Search PubMed⌕ Search

Biomedical subjects

C Feighery

Publications and source records attributed to C Feighery.

At least 55 records · Page 3Linked to original sources
PubMed1998

Diagnosis of gluten-sensitive enteropathy: is exclusive reliance on histology appropriate?

OBJECTIVE: Coeliac disease is a prevalent disorder but frequently remains undiagnosed because of varied modes of clinical presentation. In this study, methods for the detection of coeliac disease were evaluated in a clinical practice setting. METHODS: Small intestinal histology, IgA anti-endomysial and IgG anti-gliadin antibody tests were performed on 441 unselected, consecutive patients under investigation for small intestinal disease. Response to treatment and other clinical events were monitored over the ensuing years. RESULTS: Untreated coeliac disease was diagnosed in 97 patients and was excluded in 344. At clinical presentation, the endomysial antibody test was positive in 84 of the 97 untreated coeliac patients (sensitivity 87%) and negative in 340 of the 344 non-coeliac patients (specificity 99%). A typical histological lesion was found in 83 of the 97 coeliac patients (sensitivity 86%) but was absent in all 344 non-coeliacs (specificity 100%). The sensitivity of the gliadin antibody test was 69% and the specificity was 71%. CONCLUSIONS: In unselected patients attending a gastroenterology clinic, small bowel histology and endomysial antibody serology show similar predictive value in the diagnosis of coeliac disease. These results emphasize that a combination of clinical, histological and serological criteria are required for effective diagnosis of this disorder. Exclusive reliance on histology or serology will result in failure to make a diagnosis in a significant proportion of patients.

Adolescent↗
PubMed1997

Human small intestinal epithelial cells secrete interleukin-7 and differentially express two different interleukin-7 mRNA Transcripts: implications for extrathymic T-cell differentiation.

The small intestinal epithelium, composed of epithelial cells (EC) and intraepithelial T lymphocytes, is exposed to numerous ingested antigens. Small intestinal EC may act as accessory and/or antigen presenting cells for intestinal T cells, some of which may mature extrathymically and regulate local immunity and tolerance. Since interleukin-7 (IL-7) plays an essential role in T cell maturation and activation, we examined its expression by human small intestinal EC. IL-7 was detected by ELISA in supernatants from 4 of 4 epithelial layer (EpL) cultures. Using RT-PCR, IL-7 mRNA was detected in 4 EpL studied, and two distinct IL-7 transcripts were identified in 3 of the 4. The ratios of the intensities of the larger to the smaller bands varied amongst individuals. Furthermore, the intensity ratios were higher in whole-thickness intestine and lamina propria preparations than in their corresponding EpL. This is the first report of the expression of two IL-7 transcripts in human intestine and of IL-7 secretion by human small intestinal EpL cells. This supports the hypothesis that small intestinal EC may influence differentiation and/or activation of neighboring T cells. The differential expression of the two transcripts may have important implications for immune regulation in the intestinal epithelium.

Biopsy↗
PubMed1997

Antibodies to beta2-glycoprotein I--a specific marker for the antiphospholipid syndrome.

The antiphospholipid syndrome is a disorder characterized by recurrent thrombosis and the presence of antibodies specific to phospholipids. However, the diagnosis of this syndrome is hampered by the lack of a specific laboratory test. In this study an ELISA for the measurement of antibodies to solid-phase beta2-glycoprotein I (beta2-GPI) was established and compared with anticardiolipin antibodies for diagnosis of antiphospholipid syndrome. Significantly elevated levels of antibodies to beta2-GPI were found in all patients with definite antiphospholipid syndrome (median = 91 AU). Marginally elevated levels of antibodies to beta2-GPI were observed in 5% of patients with systemic lupus erythematosus (SLE; median = 4 AU), 1% with stroke (median = 3 AU), 13% with infectious mononucleosis (median = 3 AU), 10% with HIV infection (median = 3 AU) and 8% with VDRL false-positive serology for syphilis (median = 4 AU), but not in patients with rheumatoid factor, syphilis or carotid artery stenosis. In contrast, significantly raised levels of anticardiolipin antibodies were observed in 100% of patients with definite antiphospholipid syndrome, 30% with SLE, 88% with HIV infection, 94% with syphilis, 62% with infectious mononucleosis, 9% with rheumatoid factor-positive sera, 74% VDRL false-positive serology for syphilis, 47% with stroke and 0% with carotid artery stenosis. This solid-phase assay for antibodies to beta2-GPI is highly specific for the antiphospholipid syndrome and represents an advance in the laboratory diagnosis of this disorder.

Antibodies, Anticardiolipin↗
PubMed1997

Endomysium: autoantigen in coeliac disease.

In coeliac disease, dietary exposure to gluten is associated with an autoimmune response to gastrointestinal antigens, including endomysium. Measurement of autoantibodies to endomysium is a highly specific and sensitive method of diagnosing coeliac disease. Analysis of the interaction between gluten and endomysium should provide a critical insight into the pathogenesis of this condition.

Autoantibodies↗
PubMed1997

Degradation of C1-inhibitor by plasmin: implications for the control of inflammatory processes.

BACKGROUND: A correct balance between protease and inhibitor activity is critical in the maintenance of homoeostasis; excessive activation of enzyme pathways is frequently associated with inflammatory disorders. Plasmin is an enzyme ubiquitously activated in inflammatory disorder, and C1-inhibitor (C1-Inh) is a pivotal inhibitor of protease activity, which is particularly important in the regulation of enzyme cascades generated in plasma. The nature of the interaction between plasmin and C1-Inh is poorly understood. MATERIALS AND METHODS: C1-Inh was immunoadsorbed from the plasma of normal individuals (n = 21), from that of patients with systemic lupus erythematosus (n = 18) or adult respiratory distress syndrome (n = 9), and from the plasma and synovial fluid of patients with rheumatoid arthritis (n = 18). As plasmin is a putative enzyme responsible for C1-Inh was examined using SDS-PAGE. In addition, peptides cleaved from C1-Inh by plasmin were isolated and sequenced and the precise cleavage sites determined from the known primary sequence of C1-Inh. Homology models of C1-Inh were then constructed. RESULTS: Increased levels of cleaved and inactivated C1-Inh were found in each of the inflammatory disorders examined. Through SDS-PAGE analysis it was shown that plasmin rapidly degraded C1-Inh in vitro. The pattern of C1-Inh cleavage seen in vivo in patients with inflammatory disorders and that produced in vitro following incubation with plasmin were very similar. Homology models of C1-Inh indicate that the majority of the plasmin cleavage sites are adjacent to the reactive site of the inhibitor. CONCLUSIONS: This study suggests that local C1-Inh degradation by plasmin may be a central and critical event in the loss of protease inhibition during inflammation. These findings have important implications for our understanding of pathogenic mechanisms in inflammation and for the development of more effectively targeted therapeutic regimes. These findings may also explain the efficacy of anti-plasmin agents in the treatment of C1-Inh deficiency states, as they may diminish plasmin-mediated C1-Inh degradation.

Adult↗
PubMed1997

High prevalence of celiac disease among patients with insulin-dependent (type I) diabetes mellitus.

OBJECTIVES: Diagnosis of unrecognized celiac disease is potentially important. The prevalence of celiac disease in patients with insulin-dependent diabetes mellitus is uncertain. We report the prevalence of celiac disease in a stratified random sample (n = 101) of adult insulin-dependent diabetic patients (age, 18-59 yr) attending our clinic, and in an age- and sex-matched control group (n = 51). METHODS: Screening was by anti-endomysial antibody, measured by indirect immunofluorescence using sections of human umbilical cord. RESULTS: Celiac disease had not been suspected in any patient at the time of screening. Eight patients tested positive for anti-endomysial antibody, all of whom had a distal duodenal biopsy performed. Five patients had histologic evidence of celiac disease. One patient with negative histology was receiving immunosuppressive therapy for a renal-pancreas transplant. Of the five patients with abnormal histology, two improved on gluten restriction, one was unable to comply, one refused treatment, and one was lost to follow-up. No control subject tested positive for endomysial antibody. CONCLUSIONS: Patients with insulin-dependent diabetes have an increased prevalence of celiac disease. Because most cases are clinically unrecognized, consideration should be given to screening all insulin-dependent diabetes mellitus patients with endomysial antibodies.

Adolescent↗
PubMed1996

Collagenase and Dispase enzymes disrupt lymphocyte surface molecules.

Collagenase and Dispase enzymes are often used to disaggregate tissue. In this study, we examined by flow cytometry the effects of these enzyme preparations on peripheral blood lymphocyte surface marker expression. Peripheral blood mononuclear cells (PBMC) were obtained from seven healthy volunteers. Cells were incubated with collagenase (128 U/ml, type 1 A) for 3 h and overnight and with Dispase (1.6 mg/ml, grade II) for 15 min, 30 min, 1 h, 3 h and overnight. The intensity of expression of CD3, CD4, CD8, alpha beta and gamma delta T cell receptors was decreased by 25-40% in all cases, while CD4+ and CD8+ lymphocyte populations were undetectable after treatment with Dispase. Moreover, reappearance of these surface molecules did not occur following the incubation of cells in culture medium for 3 h. The results of this study emphasise the importance of considering the influence of isolation procedures on cell characteristics.

Antigens, Surface↗
PubMed1996

Anti-monocyte cytoplasmic antibodies in granulomatous disease.

Antibodies reactive with cytoplasmic components of neutrophils (ANCA) have received much attention because of their association with vasculitis and other inflammatory disorders. In this study, ELISA and immunofluorescence assays were employed to detect antimonocyte-specific antibodies and similar assays were used in parallel to detect anti-neutrophil cytoplasmic antibodies in a range of patient sera: Wegener's granulomatosis (14), Crohn's disease (46), ulcerative colitis (43), sarcoidosis (40), rheumatoid factor positive (15), and normal controls (22). Using an ELISA, anti-monocyte antibodies were detected in (figures in parentheses represent anti-neutrophil results): Wegener's granulomatosis, 79% (93%); sarcoidosis, 30% (5%); Crohn's disease, 20% (11%); ulcerative colitis, 0% (49%); rheumatoid factor-positive sera, 0% (0%). Excellent concordance (>98%) was found between the ELISA and immunofluorescence assays and all of the anti-monocyte antibodies gave a cytoplasmic pattern of staining. This is the first report demonstrating the presence of antibodies specific to the cytoplasmic components of monocytes in patients with granulomatous disease and these findings enhance our understanding of auto-antibody responses against phagocytic cell components.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

Increased numbers of CD5+ B cells and T cell receptor (TCR) gamma delta+ T cells are associated with younger age of onset in rheumatoid arthritis (RA).

Patients presenting with RA before the age of 45 years (younger onset) are known to have more aggressive disease compared with patients presenting after the age of 65 years (older onset). Coordinated expansion of circulating CD5+ B cell and TCR gamma delta+ T cell levels has been reported in patients with RA. This study assesses the peripheral blood levels of these two cell types in RA patients with younger and older onset of disease. CD5+ B cell levels were significantly elevated in the younger onset RA group (26.6+/-4.5%) compared with the older onset RA group (14.2+/-1.2%; P<0.01). TCR gamma delta+ T cell levels were also significantly raised in the young patients (4.0+/-0.9%) compared with elderly patients (1.6+/-0.2%; P<0.01). T cell levels (CD3+) were similar in both groups (young 66.4+/-3.3%; old 74.3+/-3.4% (mean+/-s.e.m.); NS). Total B cell levels (CD19+) were also similar in these groups (7.7+/-0.7% versus 8.9+/-1.8%; NS). A significant positive correlation was observed between the CD5+ B and TCR gamma delta+ T cell types in the patients (r=0.72, P<0.05). Compared with age-matched normal controls, the younger onset patients had similar CD5+ B cell and TCR gamma delta+ T cell levels to the elderly controls (CD5+ B cells 30.2+/-3.0%; TCR gamma delta+ T cells 3.0+/-0.8%). Conversely, older onset RA patients had CD5+ B cell levels similar to the young controls (12.3+/-1.9%). Spontaneous in vitro synthesis of immunoglobulins (IgM, IgA and IgG) and rheumatoid factors (IgM and IgA isotypes) were not significantly different in both patient groups. The coordinate expansion of circulating CD5+ B cells and gamma delta+ T cells seen in patients with RA presenting before 45 years of age and not after 65 years of age may suggest a potential role for these cells in more aggressive disease states.

Adult↗
PubMed1996

Increased HLA-DR and decreased CD3 on human intestinal intraepithelial lymphocytes: evidence of activation?

BACKGROUND: Activation of circulating T lymphocytes results in expression of HLA-DR, interleukin-2 receptor (IL-2R), transferrin receptor (TrR), and decreased amounts of surface CD3. AIM: To examine the activation status of human intestinal intraepithelial lymphocytes (IELs) by flow cytometry. PATIENTS AND METHODS: Duodenal biopsy specimens from 12 patients provided a source of intestinal lymphocytes. Dual colour analysis was used to compare activation marker expression by IELs with peripheral blood (PB) T lymphocytes from the same patients. RESULTS: All human IEL populations express HLA-DR and their density of expression is lower than on the small population of HLA-DR+ resting PB T lymphocytes (mean fluorescence intensity (MFI) 52.9, range 19.8-94.8 v 152.6 range, 49.1-320.3; p < 0.01). The density of CD3 was significantly reduced on IELs (MFI 465.8, range 228.7-660), compared with PB T lymphocytes (756.3, range 444.5-1573.7; p < 0.009). IL-2R was not detected on IELs; nor were the activation markers, TrR, M21 C5, or M2 B3. CONCLUSION: HLA-DR expression on IELs together with decreased CD3 expression suggest previous stimulation. However, the absence of additional markers of T cell activation may reflect a unique pathway of activation.

Adult↗
PubMed1996

A solid-phase antibody capture assay for the measurement of C1-inhibitor consumption in vivo.

C1-inhibitor (C1-Inh) is a serine esterase proteinase inhibitor (serpin) which plays an important role in regulating serine proteinases of the early inflammatory response. In this study, we describe a novel and versatile polyclonal antibody capture assay to examine C1-Inh consumption in vivo. This assay has advantages over previously described methods of measuring C1-Inh consumption as it allows the assessment of the relative amounts of native, complexed and cleaved inhibitor circulating in plasma. By using polyclonal antibodies specific for other complement proteins, the C1-Inh capture assay was adapted to measure in vivo activation of C3, C4 and factor B. C1-Inh consumption and complement activation were examined in the plasma of 21 normal individuals, 24 individuals with systemic lupus erythematosus (SLE), nine individuals with adult respiratory distress syndrome (ARDS) and in the paired plasma and synovial fluid from 18 patients with rheumatoid arthritis (RA). The C1-Inh capture assay revealed native, cleaved and complexed C1-Inh migrating at 115 kDa, 96 kDa and 209-225 kDa respectively, in normal plasma. C1-Inh consumption was increased in the plasma of all the inflammatory disorders examined, in comparison to normal plasma. It is proposed that this serpin capture assay could be adapted to the study of serpin involvement in a wide variety of inflammatory disorders.

Arthritis, Rheumatoid↗
PubMed1996

Impaired gut barrier function in malnourished patients.

The gastrointestinal tract is essential to host defence, acting as a barrier to absorption and translocation of gut antigens, including bacteria. In experimental models, protein malnutrition is permissive to gut barrier failure and endogenous infection. A clinical correlate has not been described. Intestinal morphology and barrier function to food protein antigens was studied in malnourished patients. Thirty-five individuals were evaluated, 20 malnourished patients and 15 well nourished hospital controls. Morphology was assessed from endoscopic biopsies of the second part of the duodenum, and serum immunoglobulin (Ig) G antibodies to gliadin and beta-lactoglobulin were measured. No antibody to food proteins was evident in the control group. In contrast, serum IgG antibodies to at least one antigen were present in 15 malnourished patients and to both antigens in ten (P < 0.0001 versus controls). Severely malnourished patients were more likely to have both antibodies present than those with mild or moderate malnutrition (P < 0.05). Antibody-positive malnourished patients had significantly better nutritional status than antibody-negative patients with malnutrition (P < 0.05). In no group of patients was there morphological evidence of abnormal mucosa or an immunological infiltrate. Gut barrier function is compromised in malnourished patients which suggests a mechanism that may facilitate gut-derived infection and sepsis.

Adult↗
PubMed1996

Beta-2-microglobulin, neopterin and monocyte Fc gamma receptors in opportunistic infections of HIV-positive patients.

The aim of this study was to examine serum and cellular markers of immune activation in HIV-positive (HIV+) patients with and without current opportunistic infections. Fc gamma receptor (Fc gamma R) expression on monocytes, serum neopterin and beta-2-microglobulin were studied. Thirty HIV+ patients (grouped according to Centers for Disease Control (CDC) classification) were studied and compared with 27 normal blood donor controls. HIV+ patients were further separated into three groups: 2 (CDC II), 3 (CDC III/IV without infections) and 4 (CDC III/IV with current infections). Eleven of the patients had current opportunistic infections. Results indicate that beta-microglobulin, neopterin, fc gamma RI, Fc gamma RII and Fc gamma III were significantly increased in HIV+ patients compared to controls. Further analysis of the data using Tukey-Kramer all pairwise comparison revealed that for beta-2-microglobulin the mean values for patients in groups 2, 3 and 4 were significantly different (P < 0.0001). Serum neopterin levels and the percentage of CD14+14+ monocytes expressing Fc gamma RIII showed significant differences in the mean values of group 2 and group 4; similarly, for CD4+ lymphocyte counts group 2 and group 4 were significantly different. These results indicated that beta-2-microglobulin, neopterin and CD14+ monocyte Fc gamma RIII are increased particularly in HIV+ patients with current opportunistic infections while CD4+ lymphocyte counts are reduced. The results suggest that these markers, particularly beta-2-microglobulin, could be useful indicators of the inflammatory process associated with opportunistic infection at later stages of disease where other laboratory markers may be atypical.

AIDS-Related Opportunistic Infections↗
PubMed1995

Leukocyte function-associated antigen 1 (LFA-1) and CD44 are signalling molecules for cytoskeleton-dependent morphological changes in activated T cells.

Signaling through the leukocyte function-associated antigen 1 (LFA-1) molecule has previously been shown to induce homotypic aggregation in T cells and to induce cytoskeletal changes in T lymphoma cells. In this study we describe the induction of a dendritic phenotype associated with cytoskeletal rearrangement in activated human peripheral blood T cells stimulated with monoclonal antibody SPV-L7 to LFA-1 alpha. Maximal expression of this phenotype required 72 h preactivation with phorbol myristate acetate and expression was abolished using the protein kinase C inhibitor staurosporine. Monoclonal antibody to CD18, the beta-chain of LFA-1, did not induce this phenotype. Monoclonal antibody MEM 83 to presumably a discrete epitope on LFA-1 alpha did not induce this phenotype but induced homotypic aggregation. However, a monoclonal antibody to CD44 induced a similar phenotype in activated lymphocytes. Induction of both homotypic in activated lymphocytes. Induction of both homotypic aggregation and the dendritic phenotype was abolished by preincubation with soluble intracellular adhesion molecule 1 (ICAM-1). Cytoskeletal inhibitors prevented the morphological changes in SPV-L7-activated lymphocytes. Preincubation with tyrosine kinase inhibitor, protein kinase C inhibitors, and inhibitors of new protein synthesis also prevented these morphological changes. These data suggest that discrete epitopes on LFA-1 alpha may be capable of inducing discrete signals either for homotypic aggregation or for a dendritic phenotype. As both LFA-1 and CD44 are involved in the migration of lymphocytes through high endothelial venules, these data could suggest that these molecules transduce signals resulting in cytoskeletal modification necessary for lymphocyte transmigration.

Alkaloids↗
PubMed1995

Protein kinase C isoform expression in CD45RA+ and CD45RO+ T lymphocytes.

Differences in levels of specific enzymes utilized in intracellular signalling could be a factor in the distinct signalling properties observed in memory and naive T cells. We have studied the expression of both classical and non-classical protein kinase of C (PKC) isoenzymes in CD45RA and CD45RO cells using a combination of Western blot and flow cytometric analysis. These data indicate that CD45RA cells express higher levels of PKC alpha, PKC beta and PKC delta than CD45RO cells. In addition, CD45RA+ cells show greater proliferative activity when stimulated with phorbol myristate acetate (PMA) and calcium ionophore than their CD45RO+ counterparts. Variations in the levels of these isoenzymes could be implicated in functional differences, such as proliferation and cytokine production, in these cell subsets.

Animals↗
PubMed1994

Synovial tissue macrophages and joint erosion in rheumatoid arthritis.

OBJECTIVES: To analyse the mononuclear cell populations in synovial membrane biopsies obtained before treatment from patients with rheumatoid arthritis (RA) and to correlate the findings with the degree of joint damage occurring over one year. METHODS: Multiple needle biopsy specimens were obtained from inflamed knee joints on entry to the study. The tissue samples were examined using immunohistochemical techniques. The degree of joint damage was estimated using the Larsen radiological index. RESULTS: Twelve patients were studied. It was observed that there was a significant correlation between the number of synovial tissue macrophages and the degree of joint erosion over one year (r = 0.66; p = 0.04). The synovial lining layer contained large numbers of macrophages and the cellularity of the lining layer correlated significantly with the number of macrophages infiltrating the sublining areas (r = 0.65; p = 0.01). Finally, the cellularity of the lining layer correlated with the synovial fluid levels of interleukin-6 (r = 0.66; p = 0.04). The radiological course did not correlate with infiltrating T or B lymphocyte populations, but did correlate with other previously identified indicators of the clinical course, including a high index of disease activity and IgA rheumatoid factors levels. CONCLUSION: This study suggests that synovial tissue macrophages play a critical role in the pathogenesis of joint erosion in RA.

Adult↗