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Biomedical subjects

R F Lemanske

Publications and source records attributed to R F Lemanske.

At least 73 records · Page 4Linked to original sources
PubMed1990

Late pulmonary allergic responses in actively but not passively IgE-sensitized rats.

Previous studies suggested that although rats that were passively sensitized [monoclonal murine immunoglobulin E (IgE)] would respond to pulmonary antigen challenge with an immediate increase in resistance, they exhibited no late increases in resistance, unlike late changes in rats actively sensitized to preferentially produce IgE antibody. We hypothesized that passively sensitized rats also would not develop antigen-induced pulmonary inflammation. In a blinded protocol we compared immediate responses and pulmonary resistance and inflammation at 8, 19 and 24 h after challenge with placebo antigen, with dinitrophenol-bovine serum albumin (DNP-BSA) to elicit a passively sensitized response, or with ovalbumin (OA) to elicit an actively sensitized response. Despite similar immediate responses to OA and DNP-BSA, only the rats challenged with OA had marked inflammatory changes and a significant incidence of late elevations in resistance. Inflammation scores and lung resistance were significantly correlated only in the OA group. We also observed that anesthesia with fentanyl/droperidol significantly attenuated the immediate but not the late responses to antigen challenge, compared with rats anesthetized with ketamine. We conclude that IgE-mediated immediate responses to pulmonary antigen challenge are insufficient, and may be unnecessary, to initiate antigen-induced late inflammatory changes.

Airway Resistance↗
PubMed1990

Autonomic nervous system abnormalities and asthma.

Autonomic nervous system function has been studied both in vitro and in vivo using a variety of methodologies. In asthmatic patients, beta-adrenergic hyporesponsiveness and alpha-adrenergic and cholinergic hyperresponsiveness can be frequently demonstrated. These observations have provided support for the beta blockade theory of asthma, advanced in the late 1960s by Andor Szentivanyi's experiments involving sensitized rodents. However, in addition to asthma, aberrations in autonomic nervous system function have been noted in other individuals including cystic fibrosis patients and their parents, patients with emphysema and bronchitis, and in patients (allergic rhinitis and atopic dermatitis) who have demonstrable IgE antibody responses to a variety of antigens. Thus, although these defects are not specific for asthma, it is noteworthy that these conditions share many clinical features; the ultimate phenotypic expression of these abnormalities may depend on both genetic and environmental factors that have yet to be defined.

Asthma↗
PubMed1990

Contribution of upper airways to antigen-induced late airway obstructive responses in guinea pigs.

The pathogenesis of the late asthmatic response has been of interest due to the fact that its development has been associated with airway obstruction, airway inflammation, and airway hyperresponsiveness: all features of chronic asthma. In order to study more precisely late responses, a number of animal models have been developed. Previous reports have described alterations in airway mechanics at both 3 to 6 and 17 h after antigen challenge in sensitized guinea pigs. In these experiments, however, animals were challenged through the nose with aerosolized antigen, and airway conductance was measured using whole body plethysmography while the animals breathed through the upper airways. In rats similarly challenged, the predominant immediate change in resistance occurs in the upper airways. The purpose of this study, therefore, was to evaluate the contribution made by both the upper and lower airways to late changes after allergen challenge in guinea pigs. Outbred female Hartley guinea pigs were actively or passively sensitized (IgG1 antibody response) to three different antigens and challenged either by direct tracheal insufflation (sheep gamma globulin [SGG] or oxazolone-human serum albumin [OX-HSA]) or by aerosolization (ovalbumin [OA]). Lung resistance (RL) and dynamic compliance (Cdyn) were measured in anesthetized guinea pigs through a tracheostomy tube, and specific airway conductance (SGaw) was measured in unanesthetized, nose-breathing guinea pigs using a whole body plethysmograph. Late responses were defined as a RL greater than the mean + 2 SD RL or as a decrease in SGaw from baseline greater than 2 SD from the placebo-challenged (bovine serum albumin) group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Pulmonary eosinophilia and granulomatous pulmonary arteritis induced in rats by intravenous Sephadex.

Airway eosinophilia has been proposed as a major pathogenetic event in bronchial asthma and airway hyperresponsiveness. Intravenous injection of Sephadex G200 in rats induces pulmonary and blood eosinophilia and alters pulmonary responsiveness to 5-hydroxytryptamine. To characterize the early pulmonary inflammatory responses following Sephadex administration, and to determine the timing of the onset of pulmonary eosinophilia relative to blood eosinophilia, Sprague-Dawley rats were injected intravenously with Sephadex G200 beads. Lungs and other tissues were examined by light and transmission electron microscopy at 4, 12, 24, 48, 72, and 96 hours after injection. Blood eosinophil counts were determined at 0, 24, and 96 hours after injection. Sephadex beads were trapped initially in small caliber muscular pulmonary arteries associated with terminal bronchioles and in intra-acinar locations. There was marked infiltration of eosinophils and macrophages around the beads and into arterial walls and edematous periarterial and peribronchiolar connective tissue as early as 4 hours after injection. Periarterial-peribronchiolar eosinophil aggregates peaked in density at 24 and 48 hours. Macrophages and multinucleated cells dominated the inflammatory cell responses in arteries immediately surrounding partially degraded Sephadex beads from 24 to 96 hours. Bone marrow eosinophilopoiesis and blood eosinophilia were not detected until 96 hours. We conclude that Sephadex induces pulmonary eosinophilia prior to blood eosinophilia and suggest that Sephadex may induce pulmonary release of one or more eosinophil chemotactic substance(s). This model may prove useful in the study of factors that influence eosinophil migration into the lung in various disease states.

Animals↗
PubMed1990

Beta-2 receptor agonists in asthma: a comparison.

Sympathomimetic bronchodilators with preferential specificity for the beta-2 receptor subtype are routinely used in asthma therapy. In addition to their ability to dilate bronchial smooth muscle following beta-2 receptor stimulation, these agents also inhibit mast cell mediator release and alter airway responsiveness. The importance of this class of drugs in asthma therapy has prompted the development of multiple asthma agents with the hope of achieving greater beta-2 receptor specificity, a quicker onset or more prolonged duration of action, a greater peak effect, or fewer side effects. This review compares the beta-2 agonists, as a group, with other asthma medications and, when data are available, makes comparison among various drugs within the group.

Adrenergic beta-Agonists↗
PubMed1990

Viral bronchiolitis during early life induces increased numbers of bronchiolar mast cells and airway hyperresponsiveness.

The objectives of this study were to determine the kinetics of Sendai virus-induced increases in bronchiolar mast cells and to determine whether virus-induced increases in bronchiolar mast cells were associated with increased airway responsiveness to methacholine and with altered allergic inflammatory responses to antigen stimulation. Mast cell density in intrapulmonary airways was measured in outbred CD (Crl:CDBR) rats by use of morphometric techniques at 7, 15, 30, 60, and 90 days after viral or sham inoculation. Density of bronchiolar mast cells was higher in virus-inoculated rats than in control rats at 30, 60, and 90 days after inoculation (P less than 0.01), but not at 7 or 15 days after inoculation. Total pulmonary mast cell numbers were increased in virus-inoculated rats at 30 days after inoculation. Rats at 42 days after viral inoculation had over a threefold increase in sensitivity to the concentration of nebulized metbacholine that would stimulate a 50% increase in respiratory resistance. Virus-inoculated rats sensitized to ovalbumin had over a 10-fold increase (P less than 0.02) in pulmonary neutrophils that were recovered by bronchoalveolar lavage at 4 hours after ovalbumin aerosol challenge. Virus-inoculated rats at this time also had higher densities of neutrophils in bronchiolar walls than allergen-exposed control rats. The results indicate that Sendai virus induces increases in numbers of bronchiolar mast cells at times from 30 to 90 days after inoculation, and that mast cell increases are associated with airway hyperresponsiveness to methacholine and heightened allergic airway inflammatory reactions.

Animals↗
PubMed1989

Albuterol treatment for children with asthma: a comparison of inhaled powder and aerosol.

A dose-ranging study and a 12-week treatment study were conducted in children with asthma, aged 4 to 12 years, to assess the efficacy and safety of albuterol inhaled as either an aerosol or as dry powder. Both studies were double-blind and placebo-controlled with randomized assignment to treatment. The dose-ranging study in 30 patients indicated that similar single doses of albuterol aerosol and powder had comparable effects with the intermediate doses (i.e., 180 micrograms of aerosol and 200 micrograms of powder) providing effective bronchodilation with minimal adverse effects. In the subsequent 12-week, parallel-group study, 204 children received albuterol as either aerosol, 180 micrograms, or powder, 200 micrograms four times a day. Both formulations were equally effective with no untoward cardiovascular effects and only one incident of mild tremor. Among those children who expressed a preference for one of the delivery systems, significantly more children preferred the powder (44% versus 26%, p less than 0.01). Albuterol taken four times a day as either aerosol or dry powder is both effective and well tolerated in children with asthma.

Administration, Inhalation↗
PubMed1989

Rhinovirus upper respiratory infection increases airway hyperreactivity and late asthmatic reactions.

Although viral upper respiratory infections (URIs) provoke wheezing in many asthma patients, the effect of these illnesses on the airway response to inhaled antigen is not established. The following study evaluated the effect of an experimental rhinovirus (RV) illness on airway reactivity and response to antigen in 10 adult ragweed allergic rhinitis patients. Preinfection studies included measurements of airway reactivity to histamine and ragweed antigen. Furthermore, the patients were also evaluated for late asthmatic reactions (LARs) to antigen (a 15% decrease in forced expiratory volume of the first second approximately 6 h after antigen challenge). 1 mo after baseline studies, the patients were intranasally inoculated with live RV16. All 10 patients were infected as evidenced by rhinovirus recovery in nasal washings and respiratory symptoms. Baseline FEV1 values were stable throughout the study. During the acute RV illness, there was a significant increase in airway reactivity to both histamine and ragweed antigen (P = 0.019 and 0.014, respectively). Before RV inoculation, only 1 of the 10 subjects had an LAR after antigen challenge. However, during the acute RV illness, 8 of 10 patients had an LAR (P less than 0.0085 compared with baseline); the development of LARs was independent of changes in airway reactivity and the intensity of the immediate response to antigen. Therefore, we found that not only does a RV respiratory tract illness enhance airway reactivity, but it also predisposes the allergic patient to develop LARs, which may be an important factor in virus-induced bronchial hyperresponsiveness.

Adult↗
PubMed1988

Pulmonary antigen challenge in rats passively sensitized with a monoclonal IgE antibody induces immediate but not late changes in airway mechanics.

Pulmonary antigen challenge in sensitized individuals results in isolated immediate, isolated late, or dual reactions consisting of both an immediate and late change in airway function. The immediate response appears to be dependent on the presence of IgE antibody and mast cell mediator release. Although the late phase of dual responses is considered to be related to or a continuum of the immediate hypersensitivity response, its precise pathogenesis remains to be determined. To increase both the sensitivity and specificity of analyzing the pathogenesis of IgE-dependent pulmonary responses, we have used a Sprague-Dawley rat model system in which rats are passively sensitized with a murine monoclonal IgE anti-dinitrophenol (DNP) antibody prior to challenge with DNP-bovine serum albumin (DNP-BSA). Pathogen-free rats were injected with IgE or saline in a randomized blinded protocol, and in 24 to 48 h were anesthetized with urethane (1.2 g/kg intraperitoneally) and instrumented to measure lung resistance (RL) and dynamic compliance (Cdyn). Rats were then challenged with aerosolized DNP-BSA (10 mg/ml), and RL and Cdyn monitored through 7 h after challenge. Both RL (0.30 +/- 0.10 versus 0.13 +/- 0.02 cm H2O/ml.sec-1) and Cdyn (0.41 +/- 0.10 versus 0.25 +/- 0.08 ml/cm H2O) were significantly different (p less than 0.05) in sensitized rats compared to control rats immediately after challenge. No late changes were observed in either the treated or control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1988

Rapid methylprednisolone clearance in a patient with cystic fibrosis.

A pharmacokinetic investigation of administered corticosteroids was conducted in a 16-year-old girl with cystic fibrosis (CF). Equivalent doses of methylprednisolone were given orally and intravenously on consecutive days. Oral bioavailability was essentially 100 percent, ruling out impaired absorption. Drug half-life was shorter and both clearance and volume of distribution were greater in this patient than in normal young adults. From one patient it is impossible to conclude that this unusual disposition of corticosteroids is characteristic of CF. Given the interest in use of corticosteroids in this population, and the examples of other drugs with altered pharmacokinetics in patients with CF, further investigation is warranted.

Adolescent↗
PubMed1988

Mast cell granule enhancement of neutrophil chemiluminescence responses.

Cutaneous mast cell degranulation in rats results in tissue inflammation, and this species has therefore provided a useful model to study the pathogenesis of late phase reactions (LPRs). The mast cell dependency of LPRs has been confirmed by the demonstration that isolated rat mast cell granules (MCGs), when injected intradermally into rat skin, induce patterns of tissue inflammation similar to those seen after skin testing with anti-IgE antibody. Rat LPRs are neutrophil dependent, and, further, MCG-derived inflammatory factors can chemically attract rat neutrophils in vitro. To further study the relationships among MCGs, tissue inflammation, and neutrophil function, luminol-dependent chemiluminescence (CL) responses of rat peritoneal-elicited neutrophils in response to opsonized zymosan and phorbol myristate acetate (PMA) in the presence and absence of MCGs were analyzed. When MCGs (1.0, 10, and 100 micrograms/ml) alone were added to neutrophil suspensions, a rapid concentration-dependent increase in baseline CL responses was observed; these increases (maximum of sixfold) were modest, varied with cell concentrations, and followed different time courses compared with those seen after addition of preopsonized zymosan (0.5 mg/ml) (50-fold increases that peaked in 4 to 8 minutes). However, if neutrophils were preincubated (15 minutes) in the presence of MCGs, the CL response to opsonized zymosan (1.25 mg/ml) was significantly and synergistically enhanced compared with the response seen with MCGs alone. Similar but less pronounced effects were also noted after cell activation with PMA (2.5 and 25 ng/ml). To determine which component of the MCG was responsible for this enhancing activity, additional experiments were performed. Enhancement was still observed, albeit less intense, if MCGs were prepared membrane free and washed free of readily dissociable mediators such as histamine. Histamine (10(-6) and 10(-5) mol/L) had no enhancing effect nor did preparations of MCG membranes. MCG solubilization (3 mol/L NH4HCO3) revealed that the enhancing activity resided completely in the high molecular weight (greater than 10,000 daltons) fraction. Heat treatment of the granules and sodium azide preincubation completely abolished the enhancing effect. Exogenous horseradish peroxidase, at peroxidase activity levels contained within the MCGs (1 x 10(-4) to 10(-2) U/ml), reproduced the enhancing effect. After opsonized zymosan activation, neutrophils generated less H2O2 and superoxide anion in the presence of MCGs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Neonatal viral bronchiolitis and pneumonia induces bronchiolar hypoplasia and alveolar dysplasia in rats.

The objective of this research was to determine the effects of viral bronchiolitis and pneumonia on postnatal bronchiolar and alveolar growth. Neonatal (5-day-old) and weanling (25-day-old) outbred rats were infected with parainfluenza type 1 (Sendai) virus and were studied from 0 to 110 days after inoculation by scanning and transmission electron microscopy, by light microscopic morphometry, and by analysis of airway corrosion casts. Viral infection induced necrotizing bronchiolitis and interstitial pneumonia in both age groups of rats. Viral infection had a much more marked effect on neonatal rats in the proliferative stage of lung growth than on weanlings in the equilibrated stage of lung growth. Viral infection in neonatal rats resulted in delayed or impaired growth of secondary septa into alveolar saccules. The impaired septal ingrowth was multifocal and predominantly centriacinar in distribution and was associated with alveolar enlargement and significant decreases (14 to 26%, p less than 0.01) in alveolar surface density. Total alveolar surface area in rats inoculated with virus as neonates was 22% lower (p less than 0.05) that that in control animals by 110 days after inoculation. Alveolar septa in these rats inoculated as neonates had enlarged interalveolar pores and defects compatible with mild alveolar emphysema. Airway corrosion casts prepared at 30 and 90 days after neonatal viral inoculation had terminal bronchioles that were 11 and 20% smaller in diameter (p less than 0.02), respectively, than those from age-matched control rats. The density of attachments of alveolar septa to bronchiolar walls in viral-inoculated rats at these times was significantly decreased (p less than 0.001). Viral-infected rats had elevated respiratory resistance (p less than 0.005) and decreased dynamic compliance (p less than 0.02) at 39 days after inoculation. The results indicate that viral bronchiolitis and pneumonia during early life in rats induces abnormal alveolar development and bronchiolar hypoplasia that are associated with abnormalities in pulmonary function. Continued postnatal lung growth does not compensate for early virus-induced abnormalities in alveolar and bronchiolar growth.

Animals↗
PubMed1987

Standardized extracts, foods.

While progress has been made in the areas of food allergen characterization, both the complexity of the biochemical constituents of food and the body's normal physiologic (digestion) and immunologic responses to food ingestion provide challenging obstacles to efforts aimed at developing standardized food extracts. As indicated above, while currently available food extracts can be useful in the evaluation of food hypersensitivity, the results obtained using these reagents are far from optimal. Indeed, in some cases, skin testing after rubbing a small amount of the food on the skin may be more inciteful than using commercially prepared extracts. While this approach may provide physicians with help in terms of diagnosis, purified food components will be necessary to comprehensively study the complex issues of food allergen digestion and absorption; immune response and tolerance to food allergens; and hopefully, treatment and prevention of food hypersensitivity.

Allergens↗