Search PubMed⌕ Search

Biomedical subjects

A M Ward

Publications and source records attributed to A M Ward.

At least 55 records · Page 3Linked to original sources
PubMed1992

Immunochemical identity of the 2,3,7,8-tetrachlorodibenzo-p-dioxin- and beta-naphthoflavone-induced cytochrome P-450 arachidonic acid epoxygenases in chick embryo liver: distinction from the omega-hydroxylase and the phenobarbital-induced epoxygenase.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), beta-naphthoflavone (beta NF), and phenobarbital (PB) cause marked induction of cytochrome P-450 (P-450)-mediated arachidonic acid metabolism in chick embryo liver. We show here that the P-450 arachidonic acid epoxygenases induced by TCDD and beta NF are immunochemically indistinguishable from each other and unrelated to the arachidonic acid epoxygenase induced by PB. On Western blots, IgG from an antiserum against beta NFAA, a 55-kDa P-450 arachidonic acid epoxygenase purified from beta NF-treated chick embryo liver, immunoreacted selectively and to the same extent with a 55-kDa band in liver microsomes from chick embryos treated with TCDD or beta NF. It failed to react with proteins from untreated, solvent-treated, or PB-treated embryos on immunoblots or to immunoinhibit PB-induced arachidonic acid metabolism. Anti-beta NFAA IgG immunoinhibited all arachidonic acid metabolism by reconstituted beta NFAA and formation of arachidonic epoxides (EETs) and monohydroxylated derivatives (HETEs) by microsomes from TCDD- and beta NF-treated livers; it did not inhibit omega-hydroxylation. In contrast, IgG from an antiserum against the major PB-induced chicken P-450s, 2H1 and 2H2, immunoreacted with two major PB-induced P-450s, of 48 and 49 kDa, on Western blots. It also immunoinhibited formation of EETs and HETEs by PB-treated microsomes entirely and omega-hydroxylation by 50%. It failed to react with TCDD- or beta NF-induced P-450s on Western blots or to immunoinhibit TCDD- or beta NF-induced arachidonic acid metabolism. Because other P-450s with which anti-beta NFAA and anti-PB IgG cross-reacted were inactive in arachidonic acid epoxygenation, the findings are consistent with beta NFAA being principally responsible for the epoxygenation induced by TCDD and beta NF and 2H1 and/or 2H2 being responsible for epoxygenation induced by PB. Further, the P-450 arachidonate omega-hydroxylase and the epoxygenase in livers of TCDD- or beta NF-treated embryos are immunochemically unrelated, whereas those in livers of PB-treated embryos may be partly related.

Animals↗
PubMed1991

Autoimmunity, inflammatory bowel disease and hyposplenism.

The presence or absence of nine autoantibodies were assessed in 44 patients with ulcerative colitis (17 with hyposplenism) and 22 patients with Crohn's disease (eight with hyposplenism). The purpose of the study was to determine whether hyposplenism in inflammatory bowel disease is associated with an increased tendency to autoimmunity, or whether autoimmunity is linked not to hyposplenism itself but to the underlying bowel disease. The results strongly suggest that the latter hypothesis is correct. There was a much higher frequency of autoantibodies in patients with ulcerative colitis than in those with Crohn's disease (P < or = 0.01), suggesting that autoimmune factors are more important in the pathogenesis of ulcerative colitis than in Crohn's disease.

Adolescent↗
PubMed1990

Maternal serum alpha-fetoprotein screening for open neural tube defects in twin pregnancies.

Data on maternal serum alpha-fetoprotein (AFP) levels at 13-24 weeks' gestation in 46 twin pregnancies with open neural tube defects (22 with anencephaly, 24 with open spina bifida) and 169 unaffected twins were used to estimate the detection and false-positive rates associated with different cut-off levels. Using the conventional cut-off level of 2.5 multiples of the median (MoM) for unaffected singleton pregnancies of the same gestation and laboratory, the detection rate in twins was 99 per cent for anencephaly and 89 per cent for open spina bifida, with a false-positive rate of 30 per cent. Using a 5.0 MoM cut-off level to maintain a similar false-positive rate to that found among singleton pregnancies at 16-18 weeks' gestation (about 3 per cent), the detection rate was 83 per cent for anencephaly and 39 per cent for open spina bifida. Estimates are provided of the odds of having an affected twin pregnancy given a positive AFP result as well as the odds for individual women with a raised AFP level.

Anencephaly↗
PubMed1990

Endothelial cell expression of the intercellular adhesion molecule-1 (ICAM-1) in the central nervous system of guinea pigs during acute and chronic relapsing experimental allergic encephalomyelitis.

This study investigated the expression of intercellular adhesion molecule-1 (ICAM-1; CD54) by cells of the central nervous system (CNS) during acute experimental allergic encephalomyelitis (EAE) and chronic relapsing EAE (CREAE). In the CNS of normal guinea pigs, only a few endothelial cells expressed detectable levels of ICAM-1, whereas during the active phases of the disease ICAM-1 was present on cells of the perivascular infiltrate and the endothelia of both lesion- and non-lesion-associated blood vessels. In addition, cultured cerebrovascular endothelia maintained in 'standard' culture medium did not express ICAM-1, but they could be induced to express this antigen on incubation in a lymphocyte-conditioned medium. These findings suggest that the induction of ICAM-1 on CNS endothelia may be important in antigen presentation or in promoting lymphocyte extravasation across the blood-brain barrier in inflammatory disorders of the CNS.

Animals↗
PubMed1990

C4a anaphylatoxin levels as an indicator of disease activity in systemic lupus erythematosus.

The use of a synthetic protease inhibitor, nafamstat mesilate, has enabled reliable estimations of in vivo complement activation to be made in systemic lupus erythematosus (SLE). Elevation of C3a anaphylatoxins was found in two out of 24 patients and elevation of C4a anaphylatoxins was found in 20 out of 24 patients, confirming that complement activation, predominantly by the classical pathway, is a common occurrence in the disease. Significantly higher levels of C4a anaphylatoxin were found in 16 patients, with more aggressive disease requiring supplementary treatment with azathioprine, while the remaining eight patients, with less severe disease, required purely steroid therapy. Very strong associations between elevated C4a anaphylatoxins and raised DNA antibody titres, C1q binding activity and low complement C4 levels were also observed, suggesting that anaphylatoxin measurement may be a sensitive additional method for monitoring disease activity in SLE.

Adult↗
PubMed1990

Complement activation in systemic sclerosis.

The use of a synthetic protease inhibitor, nafamstat mesilate, has enabled reliable estimations of in vivo complement activation to be made in patients with systemic sclerosis. Elevations of C3a and C4a anaphylatoxins were found in 2 and 24 out of 30 patients respectively, indicating that complement activation, predominantly by the classical pathway, is a common occurrence in the disease, even though complement C3 and C4 levels were within the reference range.

Adult↗
PubMed1989

Delayed pressure urticaria, objective evaluation of a variable disease using a dermographometer and assessment of treatment using colchicine.

A randomized double-blind placebo controlled trial of colchicine in the treatment of 13 patients with delayed pressure urticaria enabled us to assess some of the variables in this disorder. We have modified a previously described method of pressure testing using a calibrated dermographometer and shown a pressure induced papular dose response curve. Assessment of disease activity was based on the number of pressure weals which occurred, the size of delayed pressure induced papules using a dermographometer calibrated at 9.75 x 10(5) pascals for five separate time periods on the back and estimations of erythrocyte sedimentation rate and the acute phase protein levels. We have been unable to show a therapeutic effect using colchicine 0.5 mg bd for I week.

Adult↗
PubMed1989

HLA-A, B antigens and alpha 1-antitrypsin phenotypes in nodal generalised osteoarthritis and erosive osteoarthritis.

HLA-A, B and alpha 1-antitrypsin phenotypes were studied in 90 unrelated patients with established nodal generalised osteoarthritis (OA). Compared with standard reference populations, independently increased frequency of the HLA-A1B8 and MZ alpha 1-antitrypsin phenotypes were observed (27% v 11.5%, relative risk 2.79, and 12% v 3.6%, relative risk 3.73 respectively). These associations related to developed of nodal generalised OA rather than to severity as judged by the summated radiographic scores for hand OA. Ten patients had marked subchondral radiographic erosions and were further classified as erosive OA; these patients had an increased frequency of the MS alpha 1-antitrypsin phenotype (30% v 9%) and higher radiographic OA scores corrected for presence of erosions. This first report of two independent genetic markers in nodal generalised OA is of interest in relation to the increasingly recognised inflammatory component of the osteoarthritis process.

Aged↗
PubMed1988

Delayed pressure urticaria. Clinical features, laboratory investigations, and response to therapy of 44 patients.

We studied 44 patients with delayed pressure urticaria. The mean age at onset of the disease was 33 years (range, 5 to 63 years) and the mean duration of disease was 9 years (range, 1 to 40 years). After pressure stimulus, the mean onset of whealing occurred in 3 1/2 hours, the mean peak swelling occurred after 10 hours, and the mean lesion duration was 36 hours. Two thirds of patients had generalized flulike symptoms. Sixty percent had disabling nonremitting delayed pressure urticaria. Sixty-two percent had coexistent chronic idiopathic urticaria, and 27% had angioedema. Delayed pressure urticaria was confirmed by pressure tests with either a calibrated dermographometer or suspended weights. More than 50% of patients tested also had delayed dermographism. A double-blind, controlled, crossover trial of indomethacin therapy in 14 patients revealed no significant subjective improvement or reduction in area of induced wheals. We conclude: (1) The diagnosis of delayed pressure urticaria can be easily made by dermographometer testing. (2) Delayed dermographism may be the same entity as delayed pressure urticaria induced by a different method of pressure application. (3) Systemic corticosteroids remain the only known effective treatment for disabling delayed pressure urticaria.

Adolescent↗
PubMed1988

Cerebral systemic lupus erythematosus.

Cerebral systemic lupus erythematosus is uncommon in childhood. Three further cases are presented to draw attention to the unusual and varied clinical manifestations of this condition.

Brain Diseases↗
PubMed1988

Alpha 1-antitrypsin phenotypes in acute anterior uveitis.

The alpha 1-antitrypsin phenotype PiMZ has been reported to have a higher than normal incidence in patients with acute anterior uveitis, indicating an important role in the immunogenetics of this condition. We have determined the incidence of this phenotype in 72 patients with acute anterior uveitis. It was found to occur in four patients (5.6% of the total), with the highest incidence (3/34 or 8.8%, p less than 0.001) in patients negative for HLA B27 and without sacroiliac joint disease. The incidence in HLA B27 positive patients was normal. No correlation was found with the severity, bilaterality, or recurrence of uveitis. Although this increased incidence is statistically significant in comparison with the normal population incidence of 2.6%, its direct clinical significance is questionable; the most likely explanation for it includes possible linkage with other immunoregulatory genes. We also found a lower than expected incidence of the phenotype PiMS, and discuss the relevance of this finding.

Adolescent↗
PubMed1988

Immunological abnormalities 17 years after accidental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Eighteen workers were reviewed 17 years after accidental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin). Clinical assessment showed that they were in good health. A study of several biochemical and immunological parameters in these subjects and in 15 carefully matched controls showed no difference in serum concentrations of hepatic enzymes between exposed workers and controls. Although mean serum concentrations of cholesterol and triglyceride were higher in exposed subjects than in controls, the results did not reach statistical significance. Antinuclear antibodies and immune complexes were detected significantly more frequently in the peripheral blood of workers exposed to dioxin. There was no significant difference between exposed workers and controls in the number of T lymphocytes, B lymphocytes, and helper and suppressor T cell counts in peripheral blood, but the number of natural killer cells identified by the monoclonal antibody Leu-7 was significantly higher in workers exposed to dioxin.

Accidents, Occupational↗