Search PubMed⌕ Search

Biomedical subjects

C Feighery

Publications and source records attributed to C Feighery.

At least 73 records · Page 4Linked to original sources
PubMed1994

Serum IgA and IgG subclasses during treatment for acute respiratory exacerbation in cystic fibrosis: analysis of patients colonised with mucoid or non-mucoid strains of pseudomonas aeruginosa.

Patients with cystic fibrosis (CF) have a high prevalence of Pseudomonas aeruginosa infection which causes chronic infection of the mucosal surfaces of the lung. This results in recurrent immune stimulation and hypergammaglobulinemia. The present study examines the levels of circulating Ig classes, IgG and IgA subclasses in 13 adult patients with CF during acute pulmonary infection and post-exacerbation. Total serum IgG levels were raised in the patients during infection and post-treatment when compared to the normal range (mean +/- SEM: 17.21 +/- 1.4 g/l vs 16.45 +/- 1.5 g/l respectively; normal range 8-16 g/l). In contrast, total IgM (2.6 +/- 0.26 vs 2.69 +/- 2.74 g/l; normal range 0.6-2.8 g/l) and IgA levels (2.5 +/- 0.52 vs 2.41 +/- 0.48 g/l; normal range 0.5-4 g/l) remained unchanged when examined during all stages of the disease. Of the 13 patients studied, 69%, 39% and 31% had IgG, IgM and IgA levels respectively raised above the normal range values. The mean levels of individual IgG subclasses examined in this group of patients revealed values within the normal ranges, however IgG2 and IgG3 were increased in 31% and 46% of patients. Individual IgG3 levels fell in 77% (10/13) and IgG4 in 62% (8/13) of the patients post-exacerbation. With regard to IgA subclasses, significant reduction in the IgA1 levels were observed post treatment (3687 +/- 539 mg/l vs 2713 +/- 498 mg/l, p < 0.01). In contrast, IgA2 levels were increased from 279 +/- 49 mg/l to 421 +/- 69 mg/l, although statistical significance was not reached. Upon antibiotic treatment for infection, the findings in this study show that IgA1 which is susceptible to bacterial proteases is reduced with a concommitant increase in the protease resistant IgA2 subclass. Moreover, patients colonised with non-mucoid strains of P. aeroginosa had higher total IgA levels due to the raised IgA1 subclass whereas they had lower IgG levels due to low IgG2 and IgG4 subclasses.

Acute Disease↗
PubMed1993

Flow cytometric analysis of surface major histocompatibility complex class II expression on human epithelial cells prepared from small intestinal biopsies.

A technique for preparing viable, single cell suspensions of the epithelial layer of small intestinal tissue obtained endoscopically is described. Constant agitation of four biopsies for 60 min in the presence of chelating and reducing agents gave yields of 1.2-6.7 x 10(6) cells, of which 11-30% were intraepithelial lymphocytes (IEL). Passage through a nylon wool column removed dead cells. This preparation was suitable for flow cytometric analysis. Using this technique, surface MHC class II molecule expression was studied in 14 patients with normal small intestinal mucosa. Fluorescence labelling of these cells showed strong HLA-DR expression by epithelial cells (EC), DP was expressed less strongly, while little DQ expression could be detected. This technique demonstrates that small intestinal biopsies taken during routine endoscopy can yield adequate numbers of viable epithelial cells to perform flow cytometric analysis.

Adolescent↗
PubMed1993

Spontaneous in vitro production of rheumatoid factor during infectious exacerbations of cystic fibrosis: correlation with circulating immune complex levels.

Rheumatoid factor (RF) production has been demonstrated during infections, including infectious exacerbations of cystic fibrosis (CF). The aim of this study was to evaluate the relationship of RF production to infection, and examine the mechanisms involved. Serial peripheral blood mononuclear cell (PBMC) cultures with measurement of spontaneous production of IgM RF, IgA RF, total IgM and IgA, and measurement of serum levels of immune complexes were carried out during exacerbations of CF. The percentage of B cells expressing CD5 was examined in a second cohort of acutely infected CF patients, and related to IgM RF production. IgM RF production was significantly elevated during acute infection compared with convalescence (P < 0.05), stable CF subjects (P < 0.005) and normal controls (P < 0.05). IgM RF production did not correlate with total IgM production in the majority of patients, but was closely related to circulating immune complex levels in 8/10 subjects. IgA RF production did not increase significantly during infection, and did not correlate with total IgA or IgM RF production, or with circulating immune complex levels. CD5+ B cells were not increased in the CF group, and the percentage of CD5+ B cells did not correlate with IgM RF synthesis. These observations suggest that RF production during infection is specifically induced, possibly by immune complex autoimmunization, and is not simply the result of polyclonal B cell activation. Different patterns of IgM RF and IgA RF synthesis suggest different mechanisms of induction.

Acute Disease↗
PubMed1993

IL-2 enhances polyclonal IgM but not IgM-rheumatoid factor synthesis by activated human peripheral blood B cells.

IgM-rheumatoid factor (RF) is thought to be involved in the pathogenesis of rheumatoid arthritis (RA). Several cytokines are known to regulate immunoglobulin synthesis. In this study the effects of IL-2 on polyclonal IgM and IgM RF synthesis were compared. Cytokines were added to peripheral blood B cells from normal subjects and patients with RA after activation by Staphylococcus aureus Cowan 1 (SAC). The addition of IL-2, but not IL-4 or IL-6, resulted in significant enhancement of IgM synthesis in cultures from both healthy subjects and patients with RA. Similar degrees of enhancement were seen in both peripheral blood mononuclear cell and highly purified B cell cultures. IgM-RF was synthesized after activation in cultures from healthy subjects and spontaneously in cultures from RA patients. In contrast to polyclonal IgM synthesis, IL-2 failed to augment IgM-RF synthesis in cell cultures from either healthy subjects or RA patients. This study demonstrates different effects of IL-2 on IgM and IgM-RF synthesis.

Adult↗
PubMed1993

Contrasting levels of in vitro cytokine production by rheumatoid synovial tissues demonstrating different patterns of mononuclear cell infiltration.

Synovial membrane samples obtained at knee arthroplasty from 22 patients with rheumatoid arthritis (RA) were characterized histologically. Two groups were identified. Tissue samples from 15 patients demonstrated multiple focal lymphoid aggregates of mononuclear cells (group A). Samples from the remaining seven patients demonstrated diffuse mononuclear cell infiltration (group B). Samples of each synovial membrane (0.25 g) were cultured for cytokine production. The highest levels of IL-1 beta and IL-6 were produced by group A tissues: 19.1 +/- 19.6 ng/ml IL-1 beta (mean +/- s.d.) and 264.4 +/- 301.9 ng/ml IL-6, versus 3.8 +/- 6.6 ng/ml and 54.7 +/- 42.6 ng/ml respectively. Small quantities of IL-2 and IL-4 were measured in both groups: the levels of IL-2 in group A cultures were highest (P = 0.04). Moreover, using MoAbs, the most intense cytokine staining in the tissues was detected in group A. Similar total numbers of each cell subpopulation and similar quantities of immunoglobulin and rheumatoid factor synthesis were measured in both groups. It is suggested that the presence of multiple focal lymphoid aggregates associated with higher levels of cytokine production observed in group A represent a greater degree of immunological activation, and may represent a subgroup of patients with a greater potential for articular destruction.

Adult↗
PubMed1993

Mapping of the X linked form of hyper IgM syndrome (HIGM1)

X linked immunodeficiency with hyperimmunoglobulinaemia M (HIGM1), which is characterised by agammaglobulinaemia together with excess IgM production reflecting an impairment of the immunoglobulin heavy chain class switch of B lymphocytes, has been mapped to Xq26. We report multipoint linkage data in six families with HIGM1 which show that the most likely position for the gene is close to HPRT with a maximum lod score of 4.89. The finding of recombinations between HIGM1 and both HPRT and DXS42 implies that HIGM1 is not allelic to X linked lymphoproliferative disease. These data will be useful in genetic counselling in families and will also be useful in testing candidate genes.

Base Sequence↗
PubMed1993

Changes in immunological parameters during interleukin 2 and interferon 2 alpha treatment of recurrent renal cell carcinoma and malignant melanoma.

Immunological parameters were studied in patients with either advanced renal cell cancer (n = 7) or advanced malignant melanoma (n = 6) during treatment with a low-dose continuous intravenous treatment with human recombinant interleukin-2 (hr IL-2) and recombinant interferon alpha-2a. Before treatment, natural killer (NK) cell activity was found to be significantly lower in these patients than in 10 normal controls. However, the numbers of NK cells in circulation were equivalent; following incubation of the patients' peripheral blood mononuclear cells (PBMC) with IL-2 for three days normal lymphokine activated killer (LAK) cell activities were induced. Thus, in-vitro incubation with IL-2 appeared to overcome a defect in NK activity. We next examined the effect of IL-2/IFN alpha therapy on in-vitro LAK induction. Treatment significantly increased in-vitro LAK activity in eight of nine patients tested, although in-vivo LAK cell activity was not altered during treatment. The numbers of NK cells (CD16+ CD56+) in peripheral blood showed a significant increase in seven of ten patients as a result of treatment. The three patients who showed the best clinical response also showed the highest increase in expression of these phenotypic markers. T cells were found to be activated in 8/10 patients as indicated by increased co-expression of CD3 with CD25 after completion of 4-day continuous intravenous infusion of IL2. Four days before the start of treatment, cancer patient PBMC stimulated with concanavalin A (con A) produced significantly greater amounts of TNF compared to normal controls. In-vitro inducible TNF was found to decrease following treatment. Since IL-2 production and lymphocyte proliferation in response to Con A were normal in the patient group and were not altered by treatment, the reduction in TNF levels seemed not to be a general inhibitory effect. Further study of these and other changes in the immune system during IL-2/IFN alpha treatment may help to understand how these immunoregulators cause tumour destruction and to predict their usefulness in individual patients.

Adult↗
PubMed1993

Morphometric analysis of synovial membrane blood vessels in rheumatoid arthritis: associations with the immunohistologic features, synovial fluid cytokine levels and the clinical course.

The morphologic characteristics of the endothelial cells lining postcapillary venules are cytokine dependent and critical in facilitating the infiltration of mononuclear cells into synovial membrane in rheumatoid arthritis (RA). We determined the relationships between endothelial cell (EC) tallness, mononuclear cell infiltration and synovial fluid levels of interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) at different stages of RA. EC tallness was greatest in synovial tissues obtained by needle biopsy of the knee joints from 18 patients with active RA who had never received disease modifying drugs (Group 1) (p = 0.000001 versus controls). EC tallness in tissues obtained from 18 patients with advanced disease undergoing knee arthroplasty (Group 2) was greater than controls (p = 0.001) only when vessels located in focal lymphoid aggregates were considered. Vascular proliferation was noted in both groups. Synovial fluid IL-6 levels were greatest in Group 1. IL-1 beta levels were greatest in Group 2. The total numbers of infiltrating mononuclear cells and the clinical measures of disease activity were similar in both groups. The differences in EC characteristics at different stages of RA suggest changing pathogenic mechanisms as disease progresses. Disease modifying antirheumatic drugs may contribute to the findings observed.

Anti-Inflammatory Agents↗
PubMed1993

Neurofilament expression in human T lymphocytes.

The expression of intermediate filaments in normal cells is mainly determined by their embryonal developmental origin. Flow cytometry using monoclonal antibody RT97 demonstrated that neurofilament was detectable in the human HuT 78 T-cell line and on resting T lymphocytes. Expression was greatly increased on lymphocytes activated for 3 days with phorbol ester. Western blotting confirmed the presence of the 200,000 MW form of neurofilament in T lymphocytes. Stimulation of peripheral blood T cells with phorbol myristate acetate (PMA) or with anti-CD3 monoclonal antibodies resulted in a marked increase in detection of phosphorylated neurofilament on Western blotting. Stimulation of HuT 78 cells with anti-LFA-1 resulted in redistribution of neurofilament from a perinuclear spheroid core into dendritic processes. These data indicate that T cells activated through the T-cell receptor associated complex express an intermediate filament usually associated with neurally derived cells. The finding that neurofilament expression and organization are regulated by T-cell surface molecules suggests a role for this intermediate filament in T-cell function.

Blotting, Western↗
PubMed1992

Analysis of cell populations in rheumatoid arthritis synovial tissues.

Knee synovium, taken from patients with rheumatoid arthritis at the time of arthroplasty, was studied immunohistologically. Focal perivascular lymphoid infiltrates of different sizes were examined in detail to evaluate changes in cell populations as the infiltrate size increased. T cells formed the largest component of mononuclear cells of all aggregates. The large grade 3 aggregates contained substantial numbers of B cells arranged around a central venule and cells bearing the CD45RA+ phenotype. In contrast, the small grade 1 aggregates contained few B cells and the T-cell population contained relatively greater numbers of CD8+ cells. Cells bearing the CD45RO+ phenotype exceeded CD45RA+ cells in grade 1 aggregates. Detailed analysis of mononuclear cell aggregates of different sizes in the rheumatoid synovium suggests that the composition of each aggregate depends on the total number of mononuclear cells it contains.

Antigens, CD↗
PubMed1992

Prevalence of anti-Fab antibodies in patients with autoimmune and infectious diseases.

Sensitive ELISA were devised to examine the specificity of circulating IgM and IgA autoantibodies for whole human IgG, Fc and Fab fragments of human IgG. Sera from patients with autoimmune and infectious conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), tuberculosis (TB), infectious mononucleosis (IM) and cystic fibrosis (CF) were studied. Results of the ELISA assays using whole human IgG as antigen revealed that a proportion of patients in each of the groups studied had circulating IgM and IgA rheumatoid factors (RF). Fifteen normal individuals studied were negative. In the latex positive RA group, IgM RF and IgA RF had primarily anti-Fc reactivity (100% and 93% respectively), although 3/15 patients also showed IgM anti-Fab reactivity and one patient had high IgA anti-Fab activity. Patients with SLE and TB who had detectable RF levels also revealed predominantly anti-Fc specificity. In contrast, examination of 25 patients with IM showed positivity for IgM RF activity in 8% of patients using whole IgG as antigen, 24% positivity using purified Fc fragments as antigen and 45% positivity when plates were coated with Fab fragments. Similarly, a large number of CF patients (54%) also showed predominantly IgM anti-Fab activity. Of interest, 69% of the CF patients who were all studied at the time of bacterial infection had detectable IgA RF levels, with 46% of these patients showing both IgA anti-Fc and anti-Fab activity. These findings suggest that autoantibody specificities in autoimmune and infectious diseases are different.

Adolescent↗
PubMed1992

Selection of patients with the antiphospholipid syndrome by serological measurement of lupus anticoagulant activity in conjunction with anticardiolipin antibodies.

The significance of anti-cardiolipin antibodies (ACLA) in patients with a range of autoimmune and infective disorders was investigated in this study. Although lower levels of IgG and IgM ACLA were present in 77 of 400 patients' sera (19%), high antibody levels were found in less than 5% of patients. These latter patients belonged to three clinical categories: patients with connective tissue disease (CTD), infectious mononucleosis or biological false positive serology. An assay was developed to measure lupus anticoagulant (LA) activity in serum: significant LA activity was found in the CTD patients alone (in 6 of 15 tested) and all of these had high titre ACLA. Features of the antiphospholipid syndrome (APS) were present in these six patients but also in three additional CTD patients with normal LA results and high levels of ACLA. In two CTD patients with APS features, the high ACLA were of IgM isotype. These results stress the importance of measuring both ACLA and LA in an investigation of the APS: a high positive ACLA supports the diagnosis of APS, particularly in patients with autoimmune disease, whilst a high positive ACLA in association with LA activity is specific for this syndrome.

Antibodies, Antinuclear↗
PubMed1991

Effect of gold therapy on CD5+ B-cells and TCR gamma delta+ T-cells in patients with rheumatoid arthritis.

Circulating CD5+ B-cell levels in 15 patients with rheumatoid arthritis (RA) not receiving remittive therapy was significantly increased when compared to 17 normal controls (mean +/- SE: RA, 19.7 +/- 2.85%; controls, 11.6 +/- 1.67%; P less than 0.02). In contrast, 24 patients with RA receiving gold sodium thiomalate therapy (GST) had similar CD5+ B-cell levels (11.88 +/- 1.65) when compared to controls and significantly reduced levels when compared to the RA group not receiving remittive agents (P less than 0.01). Furthermore, TCR gamma delta+ T-cell levels were also assessed in these patients groups. These values were not significantly different between any of the groups (controls, 4.46 +/- 1.36%; GST, 6.88 +/- 1.73%; RA, 2.73 +/- 0.55%), although 42% of the GST treated group had gamma delta+ T-cell levels higher than the entire untreated RA group. No correlation was observed between the levels of TCR gamma delta + T-cells and CD5+ B-cells in any of these groups. These results suggested that therapy does influence the level of CD5+ B-cells and gamma delta+ T-cells in these patients.

Antigens, CD↗
PubMed1991

Induction of IgM and IgM-rheumatoid factor synthesis in vitro by indomethacin.

Indomethacin, which is thought to exert its therapeutic effect by inhibiting the synthesis of PGE2, is a commonly used first-line agent in the treatment of rheumatoid arthritis (RA). However, the effect of this drug on the humoral immune response in RA remains unclear. In this study, modulation of the in vitro synthesis of IgM and IgM-rheumatoid factor (RF) by indomethacin and prostaglandin E2 was examined in 11 patients with active RA and 10 normal controls. Indomethacin at a final concentration of 1 microgram/ml significantly enhanced IgM production (P less than 0.01) and RF production (P less than 0.02) in Staphylococcus aureus Cowan I (SAC) stimulated RA cultures when compared to controls in whom no net enhancement effect was observed. In the patients, this increase in IgM production was more pronounced than the corresponding increase in RF synthesis (P = 0.078), suggesting that IgM and IgM-RF-secreting RA plasma cells have different susceptibilities to PGE2 mediated suppression. Nonetheless, addition of PGE2 (10(-8) M final concentration) to the cultures inhibited IgM and RF production to a similar degree in the patient and control cultures. These findings demonstrate that PGE2 causes suppression of IgM and IgM auto-antibody production in vitro and that inhibition of endogenous PGE2 synthesis in RA patients treated with indomethacin results in a marked increase in the production of these antibodies.

Arthritis, Rheumatoid↗