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Biomedical subjects

R K Bush

Publications and source records attributed to R K Bush.

At least 19 recordsLinked to original sources
PubMed1992

Protein and allergen content of commercial skin test extracts for soybeans.

The protein and allergen contents of four commercial soybean skin test extracts were tested by SDS-PAGE and immunoblotting using sera from soy-allergic adults. Polyacrylamide gels stained with Coomassie Blue showed an absence of several major soybean proteins, particularly those at higher molecular weights. The acidic subunits of glycinin and beta-conglycinin, major soybean storage proteins, appear to be absent or present in much reduced amounts. Immunoblots with soy-allergic sera indicate alteration, reduction, or loss of IgE-binding in the commercial extracts as compared to extracts of soy flour. In one soy-allergic patient, skin tests revealed a negative response to three of the commercial soybean extracts and a mild response to one extract. Defatted soy flour obtained from two of the four extract manufacturers was extracted in the laboratory using a standard procedure for the isolation of soybean proteins. In one case, the extract still had an abnormal protein profile on gel electrophoresis while in the other case, the new extraction procedure gave significantly improved extraction of soy protein. Preparation methods appear to be partially responsible for the variable allergen content in commercial soybean skin test extracts.

Adult↗
PubMed1992

Bronchodilation with a potent and selective leukotriene D4 (LTD4) receptor antagonist (MK-571) in patients with asthma.

The sulfidopeptide leukotrienes LTC4, LTD4, and LTE4 can cause airway smooth muscle contraction and have been implicated in the pathophysiology of asthma. MK-571 is a selective, potent LTD4 receptor antagonist that could attenuate airway obstruction in asthma by inhibiting the actions of sulfidopeptides at the LTD4 receptor site. The objectives of this study were to investigate the potential for MK-571 to cause bronchodilation in asthma patients with existing airway obstruction and to evaluate its effect on the bronchodilation response to an inhaled beta 2-agonist (albuterol). Twelve male patients (ages 19 to 42 yr) with asthma (baseline FEV1 50 to 80% predicted) participated in this placebo-controlled, randomized, two-period, cross-over study. On separate treatment days, each patient received either MK-571 or placebo intravenously for 6 h; inhaled albuterol was administered at the fifth and sixth hour of MK-571/placebo treatment to achieve maximal bronchodilation on that study day. Spirometry (forced expiratory volume in 1 s, FEV1) was monitored at intervals throughout each study period. MK-571 caused clinically significant bronchodilation; the increase in FEV1 above baseline, 20 min after the start of the MK-571 infusion, was 22 +/- 3.9% compared with 1.3 +/- 2.3% for placebo (mean +/- SE, p < 0.01). This degree of bronchodilation was maintained throughout the MK-571 infusion. In addition, bronchodilation from inhaled albuterol appeared additive with MK-571. Finally, baseline airway obstruction correlated with the degree of bronchodilation achieved with MK-571 (r = -0.73; p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Nocturnal asthma: mechanisms and the role of theophylline in treatment.

Asthma is characterized by airway inflammation and hyper-responsiveness. Clinically, these features are manifested by attacks of cough, wheezing, and dyspnoea. Nocturnal asthma symptoms are frequent; 39% of asthmatics awaken nightly, and 94% have nocturnal awakenings at least once a month. A number of mechanisms have been hypothesized to explain the phenomenon of nocturnal asthma, including exposure to dust mite allergen, late-phase allergic reactions, effects of posture and sleep stage on airway tone, gastro-oesophageal reflex, impaired mucociliary clearance, airway cooling, and changes in circadian rhythms of circulating hormones. While no single mechanism can explain these changes, circadian rhythms may be particularly relevant. Normal airway tone increases during sleep and is magnified in asthmatics. Bronchial responsiveness to histamine and allergen challenge increases during sleep and mast cell mediator release is enhanced. Circulating eosinophils increase, which may allow their ingress into pulmonary tissue. Decreases in plasma catecholamine and cortisol levels have also been observed. All of these may influence airway tone, inflammation, and responsiveness during sleep and produce the observed clinical picture. Inhaled sympathomimetics are frequently ineffective in preventing nocturnal symptoms due to their short duration of action. While corticosteroids, cromoglycate, and anticholinergics are effective, sustained-release theophylline is particularly advantageous for controlling nocturnal symptoms. Once-daily theophylline when dosed in the evening not only controls nocturnal symptoms and improves airflow during the early morning hours, but decreases airway responsiveness to histamine as well. The close association between airway inflammation, airway hyper-responsiveness, and nocturnal asthma symptoms makes further studies of the mechanism of action of theophylline especially interesting.

Asthma↗
PubMed1990

Occupational sensitivity to Tenebrio molitor Linnaeus (yellow mealworm).

Tenebrio molitor is an abundant stored-grain pest in the northern United States. We evaluated an individual with work-related symptoms of rhinoconjunctivitis on exposure to this insect. Prick skin tests with extracts prepared from the larval, pupal, and adult-life stages were positive for the patient and for another individual with allergy to a closely related species of beetle, Alphitobius diaperinus. Specific IgE antibodies to the extracts were demonstrated by RAST. RAST inhibition demonstrated immunologic cross-reactivity between the life stages of T. molitor and also between T. molitor and A. diaperinus, as well as slight cross-reactivity with blowfly. The proteins in the extracts of each life stage were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. More than 15 protein bands were detected in each of the extracts, although the patterns of separation were different for each life stage. After immunoblotting and autoradiography, six different IgE-binding proteins were identified in the larval extract, five in the pupal extract, and seven in the adult extract, with similar IgE-binding patterns noted for the larval and adult extracts. We conclude that this patient developed IgE-mediated sensitivity to T. molitor antigens as the result of occupational exposure. This study confirms the fact that beetles of the Tenebrionid family are potentially significant allergens for workers exposed to grains or grain products.

Adult↗
PubMed1990

Allergens involved in occupational asthma caused by baby's breath (Gypsophila paniculata).

Although the floral industry deals with many potential allergens, few examples of occupational asthma exist in this industry. A 22-year-old florist experienced symptoms of rhinitis, conjunctivitis, and asthma on exposure to baby's breath. To determine the contribution of baby's breath to the patient's symptoms, an extract of baby's breath was prepared. Prick skin tests with a 1:10(-5) wt/vol concentration of the extract produced an immediate response, whereas nonexposed atopic and normal control subjects did not react. The patient's asthmatic response to baby's breath was confirmed by bronchial challenge that caused an immediate fall in FEV1 of 26.2% from baseline after inhalation of 88 breath units of the extract. With a direct RAST, the patient's serum bound 38 times the amount of IgE bound by the negative control. IgE binding in the RAST was inhibited by the baby's breath extract but not by unrelated inhibitors (ragweed and tree pollens). Immunoblotting demonstrated IgE binding to 13 protein bands in the extract with molecular weights ranging from 11.5 to 68 kd. Serum from a patient previously reported to have sensitivity to baby's breath recognized five protein bands. Three proteins with molecular weights of 27, 31, and 37 kd were recognized by both patients' sera. We conclude that this patient developed IgE-mediated sensitivity to multiple allergens in baby's breath. This study confirms the importance of this plant as a potential cause of occupational asthma in the floral industry.

Adult↗
PubMed1990

Enhanced reactive oxygen species metabolism of airspace cells and airway inflammation follow antigen challenge in human asthma.

Airflow limitation and airway inflammation follow antigen bronchoprovocation in sensitized individuals. Inflammation likely results from the interplay of several previously demonstrated factors, but the participation and persistence of enhanced reactive oxygen species (ROS) metabolism of airspace cells after antigen challenge have received more limited attention. We studied nine subjects with mild asthma by bronchoalveolar lavage before and 48 (one subject) to 72 (eight subjects) hours after antigen bronchoprovocation and compared airspace cell numbers and types, cell function, and bronchoalveolar lavage fluid protein, albumin, and immunoglobulins. Mild, but significant, airflow limitation persisted at the time of the second lavage. Eosinophil influx was a notable component of the increased airspace cells in postchallenge lavages. Airspace cells demonstrated significantly enhanced ROS metabolism, and total protein, albumin, and IgM levels were higher in postchallenge lavage specimens. Antigen bronchial challenge produces airspace inflammation, which may develop, in part, as a consequence of enhanced ROS metabolism of airspace cells.

Adult↗
PubMed1990

Identification of soybean allergens by immunoblotting with sera from soy-allergic adults.

Immunoblots were used to compare the IgE-binding proteins of various soybean products using sera from 7 soybean-allergic patients. Blotting results indicate at least two distinct individualistic patterns of IgE binding to soy proteins. Serum IgE from individuals allergic to both peanuts and soybeans binds to several proteins with molecular weights ranging from 50,000 to 60,000 daltons, while IgE from individuals allergic to soybeans, but not peanuts, binds strongly to a protein(s) with a molecular weight of 20,000 daltons. The soy products tested displayed varying amounts of IgE binding with sera from sensitive patients.

Adult↗
PubMed1990

Evaluation of symptom relief, nasal airflow, nasal cytology, and acceptability of two formulations of flunisolide nasal spray in patients with perennial allergic rhinitis.

A new formulation of intranasal flunisolide containing less propylene glycol was compared with the original formulation for efficacy and acceptability in more than 200 patients with symptoms of perennial allergic rhinitis. In this multicenter, randomized, double-blind, parallel group study, symptomatic patients were treated with either the new or the original formulation of 0.025% solution of intranasal flunisolide for 4 weeks to provide 200 micrograms flunisolide daily. Both formulations were highly effective in decreasing symptom scores as evident from patient diary reports before and after treatment (P less than .001). Similarly, nasal airflow was improved with each treatment as measured by anterior rhinomanometry (P less than .0002) and the number of patients with nasal eosinophilia decreased (P less than .01). Finally, fewer patients using the new formulation reported nasal burning or stinging and the acceptability rating of the new formulation was higher.

Administration, Topical↗
PubMed1988

Twelve-hour bronchodilation in asthma with a single aerosol dose of the anticholinergic compound glycopyrrolate.

Anticholinergic aerosols provide effective bronchodilation in some patients with obstructive lung disease. Glycopyrrolate is a quaternary ammonium anticholinergic compound that is poorly absorbed from mucus membranes, thus reducing anticholinergic side effects. In 20 adult patients with asthma, we evaluated bronchodilation to a single administration of metered-dose glycopyrrolate aerosol (GA) to ascertain its onset and duration of action along with evaluation of safety. In this randomized, double-blind, placebo-controlled, single-dose, crossover trial, bronchodilation was evaluated on five separate occasions to either placebo or a GA dose of 80, 240, 480, or 960 micrograms. Baseline spirometry for each patient on each visit was similar (mean FEV1 +/- SD of 62.2 +/- 13.6% predicted). After aerosol dosing, spirometry was measured at 30 minutes and then at hourly intervals up to 12 hours. Compared to placebo, metered-dose aerosols of 240, 480 and 960 micrograms elicited significantly greater bronchodilation at each test time. Furthermore, significant bronchodilation was noted within 30 minutes of dosing and was sustained for at least 12 hours. Bronchodilation with the 480 and 960 micrograms dose was equal, and both were greater than 240 micrograms. A subset of four asthma patients with baseline FEV1 values less than 50% predicted did not have a bronchodilating response with GA. No notable side effects occurred. Thus, a single aerosol dose of GA provides clinically significant, safe 12-hour bronchodilation in patients with asthma without severe airway obstruction (i.e., FEV1 greater than 50% predicted).

Adult↗
PubMed1988

Double-blind, placebo-controlled food challenge (DBPCFC) as an office procedure: a manual.

There is now enough experience with the use of double-blind, placebo-controlled, food challenge (DBPCFC) to recommend its use as an office procedure for most patients complaining of adverse reactions to foods. This manual discusses the practical methods required for the allergist to undertake DBPCFC in the office. Thorough histories supplemented by food allergen skin testing are used to design a DBPCFC that carefully attempts to reproduce the history of food-induced symptoms described by the patient. Precautions that must be taken are delineated before challenge, as is treatment that may be required if a reaction occurs. For those foods to which challenges are positive, longitudinal evaluation with repeated challenge at appropriate intervals help to determine whether or not the problem will resolve over a period of time.

Allergens↗
PubMed1988

Occupational sensitivity to Alphitobius diaperinus (Panzer) (lesser mealworm).

Alphitobius diaperinus is an important beetle in the grain and poultry industries. We evaluated three individuals with work-related symptoms of asthma, rhinitis, conjunctivitis, urticaria, and angioedema on exposure to the insect. Prick skin tests with extracts prepared from the larval, pupal, and adult life stages were positive in all three patients. Specific IgE antibodies to these extracts were demonstrated by RAST or radioimmunoassay. RAST and radioimmunoassay inhibition confirmed the specificity of IgE binding and further demonstrated immunologic cross-reactivity between the three life stages. Peripheral blood leukocytes from two of the individuals demonstrated significant histamine release when they were compared with cells from nonexposed atopic and normal control subjects. The proteins in the extracts of each life stage were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. More than 30 protein bands were detected in each of the extracts; however, the patterns of separation were different for each life stage. After immunoblotting and autoradiography, IgE-binding proteins were recognized by sera from all three individuals in the larval extract at 90 kilodaltons (kd), in the pupal extract at 90, 64, and 38 kd, and in the adult extract at 84 kd. Additionally, several other proteins were identified as being allergenic in some of the patients. We conclude that these three patients developed IgE-mediated sensitivity to A. diaperinus antigens as the result of occupational exposure. To our knowledge, this is the first description of sensitivity to this grain beetle.

Adult↗
PubMed1988

Sensitivity to sulfited foods among sulfite-sensitive subjects with asthma.

Eight individuals with asthma who had been diagnosed as sulfite sensitive on the basis of double-blind capsule-beverage challenges were subjected to challenges with various sulfited foods, including lettuce, shrimp, dried apricots, white grape juice, dehydrated potatoes (as mashed potatoes), and mushrooms. Four of these patients failed to respond to challenges with any of the sulfited foods. The other four patients experienced a decrease in pulmonary function on double-blind challenges with sulfited lettuce. Two of three of these patients reacted to challenges with dried apricots and white grape juice; the fourth patient has not yet been challenged with these products. Only one of these four patients reacted to challenges with dehydrated potatoes and mushrooms, and, in this case, the response to double-blind challenges with dehydrated potatoes was not consistent. None of the sulfite-sensitive subjects with asthma responded to challenges with sulfited shrimp. It is concluded that sulfite-sensitive subjects with asthma will not necessarily react after ingestion of sulfited foods. The likelihood of a reaction is dependent on the nature of the food, the level of residual sulfite, the sensitivity of the patient, and perhaps on the form of residual sulfite and the mechanism of the sulfite-induced reaction.

Adult↗
PubMed1988

The laboratory evaluation of IgE antibody to metabisulfites in patients skin test positive to metabisulfites.

An immediate-type hypersensitivity reaction has been proposed as one possible mechanism in which metabisulfites (MBSs) cause reactions. As demonstrated with certain occupational chemicals, we proposed that MBS might conjugate with human proteins, such as human serum albumin, and then cause an immunologic response. Because we had identified no reactions to MBS at the Northwestern Allergy Service, we used sera from four patients reported elsewhere as having positive skin tests and positive oral challenges to sulfites. We attempted to demonstrate, both in vitro by ELISA and in vivo by passive cutaneous transfer to monkey, evidence for IgE-mediated hypersensitivity to MBSs. Our results demonstrated that there is evidence of IgE antibody by passive transfer for one patient studied, but no evidence of IgE antibody by ELISA to an MBS-albumin conjugate in any of the four patients. This study illustrates the complexities involved in the evaluation and mechanism of MBS-induced disease and the caution with which results must be interpreted.

Animals↗