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Biomedical subjects

C Feighery

Publications and source records attributed to C Feighery.

At least 145 records · Page 8Linked to original sources

Suppressor T cell changes in active multiple sclerosis: analysis with three different monoclonal antibodies.

This study demonstrates a significant reduction in the number of both total T cells and suppressor T cells identified by monoclonal antibodies in multiple sclerosis patients in acute relapse but not in those in remission. The reduction in the number of suppressor T cells was shown by all three monoclonal antibodies used but was most clearly demonstrated using Leu 2a rather than either OKT 8 or OKT 5. These findings suggest that the choice of monoclonal antibody used in a study of suppressor T cell numbers will influence the results and may help explain the lack of agreement in previous studies.

Antibodies, Monoclonal↗

Suspected and clinically definite multiple sclerosis: the relationship between CSF immunoglobulins and clinical course.

CSF immunoglobulins were examined in 103 patients with clinically definite multiple sclerosis, 106 patients with either suspected or progressive possible multiple sclerosis and 72 patients with other neurological diseases. Raised CSF IgG index and oligoclonal banding were found in 71% and 75% of clinically definite multiple sclerosis patients respectively and both tests were abnormal in 11% of patients with other neurological diseases. The CSF IgG index and the presence of oligoclonal IgG did not relate to the severity or duration of established disease in these patients. In patients with suspected and progressive possible multiple sclerosis, both a raised IgG index and the presence of oligoclonal banding were found significantly more frequently than in the OND group. Abnormalities of these parameters were significantly correlated with the presence of an abnormal evoked response in these patients (chi 2 = 10.16 p less than 0.01). When 47 patients with suspected multiple sclerosis were studied prospectively the presence of oligoclonal banding at presentation was associated with development of further disease activity.

Brain Stem↗

Helper and suppressor T lymphocyte function in severe alcoholic liver disease.

The immune regulatory T cell status of patients with severe alcoholic liver disease (ALD) was investigated. Using monoclonal antibodies to identify lymphocyte subsets in 22 patients, a significant decrease in the percentage of T suppressor/cytotoxic cells (P less than 0.01) and increase in the percentage T helper/inducer population (P less than 0.05) was observed when the results were compared with 20 normal controls. However, when absolute numbers of these lymphocyte subsets were calculated the patient group did not differ significantly from the controls. Further studies revealed T immunoregulatory cell function to be normal. Concanavalin A induced suppressor cells resulted in equivalent inhibition of autologous cell mitogen responsiveness in the patient and control groups. In addition, purified patient T lymphocytes were demonstrated to provide normal help to and manifest normal suppression of IgG, IgA and IgM synthesis by allogeneic B cells. When spontaneous immunoglobulin synthesis by circulating mononuclear cells was investigated, a significant increase in IgA synthesis was found in the ALD patients (P less than 0.05). These results suggest that T cell immunoregulation is normal in patients with ALD and a defect in this system is not responsible for the increased synthesis of immunoglobulin observed in ALD.

Adult↗

Coeliac disease.

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Antibodies↗

Lymphoid irradiation in intractable rheumatoid arthritis: effects on the production of immunoglobulins and rheumatoid factors.

Changes in the production of immunoglobulins and rheumatoid factors (RF's) were studied in 20 patients with intractable rheumatoid arthritis (RA) following total doses of 750 rad or 2,000 rad lymphoid irradiation. Over a 12 month follow up period there was no consistent change in absolute serum or synovial fluid levels, or in synovial membrane production of either total IgG, IgA or IgM, or the corresponding RF fractions. The invitro production of immunoglobulins and IgM RF by peripheral blood mononuclear cells was also unaltered, except for one patient who had a dramatic rise in IgM RF production. Over the same period there was a significant overall reduction in disease activity following both doses of radiotherapy. It is concluded that the clinical response which occurs following lymphoid irradiation is not due to a reduction in RF production. Furthermore, the production of RF's appears to be unaffected by the changes in T cell immunity which occur following lymphoid irradiation.

Arthritis, Rheumatoid↗

Increased concanavalin A induced suppression in treated and untreated coeliac disease.

The generation of suppression by concanavalin A in peripheral blood mononuclear cells in treated and untreated coeliac subjects using an in vitro assay was found to be significantly increased when compared with controls. The response of peripheral blood mononuclear cells to the plant mitogen concanavalin A (con A) was also significantly depressed in both groups of coeliac patients. It is proposed that the depressed cell mediated immunity found in this and other studies in coeliac patients is because of increased suppression. The possible connection between these findings and the increased incidence of malignancy also found in coeliac disease is discussed.

Adolescent↗

Alpha gliadin antibody levels: a serological test for coeliac disease.

The diagnostic value in coeliac disease of circulating antibodies to casein, crude gliadin, and alpha gliadin was assessed using an adaption of the enzyme linked immunosorbent assay system. alpha Gliadin was the only antigen which consistently separated 26 patients with untreated coeliac disease from 26 normal controls and 13 patients with chronic inflammatory bowel disease. The mean assay index for the 26 patients was 3.1 (SD 1.2) compared with 1.05 (0.5) for the normal controls and 1.1 (0.6) for patients with chronic inflammatory bowel disease. The alpha gliadin antibody levels of six patients with coeliac disease who had maintained a gluten free diet for at least two years were not significantly higher than normal (1.0 (0.4)). The validity of the test was determined in 90 consecutive patients who were being investigated for the presence of coeliac disease. Levels of alpha gliadin antibody were raised in 36 out of 44 patients found to have histologically proved coeliac disease and in six out of 46 subjects whose jejunal mucosa was normal. Serial alpha gliadin concentrations were measured in 12 patients with coeliac disease who had repeat jejunal biopsies performed six months after starting a gluten free diet. The levels of antibody fell in seven of the eight patients whose jejunal mucosa improved on maintaining the diet. They remained raised in four patients who did not adhere to the diet and whose mucosa did not improve. Although a test measuring alpha gliadin antibodies is unlikely to replace jejunal biopsy in the diagnosis of coeliac disease it may be useful in screening for the disease among outpatients.

Antibodies↗

Visual evoked responses and immunoglobulin abnormalities in the diagnosis of multiple sclerosis.

Visually evoked responses (VERs), CSF IgG/albumin ratio and CSF oligoclonal IgG were examined in 136 patients with multiple sclerosis (MS) admitted to hospital for investigation, and compared to the CSF findings in 87 patients with other neurological diseases (OND). 33% of patients with OND had abnormal CSF IgG/albumin ratios but only 9% had CSF oligoclonal IgG banding. In clinically definite MS, VERs were abnormal in 87% and CSF oligoclonal banding was found in 80% of patients, but CSF oligoclonal banding was found significantly more frequently than abnormal VERs in patients with suspected MS. We were unable to show any relationship between benign MS and the absence or presence of CSF oligoclonal IgG. The significance of CSF oligoclonal IgG in the less clinically definite forms of MS will only emerge with prolonged follow-up.

Albumins↗

The specificity of wheat protein reactivity in coeliac disease.

The purpose of this study was to compare the effects of seven wheat protein fractions on the cell-mediated immune response of coeliac patients and normal individuals, by means of the leukocyte migration inhibition factor (LMIF) assay. Two preparations of milk protein were used as control antigens. Whereas milk protein had no effect on the release of LMIF by cells from either normal or coeliac patients, wheat protein preparations stimulated two types of response. A non-specific reaction was elicited from both coeliac and normal cells by crude preparations such as gliadin and Frazer's fraction III (an enzyme digest of gluten), whereas purified fractions (alpha gliadin and alpha-pel) stimulated a specific response from the cells of coeliac patients only. These results suggest that only a pure wheat protein preparation such as alpha gliadin or alpha-pel is of value in studying immunological parameters in coeliac disease.

Adult↗

Cellular response to alpha-gliadin in untreated coeliac disease.

An improved technique for the detection of alpha-gliadin sensitised mononuclear cells in the peripheral blood of untreated coeliac patients is described. This method is a modification of the direct LMIF assay, and involves exposure of lymphocytes to alpha-gliadin and the assay of the resultant lymphokine produced using normal leucocytes as indicator cells. All untreated coeliac patients, 14 of 15 treated patients, and two of 28 controls responded to alpha-gliadin. The direct LMIF assay in comparison is less sensitive, and detected sensitivity to alpha-gliadin in only four out of eight patients with untreated coeliac disease. Use of the indirect LMIF technique demonstrates that in untreated as well as treated coeliac patients there are cells sensitised to alpha-gliadin circulating in the peripheral blood. These findings may have pathogenic and diagnostic significance.

Adult↗

Histological and immunological investigation of liver-specific protein (LSP) immunized rabbits compared with patients with liver disease.

In this study 45 patients with a variety of liver diseases did not demonstrate T lymphocyte sensitivity to liver-specific protein (LSP) as assessed by lymphocyte transformation whereas LSP-immunized rabbits developed both cellular and humoral immunity to this antigen. Although these LSP-immunized rabbits demonstrated portal tract inflammation with some hepatocyte necrosis, rabbits immunized with antigens known to contaminate LSP developed similar lesions. These findings contrast with those of other investigators who have reported immune responsiveness to LSP in liver patients and chronic active hepatitis in LSP-immunized rabbits. In determining the significance of these studies it must be emphasized that all preparations of LSP contain an heterogeneous group of antigens and that the specific sensitizing antigen has yet to be identified.

Adolescent↗

Mitogen responsiveness in viral hepatitis and chronic active hepatitis: the role of reversible suppressive influences.

Depressed phytohaemagglutinin and concanavalin-A responsiveness was found in patients with acute viral hepatitis (VH) when a suboptimal mitogen stimulus was used. Normal responsiveness was observed with optimal mitogen stimulation. These findings were independent of extrinsic serum inhibitors. When viral hepatitis lymphocytes were preincubated before mitogen addition an enhanced responsiveness similar to the control group occurred. These in vitro findings are in favour of a primary defect in lymphoproliferation in viral hepatitis and do not suggest the presence of reversible suppressive influences such as an excess of short-lived suppressor cells or the presence of cell bound inhibitors. In chronic active hepatitis (CAH) lymphoproliferation induced by immediate mitogen stimulation was similar to control studies. However when CAH cells were preincubated before mitogen addition, enhanced responsiveness significantly greater than in controls occurred. It is suggested that suppressive influences are present in CAH and that their effect can be reversed by cellular preincubation.

Adolescent↗

HLA-D region-associated determinants serve as targets for human cell-mediated lysis.

Effector cells for cell-mediated lysis (CML) were generated by in vitro culture of lymphocytes from selected donors with X-irradiated cells from unrelated subjects who were HLA-D homozygous and matched to the responders for the antigens of the HLA-A and HLA-B regions. By using chromium labeled monocytes as target cells, cytotoxicity was found to correlate with presence of HLA-D region antigens matching those of the stimulating cells. Such CML reactions apparently directed at products of HLA-D, were inhibited by addition of unlabeled monocytes or B lymphocytes. These unlabeled cells had to be matched for HLA-D with the stimulating cells used to generate the effector populations. The results suggested that products of HLA-D, perhaps the DR antigens, were recognized by cytotoxic lymphocytes.

B-Lymphocytes↗

In vitro studies of suppressor cell function in human peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PBMC) from normal donors, pre-cultured at 37 degrees C for 24 hr before the addition of mitogen, demonstrated an enhanced proliferative response. This may be due to the loss of a subpopulation of suppressor cells during the incubation period. Still further enhancement was observed when pre-culturing was prolonged for 48 hr, while cells pre-incubated at 4 degrees C showed no increased responsiveness. Concanavalin A (Con A) pre-activated PBMC supressed the mitogen response of responder cells. More marked suppression was observed when the concentration of Con A used to induce the suppressor cells was increased. It was not possible to activate suppressor function in cells which had been kept in vitro for longer than 48 hr. These findings support the concept of the existence and function of suppressor cells, and that the suppressive influence is short-lived in vitro culture.

Adult↗