Biomedical subjects

M Halonen

Publications and source records attributed to M Halonen.

At least 73 records · Page 4Linked to original sources

PubMed1991

Relationship of total serum IgE levels in cord and 9-month sera of infants.

To characterize IgE levels at birth and changes in those levels during the first year of life and to identify factors that might influence IgE levels in infancy, we measured IgE levels in 1074 umbilical cord sera and in 697 sera obtained at 9 months of age in a healthy population of infants enrolled at birth into the Children's Respiratory Study in Tucson, Arizona, U.S.A. Serum IgE levels at birth and 9 months were log normally distributed with geometric means of 0.09 and 3.87 IU/ml, respectively. Cord serum IgE levels were unaffected by maternal smoking. Levels varied according to month of birth with a nadir in September. Cord and 9-month serum IgE levels were higher in boys than in girls, Hispanics compared with Anglos, and infants who developed eczema compared with those who did not, but the mean increases in log IgE from birth to 9 months were not significantly affected by these factors. A significant correlation between IgE levels at cord and 9 months was observed (r = 0.44; P less than 0.0001). Also, mean log IgE levels at 9 months in infants grouped according to cord serum IgE levels maintained the same rank order of mean values as the cord groups. These data indicate that 9-month IgE levels are influenced by cord serum IgE levels and that the main influence of gender, ethnicity and susceptibility to eczema on IgE levels occurs before birth.

Age Factors↗

PubMed1991

A longitudinal study of respiratory symptoms in a community population sample. Correlations with smoking, allergen skin-test reactivity, and serum IgE.

Chronic cough and/or phlegm, wheeze in the absence of colds, and rhinitis attributed to allergies are three of the most common respiratory symptoms encountered in community populations. In this study, we have determined the prevalence of these complaints in a random population sample (n = 1,109) using standardized questionnaires at two points in time, eight years apart. Cross-sectional prevalence and changes in symptom occurrence have been correlated with smoking status, allergen skin test reactivity, and total serum IgE levels. Our objective was to determine the individual and combined influence of these three variables on symptom prevalence. Initially, 19.2 percent of the population admitted to wheeze, 17.9 percent to cough, and 44.1 percent to allergic rhinitis. Cough and wheeze prevalence changed little over the eight-year period, while rhinitis increased 11 percent by the second survey. The occurrence of chronic cough was strongly correlated with smoking, and was not further influenced by either allergen skin reactivity or IgE level. Conversely, rhinitis prevalence was related to skin test reactivity with no additional association with smoking or IgE level. The occurrence of wheeze in the absence of colds was associated with both smoking and allergen skin reactivity. Among smokers, the prevalence was over 30 percent and was similar in both skin test positive (STP) and skin test negative (STN) individuals. However, on both surveys, STP ex-smokers and nonsmokers had significantly more wheeze than those who were STN. While the prevalence of wheeze in STN nonsmokers was low (6.8 percent), an IgE-wheeze relationship was also suggested on the second survey. In addition to these cross-sectional symptom relationships, changes in either smoking status or allergen skin reactivity during the study period were associated with changes in the prevalence of each symptom.

Adult↗

PubMed1990

Problems in defining normal limits for serum IgE.

Recommended "normal limits" for serum IgE generally assume that a single upper limit of normal can be applied to all adults. The present article describes the distribution of IgE levels in 2657 subjects in a general population sample in Tucson, Ariz. Limits of IgE defining the lower 5%, 10%, 25%, 50%, 75%, 90%, and 95% in 1569 subjects with negative allergy skin tests and without current asthma, considered a reference group, are provided by age and sex. These cutoffs are then used to compare groups with asthma and with positive allergy skin tests with the reference population. Distributions of IgE levels in these groups are vastly different, but defining an upper "limit of normal" for serum IgE is of doubtful clinical value because there is no single level of IgE that distinguishes different groups with any precision. The spread of IgE values is extremely wide in subjects with and without known allergic diseases.

Adolescent↗

PubMed1990

Anatomic basis for species differences in peripheral lung strip contraction to PAF.

Platelet-activating factor (PAF) is a very potent contractile agonist in guinea pig peripheral lung strips but is without effect on rabbit peripheral lung strips. Histological examination of guinea pig peripheral lung strips revealed a layer of smooth muscle cells in the visceral pleura that is not present in rabbit peripheral lung strips. Removal of the pleural surface of the guinea pig peripheral lung strips eliminated the ability of these tissues to contract to PAF, and the (removed) thin pleural strip contracted to PAF in a manner similar to that of intact strips. Removal of the pleural surface did not prevent these tissues from contracting to histamine or leukotriene D4 (LTD4), although potency of these agonists was somewhat reduced. The pleural smooth muscle cell layer is present throughout the pleural lining of the guinea pig lung but is thicker in lower than in upper lobes. PAF contractility is also reduced in upper compared with lower lung lobes. Thus we suggest that the pleural smooth muscle is the critical contractile element for PAF contraction of guinea pig peripheral lung strips, whereas other agonists such as histamine and LTD4 contract additional elements in these tissues.

Animals↗

PubMed1990

Effects of the PAF antagonist WEB 2086 on PAF-induced physiologic alterations and on IgE anaphylaxis in the rabbit.

The inhibitory effects of the specific platelet-activating factor (PAF) antagonist WEB 2086 on the in vivo PAF- and antigen-induced respiratory, circulatory, and hematologic alterations in the rabbit were investigated. WEB 2086 (600 micrograms/kg) given 5 min before challenge with 0.6 micrograms/kg of PAF completely inhibited the PAF-induced bronchoconstriction, period of rapid, shallow breathing, bradycardia, increase in right ventricular pressure, and hypotension. The PAF-induced thrombocytopenia, leukopenia, and basopenia were also prevented by WEB 2086 pretreatment. In contrast, the inhibitory effects of WEB 2086 on IgE anaphylaxis were much more limited. No significant inhibition of the responses in tidal volume, breathing frequency, hypotension, or bradycardia was observed in sensitized rabbits pretreated with 1 or 6 mg/kg of WEB 2086. However, WEB 2086 significantly inhibited the increase in total pulmonary resistance. Although the peak changes in dynamic lung compliance and right ventricular pressure were not or were only slightly inhibited by WEB 2086, a more rapid recovery to baseline was observed in rabbits receiving the PAF antagonist. No significant inhibition of the thrombocytopenia, leukopenia, and basopenia accompanying antigen challenge was observed in WEB 2086-pretreated rabbits. Pretreatment with the PAF antagonist prevented anaphylactic lethality. Thus, PAF appears to play a role in the lethality and the maximum increase in total pulmonary resistance of IgE systemic anaphylaxis but does not appear to be a major mediator of the other physiologic alterations, including systemic hypotension.

Anaphylaxis↗

PubMed1990

Characterization of receptors for platelet-activating factor in guinea pig lung membranes.

Platelet-activating factor (PAF) is a potent contractile agonist in guinea pig peripheral lung strips. Whether PAF acts via specific receptor sites in the lung has not been fully established. To determine if specific receptor sites could be demonstrated in guinea pig peripheral lung tissue, we performed direct radioligand binding studies in tissue homogenates with [3H]C16-PAF (1-O-hexadecyl-sn-glyceryl-3-phosphorylcholine) and the PAF antagonists [3H]WEB 2086 and [3H]RP52770. These studies demonstrated binding sites for [3H]C16-PAF of high affinity (Kd of 2.6 nM from saturation isotherms and 0.9 nM from kinetic experiments) and a mean density of 200 fmol/mg protein. Binding was inhibited to the same degree with unlabeled C16-PAF, WEB 2086, and RP52770, all with pseudo-Hill slopes of unity. [3H]WEB 2086 binding demonstrated a receptor density similar to that of [3H]C16-PAF (226 fmol/mg protein) and was inhibited to the same degree by unlabeled C16-PAF, C18-PAF, WEB 2086, and RP52770. Although antagonist inhibition yielded pseudo-Hill slopes near unity, agonist inhibition slopes were shallow, suggesting two types or states for the PAF receptors. Direct binding studies with [3H]RP52770 revealed a much larger density of binding sites (1,200 fmol/mg protein), and this binding was not inhibited with C16-PAF, C18-PAF, WEB 2086, or lyso-PAF. These results indicate that guinea pig lung has specific binding sites for [3H]C16-PAF, that WEB 2086 is an effective antagonist of C16- and C18-PAF binding at these sites, and that RP52770 binds to the PAF site but, in addition, binds to another site with a much greater density.

Animals↗

PubMed1989

Association of asthma with serum IgE levels and skin-test reactivity to allergens.

We investigated the association of self-reported asthma or allergic rhinitis with serum IgE levels and skin-test reactivity to allergens in 2657 subjects in a general-population study. Regardless of the subjects' status with respect to atopy or their age group, the prevalence of asthma was closely related to the serum IgE level standardized for age and sex (P less than 0.0001), and no asthma was present in the 177 subjects with the lowest IgE levels for their age and sex (greater than 1.46 SD below the mean). The log odds ratio increased linearly with the serum IgE level after we controlled for possible confounders and the degree of reactivity to skin tests. In contrast, allergic rhinitis appeared to be associated primarily with skin-test reactions to common aeroallergens, independently of the serum IgE level. We conclude that asthma is almost always associated with some type of IgE-related reaction and therefore has an allergic basis, although not all the allergic stimuli that cause asthma appear to have been included in the battery of common aeroallergens we used to assess atopic status. These findings challenge the concept that there are basic differences between so-called allergic ("extrinsic") and nonallergic ("intrinsic") forms of asthma.

Adolescent↗

PubMed1988

Immunoglobulin E anaphylaxis in rabbits: mechanisms of pulmonary resistance and compliance changes.

Factors causing changes in pulmonary resistance and dynamic compliance with immunoglobulin (Ig) E anaphylaxis in spontaneously breathing rabbits were assessed in ventilated rabbits using tantalum bronchography and wet-to-dry wt ratios. Ventilated rabbits demonstrated changes in resistance and compliance similar to spontaneously breathing rabbits. Chlorpheniramine pretreatment prevented increases in resistance but not decreases in compliance. Anaphylaxis constricted small (less than 1 mm) airways 20.9 +/- 16.0% (mean +/- SD) and intermediate (between 1 and 3 mm) airways 21.8 +/- 19.8%. Chlorpheniramine (10 mg/kg) prevented small airway changes and attenuated those in intermediate airways. Chlorpheniramine prevented histamine-induced constriction of small (23.6 +/- 15.7%) and intermediate (17.6 +/- 15.0%) airways. Lung wet-to-dry wt ratios were unchanged. Changes in resistance and compliance during rabbit IgE anaphylaxis are not due to changes in tidal volume or frequency. Histamine, via H1 receptors, is the principal mediator of pulmonary resistance increases but not dynamic compliance reductions. Chlorpheniramine-sensitive increases in resistance are caused by constrictions of intermediate and small airways, whereas the chlorpheniramine-resistant decrease in compliance is not caused directly by constriction of the smallest measurable airways (0.25 mm) or changes in lung water.

Airway Resistance↗

PubMed1988

A muscarinic receptor subtype modulates vagally stimulated bronchial contraction.

An in vitro preparation was developed to study vagus nerve-stimulated (preganglionic) and field-stimulated (post-ganglionic) contraction of the rabbit main stem bronchus and to compare the inhibitory effects of muscarinic antagonists on that contraction. The maximal contractile responses (20 V, 0.5 ms, 64 Hz) for either field or vagal stimulation were completely abolished by atropine (60 nM). Hexamethonium (0.1 mM) abolished the response to vagal stimulation but did not affect the field-stimulated response. To compare the effectiveness of atropine and pirenzepine as antagonists at the nerve-smooth muscle junction, inhibition studies of field-stimulated contractions were performed. Pirenzepine was 102- to 178-fold less potent than atropine when compared at the inhibitory concentration of antagonist that produced 25, 50, and 75% inhibition (IC25, IC50, and IC75, respectively), indicating that the muscarinic receptor at the nerve-smooth muscle junction is a muscarinic receptor with low affinity for pirenzepine (M2 subtype). Atropine had similar inhibitory effects on vagal- and field-stimulated contractions. In contrast, pirenzepine was more potent in inhibiting vagally stimulated contraction than field-stimulated contraction, especially at the IC25 where pirenzepine was only 8- to 22-fold less potent than atropine in inhibiting vagally stimulated contraction. These data suggest that an M1 subtype of muscarinic receptor modulates excitatory neurotransmission through bronchial parasympathetic ganglia.

Animals↗

PubMed1988

Characterization of muscarinic cholinergic receptor subtypes in human peripheral lung.

The authors have characterized the muscarinic cholinergic receptor subtypes in human peripheral lung membranes using the selective muscarinic antagonist [3H]pirenzepine [( 3H]PZ) and the classical muscarinic antagonist [3H](-)-quinuclidinyl benzilate. High-affinity binding with pharmacologic specificity was demonstrated for both radioligands. The high affinity Kd for [3H]PZ binding determined from saturation isotherms was 5.6 nM, and the Kd for [3H](-)-quinuclidinyl benzilate binding was 14.3 pM. Approximately 62% of the total muscarinic binding sites in human peripheral lung bind [3H]PZ with high affinity. There was no significant effect of the guanine nucleotide, guanyl-5'-yl imidodiphosphate, on the inhibition of [3H](-)-quinyclidinyl benzilate binding by the muscarinic agonist carbachol in peripheral lung membranes. If the muscarinic receptor with high affinity for PZ has an important role in bronchoconstriction, its characterization could result in the development of more selective bronchodilators.

Adult↗

PubMed1987

Heterogeneity of the M1 muscarinic receptor subtype between peripheral lung and cerebral cortex demonstrated by the selective antagonist AF-DX 116.

Recent studies have demonstrated that the majority of muscarinic receptors in rabbit peripheral lung homogenates bind pirenzepine with high affinity (putative M1 subtype). In experiments of AF-DX 116 inhibiting [3H](-)quinuclidinyl benzilate or [3H]pirenzepine, we found similar inhibitory constants for AF-DX 116 binding in rat heart and rabbit peripheral lung that were 4-fold smaller (i.e. of higher affinity) than the inhibitory constant for rat cerebral cortex. This result demonstrates heterogeneity of the M1 muscarinic receptor subtype between peripheral lung and cerebral cortex.

Animals↗

PubMed1987

A muscarinic receptor with high affinity for pirenzepine mediates vagally induced bronchoconstriction.

The nature of the putative muscarinic receptor subtypes involved in vagally mediated bronchoconstriction was examined in the rabbit model utilizing the classical muscarinic antagonist atropine and the selective antagonist pirenzepine. In vivo electrical stimulation of the cervical vagus nerves in anesthetized rabbits resulted in a reproducible increase in pulmonary resistance indicative of bronchoconstriction and a marked negative chronotropic effect on the heart. Both atropine and pirenzepine produced dose-related inhibition of these two vagal effects. Fifty percent inhibition of the vagally induced increase in pulmonary resistance was achieved with an infusion of pirenzepine that was only 8-fold greater than the equi-effective dose of atropine. In contrast, the dose of pirenzepine required to inhibit the vagally induced decrease in heart rate by 50% was 100-fold greater than the atropine dose. Thus, pirenzepine is markedly more potent in inhibiting vagally mediated bronchoconstriction than bradycardia. In vitro inhibition of methacholine-induced contraction of bronchial rings with atropine and pirenzepine yielded pA2 values of 8.86 and 6.88 respectively (95-fold potency ratio), demonstrating that the muscarinic receptors on airway smooth muscle cells that mediate contraction are not of the pirenzepine-sensitive subtype.

Action Potentials↗

PubMed1987

A longitudinal study of serum IgE in a community cohort: correlations with age, sex, smoking, and atopic status.

A number of factors, including age, sex, smoking habits, and atopic status have been reported in cross-sectional studies to influence levels of serum IgE. We have examined the effects of these variables on serum IgE in a community population cohort of 1109 subjects during a longitudinal study in which two serum samples were obtained 8 years apart from each subject. For the entire cohort, mean serum IgE level changed little during the follow-up period (28.9 versus 26.0 IU/ml). Most of the decreases were observed in children and young adults. Subjects more than the age of 35 years demonstrated no systematic change in serum IgE levels. By the end of follow-up (when there were few subjects still less than 16 years of age), significant relationships of IgE to age could no longer be demonstrated in nonatopic subjects. Also, in the nonatopic subjects of this cohort, there were no significant differences in IgE levels between the sexes. Among atopic subjects, there was a clear tendency for IgE to decrease with age, with atopic women more than 35 years of age demonstrating greater declines in IgE levels during follow-up than men of comparable age. The IgE levels in atopic male subjects were significantly higher than in atopic female subjects after the age of 35 years. Smoking was associated with an elevation in serum IgE. In this cohort, the smoking effect appeared to be limited to male subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1987

Intravenous platelet activating factor does not affect lung epithelial permeability.

Administration of platelet activating factor has been shown to produce lung edema in several species including the rabbit. To determine if platelet activating factor increases lung alveolar epithelial permeability, we studied the effect of intravenous platelet activating factor administration on clearance of 99mTc-DTPA from the lung of the rabbit. Intravenous platelet activating factor produced marked hemodynamic and cellular responses but did not increase the clearance of 99mTc-DTPA from lung to blood. We conclude that although platelet activating factor can induce lung edema in the rabbit, it does not produce an acute increase in alveolar epithelial permeability.

Animals↗

PubMed1987

Characterization of high affinity [3H]pirenzepine and (-)-[3H] quinuclidinyl benzilate binding to muscarinic cholinergic receptors in rabbit peripheral lung.

We have characterized the binding of the selective muscarinic antagonist [3H]pirenzepine ([3H])PZ) and the classical muscarinic antagonist (-)-[3H]quinuclidinyl benzilate ((-)-[3H]QNB) to muscarinic cholinergic sites in rabbit peripheral lung membranes. For both radioligands, high affinity binding with pharmacologic specificity was demonstrated. The high affinity Kd for [3H]PZ binding determined from saturation isotherms was 4.5 nM and the Kd for (-)-[3H]QNB binding was 6.2 pM. Comparison of the total binding capacity values determined by saturation experiments with [3H] PZ and (-)-[3H]QNB demonstrates that approximately 78% of the total muscarinic binding sites in rabbit peripheral lung bind [3H]PZ with high affinity. There was no significant effect of the guanine nucleotide, guanyl-5'-yl imidodiphosphate, on the inhibition of (-)-[3H]QNB binding by the muscarinic agonist carbachol in peripheral lung membranes. If the pulmonary muscarinic receptor with high affinity for PZ proves to have an important role in bronchoconstriction, its characterization could result in the development of more selective bronchodilators.

Animals↗

PubMed1986

The responsiveness of rabbit bronchial rings to antigen, AGEPC and histamine.

Rings of intrapulmonary bronchi isolated from rabbits producing anti-horseradish peroxidase IgE antibodies contracted when exposed to antigen. The contractile response had a lag period of about 1 min, reached a peak at 6 min and then subsided. Bronchi from rabbits with detectable levels of specific IgG (in addition to IgE) antibodies did not differ in response from those with undetectable specific IgG levels. Histamine also contracted rabbit intrapulmonary bronchi with an EC50 of 10 micro (SD 1.29). The response to antigen was completely inhibited with chlorpheniramine (30 microM). In contrast to intrapulmonary bronchi, responsiveness of mainstem bronchi to antigen was observed only occasionally, whereas histamine was equipotent on both mainstem and intrapulmonary bronchi. Thus, the amount of antigen-induced mediator release may be less in the mainstem bronchi. Acetyl glyceryl ether phosphorylcholine, in concentrations up to 10 microM, did not contract either mainstem or intrapulmonary bronchi. This study indicates that histamine is the major mediator of (and acetyl glyceryl ether phosphorylcholine does not significantly participate in) antigen-induced contraction of isolated bronchi from IgE-producing rabbits. The results provide a likely mechanism for the increase in pulmonary resistance observed in IgE anaphylaxis in this species.

Animals↗

PubMed1986

Pneumococcus-specific immunoglobulin E in cigarette smokers.

A relationship between elevated serum immunoglobulin E levels and smoking has been demonstrated in epidemiological studies. Allergy skin test data suggest that the excess immunoglobulin E of smokers is not specific for aeroallergens. It is possible that the excess immunoglobulin E is specific for microorganisms that often infect the lower respiratory tract of smokers. To investigate this possibility we utilized a radioallergosorbent test assay for detecting serum immunoglobulin E specific for Streptococcus pneumoniae, an organism commonly isolated from the respiratory tract of smokers with chronic bronchitis. We assayed sera of thirty smokers and thirty nonsmokers for immunoglobulin E specific for Streptococcus pneumoniae. Individual sera were considered positive for pneumococcus-specific immunoglobulin E if the binding was at least twice the non-specific binding at the total immunoglobulin E concentration of the particular serum. Eleven of the thirty sera of smokers and two of the thirty nonsmokers were positive for pneumococcus-specific immunoglobulin E. By chi-square analysis of these data, the prevalence of pneumococcus-specific immunoglobulin E was significantly greater in the smoking group compared with the non-smoking group (P less than 0.02). These results suggest that the excess immunoglobulin E of smokers is, at least in part, specific for microorganisms that infect the airways.

Adult↗

PubMed1986

Relationship between serum IgE and cross-sectional and longitudinal FEV1 in two cohort studies.

Evidence is accumulating that elevated levels of serum IgE may play a role in the pathogenesis of chronic airflow obstruction. We examined this question using data on 863 subjects drawn from two cohort studies which we have followed over a period of nine to 11 years. One, the Portland cohort, represents a working population aged 25 to 55 years at baseline. The second, the Screening Center cohort, spans a wider age range (18 to 87 years at baseline) and is biased towards respiratory disease. Spirometric tests and respiratory symptom questionnaires have been administered five times over a nine-year period for the Portland cohort, and over an 11-year period for the Screening Center cohort. IgE was measured one time towards the end of the follow-up. Our data confirm the finding that smokers tend to have higher IgE levels than nonsmokers. For the combined sample, geometric mean levels of IgE were 31.0 IU/ml among smokers and 17.4 IU/ml among nonsmokers. Levels among ex-smokers were intermediate. Among smokers, IgE was not related to either amount smoked or pack-years. Cross-sectionally, FEV1 was inversely related to IgE in the Screening Center cohort, but not in the Portland cohort study. Among smokers, this association was only present for those subjects with symptoms of chronic bronchitis (chronic cough/sputum production). We found no association of IgE with longitudinal rate of decline of FEV1 in either cohort. These findings are consistent with other studies and support the hypothesis that serum IgE is inversely related to function level cross-sectionally, but is not predictive of rate of decline of lung function.

Adult↗