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Biomedical subjects

H Meurs

Publications and source records attributed to H Meurs.

At least 55 records · Page 3Linked to original sources
PubMed1989

Role of phosphoinositide metabolism in functional antagonism of airway smooth muscle contraction by beta-adrenoceptor agonists.

Histamine and the muscarinic agonists, methacholine, oxotremorine, and McN-A-343, were used to contract guinea-pig tracheal smooth muscle preparations. Cumulative dose-relaxation curves with isoprenaline were performed subsequently. In addition, the concentration-dependent induction of phosphoinositide metabolism by the contractile agonists was measured in bovine tracheal smooth muscle. All agonists were found to induce a decrease of the apparent affinity of isoprenaline and a loss of relaxation, depending on the concentration and type of contractile agonist used. The differential effects of the contractile agonists, especially at higher and supramaximal concentrations, on these beta-adrenergic parameters could be explained by differences in phosphoinositide metabolism.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1989

Allosteric interactions of three muscarine antagonists at bovine tracheal smooth muscle and cardiac M2 receptors.

The kinetics of [3H]dexetimide dissociation from muscarine receptors in bovine cardiac left ventricular and tracheal smooth muscle membranes were studied in the absence and presence of three muscarine antagonists. It was found that [3H]dexetimide dissociation from cardiac muscarine receptors was monophasic and very fast (half life less than 1 min) and was slowed by the cardioselective muscarine antagonists, gallamine, methoctramine and AF-DX 116, concentration dependently. [3H]Dexetimide dissociation from tracheal muscarine receptors was biphasic, with a fast phase (half-life less than 1 min) followed after 4-5 min by a slow phase (half-life = 38.5 min). The fast component, but not the slow component, was slowed by the muscarine antagonists with concentration dependencies very similar to those found in the heart. We conclude from these data that the major population of tracheal smooth muscle muscarine receptors resembles the cardiac M2 type not only with respect to equilibrium binding affinities but also with respect to the secondary, allosteric binding site on the muscarine receptor. The results also imply that the cardiac receptor subtype is much more sensitive to allosteric modulation than the glandular/smooth muscle receptor subtype.

Animals↗
PubMed1988

Evidence for a direct relationship between phosphoinositide metabolism and airway smooth muscle contraction induced by muscarinic agonists.

The relationship between bovine tracheal muscle contraction and phosphoinositide metabolism was studied with the muscarinic agonists, methacholine, oxotremorine, and McN-A-343. Analysis of the dose-response curves for contraction and inositol phosphates accumulation with these agonists demonstrated a direct relationship between the two parameters, with a considerable reserve of inositol phosphate production for the full contractile agonists, methacholine and oxotremorine, and no reserve for the partial agonist, McN-A-343.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1988

An ordinal multivariate analysis of accident counts as functions of traffic approach volumes at intersections.

This research is concerned with the statistical analysis of accident counts at nonsignalized intersections. The objective is to develop a method for determining general (nonlinear) relationships between approach volumes and accident counts. The method must accommodate the testing of whether intersections of differing physical designs have higher or lower rates of accidents than predicted by traffic levels. It is assumed that only aggregate data are available: (1) counts of total accidents by type (e.g., injury versus property damage) without details concerning the locational position(s) of the vehicle(s) involved; and (2) aggregate traffic intensity on each intersection entry without details concerning turning volumes. The method involves the application of nonlinear multivariate methods to variables treated as ordinal scales. A case study application involving four-leg and three-leg ("T") nonsignalized major arterial intersections in the Netherlands is described. The effect of bicycle traffic on accident rates is included in the case study analysis. The results indicate that there are three groups of each of the two types of intersections based on traffic flow patterns. For each group, a different functional form was found to relate accident rates and specific variables measuring traffic volumes. There were no significant differences among the physical design categories of the intersections in each group that were not accounted for by differences in traffic intensities.

Accidents, Traffic↗
PubMed1987

Regulation of the beta-receptor-adenylate cyclase system in lymphocytes of allergic patients with asthma: possible role for protein kinase C in allergen-induced nonspecific refractoriness of adenylate cyclase.

Allergen challenge of allergic patients with asthma caused various changes in the beta-receptor-adenylate cyclase system of lymphocyte membranes from these patients. These changes included uncoupling and down regulation of beta-adrenergic receptors and nonspecific refractoriness of adenylate cyclase, as demonstrated by reduced responses to isoproterenol (beta 2), histamine (H2), 5'-guanylylimidodiphosphate, and sodium fluoride. Since these changes could be due to desensitization by enhanced plasma levels of catecholamines and/or histamine during the allergic response, we explored the effects of these agonists on the beta-receptor-adenylate cyclase system in vitro with normal lymphocytes. In addition, we assessed the effect of the tumor-promoting phorbol ester, phorbol 12-myristate 13-acetate (PMA), on this system, since phorbol esters have been demonstrated to modulate several receptor systems, presumably via activation of protein kinase C. That both the agonists and PMA may cause refractoriness of lymphocyte adenylate cyclase was demonstrated, but, however, by apparently different mechanisms. The agonists isoproterenol and histamine induced only a specific desensitization of the homologous responses, whereas PMA-induced refractoriness was nonspecific in nature. Radioligand-binding studies demonstrated that both uncoupling and down regulation contributed to the isoproterenol-induced beta-adrenergic hyporesponsiveness, whereas beta-adrenergic receptor uncoupling but not beta-adrenergic receptor down regulation was involved in PMA-induced desensitization. Histamine had no effect on the beta-adrenergic system at all. The data suggest that the agonist-induced changes in the adenylate cyclase system are specifically located at the receptors, whereas PMA-induced refractoriness can be explained by alterations distal to the receptors, presumably at the stimulatory guanine nucleotide regulatory protein. Thus, enhanced levels of catecholamines or histamine could be involved in the development of receptor-specific changes in the lymphocyte adenylate cyclase system of allergic patients with asthma. However, they are unlikely to cause the nonspecific changes distal to the receptors. The latter changes could be induced by physiologic activation of protein kinase C during the allergic response by a still unknown stimulus, possibly via the receptor-mediated turnover of phosphatidylinositol 4,5-diphosphate.

ADP-Ribosylation Factors↗
PubMed1987

The beta-adrenergic system of non-allergic patients with chronic airflow obstruction and early morning dyspnoea.

Lymphocyte beta-adrenergic receptor function and urinary excretion of catecholamines were measured in eight non-allergic patients with partially reversible chronic airflow obstruction (CAO) and early morning dyspnoea (EMD), and in eight matched healthy control subjects. In order to establish a possible relationship between the early morning dyspnoea and a reduced beta-adrenergic activity, these parameters were measured during the "morning dip" in FEV1 and in the afternoon, when lung function is maximal. No differences were observed for lymphocyte beta-adrenergic receptor characteristics (beta-receptor number, Kd, for 3H-dihydroalprenolol, and cAMP response to isoproterenol) between patients and controls, when determined at 8 AM or at 4 PM. Nor was there a significant circadian variation in these parameters present in both groups. By contrast, the patients showed a significantly reduced urinary excretion of epinephrine and norepinephrine, as measured in four-hourly urine portions collected between 8 and 12 AM and between 4 and 8 PM, respectively. In addition, the urinary excretion of epinephrine showed a significant circadian variation in the patients, which was correlated with the FEV1 (% predicted). Such a relationship was not found for norepinephrine. The results suggest that a (generalized) dysfunction of the beta-adrenergic receptor is not involved in the pathogenesis of CAO or EMD. However, reduced beta-adrenergic receptor stimulation due to decreased levels of catecholamines may contribute to the observed (variation in) airflow obstruction of the patients.

Adult↗
PubMed1986

Phorbol 12-myristate 13-acetate induces beta-adrenergic receptor uncoupling and non-specific desensitization of adenylate cyclase in human mononuclear leukocytes.

Tumour-promoting phorbol esters such as phorbol 12-myristate 13-acetate (PMA) have been reported to modulate beta-adrenergic receptor responses in various cell types, presumably by the activation of protein kinase C. In the present investigation we assessed the effect of PMA on the beta-adrenergic receptor-adenylate cyclase system of human mononuclear leukocytes (MNL). It was found that incubation of MNL with PMA resulted in a time- and concentration-dependent desensitization of isoproterenol-induced adenylate cyclase activity. However, the effect of PMA was not restricted to the beta-adrenergic receptor system, since basal adenylate cyclase activity and histamine-, prostaglandin E1-, 5'-guanylylimidodiphosphate (GppNHp)-, and NaF-stimulated values were also reduced. By contrast, no effect was found on the forskolin-induced adenylate cyclase activity. The inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate had no effect on adenylate cyclase at all, suggesting that the observed PMA effect was specifically mediated by activation of protein kinase C. The reduced beta-adrenergic response induced by PMA was not associated with a reduced beta-adrenergic receptor number, indicating uncoupling of this receptor from adenylate cyclase. Isoproterenol competition curves for 3H-dihydroalprenolol binding to membranes from untreated and PMA-treated cells demonstrated that the uncoupling was due to a reduced ability of the agonist to promote formation of the guanine nucleotide-sensitive high affinity state of the receptor. The results indicate that PMA may cause desensitization of catecholamine-responsive adenylate cyclase in MNL, and that the major locus of alteration is the guanine nucleotide regulatory protein.

Adenylyl Cyclases↗
PubMed1986

Influence of slow-release terbutaline on the circadian variation of catecholamines, histamine, and lung function in nonallergic patients with partly reversible airflow obstruction.

In order to study the mechanism underlying early morning dyspnea in patients with chronic airflow obstruction, the relation was assessed between the diurnal variation of FEV1, plasma and urinary catecholamines, and urinary histamine (metabolites) in eight nonallergic patients (mean age, 53 years). These parameters were measured both after administration of placebo and slow-release terbutaline tablets during 1 week. The fall in FEV1 at 4 A.M. coincided with a fall in both plasma and urinary epinephrine levels, whereas no correlation between pulmonary function and norepinephrine levels was observed. Histamine and N tau -methylhistamine excretion were found within the normal range without a circadian rhythm, suggesting no important role for histamine in the occurrence of early morning dyspnea in this nonallergic patient group. Administration of slow-release terbutaline during 1 week prevented the nocturnal fall in FEV1. Terbutaline treatment suppressed plasma and urinary levels of epinephrine significantly without any effect on norepinephrine. We conclude that epinephrine appears to be an important factor in the regulation of the bronchial smooth muscle tone in patients with early morning dyspnea.

Adult↗
PubMed1986

Specific immunological modulation of lymphocyte adenylate cyclase in asthmatic patients after allergenic bronchial provocation.

Adenylate cyclase responses to isoproterenol, histamine, 5'-guanylylimidodiphosphate (GppNHp) and NaF were measured in lymphocyte membranes of allergic asthmatic patients and healthy control subjects, just before and 24 h after inhalation challenge with house dust mite allergen or histamine. In the nonacute phase before the challenges, the adenylate cyclase responses in the cell membranes of the patients were not significantly different from those in membranes of the control subjects. House dust mite challenge caused a significant decrease of all adenylate cyclase responses in the cell membranes of the patients by about 40-50%. By contrast, histamine provocation of the patients had no effect on these parameters, nor was there any effect of both challenges on the adenylate cyclase activity of the control membranes. The results indicate that allergen-induced asthmatic reactions may cause nonspecific refractoriness of lymphocyte adenylate cyclase. Since histamine-induced bronchial obstruction had no effect in the patients, it appears that the adenylate cyclase response is specifically modulated by the allergic process.

Adenylyl Cyclases↗
PubMed1985

Effect of oral slow-release terbutaline on early morning dyspnoea.

Eight male patients with partly reversible airflow obstruction, who had a diurnal variation in peak expiratory flow rate (PEFR) of more than 20% were treated with placebo and slow-release terbutaline tablets (5 mg at 08.00 hours and 10 mg at 20.00 hours) for 8 days. On Day 8 of each period, PEFR and serum terbutaline were measured at 4 and 2-h intervals, respectively. PEFR on the terbutaline day showed a significant increase at 08.00, 12.00, 24.00, 04.00 and 08.00 hours as compared to the placebo day. Slow-release terbutaline prevented early morning dyspnoea. The serum concentration was 3.3 ng/ml during the day and 3.5 ng/ml during the night. During terbutaline therapy the patients reported fewer complaints than during the placebo period. It was concluded that slow-release terbutaline tablets are suitable for twice daily treatment.

Administration, Oral↗
PubMed1985

Effect of beta-adrenergic stimulation on the circulatory lymphocyte count: studies in normals and in patients with chronic airflow obstruction.

In eight non-allergic patients with chronic airflow obstruction (CAO) and eight age and sex matched, healthy control subjects the circadian variation in circulatory lymphocyte count was studied in relation to serum cortisol and urinary epinephrine levels. In addition, we investigated the effect of the beta-adrenergic agent terbutaline on the lymphocyte count in two ways: as a long-term effect after 8 days of oral slow-release terbutaline with constant diurnal and nocturnal serum levels in patients, and as a short-term effect by a constant rate infusion of 0.2 micrograms/min over 4 hr in normals. Both patients and controls showed similar circadian patterns of urinary epinephrine excretion and lymphocyte counts. Patients with CAO, however, had significantly lower epinephrine levels and significantly higher lymphocyte counts at all hours of observation (every 4 hr from 0800 to 0800 hr the next day), as compared with normal controls. After 8 days of slow-release terbutaline the lymphocyte count in the patient group decreased to levels not significantly different from that of normals. The circadian rhythm of the lymphocytes, however, persisted under terbutaline therapy. No correlation existed between the lymphocyte count modulating factor, serum cortisol and the lymphocyte count over 24 hr. On placebo infusion in the control persons an increase of lymphocytes over 4 hr occurred, as a consequence of circadian rhythmicity. On terbutaline infusion a significant increase of lymphocytes after 1 hr was followed by a decrease to levels significantly below those on the placebo day. The same pattern was found in the leucocyte count. From this study it is concluded that beta-adrenergic stimulation corrects the relative lymphocytosis to counts comparable with normals. Other coinciding factors must regulate, however, the circadian rhythmicity.

Adult↗
PubMed1985

Reduced adenylate cyclase responsiveness to histamine in lymphocyte membranes of allergic asthmatic patients after allergen challenge.

The adenylate cyclase response to histamine was measured in lymphocyte membranes of allergic asthmatic patients and healthy control subjects, just before and 24 h after inhalation challenge with house dust mite allergen. In the non-acute phase before allergen challenge, the histamine response in the membranes of the patients was not significantly different from that in membranes of the control subjects. After the house dust mite-induced asthmatic reaction, however, the adenylate cyclase response to histamine in the membranes of the patients was significantly reduced by 47%, whereas allergen inhalation had no effect on the histamine response of the control membranes. The results suggest that allergic asthmatic reactions may cause reduced lymphocyte adenylate cyclase responsiveness to histamine. A similar mechanism in the airways might contribute to allergen-induced enhanced airway reactivity to histamine.

Adenylyl Cyclases↗
PubMed1984

Protective effect of oral oxyphenonium bromide, terbutaline and theophylline against the bronchial obstructive effects of inhaled histamine, acetylcholine and propranolol.

The protective effects of oxyphenonium bromide, terbutaline and theophylline were compared in 8 asthmatic patients by determination of the degree of non-specific airway reactivity after 1 week of oral treatment according to a fixed dose scheme in a double-blind random order: oxyphenonium bromide 3 X 10 mg; terbutaline 3 X 5 mg; theophylline 2 X 300 mg and placebo. Controlled, standardized inhalation provocation tests were carried out with histamine, acetylcholine and propranolol. The study was monitored by measuring blood concentrations of the 3 drugs, and their effect on the plasma cAMP concentration was also determined. Significant protection by oxyphenonium bromide against the bronchial obstructive effects of acetylcholine and propranolol was observed, but not against the effect of inhaled histamine. The other two drugs provided no significant protection against the inhaled agents. The absence of any protective effect of terbutaline and theophylline might have resulted from too low a blood concentration. The observed differences in protection could not be explained by changes in pulmonary function. The study suggests dissociation between the bronchodilating effect of a drug and its protective effect against inhaled substances.

Acetylcholine↗
PubMed1984

Protective effect of choline theophyllinate on histamine, acetylcholine, and propranolol-induced airflow obstruction.

The protective effect of choline theophyllinate, 600 mg orally, was studied by examining the effects on inhaled histamine, acetylcholine, and propranolol in 19 asthmatic patients. Only 9 of them showed a propranolol threshold. This bronchodilator significantly increased the threshold values of histamine and acetylcholine, but showed no protective effect on propranolol thresholds. The histamine threshold changed from 2(2.5 +/- (SD)1.2) to 2(3.8 +/- 1.0) mg/ml (p less than 0.001). With acetylcholine an initial value of 2(4.2 +/- 1.4 mg/ml was determined, which changed to 2(5.5 +/- 1.1 mg/ml (p less than 0.01). The propranolol threshold changed from 1.17% +/- 0.40 to 1.36% +/- 0.40 indicating that theophylline has no statistically significant protective effect on propranolol inhalation. The reproducibility of the challenges was assessed in 8 control patients. A placebo did not significantly change the initial airway reactivity to the three agents. The protective effect of choline theophyllinate on histamine and acetylcholine correlated with the initial degree of reactivity on both agents (r = -0.60; p less than 0.01 and r = -0.84; p less than 0.001, respectively), whereas no significant correlation with the degree of bronchodilation was observed. The latter observation indicates that the protective effect of theophylline does not depend on its bronchodilating activity.

Acetylcholine↗
PubMed1984

Dynamics of the lymphocyte beta-adrenoceptor system in patients with allergic bronchial asthma.

It has been proposed that reduced beta-adrenergic responsiveness plays an important role in the increased airway reactivity of asthmatic patients. This hypothesis has been supported by studies showing reduced beta-adrenergic responsiveness in lymphocytes of asthmatic patients, predominantly during the occurrence of active and severe symptoms. Little is known about the mechanism underlying this relationship and its clinical relevance with respect to bronchial hyperreactivity. Therefore, in this study we assessed the status of the beta-adrenergic receptor-adenylate cyclase system in lymphocytes of allergic asthmatic patients in relation to parameters of bronchial hyperreactivity. This was performed before and after challenge with house-dust mite allergen, as a possible modulating factor of beta-adrenergic responsiveness. It was shown that lymphocytes of 'stable' allergic asthmatic patients with increased airway reactivity may have normal beta-adrenergic responsiveness and a normal beta-adrenergic receptor number. After allergen challenge, however, a group of 12 patients developed reduced beta-adrenergic responsiveness, which could be partially attributed to changes in the beta-adrenergic receptor number, while changes distal to the receptor also occurred. The results indicate that reduced beta-adrenergic responsiveness in lymphocytes of allergic asthmatic patients is a consequence of an active disease state rather than the reflection of a primary aetiological factor. A number of the patients concomitantly developed enhanced bronchial reactivity to propranolol after allergen challenge, which might indicate that reduced beta-adrenergic receptor function also occurs at the level of the bronchial tree. In five of the patients it was shown that beta-adrenergic hyporesponsiveness could be restored after environmental control in combination with drug treatment, thus indicating the dynamic character of the lymphocyte beta-adrenergic receptor system in asthmatic patients.

Adenylyl Cyclases↗
PubMed1983

Comparison of antibody measurements against Aspergillus fumigatus by means of double-diffusion and enzyme-linked immunosorbent assay (ELISA).

IgG antibody titers against Aspergillus fumigatus from different sera were measured by means of a standardized ELISA and compared with precipitates measured by double diffusion (D.D.). There was a significant correlation between the number of precipitates and the ELISA IgG titers in the 758 sera examined. However, in several individual sera within this group, large deviations between these two immunologic parameters were found. Further analysis indicated that ELISA detects antibodies against nonprecipitating antigenic components in addition to the antibodies detected by D.D. Furthermore, not all precipitating antigenic components appear to play a role in the detection of antibodies against A. fumigatus by ELISA. Patients with aspergillosis largely show increased titers of IgG antibody by ELISA even when the results of D.D. are negative, except those of patients with Aspergillus-provoked asthma which fall within a normal range.

Alveolitis, Extrinsic Allergic↗