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J L Devalia

Publications and source records attributed to J L Devalia.

13 recordsLinked to original sources
PubMed1992

Topical glucocorticoids inhibit activation by allergen in the upper respiratory tract.

We have studied the effect of a topically administered glucocorticoid, fluticasone propionate (FP), on infiltration and activation of eosinophils in the nasal mucosa after provocation with allergen. Forty-four patients with seasonal allergic rhinitis entered a double-blind, crossover study in which they underwent treatment with either FP (200 micrograms once daily) or identical placebo for 2 weeks. Patients then underwent nasal-allergen provocation followed by nasal lavage and biopsy at one of several time points between 0 and 8 hours. Patients subsequently received the alternate treatment for 2 weeks before repeat allergen provocation, nasal lavage, and biopsy, as before. Biopsy specimens of nasal mucosa obtained during the immediate allergic response demonstrated an influx of eosinophils (stained by monoclonal antibody EG1) of similar magnitude during both FP and placebo treatment. Significantly, fewer eosinophils in these biopsy specimens were activated (stained by monoclonal antibody EG2) after treatment with FP compared with that after placebo treatment (median values, 8.8 and 36.6 cells per square millimeter, respectively; p less than 0.02). The concentration of eosinophil cationic protein in nasal lavage fluid was significantly elevated above baseline from 2 to 8 hours after allergen, and this increase was abolished by treatment with FP. These results suggest that topical glucocorticoids inhibit allergen-induced activation of eosinophils in allergic rhinitis.

Administration, Topical↗
PubMed1992

The effects of salmeterol and salbutamol on ciliary beat frequency of cultured human bronchial epithelial cells, in vitro.

Studies investigating mechanisms of mucociliary clearance have suggested that beta 2-adrenergic agents may significantly influence ciliary activity of epithelial cells and therefore play a vital role in the maintenance of functional integrity of the airways. We have cultured human bronchial epithelial cells, from surgical explants and investigated the effects of salbutamol and salmeterol, in a time- and dose-dependent manner, on the ciliary beat frequency (CBF) of these cells. Prior to and at several times after exposure to either salbutamol (10(-8) to 10(-3) M) or salmeterol (10(-8) to 10(-4) M), the epithelial cells were monitored for CBF and on the basis of data obtained from these studies, the effect of 10(-6) M propranolol was investigated in the presence of optimal concentrations of salbutamol and salmeterol. Salbutamol was optimally active at a concentration of 10(-4) M and caused a transient but significant increase in the CBF from baseline level of 8.6 +/- 0.4 to 9.6 +/- 0.5 Hz (P < 0.05), after 2 h incubation. In contrast, salmeterol was maximally active at a concentration of 10(-6) M and caused a significantly rapid and prolonged increase in CBF from a baseline value of 9.2 +/- 0.4 to 10.9 +/- 0.6 Hz (P < 0.02) and 10.6 +/- 0.8 Hz (P < 0.05) after 15 min and 24 h incubation, respectively. Propranolol (10(-6) M) abrogated the salbutamol- but not the salmeterol-induced increases in CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1992

Asthma. Epithelial cells.

The airway epithelium is the first line of defence against air-borne dusts, vapour, gases and fumes and plays a vital role in the maintenance of physico-chemical homoeostasis. Perturbation of the epithelial cells which predominate within this barrier, may bring about adverse changes in and around the surrounding tissues playing a part in the pathogenesis of asthma. Although the specific mechanism(s) which partake in pathogenesis are not clear, several have been proposed. These include: (1) increased synthesis and release of inflammatory mediators and decreased synthesis of protective mediators; (2) synthesis of inflammatory cytokines; (3) modulation of cell adhesion molecules, important in determination of epithelial architecture; and (4) immunoregulation of the inflammatory cell types. It is likely that these operate together and interact to produce, initially functional changes in the epithelium, which lead eventually to the structural changes that are characteristic of the airway epithelium of asthmatics.

Asthma↗
PubMed1992

The effect of human eosinophils on cultured human nasal epithelial cell activity and the influence of nedocromil sodium in vitro.

Although there is increasing evidence of a pathogenic role for eosinophils in the airway epithelium, there is little direct evidence which demonstrates that eosinophils influence epithelial cell activity in humans. We have cultured human nasal epithelial cells in vitro and studied the effect of isolated human eosinophils on the ciliary beat frequency (CBF) and cell membrane integrity of these cells after incubation in the absence or presence of 0.1 microM phorbol 12-myristate 13-acetate (PMA) or 0.1 mg/ml opsonized latex beads and the absence or presence of 10(-5) M nedocromil sodium. CBF was monitored by an analogue contrast-enhancement technique, and cell damage was assessed by release of 51Cr from the cells. Cell cultures were also assessed for the percentage of eosinophil cationic protein (ECP) released into the medium at the end of incubation. Neither 0.1 microM PMA, 0.1 mg/ml opsonized latex beads, 10(-5) M nedocromil sodium, nor eosinophils alone altered the CBF of the epithelial cells. PMA-stimulated eosinophils, however, attenuated the CBF significantly, from 10.2 +/- 0.3 to 8.8 +/- 0.4 Hz (P less than 0.05) after 15 h of incubation. Similarly, opsonized latex bead-stimulated eosinophils led to a significant attenuation of CBF from 9.2 +/- 0.3 to 8.4 +/- 0.3 Hz (P less than 0.05), 6.9 +/- 0.5 Hz (P less than 0.001), and 7.5 +/- 0.3 Hz (P less than 0.001) after 2, 15, and 24 h of incubation, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Histidine decarboxylases from bacteria that colonise the human respiratory tract.

We investigated whether production of histamine by bacteria isolated from sputum of patients with infective lung diseases could be attributed to the presence of histidine decarboxylase (HD). Twenty gram-positive and 20 gram-negative organisms were studied for their ability to decarboxylate 14C-histidine in vitro over the pH range 4.5-7.5. Of the bacteria investigated, lysates from the gram-negative species Haemophilus influenzae, H. parainfluenzae, Moraxella (Branhamella) catarrhalis and Pseudomonas aeruginosa liberated 14CO2 and histamine from 14C-histidine in the presence of the cofactor pyridoxal phosphate. In contrast, results obtained in the absence of cofactor were similar to those of negative (lysate-free) controls suggesting that the HD enzymes of these species resembled those previously described in other gram-negative bacteria. No HD activity was detected over this pH range in lysates from gram-positive species. This finding correlated with earlier observations that these gram-positive organisms did not produce histamine in vitro.

Carbon Dioxide↗
PubMed1990

The effects of topical fluticasone propionate on allergen-induced immediate nasal airways response and eosinophil activation: preliminary results.

Nasal application of grass pollen allergen in atopic individuals with seasonal rhinitis leads to an early rise in nasal airways resistance. The effects of fluticasone propionate, a powerful, topically active glucocorticosteroid, on nasal airways resistance and cellular infiltration of the nasal mucous membrane were investigated. Fluticasone propionate blunted the rise in nasal airway resistance following allergen challenge (P = 0.089). Although this glucocorticosteroid did not affect the total number of eosinophils in biopsies of nasal mucous membrane, the number of activated eosinophils was significantly reduced (P less than 0.05).

Administration, Topical↗
PubMed1990

Culture and comparison of human bronchial and nasal epithelial cells in vitro.

Human nasal and bronchial epithelial cells were cultured in vitro and compared morphologically and functionally. Morphologic assessment by both light and electron microscope and indirect immunoperoxidase staining techniques confirmed the identity of the two cell types as being epithelial. Light microscopy of confluent cultures revealed tightly packed cell monolayers, whilst electron microscopy showed that cells were linked by tight junctions. Estimation of cell size by planimetry found these cells to have a mean width of 10.6 +/- 1.1 microns for nasal cells and a mean width of 10.2 +/- 1.0 microns for bronchial cells. A high proportion of both the nasal and the bronchial cells exhibited features of the mature ciliated cell types, and constituted between 50 and 76% of the total cells at the earlier stages of culture although this decreased to between 16 and 23% of the total by 4 weeks in culture. The ciliary beat frequencies of the nasal and bronchial cells were found to be similar at 10.8 +/- 0.7 Hz and 11.8 +/- 2.3 Hz, respectively. The cilial beat on adjacent cells was synchronous, suggesting the presence of intercellular communication between the neighbouring cells. These studies demonstrated that there was little difference between the cultured nasal and bronchial epithelial cells with respect to either their morphology or ciliary activity.

Bronchi↗
PubMed1989

Histamine synthesis by respiratory tract micro-organisms: possible role in pathogenicity.

Five bacterial species considered to be potential pathogens in acute exacerbations of chronic bronchitis, cystic fibrosis, and pneumonia--Branhamella catarrhalis, Haemophilus parainfluenzae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae--were evaluated for their potential to synthesise histamine in vitro. Bacterial species commonly isolated from infected sputum but generally not considered to be pathogenic--Enterobacteriacae, Neisseria pharyngis, coagulase negative staphylococci, alpha-haemolytic streptococci, and Candida albicans--were similarly studied. Of the "pathogens", the Gram negative species B catarrhalis, H parainfluenzae and Ps aeruginosa synthesised clinically important amounts of histamine; this was not the case for the Gram positive species S aureus and S pneumoniae. Of the "non-pathogenic" species, only the Enterobacteriacae, as a group, were found to synthesise clinically important amounts of histamine. These results show that some Gram negative bacteria, associated with acute exacerbations in respiratory infections, produce histamine and possibly other inflammatory mediators, which may contribute to their pathogenecity in the lower respiratory tract in vivo.

Bacteria↗
PubMed1988

Histamine and Nt-methylhistamine in the circulation during intravenous infusion of histamine in normal volunteers.

Plasma levels of histamine and Nt-methylhistamine were measured simultaneously by high performance liquid chromatography during the intravenous infusion of histamine acid phosphate in six normal volunteers. Progressive, dose-related increases in plasma histamine were noted, reaching a maximum value of 3.1 +/- 0.14 ng ml-1 corresponding to a maximum infusion rate of 180 ng kg-1 min-1 (means +/- SEM). Increases in plasma histamine were accompanied by a significant dose-related fall in mean diastolic blood pressure (baseline 74.0 +/- 4.4 mm Hg falling to 60.0 +/- 3.3 mm Hg at maximum infusion rate, p less than 0.001) and an increase in pulse rate (baseline 76.3 +/- 2.8 beats min-1 rising to 89.24 beats min-1 at maximum infusion rate, p less than 0.05). All subjects exhibited facial flushing, the threshold plasma histamine level for this effect being 1.3 +/- 0.15 ng ml-1 corresponding to an infusion rate of 60 ng kg-1 min-1. Elevation of plasma Nt-methylhistamine was seen in only one subject, who exhibited a level of 0.5 ng ml-1 at the highest infusion rate. These results suggest that measurements of plasma Nt-methylhistamine are unlikely to provide a useful index of histamine release into the circulation.

Adult↗
PubMed1986

Synthesis of histamine by Haemophilus influenzae.

Recent findings suggest that bacteria might contribute to histamine concentrations in the sputum of patients with infective lung disease. Ten isolates of Haemophilus influenzae from patients with acute exacerbation of chronic bronchitis and emphysema, together with two reference strains, were incubated at 37 degrees C for 72 hours. Serial estimations of histamine concentrations by high pressure liquid chromatography showed significant increases at 24 and 48 hours; no increases were evident in the control samples. These findings suggest that H influenzae might contribute to inflammation and limited airflow in infective lung disease by producing histamine.

Bronchitis↗
PubMed1986

De novo generation of histamine in sputum and the effect of antibiotics.

We have performed experiments to test the hypothesis that bacteria may contribute to the presence of histamine in sputum. Sputum samples obtained from 7 patients with exacerbations of chronic bronchitis and 7 patients with cystic fibrosis were incubated at 37 degrees C for 72 hours. Serial sputum histamine estimations, performed by a recently-developed HPLC technique, showed large, progressive increases in both groups of samples. Both the pre-heating of samples at 100 degrees C prior to incubation and the addition of antibiotics to the incubates substantially reduced these increases. These findings strongly suggest that bacteria may contribute to sputum histamine in infective lung disease.

Adult↗
PubMedDate not supplied

Human nasal and bronchial epithelial cells in culture: an overview of their characteristics and function.

Our studies have demonstrated it is possible to culture both human nasal and bronchial epithelial cells to confluency under similar conditions in vitro. These cells are similar morphologically, histologically, and functionally and resemble the cells in vivo. Studies of ciliary activity demonstrate that these cells react toward various agonist and antagonist agents in a similar manner as the cells reported in vivo and consequently will prove to be a valuable model for the evaluation of various therapeutic agents used in the management of infective lung diseases. Similarly studies on the effect of histamine have demonstrated that histamine probably does lead to an increase in bronchial epithelial permeability in vivo and that this effect is likely to be mediated via stimulation of H-1 receptors. Again this could be of clinical relevance when formulating appropriate therapy. The finding that human tracheal and nasal epithelial cells in culture are capable of synthesizing PGE2 could have important clinical implications because this compound is thought to be a putative epithelium-derived relaxing factor. Although this finding awaits confirmation, similar studies with bronchial epithelial cells in vitro would provide a useful tool for study of the function of the bronchial epithelium and its role in the pathogenesis of diseases such as asthma and chronic bronchitis.

Bronchi↗