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Biomedical subjects

R Ellul-Micallef

Publications and source records attributed to R Ellul-Micallef.

At least 19 recordsLinked to original sources
PubMed2001

Interferon gamma induction in human melanoma cell/allogeneic leukocyte co-cultures is enhanced by interleukin 18 but drug resistant melanoma cells are poorer inducers of IFN-gamma.

Human melanoma Colo 679 cells were made resistant to doxorubicin (adriamycin, ADM) by continuous exposure to ascending concentrations of the drug and Colo/ADM80; a variant which grew continuously in the presence of 80 ng/ml of ADM was thus established. Human peripheral blood mononuclear cells (PBMC) produced interferon gamma (IFN-gamma) when cultured with mitomycin C (MMC)-treated parental Colo 679 cells. The synthesis of IFN-gamma was synergistically enhanced by adding interleukin-18 (IL-18) and this was IL-12-dependent because a neutralizing antibody against IL-12 almost completely inhibited IFN-gamma production while control antibodies (Abs) were inactive. The cellular sources of IFN-gamma were found to be B cells, CD8+ T cells and CD4+ T cells as revealed by flow cytometry after double staining for surface antigens and staining for intracellular IFN-gamma. Interestingly, the resistant cell line induced much less IFN-gamma production than the parental cell line under the same co-culture conditions; however, IL-18 could still enhance the production of IFN-gamma. In conclusion, our study shows that acquired resistance to anti-cancer agents can also reduce immune responses to cancer cells. However, the immunostimulatory cytokine IL-18 could still enhance IFN-gamma production in drug resistant tumor cell-PBMC cultures indicating that such immunostimulatory agents could still be beneficial in immunotherapy for patients with recurrent drug resistant tumors.

Coculture Techniques↗
PubMed2001

Mutation screening of the muscarinic M(2) and M(3) receptor genes in normal and asthmatic subjects.

1. Muscarinic receptors are important in the development of airway hyperresponsiveness, and dysfunction of these receptors has been suggested to be present in asthma. 2. The human muscarinic M(2) and M(3) receptor genes were screened for polymorphic variation using single-stranded conformation polymorphism (SSCP) analysis, complemented by direct fluorescent sequencing. Forty-six random DNA samples and 46 respiratory physician diagnosed asthmatic samples were used as a template for analysis. 3. Within the muscarinic M(2) receptor gene, we identified two degenerate single base substitutions (1197T-->C, Thr-->Thr and 976A-->C, Arg-->Arg) in one random and one asthmatic sample respectively. Analysis of the 3' UTR region revealed an additional 'A' at bp 1793 (c.f. ATG). This was present in all of 49 samples analysed by sequencing or BsmI digest, suggesting that the published sequence (GenBank Accession NO: M16404) is incorrect. A common 3' UTR polymorphism (T-->A) was found at bp 1696 (c.f. ATG) (allelic frequency=65%, n=60), but this does not alter transcription factor recognition sites. 4. We were unable to identify any polymorphic variation within the muscarinic M(3) coding region or the flanking regions investigated, using the methods described. 5. The coding regions for the human muscarinic M(2) and M(3) receptor genes are both highly conserved. These data suggest that polymorphic variation within these coding sequences is unlikely to account for inter-individual variability in response to methacholine or anticholinergic therapy. The potential functional significance of the muscarinic M(2) receptor 3' UTR polymorphism (bp 1696) remains to be determined.

3' Untranslated Regions↗
PubMed1998

Selenium, glutathione peroxidase and superoxide dismutase in maltese asthmatic patients: effect of glucocorticoid administration.

Oxidative processes, mediated by free radical chemistry, are recognized to contribute significantly to the inflammatory pathology of bronchial asthma. This study analysed the degree of defence against reactive oxygen species in Maltese, asthmatic patients and in normal individuals, by measuring plasma selenium concentration, erythrocyte glutathione peroxidase (GSH-Px) activity and erythrocyte superoxide dismutase (SOD) activity, in order to determine their antioxidant status. The effect of glucocorticoids on the status of these antioxidants in patients was also investigated. The measurement of antioxidant status was carried out both in mild (n = 22) and severe (n = 37) asthmatics, as well as in healthy controls (n = 49). The same antioxidant profile was then investigated in a group of 16 severe asthmatics following treatment for 4 weeks with inhaled beclomethasone dipropionate (750 micrograms twice daily), and in a second group of 16 patients suffering from severe asthma, following 2-weeks treatment with oral prednisolone (15 mg daily during the first week and 10 mg daily during the second). No statistically significant difference was found in the plasma selenium concentrations and erythrocyte glutathione peroxidase activities between patients and controls. Both mild and severe asthmatics, however, exhibited a statistically significant lower erythrocyte superoxide dismutase activity than normal subjects (mild asthmatics: 62.9 (2.9) SOD 525 U/ml, severe asthmatics: 60.6 (1.9) SOD 525 U/ml, normal: 68.5 (1.1) SOD 525 U/ml, P < 0.01). Inhaled beclomethasone dipropionate exerted no effect on this antioxidant profile, while prednisolone caused a significant increase in plasma selenium concentration over pretreatment values (pretreatment: 118.3 (4.4) ng/ml, post-treatment: 138.1 (4.6 ng/ml, P < 0.01). It is thus suggested that asthmatic patients in Malta might be more susceptible to superoxide-induced damage than normal individuals. The reason for the prednisolone-induced augmentation of plasma selenium could not be determined from this study. It is postulated that the drug may decrease the excretion rate of the element, and may thus exert a positive antioxidant effect in individuals of established low selenium status.

Administration, Inhalation↗
PubMed1984

The spectrum of bronchial asthma in Kuwait.

Kuwait, situated in the north-west corner of the Arabian Gulf, has an arid climate with very hot dry summers and mild winters. Sandstorms are a regular climatic feature, occurring most frequently in summer. Before the mid-1950s allergy was not considered to be a problem. Since then it has become a major cause of morbidity; 18% of the population are reported to suffer from its manifestations. Over the past 3 years 1000 asthmatic patients attending a central clinic have been carefully studied. The present paper analyses various aspects of the asthmatic condition in this desert country.

Adult↗
PubMed1983

Effect of terbutaline sulphate in chronic "allergic" cough.

The effects of terbutaline sulphate were studied in 30 patients who presented with chronic cough at an allergy clinic. After a three week baseline period terbutaline and its placebo were given for two periods of three weeks each in a randomised, double blind, crossover manner. Patients kept a daily record of day and night cough scores and peak expiratory flow readings. Twenty one patients responded to terbutaline; placebo produced no significant effect. Both day and night cough scores (p less than 0.001) and peak expiratory flow rates were significantly improved (p less than 0.05) by the end of the first week of treatment with terbutaline. This improvement was achieved with only a fairly small change in airway calibre.

Adolescent↗
PubMed1983

Acute dose-response studies in bronchial asthma with a new corticosteroid, budesonide.

1 Budesonide is an epimeric mixture of a new synthetic non-halogenated glucocorticoid (16 alpha, 17 alpha,-(22R,S)-prophylmethylenedioxypregna-1,4-diene-11/3,21-diol-3, 20-dione). 2 Acute dose response studies with three different inhaled doses of budesonide, have been carried out in a group of 12 chronic asthmatic patients. 3 The lowest dose (100 micrograms) of inhaled budesonide produced a more marked effect in relieving airflow obstruction, than a much larger (1600 micrograms) oral dose of the drug. 4 When the area under the curve for peak expiratory flow rate values was calculated, a dose-response relationship could be seen between the different inhaled doses. 5 It appears that budesonide has a predominantly local anti-asthmatic action in the lung.

Administration, Oral↗
PubMed1983

Effect of oral sodium cromoglycate and ketotifen in fish-induced bronchial asthma.

The effects of sodium cromoglycate and ketotifen were studied in a group of 20 patients in whom fish repeatedly provoked an attack of wheezing and dyspnoea within one hour of its being eaten. Fish ingestion resulted in a fall in forced expiratory volume in one second (FEV1) of at least 15%. All patients had a weal greater than 4 mm in response to fish antigen in the skinprick test and most had blood eosinophilia and raised serum IgE levels. Administration of drugs and placebos was carried out under double-blind conditions, in a randomised fashion, on different days. Cromoglycate blocked the fall in FEV1 either completely or significantly in 16 patients. Ketotifen did not appear to have any significant effect in the group as a whole.

Adult↗
PubMed1982

The acute effects of corticosteroids in bronchial asthma.

Corticosteroids have now been used in the treatment of bronchial asthma for about 30 years but objective physiological evidence of their effects in this condition has only become available over the past 8 years. Studies with oral prednisolone, intravenous prednisolone and hydrocortisone, as well as with inhaled budesonide, in patients with chronic bronchial asthma, have shown that there is a time lag between the administration of these drugs and the onset of improvement in the patients' conditions. This time lag is even longer when corticosteroids are given to patients with severe asthma. It appears that these drugs exert an effect on both the central and the peripheral airways. Unlike bronchodilators corticosteroids do not appear to increase the degree of ventilation perfusion mismatching present in asthma. They have been shown to decrease the alveolar-arterial oxygen tension gradient and the venous admixture effect with a consequent rise in arterial oxygen tension. It is still uncertain how corticosteroids work in asthma; it seems, however, that one of the ways may be through their effects on the beta adrenergic receptors.

Asthma↗
PubMed1980

The effect of oral prednisolone on gas exchange in chronic bronchial asthma.

Patients with bronchial asthma frequently have a fall in arterial oxygen tension following bronchodilator treatment in spite of a reduction in airway resistance. Administration of 0.11 mM (40 mg) prednisolone in a single dose resulted in an improvement of both airway obstruction and hypoxaemia in chronic asthmatic patients. The arterial oxygen tension, alveolar-arterial oxygen tension difference and venous admixture effect all showed a statistically significant improvement as did the dynamic lung volumes and specific airway conductance.

Administration, Oral↗
PubMed1980

The hypereosinophilic syndrome--a diagnostic enigma.

The hypereosinophilic syndrome groups together a number of conditions in which eosinophilia occurs for no apparently identifiable cause. Initial reports indicated a uniformly grave prognosis but recent observations suggest a more favourable outcome in certain cases. Two patients with hypereosinophilic syndrome are described whose course of disease and outcome have been completely different.

Adolescent↗
PubMed1980

Use of a special inhaler attachment in asthmatic children.

Asthmatics often find difficulties in using an aerosol inhaler correctly as they are unable to co-ordinate the release of a bolus of drug to coincide with an inspiratory effort. This is especially the case with children. The addition of a special attachment to an ordinary inhaler overcame this problem. Twelve asthmatic children produced significantly better PEFR measurements when 0.25 mg terbutaline sulphate was administered via an inhaler with the attachment than when an ordinary inhaler was used alone.

Aerosols↗
PubMed1980

Budesonide: a new corticosteroid in bronchial asthma.

The time course of response to budesonide in a dose of 1000 microgram administered by inhalation, 800 microgram given by the oral route, and 40 microgram prednisolone administered orally, has been investigated in 12 patients suffering from chronic bronchial asthma. Budesonide is an epimeric mixture of a non-halogenated glucocorticoid, 16 alpha, 17 alpha-(22R,S)-propylmethylenedioxypregna-1,4-diene-11 beta, 21-diol-3,20-dione. Inhaled budesonide and prednisolone produced a statistically significant increase in PEF 2 h after being administered. The peak effect appeared to occur between 6 and 7 h after budesonide inhalation and about 9 h following prednisolone. When given orally, budesonide failed to produce any substantial changes in PEF.

Administration, Oral↗
PubMed1975

Effect of intravenous prednisolone in asthmatics with diminished adrenergic responsiveness.

The beta effects of adrenergic stimulation are often diminished in asthmatics in whom the condition is active. Corticosteroids are thought to lower the threshold of beta-adrenergic receptors to the response of catecholamines. A single intravenous injection of 40 mg prednisolone appeared to restore responsiveness to inhaled isoprenaline in eight out of ten chronic asthmatics who were previously non-responsive to catecholamines.

Adult↗
PubMed1975

Intravenous prednisolone in chronic bronchial asthma.

A single injection of 40 mg prednisolone phosphate was given to 10 patients with chronic bronchial asthma. Changes in pulmonary function were followed over a 30-hour period. Statistically significant changes occurred in the tests employed one hour after the injection of prednisolone. The maximum change for the group as a whole was seen to occur after eight hours. This time course of response is very similar to that obtained in previous studies on similar groups of patients with oral prednisolone where the peak effect occurred nine hours after the drug had been given. Intravenous hydrocortisone produces a much earlier peak effect, at five hours, when it is administered to chronic asthmatic patients.

Adolescent↗