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Biomedical subjects

S Holgate

Publications and source records attributed to S Holgate.

41 records · Page 3Linked to original sources

The role of histamine in allergen and adenosine-induced bronchoconstriction.

We have investigated the role of histamine in allergen and adenosine-5'-monophosphate (AMP)-induced bronchoconstriction in asthmatic subjects by performing inhalation challenge tests with histamine, AMP and allergen after treatment with placebo or the potent H1 histamine receptor antagonist, terfenadine. Single concentrations of each agonist which had previously been shown to produce a 30% fall in FEV1 were used. After placebo, AMP and histamine both produced rapid bronchoconstriction reaching a maximum within 5 min and returning to within 10% of baseline after 25 min. Terfenadine inhibited this reaction to histamine completely and to AMP by 86%. The response to allergen was slower in onset and was sustained over 45 min and was inhibited 50% by terfenadine. We interpret these results as reflecting the contribution of histamine to the various airway challenges, both histamine and newly generated mediators comprise the response to allergen, whereas AMP selectively enhances mast cell degranulation without affecting the production of arachidonic acid derived mediators.

Adenosine Monophosphate↗

Induction of nitric oxide synthase in asthma.

Nitric oxide (NO) is a mediator of vasodilatation and bronchodilatation synthesised from L-arginine by the enzyme NO synthase, which is either constitutive or induced by lipopolysaccharides and/or cytokines. The presence and function of NO synthase in normal or diseased lung is not yet clear. Asthma is characterised by bronchial hyperresponsiveness, epithelial damage, inflammation, and increased cytokine production. To investigate the presence of NO synthase in asthma, we immunostained bronchial biopsies from non-steroid-treated people with asthma and non-asthmatic controls with specific polyvalent antisera to purified inducible NO synthase and to a selected peptide sequence of the same enzyme. Immunoreactivity was seen in the epithelium and some inflammatory cells in 22 of 23 biopsies from people with asthma, but in only 2 of 20 controls. To assess the relation of cytokines to NO synthase induction, bronchial epithelial cells in culture were stimulated with tumour necrosis factor (TNF alpha). Inducible enzyme immunoreactivity was found only in the treated cells. The existence of inducible NO synthase in human lungs suggests that increased production of NO, probably induced by cytokines, may be relevant to the pathology of asthma.

Adult↗

Time-compressed speech discrimination, reading readiness and the effect of clinical method.

Time-compressed speech discrimination was examined on kindergarten-age children grouped according to scores on the Lindamood Auditory Comprehension Test (LAC). In experiment 1, 34 children were equally divided into two groups based upon the LAC, and administered the Word Intelligibility by Picture Identification Test (WIPI) at 0, 30 and 60% time compression. In experiment 2, 32 children were similary grouped and administered the WIPI at 0 and 60% time compression with 60% always administered first. Significant main effects for time compression and test group were found. The effects of clinical method and clinical implications are discussed.

Child↗