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Biomedical subjects

A B Becker

Publications and source records attributed to A B Becker.

At least 19 recordsLinked to original sources
PubMed1996

Increased response to antigen and histamine release in smaller sensitized canine bronchi.

We studied the Schultz-Dale response in vitro in large and small size branches from 3rd to 6th generation bronchi from ragweed-sensitized dogs. The response to electric field stimulation (EFS) increased after antigen from 65.56 +/- 8.11 to 78.6 +/- 9.0 mN/mm2 of smooth muscle (P < 0.01), but no topographical difference was observed. The response to ragweed (% of the response to EFS) was 158.3 +/- 12 and 67.1 +/- 11.7 in strips from small and large branches respectively (P < 0.01), while no difference was observed between generations; when clustering bronchi according to dimension, it was 129.9 +/- 13.4 in small and 71.9 +/- 19.8 in large bronchi (P < 0.01). Histamine released from small and large branches was 2.90 +/- 1.01 and 0.76 +/- 0.20 (ng/mg of tissue) respectively (P < 0.05); no difference was found between generations. In conclusion, in sensitized dogs a greater response to antigen, which involves a higher histamine release, occurs in small compared to large bronchi. We suggest that control of distribution of ventilation occurs mainly at small bronchi level, which becomes the elective tissue to study the Schultz-Dale response. Finally, the classification of bronchi into generations is inadequate to study allergic bronchospasm.

Allergens↗
PubMed1996

Cross-reactivity and molecular mass of the epsilon chains of the IgE antibodies in dogs, humans, rats, and mice.

We report the cross-reactivities and comparative molecular masses of the IgE epsilon chains in humans, rats, mice, and dogs. Monoclonal human, rat, and mouse IgE, and our purified polyclonal dog IgE were used in the study. IgE of the 4 species, separated by SDS-PAGE, were analyzed by immunoblotting with polyclonal and monoclonal antihuman IgE, polyclonal and monoclonal antimouse IgE, monoclonal antirat IgE, and polyclonal antidog IgE antibodies. The polyclonal antihuman and polyclonal antimouse IgE cross-reacted with the IgE of the other 3 species, while their monoclonal forms cross-reacted with dog IgE only. Polyclonal antidog IgE cross-reacted with human and mouse IgE, while the monoclonal antirat IgE did not cross-react with any other species. "Reverse' passive cutaneous anaphylaxis in ragweed-sensitized dogs revealed that polyclonal antihuman and polyclonal antimouse IgE were able to elicit positive skin responses, and monoclonal antihuman, antirat, and antimouse IgE antibodies were not. The molecular masses of the epsilon chains were 77 kDa for mice, 75 kDa for rats and dogs, and 70 kDa for humans.

Animals↗
PubMed1995

Identification of a dog IgD-like molecule by a monoclonal antibody.

IgD has not been identified in dogs. We produced a monoclonal antibody (mAb) designated 9B during the production of hybridomas to dog IgE. Using Western blot analysis under non-reducing conditions, the mAb (9B) recognized a predominant protein band of 185 kDa which was also recognized by anti-dog IgG F(ab')2, suggesting that this 185 kDa protein is an immunoglobulin (Ig) containing light chains. Under reducing conditions, the mAb (9B) recognized only one protein band of 55 kDa which presented a distinct molecular weight (MW) and immunoreactivity from the dog tau, mu, alpha, and epsilon chains. The 55 kDa band did not react with anti-dog IgE, IgM, IgA, and IgG, but did react with the mAb (9B). The MW was 75 kDa for the epsilon chain, 77.5 kDa for the mu chain, 58 kDa for the alpha chain, and 52 kDa for the tau chain. Further, by immunofluorescent staining, this Ig recognized by the mAb (9B) was found on the surface of dog lymphocytes. Studies of this dog Ig with the mAb revealed that this Ig bound to protein A and protein G-Sepharose, and that its enzyme-linked immunosorbent assay (ELISA) activity as measured by the mAb (9B) did not change after heating at 56 degrees C for 2 h. Ragweed-specific IgG, IgE, and this newly defined Ig significantly increased when dogs were immunized with ragweed extract. These data suggest that this Ig is a previously unrecognized IgD-like molecule in dogs.

Allergens↗
PubMed1995

Antiasthmatic effects of a leukotriene biosynthesis inhibitor (MK-0591) in allergic dogs.

Peptidoleukotrienes may be important mediators of human bronchial asthma. Accordingly, the effects of a selective leukotriene (LT) biosynthesis inhibitor (MK-0591) were assessed in allergic dogs characterized by acute bronchoconstriction and subsequent airway hyperresponsiveness induced by inhaled ragweed allergen. Peak acute increases in airway resistance (Rrs) induced by ragweed were associated with increased bronchoalveolar lavage histamine concentration, and neither parameter was inhibited by MK-0591 (8 micrograms.kg-1.min-1 i.v.). However, the duration of the bronchoconstriction was significantly decreased by MK-0591, with a reduction in the area under the curve of 40% (P < 0.05). Associated with the acute bronchoconstriction in placebo-treated animals was a fivefold increase in urinary LTE4 excretion (as seen with allergic asthmatic patients), which was reduced to < 10% of basal values by MK-0591. Similarly, whole blood LTB4 biosynthesis was abolished in the MK-0591-treated animals. Bronchial hyperresponsiveness preallergen (measured as the percent concentration of acetylecholine required to increase Rrs by 5 cmH2O.l-1.s) tended to improve with MK-0591 (0.41 +/- 0.15 vs. 0.23 +/- 0.05%). Five hours after allergen inhalation, the percent concentration declined substantially in the placebo group (0.07 +/- 0.02%; P < 0.01), revealing an increased airway responsiveness that was significantly blunted by MK-0591 (0.26 +/- 0.07%; P < 0.001). These data suggest that selective inhibition of LT biosynthesis by novel compounds such as MK-0591 may modify the airway changes associated with bronchial hyperresponsiveness, as well as offer symptomatic relief in asthma.

5-Lipoxygenase-Activating Proteins↗
PubMed1995

Effects of rhIL-11 on normal dogs and after sublethal radiation.

The effects of recombinant human interleukin-11 (rhIL-11) were studied in normal dogs and dogs given otherwise sublethal total-body irradiation (TBI) without marrow transplantation. Ten normal dogs were given rhIL-11 subcutaneously, twice daily for 14 days at varying doses, two dogs at 30 micrograms/kg/day, four dogs at 60 micrograms/kg/day, two dogs at 120 micrograms/kg/day, and two dogs at 240 micrograms/kg/day. Peripheral blood platelet counts increased in all dogs. The increase in platelet counts ranged from 1.4 to 3.1 times the pre-treatment level. The greater increases of platelets were associated with higher doses (p = 0.01). No change in platelet size was evident except at the dose of 240 micrograms/kg/day. There were no changes in the total white blood cell (WBC) count or differential. A higher proportion of megakaryocytes with a DNA content of 32N/64N was observed in dogs treated with rhIL-11 at day 7 (n = 6) than for control dogs that did not receive rhIL-11 (n = 7; p = 0.01). In both peripheral blood and marrow, significantly increased hematopoietic progenitors (i.e, colony-forming unit granulocyte/macrophage [CFU-GM]) were present 7 and 14 days after the start of treatment. Concentrations of serum fibrinogen increased by a median of 155 mg/dL at day 7 of rhIL-11 (p < 0.01). Cholesterol also increased by a median of 52 mg/dL at day 14 (p < 0.01). There was a single death of a non-irradiated dog from pneumonitis on day 15 after the start of rhIL-11 administration at a dose of 120 micrograms/kg/day. All other non-irradiated dogs tolerated rhIL-11 without any significant adverse effects. Five dogs were given 200 cGy TBI without marrow grafting, followed by 240 micrograms/kg/day rhIL-11 subcutaneously in two divided doses for 28 days starting within 2 hours of TBI. The results in this group were compared with 10 dogs that had previously or concurrently been given 200 cGy without marrow grafting or hematopoietic growth factors. Two of the five treatment dogs died of pneumonitis on day 13 compared to one death among 10 control dogs on day 24. Among dogs that survived to hematologic recovery, the rhIL-11 dogs had decreased platelet counts (< 150,000) for a median of 24 days (range = 24 to 41) compared to a median of 28 days (range = 21-40) for the control group. Treatment with rhIL-11 increased platelet counts, platelet size, ploidy number of megakaryocytes, and marrow and peripheral blood CFU-GM in normal dogs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Nasal patency in children with allergic rhinitis: correlation of objective and subjective assessments.

BACKGROUND: Children with allergic rhinitis may have difficulty with self-assessment of nasal symptoms. OBJECTIVE: To correlate objective and subjective assessments of nasal stuffiness in children with seasonal allergic rhinitis. METHODS: Children, aged 6 to 12 years, with seasonal allergic rhinitis recorded their degree of nasal obstruction on two separate occasions using a nasal stuffiness score and a visual analogue scale. Physicians also assessed the degree of nasal obstruction using a visual analogue scale. Anterior rhinometry was performed and saccharin transient time was also measured. Correlations between subjective scores and objective measurements were calculated using Spearman correlation coefficients. RESULTS: Patient's nasal stuffiness scores correlated with their visual analogue assessment (r = .45, P = .0001). Patients visual analogue assessments did not correlate with anterior nasal airflow (r = -.12, P > .05). Physicians' visual analogue assessment correlated better with nasal airflow than childrens' assessment (r = -.41, P = .0001). Saccharin transit time was not helpful in assessment of degree of nasal obstruction. CONCLUSION: Children appear to have difficulty in self-assessment of nasal symptoms, and to be poor judges of the presence or severity of nasal obstruction. In studies of allergic rhinitis in children, objective measurements should be performed, if possible, to facilitate more accurate interpretation of data.

Child↗
PubMed1994

Binding properties of protein A and protein G for human IgE.

We studied the binding of protein A and protein G to human monoclonal and polyclonal IgE. An ELISA was used to measure human IgE. Protein A-Sepharose did not bind to monoclonal IgE, but bound to 12-14% of serum polyclonal IgE and to -3% of the polyclonal IgE purified from the serum. No difference in binding to protein A was found between IgE from an allergic patient and that from a non-allergic subject. Protein G bound to neither polyclonal IgE nor monoclonal IgE. Thus, protein G is better than protein A with respect to separation of IgE from IgG.

Humans↗
PubMed1994

Effect of nebulized ipratropium bromide on intraocular pressures in children.

STUDY OBJECTIVE: To evaluate the effects of nebulized ipratropium bromide on intraocular pressures and pupillary responses in children with asthma. DESIGN: A double-blind, randomized, crossover study. SETTING: Children's Hospital of Winnipeg, University of Manitoba. PATIENTS OR PARTICIPANTS: Age 6 to 17 years with asthma. INTERVENTION: Nebulized ipratropium bromide added to albuterol sulfate, albuterol alone, or saline solution was given by face mask and nebulizer. Before and 0.5 h after nebulization, intraocular pressures (mm Hg), pupillary size (mm), and pupillary responses were measured. In a subsequent open study, patients who had been admitted to hospital with acute asthma who were treated with nebulized ipratropium bromide were recruited for measurement of intraocular pressures, pupillary size, and pupillary responses. MEASUREMENTS AND RESULTS: Twenty patients completed the double-blind study, and 26 patients completed the open study. There were no changes in intraocular pressures, pupillary size, or pupillary response after any treatment on any study day in either the double-blind or the open studies. CONCLUSION: In children with asthma, who have no pre-existing ocular abnormalities, the risk of an adverse reaction to nebulized ipratropium bromide delivered by face mask inadvertently absorbed in the eye is extremely small.

Adolescent↗
PubMed1993

Identification of glutamate-169 as the third zinc-binding residue in proteinase III, a member of the family of insulin-degrading enzymes.

A novel active site has been identified in a family of zinc-dependent metalloendopeptidases that includes bacterial proteinase III, the human and Drosophila insulin-degrading enzymes, and the processing-enhancing protein subunit of the mitochondrial processing proteinase. None of these enzymes contains the conserved active site described in most other metalloendopeptidases, HEXXH; instead, all four contain an inversion of this motif, HXXEH. Prior mutagenesis studies of proteinase III indicate that the two histidines are essential for co-ordinating the zinc atom, while all three residues are required for enzyme activity. To identify the third zinc-binding residue in this protein family, three glutamates downstream from the active site were mutated to glutamine in proteinase III. The mutant proteins were expressed and their ability to degrade insulin was compared with the wild-type enzyme. The glutamate-204 mutant was as active as the wild-type protein, the glutamate-162 mutant retained 20% of the activity of the wild-type enzyme and the glutamate-169 mutant was completely devoid of insulin-degrading activity. The purified wild-type and glutamate-204 mutant enzymes were found to contain nearly stoichiometric levels of zinc by atomic absorption spectrophotometry, whereas the glutamate-162 mutant had a slight reduction in the level of zinc, and the glutamate-169 mutant retained less than 0.3 mol of zinc/mol of enzyme. These findings are consistent with glutamate-169 being the third zinc-binding residue in proteinase III.

Amino Acid Sequence↗
PubMed1993

Treatment of allergic rhinitis with intranasal corticosteroids in patients with mild asthma: effect on lower airway responsiveness.

The effect of treatment of allergic rhinitis with intranasal corticosteroids on lower airway responsiveness was assessed in a randomized, double-blind, placebo-controlled, crossover study. Twenty-one young patients with perennial allergic rhinitis and asthma, with documented lower airway hyperresponsiveness (PC20 methacholine < 8 mg/ml), were treated with intranasal aqueous beclomethasone dipropionate and placebo, each given for 4 weeks. Patients recorded rhinitis and asthma symptom scores and monitored peak expiratory flow rates every morning and evening. Patients recorded global assessment of rhinitis and global asthma symptom scores at the beginning and end of each treatment. PC20 methacholine was performed at baseline and at the end of each treatment period. Intranasal beclomethasone dipropionate significantly reduced global rhinitis symptom scores (p = 0.05) after 4 weeks of treatment. Global asthma scores did not change significantly (p = 0.2). Geometric mean PC20 methacholine improved significantly after 4 weeks of intranasal beclomethasone, but not after placebo (p = 0.04). Daily morning and evening rhinitis symptom scores were lower in patients treated with intranasal corticosteroids over the first 4 weeks of treatment, but carryover effect of steroids precluded comparative analysis of the second 4-week block (morning p = 0.06, evening p = 0.03). Morning asthma scores tended to decrease (p = 0.07). Evening asthma scores were significantly decreased at weeks 2 and 3 (p = 0.001, p = 0.02, respectively). No change in peak expiratory flow rate was seen. This study confirms that treatment of inflammation in the upper airways indirectly improves asthma symptoms and decreases bronchial hyperreactivity. Ignoring inflammation in the upper airway may lead to suboptimal results in asthma treatment.

Administration, Intranasal↗
PubMed1993

Binding of dog immunoglobulins G, A, M, and E to concanavalin A.

The binding of dog immunoglobulins G, A, M and E to concanavalin A (Con A) has been investigated. A passive cutaneous anaphylaxis test was used for measurement of dog IgE, and enzyme-linked immunosorbent assay was used for measurement of dog IgG, IgA and IgM. After the dog serum fraction was applied to a Con A-Sepharose column, sequential elution with different buffers was performed; 100% of IgE and IgM, 60% of IgG and 58% of IgA bound to the Con A-Sepharose. IgE was eluted by mannose, methylglucose, and methylmannoside. IgG was eluted by glucose, mannose, methylglucose, and methylmannoside. IgA and IgM were eluted by methylmannoside only. This provides a useful technique in the purification of dog immunoglobulins, especially dog IgE.

Animals↗
PubMed1993

Purification and identification of polyclonal IgE antibodies from ragweed-sensitized dog sera.

We have purified and characterized polyclonal dog IgE. Serum IgE was precipitated by (NH4)2SO4 and then purified by two different procedures. Ion exchange on DEAE-Sephacel, followed by HPLC using Tonen hydroxylapatite and then Protein G-Sepharose, produced a highly purified IgE fraction (No. 1) free of IgG, IgA and IgM as measured by ELISA, but recovery of IgE as measured by passive cutaneous anaphylaxis was low. Gel filtration on Sephacryl S-300, Con A-Sepharose and Protein G-Sepharose recovered 18% of initial IgE, 0.02% IgG, 0.4% IgM and 0.3% IgA. This IgE fraction (No. 2) was used to induce antibody production in rabbits. Western blot analysis was then performed for dog IgE fractions No. 1 and 2. Using the rabbit anti-dog IgE, a prominent IgE band with an apparent molecular mass of 226 kD was identified in fractions No. 1 and 2 subjected to nonreducing SDS-PAGE. This band also reacted with anti-human IgE, but not with anti-dog IgG or anti-dog IgA. Under reducing conditions the approximate molecular mass for the IgE & chain, estimated by Western blot using rabbit anti-dog IgE, was 73 kD, providing a molecular mass of 196 kD for dog IgE.

Allergens↗
PubMed1993

Bronchoalveolar eosinophilic cells in a canine model of asthma: two distinctive populations.

In a canine model of asthma, the identity and relationships of two types of cells with eosinophilic granules found in bronchoalveolar lavage (BAL) were investigated. Five female and three male newborn mongrel dogs were sensitized by intraperitoneal injection of 500 micrograms ragweed in 30 mg aluminum hydroxide repeated weekly for 8 weeks and then biweekly until 16 weeks of age. Three female and two male littermate controls received 30 mg aluminum hydroxide. From 4 months of age, dogs received six breaths of wet-nebulized ragweed solution through an endotracheal tube bimonthly. Bronchoalveolar lavage was performed 2 months or more after the last exposure to ragweed and was repeated 5 hours after ragweed inhalation. Dogs studied were 15 to 38 months of age. Eosinophilic cell populations were determined in BAL and peripheral blood; cells were examined by light and electron microscopy. Two eosinophilic cell types were in BAL: an eosinophil and an atypical cell with globule leukocyte characteristics. Specific microgranules, a constant feature of eosinophils, were prominent in the atypical cell and suggest a relationship to the eosinophil granulocyte series for the atypical cell and cells identified by others as globule leukocytes. In ragweed sensitized animals, there were more eosinophilic cells in BAL fluid and more eosinophils in peripheral blood. There was a proportional increase in BAL eosinophils 5 hours after ragweed inhalation and a corresponding decline in peripheral blood eosinophils. There was no increase in numbers of eosinophils in the sensitized animals; eosinophil and atypical cell numbers in littermate controls were unchanged.

Allergens↗
PubMed1993

Trends in physician-diagnosed asthma prevalence in Manitoba between 1980 and 1990.

We attempted to assess recent changes in the prevalence of physician-diagnosed asthma and the possible influence of diagnostic exchange on these trends. The routinely collected data of the provincial Health Insurance Plan (physicians' claims) were used to determine the annual prevalence of physician-diagnosed asthma in Manitoba. Results indicate that the prevalence of physician-diagnosed asthma increased for all age groups in both male and female subjects between 1980 and 1990. The average increases were the highest in the age group 5 to 14 years for both sexes. The average increases varied with age and there were significant differences between the two sexes. There was evidence of increasing diagnostic exchange, that is, a tendency to label patients with asthma instead of alternative diagnoses. This was particularly prominent in those younger than 35 years of age. However, the increased prevalence of physician-diagnosed asthma, even for the younger population, cannot be fully explained by diagnostic exchange.

Adolescent↗
PubMed1993

Measurement of ragweed-specific IgE in canine serum by use of enzyme-linked immunosorbent assays, containing polyclonal and monoclonal antibodies.

Using polyclonal rabbit and monoclonal mouse anti-dog IgE antibodies, we developed ELISA for measurement of ragweed-specific IgE in canine serum. In the ELISA, microtitration plates were coated with ragweed extract and sequentially incubated with canine serum, purified monoclonal or polyclonal anti-dog IgE, and conjugated goat antibody to mouse IgG or rabbit IgG. Serum ragweed-specific IgE values were measured by the 2 ELISA in serum samples from 60 ragweed-allergic dogs and in serum from 10 control dogs. Passive cutaneous anaphylaxis (PCA) tests were performed on these sera to compare results with those of the ELISA. Mean coefficient of variation between assays was 0.20 +/- 0.10 for the assay using the polyclonal antibody and was 0.17 +/- 0.10 for that using monoclonal antibody. Sensitivity was 0.6 U/ml for the ELISA, using polyclonal antibody, and 2.5 U/ml for the ELISA, using monoclonal antibody. Serum ragweed-specific IgE values measured by the 2 ELISA strongly correlated with PCA titers (P < 0.0000), but the ELISA using polyclonal antibody had higher correlation with PCA titer (r = 0.84) than the ELISA using monoclonal antibody (r = 0.59). The geometric mean ragweed-specific IgE value measured by the 2 ELISA and by PCA testing, was significantly higher (P < 0.0000). in allergic dogs than in control dogs. The 2 ELISA were specific, sensitive, and reproducible for measurement of ragweed-specific IgE in canine serum.

Allergens↗
PubMed1992

Biochemical and ultrastructural studies suggest that the effects of thapsigargin on human platelets are mediated by changes in intracellular calcium but not by intracellular histamine.

The involvement of intracellular histamine in thapsigargin (Tg)-induced platelet aggregation was studied. Platelet aggregation induced by 0.25 and 0.5 microM Tg was not accompanied by a rise in intracellular histamine but a significant (p < 0.01) increase in the level of intracellular histamine was observed at 1 microM Tg. Preincubation of platelets with inhibitors of histamine metabolizing enzymes had little effect on intracellular histamine levels in platelets stimulated by 0.5 microM Tg. In addition, the inhibitors of histidine decarboxylase (HDC), alpha-methyl histidine (alpha-MH) and alpha-fluoromethyl histidine (alpha-FMH) failed to inhibit Tg-induced aggregation. The intracellular histamine receptor antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine. HCl (DPPE), inhibited Tg-induced aggregation but with IC50 values dependent on the concentration of agonist used. The inhibitory effects of DPPE on Tg-induced aggregation were not reversed by the addition of histamine to saponin-permeabilized platelets suggesting non-histamine mediated effects of DPPE on Tg-induced aggregation. Tg stimulated an increase in the cytosolic free calcium concentration which was unaffected by DPPE indicating that the effects of DPPE are also not due to the inhibition of mobilization of cytosolic calcium. The ultrastructural studies suggest that the major Tg-induced changes (pseudopod formation and granule centralization) are consistent with a primary role for Tg to mobilize calcium; DPPE had very little effect on these ultrastructural changes. The results indicate that the effects of Tg on human platelets are mediated by an increase in cytosolic calcium but not by intracellular histamine.

Blood Platelets↗