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Biomedical subjects

J D Pollard

Publications and source records attributed to J D Pollard.

At least 73 records · Page 4Linked to original sources
PubMed1990

Immunopathological factors in peripheral nerve allograft rejection: quantification of lymphocyte invasion and major histocompatibility complex expression.

The numbers of helper T and cytotoxic T lymphocytes and macrophages were quantified, and the expression of major histocompatibility complex (MHC) class I and class II molecules was examined in rat peripheral nerve allografts from 1 to 14 days after implantation, using the indirect immunoperoxidase method for light and electron microscopy. Two centimetre segments of peripheral nerve freshly obtained from inbred Dark Agouti strain rats were inserted in a gap created in n. fibularis or n. tibialis of young adult inbred Wistar strain rats, using fascicular nerve repair techniques under general anaesthesia. There was a gradual increase in the number of helper T and cytotoxic/suppressor T cells from day 2 with peak numbers of both types of T cells observed around day 7. The results suggest that the critical time for T cell proliferation is between day 6 and day 7 post-operatively. The number of macrophages increased over 10 days, with peak numbers being observed at day 10 post-operatively. This is in accord with the pattern of rejection observed in allografts of other tissue. Schwann cells were found to express MHC class I and class II molecules by day 2 post-operatively, which is well before there is any substantial T cell and macrophage infiltration. It may be that the donor Schwann cells act as antigen presenting cells, triggering the immune response and finally becoming a target of the rejection process.

Animals↗
PubMed1990

HLA antigens in chronic inflammatory demyelinating polyneuropathy.

HLA typing of 71 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) showed an overall increase in frequencies of HLA-A3, -B7, -DR2 as well as concomitantly decreased frequencies of HLA-44 and DR7. The strongest associations were seen with HLA-DR2, -DR7 and -B44 in CIDP overall, although they did not reach statistical significance.

Chronic Disease↗
PubMed1990

Cyclosporin A in the treatment of chronic demyelinating polyradiculoneuropathy.

Eight patients with chronic inflammatory demyelinating polyneuropathy, five of whom had an associated paraproteinaemia, were treated with cyclosporin in a pilot, uncontrolled study for periods up to three and a half years after failing to respond adequately to corticosteroid and azathioprine therapy and plasmapheresis. Three patients had an excellent response, two with complete remission. In other cases it was possible to reduce the corticosteroid therapy and frequency of plasmapheresis. There were no serious complications of the treatment.

Adrenal Cortex Hormones↗
PubMed1990

Mitomycin C induces a delayed and prolonged demyelination and conduction block due to Schwann cell destruction.

The intraneural injection of 25 micrograms/ml of mitomycin C produced a prolonged conduction block of delayed onset within the injected nerve. No change in electrophysiological parameters was seen for 6 days after injection, but thereafter a marked drop in the compound muscle action potential (CMAP) amplitude from stimulation proximal to the site of injection occurred, with recovery not being complete until day 97. CMAP amplitude from stimulation distal to the injection site remained unchanged. The reason for this prolonged period of conduction block was apparent from histological examination of the nerve. Light and electron microscope studies demonstrated Schwann cell death, clearly evident at day 8 and followed by subsequent macrophage removal of myelin and Schwann cell debris. Remyelination was not seen until day 40. Hence for periods of about 30 days naked axons persisted through the area of injection. Schwann cells associated with unmyelinated fibres were relatively unaffected, suggesting that myelinating Schwann cells were vulnerable to this agent by virtue of the metabolic processes associated with their myelin maintenance and renewal. These findings indicate that mitomycin C injected intraneurally provides an excellent model to study the effects of Schwann cell disease.

Action Potentials↗
PubMed1989

Induction of experimental allergic neuritis with synthetic peptides from myelin P2 protein.

P2 protein and 4 synthetic peptides were tested for induction of experimental allergic neuritis (EAN). A peptide comprising the residues 62-78 of the bovine P2 protein sequence has been shown to contain an important neuritogenic determinant. A peptide comprising residues 66-78 produced no clinical symptoms of EAN. These results indicate that some or all of the residues 62 65 (Ile-Ser-Phe-Lys), are necessary for EAN induction.

Amino Acid Sequence↗
PubMed1989

Gm haplotypes in inflammatory demyelinating polyneuropathies.

The possible association of Gm haplotypes with inflammatory neuropathies has been studied in 59 patients with Guillain-Barré syndrome and 55 patients with chronic inflammatory demyelinating polyradiculoneuropathy. The frequency of Gm haplotype 1,2,17;21 (or z,a,x;g) was significantly raised in the patients with Guillain-Barré syndrome. These findings provide further evidence for an association of chromosome 14 genes with inflammatory neuropathies.

Demyelinating Diseases↗
PubMed1989

IgG immunoadsorption in experimental allergic neuritis: effect on antibody levels and clinical course.

The effect of IgG immunoadsorption upon the course of chronic experimental allergic neuritis (EAN) is described. Miniature membrane plasma separators coupled with a Protein A (PA)-Sepharose immunoadsorbent column were used to perform upon conscious rabbits 5 IgG immunoadsorption treatments over 6 days. Quantitation of anti-myelin IgG and IgM by ELISA revealed that 55-65% of plasma IgG was removed per treatment. Rapid post-treatment antibody rebound was observed for anti-myelin IgG although no antibody overshoot above control levels could be observed. Anti-myelin IgM levels remained relatively unaffected by PA immunoadsorption. Comparisons of clinical scores between control and treatment animals showed that IgG immunoadsorption was significantly beneficial (day 1 post-treatment p less than 0.001; day 2 post-treatment p less than 0.05). However, rapid relapse was observed in all treatment animals such that by day 3 post-treatment no significant clinical difference between control and treatment groups could be observed. IgG immunoadsorption suppresses the clinical progression of chronic EAN in a manner similar to that seen with plasma exchange. This finding suggests that antibody modulates early disease pathogenesis.

Animals↗
PubMed1989

Experimental allergic neuritis: effect of plasma infusions.

The effect of intravenous fresh frozen plasma (FFP) and artificial plasma infusions upon the clinical course of chronic experimental allergic neuritis (EAN) in the rabbit was investigated. A total of 12 animals allocated to treatment groups received rabbit FFP or a gelatin plasma expander Haemaccel (Hoechst) and were compared to 13 control non-treated animals. Animals receiving Haemaccel at a rate of 15 ml/kg/day for 7 days showed no significant clinical benefit at any stage. However, animals receiving 15 ml/kg/day FFP for 8 days showed significant clinical benefit during treatment initiated at the onset of definite neurological symptoms of EAN (Mann-Whitney U test, day 4 post-allocation P less than 0.05; day 6 post-allocation P less than 0.01; day 8 post-allocation P less than 0.05). Relapse was observed after cessation of treatment such that comparisons of clinical scores at day 14 and 22 post-allocation revealed no significant differences. Analysis of plasma anti-myelin IgG levels by ELISA showed that non-immunogenic plasma volume expansion decreased anti-myelin IgG concentrations immediately by an average of 34% but had no long-term effect. In contrast, anti-myelin IgG concentrations in FFP infused animals were significantly decreased, compared to controls, when measured 24 h after the last infusion (Student's t-test P less than 0.05). Identical percentage weight losses for both control and treatment groups post-allocation indicated that this decrease was immunologically mediated and not due to plasma dilution. Similar plasma cortisol concentrations measured in both groups showed no significant artifactual induction of endogenous steroid production. Infusions of FFP during early disease progression are able to mediate clinical remission in animals with chronic EAN.

Animals↗
PubMed1988

Neuroimmunological electron microscopy with microwave-accelerated fixation.

Immunoelectron microscopy is an important tool used to determine the precise location of immune complexes. Standard concentrations of glutaraldehyde destroy these complexes. This paper describes a method in which the period of glutaraldehyde fixation is shortened by concomitant microwave treatment. Using 1.25% glutaraldehyde and microwave fixation ideal preservation and demonstration of MHC class I antigen on Schwann cells was obtained by the peroxidase method.

Aldehydes↗
PubMed1988

Membrane plasma exchange in experimental allergic neuritis: effect on antibody levels and clinical course.

The effect of membrane plasma exchange on the course of chronic experimental allergic neuritis in rabbits is described. Using miniature membrane plasma separators conscious animals were treated with 4 exchanges over 5 days removing one plasma volume per procedure and using a non-immunogenic gelatin plasma solution as replacement. Comparisons of clinical scores between control and treated groups indicated that treated animals received significant benefit from plasma exchange (day 1 post-treatment P less than 0.002; day 3 post-treatment P less than 0.01). However, relapse was observed in all plasma exchanged animals such that by day 8 post-treatment there was no significant difference in clinical scores between the two groups. Quantitation of anti-myelin IgG and IgM by ELISA assay showed that 55-60% of circulating antibody was removed per exchange. Rapid post-exchange antibody rebound was observed for both IgG and IgM so that pre-exchange levels were re-established within 24-48 h. However, no significant overshoot in circulating levels of anti-myelin IgG nor IgM could be observed. It is probable that long-term remission as a result of therapeutic plasma exchange is a function of effective circulating plasma removal and if present, the suppression of ongoing antigenic stimuli.

Animals↗
PubMed1988

Peripheral neuropathy associated with mitochondrial myopathy.

Twenty patients with mitochondrial myopathy were investigated for the presence of peripheral neuropathy. There were clinical features of a mild sensorimotor neuropathy in five patients (25%) and nerve conduction studies were abnormal in 10 patients (50%). Electrophysiological studies of the whole group showed significant impairment of motor and sensory conduction compared with controls. Sural nerve biopsy and morphometric studies were performed on four patients with clinical neuropathy. There was a reduction in density of myelinated fibres and electron microscopic features of axonal degeneration affecting myelinated and unmyelinated fibres were in evidence. Abnormal mitochondria containing paracrystalline inclusions were seen in the Schwann cell cytoplasm of two nerves.

Adolescent↗
PubMed1988

Absence of antimyelin antibodies and serum demyelinating factors in most patients with chronic inflammatory demyelinating polyradiculoneuropathy.

Patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) often respond to plasma exchange. One explanation for this is that circulating factors, such as antibodies or toxic factors, are removed from the serum. We studied CIDP nerves and CIDP sera for the presence of antibodies to myelin, Schwann cells and galactocerebroside, using immunofluorescence and enzyme-linked immunosorbent assays. On 1 of 28 CIDP nerve biopsies there was evidence of an IgG antibody bound to myelin. One of 57 CIDP sera had evidence of an antimyelin antibody, compared with 12 of 68 Guillain-Barré syndrome sera. We failed to find evidence of antibodies to Schwann cells or galactocerebroside in CIDP. The serum from only 1 of 11 patients showed demyelinating activity after direct intraneural injection. Thus these techniques do not demonstrate the presence of humoral factors to the tested antigens in the majority of CIDP patients. However, more sensitive methods may demonstrate antibodies to these antigens. Alternatively, CIDP may be associated with antibodies or factors toxic to other antigens, or else the response to plasma exchange may not be due to removal of a humoral factor.

Autoantibodies↗
PubMed1987

Chronic inflammatory demyelinating polyradiculoneuropathy associated with pregnancy.

In a series of 61 patients with the relapsing variety of chronic inflammatory demyelinating polyneuropathy, there were 16 women of childbearing age, 9 of whom became pregnant. In 4 of these women, the onset of neuropathy occurred in pregnancy and in the other 5 relapses occurred during pregnancy. There was a significant increase in the number of relapses during the year of pregnancy, and a tendency for symptoms to worsen during the third trimester or immediate postpartum period. It is concluded that there is an increased risk of relapse of chronic inflammatory demyelinating polyneuropathy in pregnancy.

Adolescent↗
PubMed1987

Class II antigen expression and inflammatory cells in the Guillain-Barré syndrome.

Monoclonal antibodies to T-lymphocyte subsets and Class II molecules (Ia) have been used to characterize the inflammatory infiltrate in nerve tissue biopsied from 2 patients in the acute phase of Guillain-Barré syndrome; the findings were compared with those in control nerve specimens. Normal control nerve was treated in the same way. In normal nerves, Class II molecules are expressed on endothelial cells and on occasional mononuclear and perineurial cells. In Guillain-Barré nerves the inflammatory infiltrate consisted mainly of Class II-positive cells of the monocyte-macrophage lineage and of lesser numbers of T4 and T8 lymphoid cells. T4 cells predominated in perivascular collections. In the more severely affected patient, there was a marked increase of Class II molecules expressed on endothelial cells, perineurial cells, and most Schwann cells. Schwann cells associated with unmyelinated fibers and the Schwann cell processes of denervated Büngner bands all expressed Class II molecules. These histological changes were less marked in the more mildly affected patient. It is suggested that the expression of Class II molecules on the myelin forming cell, the Schwann cell, has important implications for the pathogenesis of the demyelination that occurs in Guillain-Barré syndrome.

Antibodies, Monoclonal↗
PubMed1987

Proteinase induced demyelination. An electrophysiological and histological study.

The physiological and histological changes following injection of 10 microliter of proteinase K into the rat tibial nerve have been compared with those induced by proteinase K and specific inhibitor phenylmethylsulphonyl fluoride (PMSF) and also by rabbit experimental allergic neuritis (EAN) serum. Proteinase K and PMSF produced no significant change. Proteinase K alone resulted in progressive conduction block which was complete by about 8 h, and a slowing of motor conduction across the injection site. These changes were very similar to those induced by EAN serum. Histological examination showed early intramyelinic oedema and swelling of Schwann cell cytoplasm, followed by vesicular degeneration of myelin and removal by macrophages. At day 6 the demyelination was most prominent in a perivascular distribution. These changes share many similar features to those seen in EAN and are consistent with the postulate that the final common pathway for myelin destruction in the demyelinating diseases involves proteinases released by macrophages.

Action Potentials↗
PubMed1987

Chronic experimental allergic neuritis. An electrophysiological and histological study in the rabbit.

Ten adult outbred New Zealand white rabbits were inoculated with a single multiportal dose of purified bovine peripheral nerve myelin and Freund's adjuvant containing 500 mg of nerve antigen. Seven animals developed chronic relapsing or progressive disease which was followed by clinical examination for 14 months. Electrophysiological studies showed marked slowing of motor conduction velocity, dispersion of the evoked muscle action potential (MAP) and reduction in amplitude of the MAP derived from distal stimulation. Histological examination of the peripheral nervous system showed at 12 months a marked hypertrophic neuropathy in the nerve roots with well developed onion bulbs, active demyelination and a moderate nerve fibre loss. It is suggested that these animals provide a reliable and predictable model for human chronic inflammatory demyelinating polyneuropathy (CIDP) which should prove valuable for therapeutic trials and studies of pathogenetic mechanisms.

Animals↗
PubMed1987

Linear response curves from an ELISA assay: measurement of anti-myelin IgG and IgM during experimental allergic neuritis.

An ELISA method for generating linear dose-response curves for measuring anti-myelin IgG and IgM is described. Linearity is achieved without logarithmic transformations. This test is used to measure plasma levels of anti-myelin antibodies in rabbits with EAN. Results are expressed as relative concentrations of antibody in arbitary mass units with 95% confidence limits fitted by inverse prediction. In the 8 animals studied, appearance of anti-myelin antibody always preceded onset of clinical signs and neither anti-myelin IgG nor IgM could be detected in any animal pre-inoculation. Five out of 8 animals displayed steady and progressive increases in anti-myelin IgG with the remaining 3 animals showing plateaus in IgG levels 21-30 days post-inoculation. Increases in anti-myelin IgG were generally parallelled by increases in disease severity. However, 2 animals showed recovery and relapse from EAN with no change in plasma levels of anti-myelin IgG. Patterns of production of anti-myelin IgM varied with some animals displaying early peaks while others showed gradual increases.

Animals↗