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Biomedical subjects

J B Winer

Publications and source records attributed to J B Winer.

At least 37 records · Page 2Linked to original sources
PubMed1996

Isolation and characterisation of T lymphocytes from sural nerve biopsies in patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy.

OBJECTIVES: To characterise cultured T lymphocytes from nerve biopsies in patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Sural nerve biopsies, obtained from six patients with Guillain-Barré syndrome, four with CIDP, and six controls with other neuropathies, were cultured with 20 U/ml recombinant interleukin-2 (IL-2) for eight weeks. Flow cytometry was used to determine the phenotype of cultured T lymphocytes. Their proliferative responses to a range of bacterial antigens were also examined. RESULTS: T cell lines were established from four of six patients with Guillain-Barré syndrome, one of four with CIDP, one patient with peripheral nerve vasculitis, and none of five controls with non-inflammatory neuropathies. One of these T cell lines from a patient with Guillain-Barré syndrome, preceded by Campylobacter jejuni infection, consisted entirely of gamma delta TCR+ T lymphocytes. The peripheral blood of this patient also contained an increased frequency of gamma delta T cells when stimulated with C jejuni. The nerve derived T cell lines failed to show a proliferative response to bacterial antigens or to a preparation of myelin proteins. CONCLUSIONS: A new technique to isolate T cells from nerve biopsies in patients with Guillain-Barré syndrome and CIDP is reported. This technique may prove to be a useful tool in the investigation of the pathogenesis of other inflammatory neuropathies such as peripheral nerve vasculitis. The isolation of a gamma delta TCR+ nerve T cell line is of interest because of the possibility that these cells might respond to glycolipid epitopes common to C jejuni and peripheral nerve gangliosides.

Antigens, CD↗
PubMed1994

Tumour necrosis factor-alpha and other cytokines in Guillain-Barré syndrome.

The efficacy of plasma exchange implicates myelinotoxic humoral factors in the pathogenesis of Guillain-Barré syndrome. Candidate factors include autoantibodies to peripheral nerve myelin, which are not unique to Guillain-Barré syndrome; and cytokines such as tumour necrosis factor-alpha (TNF-alpha) which are T cell/macrophage products. Plasma cytokine concentrations were determined in 26 patients with Guillain-Barré syndrome undergoing plasma exchange, 25 with other acute neurological diseases, and 40 healthy controls. Raised TNF-alpha concentrations (> 25 pg/ml) were found in seven of 26 patients with Guillain-Barré syndrome v none of 23 disease controls (p = 0.001). The peak grade of clinical deficit correlated with TNF-alpha concentrations (r = 0.6, p < 0.01). There was no significant difference between interleukin-1 beta or interferon-gamma concentrations in patients and disease controls. The data suggest that TNF-alpha may be a critical factor in the pathogenesis of Guillain-Barré syndrome.

Cytokines↗
PubMed1993

Mitochondrial myopathy associated with sudden death in young adults and a novel mutation in the mitochondrial DNA leucine transfer RNA(UUR) gene.

A family exhibited maternal inheritance of a variable syndrome comprising ocular, neck and proximal upper limb weakness, psychiatric features, and sudden death. Of 15 definitely or probably affected individuals, 7 had died in early adult life, probably of respiratory failure. A novel point mutation of mitochondrial DNA, in a transfer RNA gene at position 3251, was detected in all living affected family members.

Adult↗
PubMed1992

A study of neuropathy in HIV infection.

A prospective study of possible aetiological factors for neuropathy associated with HIV infection was performed in 80 patients and 28 homosexual controls. At entry to the study twelve patients (15 per cent) had evidence of a generalized neuropathy not due to any other cause and a further three patients developed symptomatic neuropathy during a mean (SD) follow-up of 20 (7.5) months. All but two of these neuropathies were of the distal symmetrical sensory type. Electrophysiology was consistent with an axonal pathology and nerve biopsy confirmed this as the major pathological change. Warming threshold was the diagnostic test most frequently abnormal, sometimes in the absence of other electrophysiological abnormalities. No association was seen with opportunistic infection (cytomegalovirus, herpes simplex, Pneumocystis pneumonia, toxoplasmosis, Cryptococcus infection or tuberculosis). HIV proviral DNA could not be detected in paraffin sections of peripheral nerve in six patients with neuropathy. The presence of the neuropathy did not show significant correlation with depression of the number of CD4+ T cells in the blood, impaired T cell function tests, or IgG, IgM, or IgA levels. Immune complexes containing C1q, but not those containing IgG, IgM, IgA or C3c, were significantly more common among neuropathic patients (p = 0.01).

AIDS-Related Opportunistic Infections↗
PubMed1991

A clinicopathological study of the Guillain-Barré syndrome. Nine cases and literature review.

The postmortem findings are reported from 9 cases of the Guillain-Barré syndrome with survival between 10 days and 1 yr. In 8 cases there was multifocal loss of myelin throughout the peripheral nervous system with relative preservation of axons. In 1 case there was predominant loss of axons. Inflammatory mononuclear cell infiltration was present in the peripheral nervous system of all cases except 1 case surviving a year. The extent and severity of cell infiltration was variable, usually being less prominent than in previous reports, and sometimes sparing nerves in which myelin destruction was severe. Vesicular dissolution of myelin noted by electron microscopy was considered to be a postmortem artefact. In cases examined within 30 days after the onset, immunohistochemical studies with monoclonal antibodies identified more leucocytes (PD7/2B11+) and T cells (UCHL1+) in the endoneurium than in cases examined later or control cases. These findings and recent single case reports indicate that the pathology of the Guillian-Barré syndrome is variable. This variability may reflect differences in pathogenesis, with greater cell-mediated immunity in some cases and greater antibody targeted macrophage-mediated demyelination in others.

Adolescent↗
PubMed1988

Severe Guillain-Barré syndrome: an association with IgA anti-cardiolipin antibody in a series of 92 patients.

To determine whether anti-cardiolipin antibodies (ACA) are associated with acute Guillain-Barré syndrome (GBS), we studied sera from 92 patients with GBS, 82 age- and sex-matched hospital controls and 24 patients with uncomplicated cytomegalovirus or Campylobacter jejuni infection, using an isotype-specific ACA enzyme-linked immunosorbent assay (ELISA). IgA ACA titres (but not IgG ACA or IgM ACA) were significantly elevated (P = 0.002) in GBS patients compared to controls, and associated with peak disease severity (P = 0.01), but not initial or residual disability, nor duration of neuropathy. Abnormal IgG ACA may cause or result from myelin damage in GBS.

Acute Disease↗
PubMed1988

HLA antigens in the Guillain-Barré syndrome.

HLA typing for class I and II antigens was performed on 89 caucasoid patients with Guillain-Barré syndrome and compared with controls. No significant association, between HLA type and susceptibility to disease, prognosis at 12 months or antecedent event was discovered. HLA antigen DR2 was more frequent among patients with the most profound muscle weakness.

Campylobacter Infections↗
PubMed1988

A prospective study of acute idiopathic neuropathy. I. Clinical features and their prognostic value.

A prospective study in South-East England during 15 months in 1983-1984 recruited 100 patients with acute idiopathic neuropathy. After 12 months 67% had recovered completely, 20% were still significantly disabled and 13% had died. Ten of the 13 deaths were attributable to the neuropathy. The major features in the initial assessment which were associated with persistent disability were the time taken to become bedbound, requirement for ventilation, age greater than 40 years, and small or absent compound abductor pollicis brevis muscle action potentials elicited by stimulation of the median nerve at the wrist. These four variables have been combined in a statistical model to predict outcome for individual patients with acute idiopathic neuropathy.

Adolescent↗
PubMed1988

A prospective study of acute idiopathic neuropathy. II. Antecedent events.

The incidence of antecedent events and serological evidence of preceding infection were studied in 100 patients with acute idiopathic neuropathy and age and sex matched control subjects in South-East England. Symptoms of respiratory infections occurred within one month before onset of neuropathic symptoms in 38% of patients and 12% of controls (p less than 0.001) and symptoms of gastrointestinal infections in 17% of patients and 3% of controls (p less than 0.005). Immunisations, insect bites and animal contact were equally common in the patient and control subjects. Eight per cent of patients had undergone an operation within the preceding 3 months. Six per cent of patients had co-existing "autoimmune" diseases. Serological evidence of recent infection was identified in 31% of patients. Campylobacter jejuni (14%) and cytomegalovirus (11%) were both significantly more frequently demonstrated in patients than controls. Serological evidence of recent infection with mycoplasma (1%), Epstein Barr virus (1-2%) and parvovirus B19 (4%) was also identified in the patients but not more frequently than in the controls. Possible explanations for the association of these agents with acute idiopathic neuropathy include possession of antigens shared with myelin and inhibition of suppressor mechanisms.

Adolescent↗
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↗
PubMed1988

Identification of patients at risk of arrhythmia in the Guillain-Barré syndrome.

The frequency of autonomic dysfunction and significant arrhythmia was investigated in a series of 100 patients who presented with an acute idiopathic neuropathy considered to be due to Guillain-Barré syndrome. Eleven of 33 patients requiring ventilation developed serious cardiac rhythm disturbances and seven of these patients died. Approximately 25 per cent of patients had a sinus tachycardia or raised systolic blood pressure and half had reduced sinus arrhythmia indicated by an abnormally low R-R interval variation on deep breathing. Systolic hypertension and reduced R-R interval variation were significantly more common in patients who subsequently developed serious arrhythmias than those who did not. Only those patients that required ventilation developed serious arrhythmias and these were often preceded by wide fluctuations of pulse or blood pressure and transient asystole following tracheal suction.

Adolescent↗