7.7 (SD2.7) ng/ml, respectively, P = 0.03). This difference was attributable to five of the 10 primary progressive patients who had persistently raised sE-selectin concentrations, with relatively inactive MRI studies. No correlation could be found between sE-selectin concentrations and Gd enhancement on MRI, but a close correlation existed between mean concentrations of sE-selectin and TNF alpha (r = 0.71, P < 0.001). Despite raised sE-selectin and TNF alpha concentrations, primary progressive patients had normal CRP concentrations (1.03 (SD1.14) mg/l), which were significantly lower than the relapsing remitting (3.16 (SD2.54) mg/l) and secondary progressive patients (2.28 (SD2.1) mg/l, P = 0.03). Raised CRP concentrations did correlate with infectious episodes, clinical relapse, and Gd enhancement, and were significantly raised when no MRI activity was found. Concentrations of vWF were normal in all patient groups. CONCLUSIONS: The results further high-light the differences between patients with primary progressive and those with relapsing remitting/secondary progressive multiple sclerosis.

Adult↗