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Biomedical subjects

M K Church

Publications and source records attributed to M K Church.

208 records · Page 12Linked to original sources
PubMed1972

The inhibition by dexamethasone and disodium cromoglycate of anaphylactic bronchoconstriction in the rat.

1. A method for the measurement of anaphylactic bronchoconstriction in the rat is described.2. Dexamethasone inhibited this response in a dose-related manner.3. Disodium cromoglycate antagonized the response. A bell-shaped dose-response curve was obtained with peak activity at 1 mg/kg i.v.4. Meclofenamate was not active when given alone or in combination with dexamethasone.5. Methysergide significantly inhibited the response. Mepyramine, atropine, propranolol and adrenalectomy did not significantly modify the response.6. The relationships of anaphylactic bronchoconstriction in the rat to anaphylactic bronchoconstriction in the guinea-pig and to human asthma are discussed.

Adrenalectomy↗
PubMedDate not supplied

Genetic and environmental influences on airway inflammation in asthma.

The clear recognition that asthma has an inflammatory basis has led to a search for genetic and environmental causes. Genetic linkage studies provide evidence for allelic association between polymorphic markers of interleukin-9 on chromosome 5 and a principal component of the allergic phenotype, log IgE. Further studies that intrauterine environmental factors are an important determinant of the allergic phenotype in addition to allergen exposure during the first year of life. Once sensitised, the respiratory mucosa provides the allergic interface between the environment and internal milieux involving autacoid and cytokine release from mast cells. Up-regulation of endothelial cell adhesion molecules, specifically E-selectin and ICAM-1, is responsible for the leucocyte recruitment of the late-phase asthmatic response, while recruitment of T cells and their subsequent activation contribute to the ongoing inflammatory response of asthma. The epithelium is the origin and target tissue for the inflammatory response, resulting in detachment of suprabasal cells, up-regulation of adhesion molecules and enhanced mediator and cytokine secretion. These latter findings, being more evident in severe chronic disease, suggest that the 'formed' airway elements are also important in mediating the ongoing inflammation characteristic of asthma.

Allergens↗
PubMedDate not supplied

Multiple cytokine mRNA expression in human mast cells stimulated via Fc epsilon RI.

Cross-linkage of Fc epsilon RI on human lung mast cells purified by affinity magnetic selection with monoclonal antibody YB5.B8 against c-kit (purity > 90%) expressed mRNA for multiple cytokines. There was no constitutive expression of interleukin (IL)-4 mRNA. Mast cell stimulation with anti-IgE induced IL-4 mRNA expression which appeared maximal at 2 h and waned slowly over the next 24 h. IL-5, IL-6, IL-8 and tumour necrosis factor (TNF)-alpha mRNA were constitutively expressed. Mast cell activation with anti-IgE led to an increase of IL-5 and TNF-alpha mRNA signals within 2 h and which persisted for at least 24-48 h. On the other hand, IL-6 and IL-8 mRNA expression were not affected by anti-IgE challenge.

Antibodies, Anti-Idiotypic↗
PubMedDate not supplied

Histamine releasability after adenosine challenge in subjects with allergic and non-allergic rhinitis: possible implications for mast cell priming.

Nasal provocation with adenosine 5'-monophosphate elicits nasal symptoms in subjects with rhinitis. Histamine released from airway mast cells may play a role in adenosine-induced nasal responses. To investigate the possible role of histamine in mediating adenosine-induced nasal responses, we measured its release in the fluid obtained by nasal lavage after adenosine 5'-monophosphate, guanosine 5'-monophosphate, and placebo instillations. Nasal lavages were performed before and 3, 5, 10, 15, 30 and 45 min after challenge with adenosine 5'-monophosphate, guanosine 5'-monophosphate, and normal saline in 11 patients with rhinitis and 7 normal subjects in a double-blind randomized placebo-controlled cross-over study to evaluate symptoms and to monitor changes in histamine levels. No symptoms or significant increases in histamine were observed after guanosine 5'-monophosphate and placebo challenge. Symptom scores increased in response to adenosine 5'-monophosphate challenge in the rhinitic subjects but not in the normal controls. Nasal provocation with adenosine elicited a significant release of histamine in the nasal lavage fluids with an immediate peak response: its median (range) concentration increased from the baseline value of 1.33 (0.16-14.54) ng/mL to 2.68 (0.31-61.11) ng/mL at 3 min. However, increased histamine levels were not associated with nasal symptom scores. When compared to non-atopic subjects, significantly higher levels of histamine were seen in the nasal lavage fluids of the atopic subjects following adenosine challenge. In the atopic subjects, the median (range) histamine concentration increased from the baseline value of 1.54 (0.16-14.54) ng/mL to that of 4.21 (0.70-61.11) ng/mL at 3 min, whereas no increment was seen in the non-atopic subjects, their histamine concentration being 0.81 (0.29-5.56) ng/mL and 0.74 (0.31-14.25) ng/mL at baseline and 3 min after adenosine challenge respectively. These findings indicate that adenosine elicits nasal responses in patients with rhinitis but not in normal controls. Moreover, adenosine elicits an immediate rise in histamine levels in the nasal lavage fluid, with the highest rise in atopic compared to non-atopic volunteers, suggesting that the nasal responses to adenosine may be an index of mast cell priming.

Adenosine Monophosphate↗