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Biomedical subjects

W W Busse

Publications and source records attributed to W W Busse.

At least 217 records · Page 12Linked to original sources
PubMed1982

Granulocyte chemiluminescence in adolescent patients with cystic fibrosis.

The granulocyte chemiluminescence (CL) response is the result of activating its cellular "respiratory burst" and oxidative metabolism. The resulting light emission is an indication of intact metabolic events important in bactericidal activity. Patients with cystic fibrosis have recurrent pulmonary infections. To determine whether granulocytes from patients with CF have defective oxidative metabolism, CL was assayed in 8 patients and compared with that in normal control subjects. In CF, the peak CL response to opsonized zymosan is normal. If, however, the time required for peak light emission is compared with the NIH Clinical Score, a significant correlation is found. Granulocytes from patients with airway disease and more severe CF have a more rapid onset of the CL response. Although the clinical significance of this observation is not established, granulocytes from patients with CF appeared "primed" in their responses to a phagocytic stimulus.

Adolescent↗
PubMed1981

Contribution of vascular smooth muscle to contractile responses of guinea-pig isolated lung parenchymal strips.

Parenchymal strips, isolated from the guinea-pig lung, were stimulated transmurally at different electrical frequencies in vitro. Frequency-response analyses for contraction were obtained on paired strips in the absence or presence of antagonists. Tetrodotoxin was shown to block the effects of electrical stimulation, demonstrating that the contractile response was due to activation of efferent neurons in the tissue. Phentolamine, 10(-5) M, and atropine, 10(-6) M, antagonists demonstrated to be selective for blocking alpha-adrenergic and muscarinic receptors, respectively, produced inhibition of the contractile effects of electrical stimulation. When analyzed at the level of the frequency required to produce a contraction equal to 10% of the maximum produced by histamine, the EF10, the frequency-response curves were shifted 3- to 4-fold to the right by each receptor antagonist. Combination of the two receptor antagonists produced a greater degree of blockade than either alone and, at the maximum frequency utilized (32 Hz), the contractile response did not reach the EF10 in al tissues. Propranolol, 10(-6) M, did not alter the effects of electrical stimulation, but increased the magnitude of contraction produced by exogenously applied norepinephrine. In tissues taken from reserpine-pretreated animals, phentolamine did not produce a statistically significant change in EF10 for electrical stimulation. The data provide evidence that both vascular and airway smooth muscles are present and contribute to contractile responses in the guinea-pig lung parenchymal strip.

Animals↗
PubMed1981

The granulocyte response to the phosphodiesterase inhibitor RO 20-1724 in asthma.

Isolated human granulocytes secrete the lysosomal enzyme beta glucuronidase when incubated with complement-activated zymosan particles. Isoproterenol inhibits this release, and the beta adrenergic response is associated with an increase in granulocyte cyclic adenosine monophosphate (cAMP) levels. In asthma, the beta adrenergic responsiveness is impaired. Cyclic AMP concentration in the granulocyte is also influenced by phosphodiesterase hydrolysis of this cyclic nucleotide. We found that the potent phosphodiesterase inhibitor, RO 20-1724, inhibited zymosan-stimulated beta glucuronidase release from granulocytes in a dose-dependent fashion (10(-8) to 10(-4) M). The inhibition of lysosomal enzyme release by RO 20-1724 was associated with an increase in granulocyte cAMP. Granulocytes were also isolated from asthmatic patients and the RO 20-1724 inhibition of beta glucuronidase release was compared with the response in normal subjects. The negative log molar median effective dose (ED50) value (mean +/- SE) was 5.98 +/- 0.69 in normal subjects and 5.90 +/- 0.63 in asthmatics. These observations suggest that the granulocyte metabolism modulated by the RO 20-1724-sensitive phosphodiesterase is equally responsive to this potent phosphodiesterase inhibitor in normal and asthmatic leukocytes.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1981

A multicenter study on skin-test reactivity of human volunteers to venom as compared with whole body Hymenoptera antigens.

Twenty-four control and 104 stinging insect-allergic patients were tested in this multicenter study, which compared the utility of individual venom and whole body extract (WBE) preparations for diagnosis. This study indicates that venom skin testing is more specific and more reliable than is testing with WBE. There was a high rate of WBE skin-test reactivity among controls. False-positive skin testing with venom was not a problem at concentrations of 1 microgram/ml or less. Only one mild and easily treated adverse reaction occurred in this study.

Antigens↗
PubMed1981

Cortisol protection of the granulocyte response to isoproterenol during an in vitro influenza virus incubation.

Isolated human polymorphonuclear leukocytes (PMNs) release beta glucuronidase (BG) lysosomal enzyme during incubation with complement-activated zymosan particles. In asthma, isoproterenol (ISO) and histamine (HIS) inhibition of PMN lysosomal enzyme release is impaired while the prostaglandin E1 (PGE1) response is normal. During a respiratory infection provoking asthma, the PMN response to ISO is further impaired. The PMN response to ISO, HIS, and PGE1 is similarly impaired following an in vitro incubation with a live influenza bivalent (A + B) vaccine. In the following study, granulocytes were isolated from normal (n = 10) and asthma patients (n = 29). The isolated cells were incubated with the bivalent influenza vaccine (1 PMN:1 egg infective dose50) for 30 min. Following this in vitro virus incubation, granulocytes from normal and asthma patients had an imparied response to ISO, HIS, and PGE1. Granulocytes from asthma patients having a history of wheezing with respiratory illnesses did not have a greater impairment in the agonist response following virus incubation than normals or allergic asthma patients. However, in asthma patients (n = 6) receiving prednisone (10 to 20 mg/day), the in vitro vaccine incubation did not impair the PMN ISO response. A similar protective effect was found if granulocytes were incubated with hydrocortisone (1,4 X 10(-4) M) prior to exposure to the influenza vaccine.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1981

Development of allergic bronchopulmonary aspergillosis during treatment of severe asthma with systemic corticosteroids.

Rapid clinical improvement of allergic bronchopulmonary aspergillosis (ABPA) is usually noted with corticosteroid therapy. We report a case of ABPA that developed in patient who was being treated with prednisone on a maintenance basis for severe asthma. Recovery from the short-term episode of ABPA was protracted and required higher doses of corticosteroids for control of the syndrome than usually necessary. It is suggested that corticosteroids do not prevent the development of ABPA, and that patients who develop the syndrome while on corticosteroids may have a protracted course with poor response to the usually effective doses of corticosteroids.

Adrenal Cortex Hormones↗
PubMed1981

Peanut oil is not allergenic to peanut-sensitive individuals.

Ten peanut-sensitive patients were enrolled in a double-blind crossover trial to determine whether ingestion of peanut oil can induce adverse reactions in such individuals. All patients had experienced prior allergic reactions to peanut ingestion, including any of the following: generalized urticaria, angioedema, abdominal cramps, vomiting, diarrhea, bronchospasm, or shock. All patients had elevated levels of serum IgE antibodies to both crude peanut extract and the purified peanut allergen, Peanut-I, by RAST assay; binding values ranged from 2 to 26 times that of negative control serum. All patients demonstrated negative puncture skin tests to both peanut oil and olive oil (control). At 30-min intervals, patients ingested 1, 2, and 5 ml of either oil contained in 1 ml capsules while under constant observation. These quantities exceed the maximum estimated dose of peanut oil that would occur in single meals. Patients returned 2 wk later for ingestion challenge with the remaining oil. No untoward reactions were observed with either peanut oil or olive oil. Peanut oil ingestion does not pose a risk to peanut-sensitive individuals.

Adolescent↗
PubMed1981

Analysis of granulocyte beta-adrenergic response in cystic fibrosis: correlation of decreased responsiveness with disease severity.

Granulocytes from 21 nonasthmatic cystic fibrosis (CF) patients were isolated and the effects of isoproterenol, histamine, and prostaglandin E1 upon zymosan-induced beta-glucuronidase release was measured. Granulocytes from CF patients contained significantly less total beta-glucuronidase activity compared with those from control subjects, but response to zymosan stimulation was normal. Compared with those from control subjects, the granulocytes from CF patients with severe airway disease (% predicted FEV1 less than 60) had significantly reduced responsiveness to isoproterenol, which correlated with both the % predicted FEV1 values and the NIH clinical score. In this same population of CF patients, granulocyte responsiveness to PGE1 was also decreased compared with that of the control subjects, but the degree of impairment was not as severe as that observed with isoproterenol nor did it correlate with disease severity. Histamine responsiveness, however, was normal. Our findings suggest that abnormal beta-adrenergic responses may reflect the severity of airway disease and clinical score.

Adolescent↗
PubMed1981

Altered luminol-dependent granulocyte chemiluminescence during an in vitro incubation with an influenza vaccine.

Polymorphonuclear leukocyte particle phagocytosis stimulates the "respiratory burst." The changes in oxidative metabolism are associated with the release of highly reactive species, superoxide, hydrogen peroxide, singlet oxygen, and the hydroxyl radical. As these substances return to a ground stage, there is a photon release with resulting light emission (chemiluminescence). The in vitro incubation of polymorphonuclear leukocytes with a live bivalent (A + B) influenza has been shown to impair isoproterenol and histamine inhibition of zymosan-stimulated lysosomal enzyme release. The effects of this vaccine on granulocyte oxidative metabolism were assayed with chemiluminescence. Ficoll-hypaque isolated granulocytes were incubated (37 degrees C) with the influenza virus. During this incubation there was stimulation of the granulocyte chemiluminescence, which was proportional to the virus dose, prevented by treatment with cytochalasin B, and reduced by catalase and sodium benzoate but not by superoxide dismutase. Polymorphonuclear leukocytes incubated with the influenza vaccine viruses had a marked reduction in chemiluminescence response to zymosan particles when compared with nonvirus-treated cells. The mechanism of this reduced or refractory response after virus incubation remains to be established.

Catalase↗
PubMed1981

Parainfluenza 3 infection blocks the ability of a beta adrenergic receptor agonist to inhibit antigen-induced contraction of guinea pig isolated airway smooth muscle.

Guinea pigs, actively sensitized to ovalbumin, were inoculated by nasal insufflation with parainfluenza 3 or virus growth medium 4 d before performing in vitro pharmacological studies on tracheal and bronchial smooth muscle. In each airway segment, cumulative dose-response effects of ovalbumin were obtained in the absence and presence of a maximally effective concentration of a beta adrenergic receptor agonist, sulfonterol. Sulfonterol shifted the dose-response curve to the right and reduced the maximum smooth muscle contractile response to ovalbumin. Virus infection did not alter the dose-response effects of ovalbumin. However, the magnitude of the inhibitory effects of sulfonterol was smaller in segments taken from animals inoculated with virus. Blockade by virus infection of the inhibitory effect of sulfonterol was reversed when the concentrations of beta agonist were increased. Sulfonterol did not alter the dose-response effects of histamine at any of the concentrations that markedly antagonized the effects of ovalbumin. Virus infection did not alter the sensitivities to sulfonterol or papaverine in producing relaxation in either airway segment. The magnitude of relaxation produced by papaverine was significantly larger in bronchial rings taken from animals infected with virus for 4 d, but there was no alteration by virus of the dose-response effects of histamine or carbachol. In experiments measuring antigen-induced release of slow reacting substance of anaphylaxis and histamine from minced lung, virus infection did not alter the sensitivity or the maximum effects of ovalbumin. Also, the ability of sulfonterol to inhibit the release of slow reacting substance of anaphylaxis and histamine was not affected by virus infection.These results demonstrate that infection of guinea pigs with respiratory virus results in a selective blockade of the beta adrenergic-mediated inhibition of antigen-induced contraction of airway smooth muscle. The guinea pig may serve as a useful model in physiological studies of virus-induced asthma.

Adrenergic beta-Agonists↗
PubMed1980

Dimaprit inhibition of zymosan-stimulated beta-glucuronidase release from human granulocytes.

Histamine inhibits the in vitro release of granulocytic lysosomal beta-glucuronidase when incubated with complement activated zymosan particles and this is an H2-receptor response. The highly specific histamine H2-receptor agonist, dimaprit, also inhibits this secretory enzyme release but is less potent (-log molar ED50 6.71 with histamine vs. -log ED50 5.97 with dimaprit, p less than 0.05). No change in beta-glucuronidase release was found with the H1-agonst, 2-(2 pyridyl)-ethylamine. The antagonist activity of metiamide was similar with the two agonists (KB = 2.9 x 10(-8) M with histamine and KB = 3.6 x 10(-8) M with dimaprit). Diphenhydramine did not change the granulocyte response to either histamine or dimaprit.

Adult↗
PubMed1980

Characterization of granulocyte beta adrenergic receptors in atopic eczema.

The binding of (-)-3H-dihydroalprenolol (3H-DHA) and 125I-hydroxybenzylpindolol (125I-HYP) to the beta-adrenergic receptors in homogenized granulocyte preparations from control subjects and patients with atopic eczema was characterized. No difference was found for the affinity (KD=2 X 10(-9) M) or the total number of high-affinity binding sites (1,200 to 1,600 per cell) with 3H-DHA or 125I-HYP (KD 1.6 X 10(-10) M) in granulocytes from the two study populations. Scatchard plots of the data obtained from DHA binding isotherms suggested that negative cooperativity may exist as a property of the beta 2-receptor. Granulocyte preparations from control subjects and patients with atopic eczema also showed propranolol protectable 3H-DHA binding with a KD of 10(-7) M. It is not clear whether these 3H-DHA binding sites represent physiologically significant beta-adrenergic receptors at these concentrations of radioligand. It was found that 15,000 to 20,000 binding sites of this lower affinity for DHA exist per cell in granulocytes from the two populations of subjects. These data suggest that the reduced isoproterenol responsiveness of granulocytes from patients with atopic eczema is not the result of abnormal or reduced numbers of beta-adrenergic receptors.

Adult↗
PubMed1980

The effect of exercise on the granulocyte response to isoproterenol in the trained athlete and unconditioned individual.

Many factors will influence the tissue response to catecholamine stimulation. Isolated human granulocytes (PMNs) release the lysosomal enzyme beta-glucuronidase following incubation with complement-activated zymosan particles. Isoproterenol, histamine, and prostaglandin E1 (PGE1) inhibit this PMN release of beta-glucuronidase. The effect of exercise on this in vitro granulocyte response was studied in two groups: highly conditioned marathon runners (n = 6) and unconditioned subjects (n = 7). A 13-km run did not produce leukocytosis in the highly conditioned marathon runners and the granulocyte response to isoproterenol was unchanged in cells obtained immediately following the run. In contrast, the seven unconditioned subjects exercised to a maximal response on the treadmill. Following exercise there was an increase in plasma catecholamines, a significant leukocytosis, and granulocytes from the immediate postexercise period responded less well to isoproterenol.

Adult↗
PubMed1980

Effect of Bordetella pertussis vaccination in mice and the isolated tracheal response to isoprenaline.

The administration of Bordetella pertussis vaccine to mice has been associated with the development of an impaired beta-adrenoceptor responsiveness and in many respects has resembled human asthma. Trachea (n = 12) were isolated from Swiss-Webster mice 5 days following the intraperitoneal administration of 2 x 10(9) B. pertussis organisms. The tracheal smooth muscle response to carbachol was measured and compared with that found in trachea from unvaccinated mice (n = 15). The contractile response was similar in both groups. The tracheal smooth muscle relaxant effects of isoproterenol were measured in these two groups. The EC50 value for isoprenaline (6.5 x 10(-7) M) in trachea from B. pertussis treated mice was significantly (P < 0.05) greater than that noted in the control animals (2.3 x 10(-7) M). These studies demonstrated that in tracheal smooth muscle isolated from B. pertussis vaccinated mice, the relaxant effects of isoprenaline are impaired.

Animals↗
PubMed1980

Impaired in vitro beta-adrenergic granulocyte response in chronic obstructive pulmonary disease.

Isoproterenol (ISO), histamine (HIS), and prostaglandin E1 (PGE1) inhibit the in vitro release of the lysosomal enzyme, beta-glucuronidase, from polymorphonuclear leukocytes (PMN) during incubation with complement-coated zymosan particles. In asthma, this granulocyte response to ISO and HIS is impaired. Using this in vitro cell model to assess granulocyte beta-adrenergic response, we studied 23 patients with chronic obstructive pulmonary disease (COPD). All had long-standing disease and severe obstruction (FEV1 = 37.5% of predicted). The granulocyte response to HIS challenge in patients with COPD was normal when compared to control subjects, in contrast to the response from the asthmatic group. The granulocyte response to ISO challenge in patients with COPD, however, was reduced compared to control subjects, but not to the degree found in the asthmatics. This demonstrated that reduced granulocyte response to ISO is not limited to asthmatics, but can be found as well in other obstructive diseases of the lung.

Adrenergic beta-Agonists↗
PubMed1980

Reduced granulocyte response to isoproterenol, histamine, and prostaglandin E1 after in vitro incubation with Rhinovirus 16.

Rhinovirus respiratory infections have been frequently associated with the precipitation of an asthma attack. As an explanation for virus-provoked asthma, it has been proposed that viruses or their products may alter beta-adrenergic responsiveness. Isolated human granulocytes have provided an in vitro study model for this problem. Granulocyte release of the lysosomal enzyme beta-glucuronidase (BG) occurred after incubation with complement-activated zymosan particles, and this release was inhibited by isoproterenol (ISO), histamine (HIS) acting via its H2 receptor, and prostaglandin E1 (PGE1). In asthma, the granulocyte response to HIS and ISO was impaired, and the ISO impairment was accentuated during virus-provoked asthma. After an in vitro incubation of polymorphonuclear leukocytes (PMN) with rhinovirus 16, the granulocyte response to ISO, HIS, and PGE1 was significantly reduced. This change in agonist response was proportional to the virus dosage, maximal at 37 degrees C and after a 60-min incubation period, and occurred with heat or UV-inactivated virus. It is possible that impaired beta-adrenergic responsiveness may also develop in other tissues, such as the airway smooth muscle, and thus explain, in part, wheezing during viral respiratory infections.

Glucuronidase↗
PubMed1979

Impaired H2 histamine granulocyte response in active atopic eczema.

Many clinical abnormalities in atopic eczema have been attributed to an imbalance in autonomic nervous system control, specifically a partial blockade of beta-adrenergic responsiveness. The lysosomal enzyme beta-glucuronidase is released from granulocytes during in vitro incubation with complement-activated zymosan particles. Isoproterenol will inhibit the release of this lysosomal enzyme from the granulocyte and the isoproterenol effect is associated with increased granulocyte cyclic AMP formation. In atopic eczema and asthma, this granulocyte response to isoproterenol is impaired. Histamine also inhibits in vitro zymosan induced release of beta-glucuronidase and this is an H2 histamine effect. In asthma, this H2 histamine response is diminished. In the following study, we found a similar impairment in histamine inhibition of beta-glucuronidase release and formation of granulocyte cAMP in atopic eczema. This defect was found only in granulocytes from patients with active eczema. Thus in active atopic eczema, defects in the pharmacological response of the granulocyte are not limited to beta-adrenergic agonists but include H2 histamine activity.

Adult↗