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Biomedical subjects

C Feighery

Publications and source records attributed to C Feighery.

At least 127 records · Page 7Linked to original sources

Humoral response to alpha gliadin as serological screening test for coeliac disease.

The diagnostic value of measuring alpha gliadin antibodies in children with suspected coeliac disease has been evaluated prospectively. Jejunal biopsy and alpha gliadin antibody measurements were performed in 77 consecutive children who were being investigated for a suspected malabsorption syndrome. The typical small intestinal histological lesion of coeliac disease was found, and this diagnosis was subsequently confirmed clinically in 20 children. Raised IgG alpha gliadin antibody concentrations were found in 19 (95%). Fifty of 57 patients (88%) with a normal jejunal mucosa had normal alpha gliadin antibody concentrations. These results are similar to those previously reported in a prospective study of adult patients with coeliac disease and indicate that measurement of alpha gliadin antibody is a highly sensitive and specific screening test for childhood coeliac disease.

Adolescent↗

Histological changes associated with wheat protein antibodies in the absence of villous atrophy.

A retrospective study was conducted to assess the association of alpha-gliadin antibodies with intraepithelial lymphocyte counts. Twelve subjects with apparently normal small intestinal histology and raised alpha-gliadin antibody titres had significantly increased intraepithelial lymphocyte counts (42 (SEM) 5.9) when compared with 16 subjects with normal alpha-gliadin antibody titres (17 (3.2); p less than 0.001). These findings show that in the absence of gross pathology raised alpha-gliadin antibody titres are associated with increased numbers of intraepithelial lymphocytes and may reflect continuous immunological processes in the small intestine.

Antibodies↗

Three possible laboratory indexes of disease activity in multiple sclerosis.

In a search for an objective measure of disease activity in MS, we studied three laboratory indexes in 15 patients over 12 months, relating them to the occurrence of relapse and the development of increased disability. Relapse was associated with detection of myelin basic protein (MBP) in the CSF (p less than 0.01), but not with decreased numbers of peripheral blood T lymphocytes. Persistently low T-cell numbers and more frequent detection of MBP in remission were associated with increased disability (p less than 0.01). There were no associations between other CSF abnormalities and either relapse or increased disability.

Adult↗

Immunoperoxidase demonstration of the cellular composition of the normal and coeliac small bowel.

Immunohistological analysis of the cellular composition of the small intestinal mucosa in a group of untreated and treated coeliac patients and non-coeliac control subjects was performed using monoclonal antibodies and an immunoperoxidase technique. A characteristic cellular distribution was observed within the normal mucosa. The intraepithelial and lamina propria compartments were occupied mainly by T suppressor/cytotoxic and T helper/inducer cells respectively. Further subdivision of lamina propria T helper/inducer cells with the Leu 8 antibody revealed that these were of the Leu 3a+ Leu 8- phenotype. Macrophages, defined by the RFD7 antibody, were seen to occupy the same microenvironment as T helper/inducer cells. T cells expressing the T cell activation antigen defined by anti-Ta1 were found with the normal lamina propria, although few cells were identified by the anti-Tac antibody. HLA-Dr antigens were expressed by stellate cells within the lamina propria, and also by the epithelial cells of the villi, but not by normal crypt epithelial cells. In untreated coeliac patients the distribution of the various cell types was essentially unchanged, although the number of these cells was markedly increased, including those which expressed the Ta1 antigen. A significant deviation from normal in the expression of HLA-DR antigens was found in the coeliac small bowel: these antigens were expressed not only on the villous epithelial cells but also on the epithelial cells of the crypts. Immunohistological findings in the treated coeliac patients were intermediate between the normal and untreated coeliac groups, and were completely normal in those patients with complete histological resolution of their disease. These results suggest that coeliac disease is accompanied by an enhanced stimulation of the normal mucosal immune response and do not imply a primary pathogenic role for the immune system in this disease.

Antigens, Surface↗

Humoral response to wheat protein in patients with coeliac disease and enteropathy associated T cell lymphoma.

Features that might distinguish uncomplicated coeliac disease from enteropathy associated T cell lymphoma were investigated. Of 76 patients with coeliac disease, 71 (93%) had raised levels of alpha gliadin antibody and all responded clinically and histologically to treatment with a gluten free diet. In contrast, none of 16 patients with enteropathy associated T cell lymphoma had raised levels of alpha gliadin antibody, and treatment with a gluten free diet resulted in histological improvement in one and transient clinical improvement in six patients. The ratio of women to men was 2.2:1 in the group with coeliac disease and 1:1.6 in the patients with enteropathy associated T cell lymphoma. Thus patients with enteropathy associated T cell lymphoma do not display a humoral immune response to wheat protein (alpha gliadin), rarely respond to a gluten free diet, and are often men. Patients with uncomplicated coeliac disease usually have raised levels of alpha gliadin antibody, always respond to a gluten free diet, and are frequently women. These findings suggest the presence of two separate forms of enteropathy: one is benign and sensitive to wheat protein whereas the other runs a malignant course.

Adult↗

Lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized study comparing 750-rad treatment with 2,000-rad treatment.

Twenty patients with intractable rheumatoid arthritis were treated with 750-rad or 2,000-rad lymphoid irradiation in a randomized double-blind comparative study. Over a 12-month followup period, there was a significant improvement in 4 of 7 and 6 of 7 standard parameters of disease activity following treatment with 750 rads and 2,000 rads, respectively. Transient, short-term toxicity was less frequent with the lower dose. In both groups, there was a sustained peripheral blood lymphopenia, a selective depletion of T helper (Leu-3a+) lymphocytes, and reduced in vitro mitogen responses. These changes did not occur, however, in synovial fluid. These results suggest that 750-rad lymphoid irradiation is as effective as, but less toxic than, that with 2,000 rads in the management of patients with intractable rheumatoid arthritis.

Adult↗

Effects of gold therapy on the synthesis and quantity of serum and synovial fluid IgM, IgG, and IgA rheumatoid factors in rheumatoid arthritis patients.

Eleven patients with active rheumatoid arthritis were monitored prospectively while receiving up to 1 gm of gold sodium thiomalate. There was a significant decrease in serum and synovial fluid IgG, IgA, and IgM rheumatoid factor (RF) levels over the period of study. Comparison of changes in serum RF and total immunoglobulin levels indicated a selective effect on RF production. These observations were supported by changes in the spontaneous in vitro production of IgM-RF and total IgM by peripheral blood mononuclear cells. Studies of synovial membrane synthesis showed a downward trend in immunoglobulin and RF production, but this did not reach statistical significance. A differential effect on the various RF classes was also noted. The most profound effect was on IgM-RF production; whereas, changes in IgG-RF production were least affected. These results suggest a selective and differential effect of gold salts on RF production.

Adult↗

Peripheral blood T lymphocyte changes in multiple sclerosis: a marker of disease progression rather than of relapse?

A serial study of peripheral blood T lymphocytes in 27 patients with clinically definite multiple sclerosis and 11 healthy controls was carried out over a 12 month period. This showed that contrary to many previous reports, relapses were not consistently associated with reduced numbers of peripheral blood suppressor T lymphocytes or any other T cells. Persistently low T cells numbers, including both the helper and suppressor T cell subsets, were, however, associated with disease activity as measured by the development of increased disability during the course of the study. This was true both for the patients with relapsing/remitting disease and those with progressive disease. The importance of carrying out a serial study was emphasised by the consistent and significant differences that were detected between individuals in both the control and the patient groups. A serial study is the most reliable means by which clinical events can clearly be correlated with laboratory estimations. The association in this study between the development of increased disability and persistently low levels of peripheral blood T lymphocytes suggest that both may be related to the underlying disease process in multiple sclerosis.

Adult↗

Chronic granulomatous disease presenting as an oculomucocutaneous syndrome mimicking Behçet's syndrome.

A female patient who presented for the first time at the age of 19 with oculomucocutaneous syndrome was found to have an absolute deficiency of neutrophil peroxide production. Neutrophil peroxide production as measured by chemiluminescence was zero on stimulation with opsonized zymosan. Direct membrane stimulation with FMLP and calcium ionophore also failed to elicit peroxide production. The diagnosis of chronic granulomatous disease should be considered in young patients with oculomucocutaneous syndrome.

Adult↗

A clinical and laboratory study of benign multiple sclerosis.

In a hospital-based study of 400 patients with multiple sclerosis (MS), 42 per cent of patients who had had MS for 10 years or more had benign disease. Early age of onset and a long first remission were significantly associated with a good prognosis. There was a suggestion that initial presentation with paraesthesiae and possibly optic neuritis were associated with a benign prognosis, but the only significant finding was the association between limb weakness and a poor outcome (p less than 0.05). Fewer patients with benign disease had a progressive element to their disease than those in the more disabled group (p less than 0.001). The only laboratory test which was associated with a benign prognosis was the absence of CSF myelin basic protein in remission. Abnormalities of visual evoked response, CSF IgG and peripheral blood T lymphocytes appeared to have no value in assessing prognosis in the patients studied.

Adult↗

The immunological consequences of gold therapy: a prospective study in patients with rheumatoid arthritis.

Gold sodium thiomalate (GST) is known to modify the disease process in patients with active rheumatoid arthritis (RA). To help understand the mechanism of action of GST, several immunological parameters were prospectively evaluated in 10 patients with active RA following the introduction of gold therapy. Before therapy, absolute numbers of peripheral blood T suppressor/cytotoxic lymphocytes were significantly depressed (P less than 0.01) and a raised T helper/T suppressor cell ratio was found. After 1 g of GST, an absolute reduction in total lymphocyte numbers including HLA/DR positive mononuclear cells, was evident (P less than 0.01). This lymphopenic effect was not selective for a single population since the proportions of T cells, T cell subsets and B cells remained unchanged. Lymphocyte function was also examined. Raised in vitro production of IgG (P less than 0.01) and IgA (P less than 0.05) was found before therapy. After GST, in vitro immunoglobulin synthesis was reduced and this was significant with respect to the IgM (P less than 0.001) and IgA (P less than 0.01) isotypes. Similarly, a parallel reduction in serum immunoglobulin levels developed. GST therapy was also associated with a reduced proliferative response to phytohaemagglutinin, concanavalin A and pokeweed mitogen in the initial phase of gold administration. The significant finding in this study suggest that the in vivo immunosuppressive effect of GST is explained not only by impaired mononuclear cell function but also by a significant reduction in T and B lymphocyte numbers.

Arthritis, Rheumatoid↗

Studies on the accessory requirement for T lymphocyte activation by concanavalin A.

In this study we have examined the interactions between accessory cells (AC) and T cells in response to Con A. Highly purified peripheral blood T cells and AC exposed to a variety of treatments were used. We found that untreated AC provided optimal help for T cell proliferation and this was not mediated by soluble factors since whole cells could not be replaced with supernatants from activated AC. Furthermore, cycloheximide-treated AC were able to supply the accessory signal although unable to elaborate soluble activation factors. To find out more about the accessory signal, we examined the ability of monocytes mildly fixed with glutaraldehyde to supply help. These cells were completely unable to perform as AC, although they were viable and had unaltered surface antigen expression. They could not secrete activation factors, but this alone could not explain their inability to supply help because this function was not restored with the addition of soluble activation factors. This indicated that AC-T cell contact was of prime importance to accessory function. To investigate the possibility that AC work by cross-linking structures on the lymphocyte surface, we attempted to substitute for the soluble Con A plus AC with Con A bound to the surface of erythrocytes. Comparable stimulation was observed, suggesting that the cross-linking of Con A-bound structures on the lymphocyte surface generates the accessory signal.

Antigen-Presenting Cells↗

Possible in vivo modulation of Leu 2a expression on suppressor T cells in active multiple sclerosis.

Reduced numbers of suppressor T lymphocytes were identified by monoclonal antibodies in the peripheral blood of patients with multiple sclerosis (MS) in acute relapse. In vitro culture of cells from these patients resulted in a significant increase in the number of cells identified with the suppressor T cell marker Leu 2a but not OKT 8. The expression of other T cell antigens (Leu 4 and Leu 3a) remained unchanged. This change in Leu 2a expression did not occur when cells from healthy controls were similarly treated.

Antibodies, Monoclonal↗

CSF myelin basic protein in multiple sclerosis.

Cerebrospinal fluid (CSF) from 221 patients with multiple sclerosis (MS) and 85 patients with other neurological disorders (OND) was examined using a competitive radioimmunoassay for myelin basic protein (MBP) immunoreactivity. MBP was found in 46 of 55 MS patients (84%) examined within six weeks of relapse but in only 11 of 85 patients (13%) with OND. There was a significant correlation between the concentration of MBP in the CSF and relapse severity in patients seen within four weeks of the onset of symptoms (p less than 0.01). Of 44 patients in remission, MBP was detected in 12, and these patients had a significantly higher tendency to subsequent relapse (p less than 0.05). In 72 patients with progressive disease the presence of MBP in the CSF reflected the confidence of clinical diagnosis. The results of this study suggest that measurement of MBP in the CSF gives an objective method of monitoring disease activity in patient with MS.

Acute Disease↗