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Biomedical subjects

F E Simons

Publications and source records attributed to F E Simons.

At least 55 records · Page 3Linked to original sources
PubMed1998

Human IP-10 selectively promotes dominance of polyclonally activated and environmental antigen-driven IFN-gamma over IL-4 responses.

Human interferon-inducible protein 10 (IP-10) differs from most chemokines in its apparent specificity for activated T lymphocytes. We hypothesized that IP-10 was relevant not only for recruiting T cells to inflammatory sites, but also for regulating cytokine synthesis patterns. We examined the effect of recombinant human IP-10 (rhIP-10) on human interferon gamma (IFN-gamma) and interleukin 4 (IL-4) production by fresh peripheral blood mononuclear cells. We demonstrate for the first time that this CXC chemokine selectively up-regulates human T cell cytokine synthesis, with enhancement selectively targeted to promotion of Th1-like dominance. Superantigen (TSST-1), soluble anti-CD3 mAb, and phytohemagglutinin were used to activate distinct intracellular signaling pathways, thereby inducing quantitatively different IFN-gamma:IL-4 ratios. Selective enhancement of IFN-gamma responses was consistently observed, with median increases of 105-470%. Environmental antigens (Ag) were used to evaluate IP-10's effect on CD4-dependent, chloroquine-sensitive cytokine synthesis. Ag-driven IFN-gamma responses exhibited median 19- to 30-fold increases in the presence of nanomolar concentrations of rhIP-10. IL-4 responses were neither enhanced nor inhibited under any of the conditions tested. These findings suggest a potential role for this T cell-focused chemokine in maintenance of the default Th1-like responses usually seen to environmental Ag and indicate a potential application in the modulation of Ag-driven responses in vivo.

Adolescent↗
PubMed1998

Expression and rapid purification of an Aedes aegypti salivary allergen by a baculovirus system.

Mosquito salivary proteins cause allergic reactions in humans. Recombinant salivary allergens will facilitate both the diagnosis and immunotherapy of mosquito allergy. The Aed a 1, a 68-kD apyrase in the saliva of Aedes aegypti, has been demonstrated to be an allergen which binds to the IgE of mosquito-allergic subjects. The baculovirus expression vector pBlueBacHis C equipped with an N-terminal histidine tag was used to express the Aed a 1 protein. The cDNA coding for the 3' significant portion of Aed a 1 (Aed a 1 3') (150-562 amino acid residues) was cloned into pBlueBacHis C. The rAed a 1 3' protein expressed by recombinant baculovirus was verified by immunoblot using anti-Aed a 1 and anti-histidine antibodies, respectively. The histidine-tagged fusion protein was purified to apparent homogeneity from infected Sf9 cells by Ni2+ resin affinity chromatography. Both immunoblot and ELISA showed that the purified rAed a 1 3' binds to the IgE and IgG in mosquito allergic sera, indicating that the antigenicity of the rAed a 1 3' is identical to the native Aed a 1 of Aedes aegypti saliva.

Aedes↗
PubMed1998

A mouse model of mosquito allergy for study of antigen-specific IgE and IgG subclass responses, lymphocyte proliferation, and IL-4 and IFN-gamma production.

To date, there are no ideal animal models for study of natural sensitization leading to IgE- and lymphocyte-mediated hypersensitivities. We established such a model in which four BALB/c mice were each sensitized by exposure to at least 16 mosquito Aedes aegypti bites, twice a week for 4 weeks. Four non-exposed control mice were also studied. Mosquito A. aegypti head and thorax extract, saliva, and two recombinant salivary allergens (rAed a 1 and rAed a 2) were used in vitro as antigens. Intradermal tests were performed. Serum mosquito antigen-specific IgG, IgG1, IgG2a, and total IgE were measured by ELISA; specific IgE was measured by passive cutaneous anaphylaxis (PCA). IgE responses to each antigen in the saliva were analyzed using Western blotting. Spleen lymphocyte proliferation assays were performed to determine the cell-mediated hypersensitivity response. Antigen-induced IL-4 and IFN-gamma production in the spleen lymphocytes were evaluated using ELISA. After 4 weeks, all 4 mosquito-sensitized mice developed a positive immediate wheal 20 min after skin tests with mosquito antigens, and a positive delayed papule 24 h later, while control mice did not. Also, the sensitized mice had a positive PCA response, which correlated significantly with total IgE levels (r = 0.84, p<0.05), confirming the presence of antigen-specific IgE, while none of control mice had a positive response. Antigen-specific IgG1, but not IgG2a, was increased in the sensitized mice (p<0.01). Western blotting showed that 5 of the 8 antigens which elicited mouse IgE responses, including 2 major antigens, also elicited human IgE responses. The mean lymphocyte proliferation response to mosquito antigens also elicited human IgE responses. The mean lymphocyte proliferation response to mosquito antigens was significantly increased in the sensitized mice (p<0.05). IL-4 production was significantly increased and IFN-gamma production was decreased, further suggesting that a Th2 immune response predominates despite the development of the delayed skin reaction. This new model of natural sensitization without using an adjuvant is potentially useful for the study of other allergic disorders as well as mosquito allergy.

Allergens↗
PubMed1997

A comparison of beclomethasone, salmeterol, and placebo in children with asthma. Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group.

BACKGROUND: An inhaled glucocorticoid is currently the medication of choice for long-term control of persistent asthma in children. The role of long-acting beta2-adrenergic-receptor agonists, such as salmeterol, needs to be defined. METHODS: We conducted a randomized, double-blind, placebo-controlled, parallel-group, one-year study of 241 children (mean [+/-SD] age, 9.3+/-2.4 years) with clinically stable asthma and less than one month of prior glucocorticoid use. We compared inhaled beclomethasone dipropionate (200 microg twice daily) with salmeterol xinafoate (50 microg twice daily) and placebo (lactose). The primary outcome measure, airway responsiveness (as assessed with a methacholine challenge) was evaluated before treatment; after 3, 6, 9, and 12 months of treatment (12 and 36 hours after study medications had been withheld); and 2 weeks after the end of treatment. Spirometry, symptoms, use of rescue medication (200 microg of albuterol inhaled as needed), and adverse effects were also assessed. RESULTS: During months 1 through 12 overall, beclomethasone was associated with significantly less airway hyperresponsiveness than salmeterol (P= 0.003) or placebo (P<0.001). This effect was lost two weeks after treatment had been stopped. As compared with placebo, beclomethasone was associated with less variability between morning and evening in the peak expiratory flow (P=0.002), as was salmeterol (P=0.02). Beclomethasone was also associated with a reduced need for albuterol as rescue therapy (P<0.001) and fewer withdrawals because of asthma exacerbations (P=0.03), but salmeterol was not (P=0.09 and 0.55, respectively). During months 1 through 12, linear growth was 3.96 cm in the children receiving beclomethasone, as compared with 5.40 cm in the salmeterol group (P=0.004) and 5.04 cm in the placebo group (P=0.018). Height was not measured after treatment ended. CONCLUSIONS: Beclomethasone was effective in reducing airway hyperresponsiveness and in controlling symptoms of asthma, but it was associated with decreased linear growth. Salmeterol was not as effective as beclomethasone in reducing airway hyperresponsiveness or in controlling symptoms; however, it was an effective bronchodilator and was not associated with rebound airway hyperresponsiveness, masking of symptoms, or adverse effects.

Administration, Inhalation↗
PubMed1997

Heterogeneity of polyclonal IgE characterized by differential charge, affinity to protein A, and antigenicity.

Functional and physical heterogeneity of polyclonal IgE has been reported. Extremely low serum concentrations of IgE have limited the study of these important differences. We have purified polyclonal dog IgE and developed polyclonal and monoclonal (mAb C2) anti-dog IgE antibodies. In this study chromatofocusing of dog IgE revealed two biologically active IgE fractions: IgE1 eluted at pH 5.0, and IgE2 eluted at pH 4.7. The two IgE subforms (IgEs) exhibited typical IgE characteristics: positive in the 48-hour passive cutaneous anaphylaxis response, heat-labile, identical molecular weight, and reactive to polyclonal anti-dog IgE. However, the two IgEs were found to be significantly heterogeneous. IgE1 bound to protein A and did not react with mAb C2 in ELISA and isoelectric focusing-immunoblotting, whereas IgE2 did not bind to protein A and reacted with mAb C2. Further, in sodium dodecylsulfate-polyacrylamide gel electrophoresis and immunoblotting, IgE2, but not IgE1, reacted with seven well-defined mAb anti-human IgE antibodies and an mAb anti-mouse IgE antibody, even though both IgE1 and IgE2 reacted with polyclonal anti-human and anti-mouse IgE. Neuraminidase or endoglycosidase treatment did not abolish the differential antigenicity and charge of IgE1 and IgE2, although the antigenicity of IgE2 was significantly reduced after incubation with endoglycosidase. These data suggest that carbohydrate moieties are not involved in the observed differences in antigenicity and charge and that the two IgE molecules represent distinct isotypes. In studies with seven purified IgE fractions obtained from different ragweed-allergic dogs, the distribution of ragweed IgE2 varied 200-fold, whereas ragweed total IgE levels varied only fourfold. This raises the possibility of a relationship between different IgEs and the allergic response.

Animals↗
PubMed1997

Cross-reactivity of skin and serum specific IgE responses and allergen analysis for three mosquito species with worldwide distribution.

BACKGROUND: Allergic reactions to mosquito bites are a common problem worldwide. Cross-reactive immunologic responses have not been reported. OBJECTIVE: For the three most common mosquito species, Aedes (Ae.) vexans, Ae. aegypti, and Culex (Cx.) quinquefaciatus, we investigated skin and serum specific IgE responses and analyzed salivary allergens. METHODS: Locally, Ae. vexans is a major pest, but Ae. aegypti and Cx. quinquefaciatus are not found. We studied 41 subjects living in Manitoba, using (1) skin bite tests, (2) ELISA to measure serum mosquito saliva- or salivary gland-specific IgE, (3) ELISA inhibition tests, and (4) sodium dodecylsulfate-polyacrylamide gel electrophoresis and immunoblotting. RESULTS: Twenty-nine of the 41 subjects had skin reactions to Ae. vexans bites. Twenty-two of the 29 also reacted to Ae. aegypti bites. Mean serum mosquito-IgE levels to each of the three species were significantly higher in the reactive subjects than in the nonreactive subjects. Significant intercorrelations were found among skin reactions and mosquito-specific IgE levels for the three species. The Ae. aegypti-IgE ELISA reaction could be inhibited by addition of each mosquito extract. The serum IgE and IgG from Manitobans reacted with the antigens of all three species. A 37 kd allergen in each of the three species was recognized by the antibody against a recombinant Ae. aegypti saliva protein. CONCLUSIONS: Strong cross-reactive skin and IgE responses and species-shared antigens exist among the three mosquito species studied.

Adult↗
PubMed1997

Peripheral H1-blockade effect of fexofenadine.

BACKGROUND: Studies of the suppressive effect of H1-receptor antagonists on the histamine-induced wheal and flare are useful for assessing peripheral H1-blockade. OBJECTIVE: To compare the peripheral H1-blockade produced by fexofenadine, 60 mg twice daily or 120 mg once daily; loratadine, 10 mg once daily; and placebo during 24 hours. METHODS: In this randomized, double-blind, single-dose, crossover study in 20 subjects, the wheals and flares produced by epicutaneous tests with histamine phosphate 1 mg/mL were measured before and at intervals (20, 40, 60 minutes, hourly until 12 hours, and 24 hours) after the ingestion of fexofenadine, 60 mg twice daily; fexofenadine, 120 mg once daily; loratadine, 10 mg once daily; or placebo. RESULTS: All active medications effectively suppressed the histamine-induced wheal and flare for 24 hours compared with placebo. Fexofenadine 60 mg twice daily and fexofenadine 120 mg once daily had a faster onset of action than loratadine in this experimental model. CONCLUSIONS: Peripheral H1-blockade studies are useful for investigation of the differences among H1-receptor antagonists. They complement large clinical trials in which efficacy is subjectively assessed using symptom scores, and which are more likely to demonstrate similarities among the different medications in this class, and among different doses of the same H1-receptor antagonist.

Adult↗
PubMed1997

Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment.

OBJECTIVES: The long-acting beta2-adrenergic agonist salmeterol prevents exercise-induced asthma, but tolerance may develop to its bronchoprotective effect. We wanted to ascertain if the development of tolerance could be prevented by using a low-dose treatment regimen of 50 microg once daily, instead of the usual dose of 50 microg twice daily, in adolescents receiving regular glucocorticoid inhalations. Methods. In a randomized, double-blind, 2x28-day crossover study, we administered salmeterol (50 microg) or placebo once daily via a metered-dose inhaler and Nebulizer Chronolog device to monitor compliance. Exercise challenge tests were performed 1 and 9 hours after salmeterol or placebo inhalation on the 1st and 28th day of each treatment period. The primary outcome variable was the maximum decrease in percent predicted FEV1 postexercise. RESULTS: Fourteen subjects with a mean age of 13.1 years completed the study. The first dose of salmeterol had an excellent bronchoprotective effect against exercise-induced asthma at 1 and 9 hours. After the 28th consecutive daily dose of salmeterol, the bronchoprotective effect was significantly greater than that of placebo at 1 hour, but not at 9 hours. CONCLUSIONS: We conclude that a single 50-microg dose of salmeterol has an excellent protective effect against exercise-induced asthma for at least 9 hours, but that this effect may wane during regular once-daily salmeterol treatment, despite the reduced frequency of dosing and despite concomitant use of inhaled glucocorticoids.

Administration, Inhalation↗
PubMed1996

Pharmacokinetics of the orally administered decongestants pseudoephedrine and phenylpropanolamine in children.

BACKGROUND: There is little published, objective information about pseudoephedrine and phenylpropanolamine in the treatment of children. Our goal was to determine the pharmacokinetics of these medications in young subjects. METHODS: In two sequential double-blind, parallel-group, single-dose studies, 21 children received either pseudoephedrine, 30 or 60 mg, or placebo, and 20 children received either phenylpropanolamine, 20 or 37.5 mg, or placebo. Before dosing and at intervals up to 7 hours after dosing, serum pseudoephedrine or phenylpropanolamine concentrations were measured, and pulse and blood pressure were recorded. In two children receiving each drug, these tests were also performed at 12 and 24 hours, and urine was collected from 0 to 12 and from 12 to 24 hours. RESULTS: In children, the mean (+/-SEM) terminal elimination half-life values for pseudoephedrine, 3.1 +/- 0.5 hours, and for phenylpropanolamine, 2.6 +/- 0.6 hours, were significantly shorter than those found by other investigators in adults. Pharmacokinetics were not dose dependent in the dose ranges studied. CONCLUSION: Further studies of pseudoephedrine and phenylpropanolamine should be performed in children with the use of objective measurements. The widespread use of these medications in young subjects should be reevaluated.

Administration, Oral↗
PubMed1996

Immunologic mechanisms in mosquito allergy: correlation of skin reactions with specific IgE and IgG antibodies and lymphocyte proliferation response to mosquito antigens.

BACKGROUND: Allergic reactions to mosquito bites are a common problem. Although IgE-mediated hypersensitivity has been reported, other immunologic mechanisms may be involved. OBJECTIVES: To study the relationship between skin bite reactions and immunologic parameters. METHODS: Forty-one subjects were experimentally exposed to mosquito (Aedes vexans) bites. Immediate and delayed skin reactions were traced at 20 minutes and 24 hours, respectively, after the bites. Sera were analyzed for mosquito salivary gland-specific IgE (mosquito-IgE) and IgG (mosquito-IgG) by ELISA. Lymphocyte proliferation assays with mosquito extract were also performed. RESULTS: One of 41 subjects had only a delayed skin reaction to the bite, 23 had both immediate and delayed reactions, 6 had only immediate reactions, and 11 had no reaction. The mean mosquito-IgE and -IgG concentrations were higher in the subjects with immediate reactions than in those without immediate reactions (P < .007). The mean lymphocyte proliferation stimulation index was higher in the subjects with delayed reactions than in those without delayed reactions (P < .015). Further, both mosquito-IgE and -IgG levels correlated with skin immediate and delayed reactions (P < .04), while lymphocyte proliferation indices only correlated with skin delayed reactions (P < .006). Inverse correlations were found between the size of skin reactions and the number of years lived in Canada (P < .04), but not with age. CONCLUSION: These results indicate that IgE-, lymphocyte- and, probably, local IgG immune-complex-mediated hypersensitivities are involved in mosquito allergy. Naturally acquired desensitization to mosquito bites occurs during long-term exposure.

Adult↗
PubMed1996

The eternal triangle: benefit, risk, and cost of therapeutic agents.

Some people can undoubtedly tolerate a first-generation H1-receptor antagonist without sedation or other CNS adverse effects, but others cannot. There is no rapid, reliable way of differentiating these two populations. A history of presence or absence of subjective somnolence from one H1-receptor antagonist is not necessarily reliable and has no consistently useful predictive value for subsequent experience with other H1-receptor antagonists. As H1-receptor antagonists are used primarily to treat non-life-threatening disorders, safety should be a prime consideration in selecting one for use, and is surely as important a concern as efficacy and low cost. If your pilot is not permitted to take these medications before going to work, why should your taxi driver, your child's school bus driver, your dentist, your nurse, or your office assistant, to name a few examples, be allowed to do so? When the broad issue of safety is considered, first-generation H1-receptor antagonists may not be as cost-effective as they appear to be. The inherent benefit of any medication is inextricably linked with the inherent risk. It is incumbent on those promulgating the use of the older H1-receptor antagonists to define these benefits and risk further. Lowering the cost of the second-generation, relatively nonsedating H1-receptor antagonists so they are no longer the most expensive medications used in treatment of allergic rhinitis would also help solve the problem of the eternal triangle as it pertains to therapeutic use of H1-receptor antagonists.

Brain Diseases↗
PubMed1996

Comparison of proteins, IgE, and IgG binding antigens, and skin reactivity in commercial and laboratory-made mosquito extracts.

BACKGROUND: Commercial extracts are available for the diagnosis and treatment of mosquito allergy, but their antigen content has never been analyzed. OBJECTIVE: We wanted to analyze commercially available mosquito extracts and to compare these extracts with different laboratory preparations. METHODS: Seven commercially available mosquito whole body extracts from six companies and four laboratory mosquito preparations including saliva extract were studied. Epicutaneous tests and measurement of protein concentration were performed. Protein components were identified by sodium sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and silver stain. IgE and IgG binding antigens were analyzed by SDS-PAGE and immunoblotting with sera from mosquito-allergic subjects. RESULTS: The seven commercial materials produced wheals and papules ranging from 0 to 36 mm2. Their protein concentrations varied from 0.1 to 4.9 mg/mL. There were significant differences in their protein and antigen components. Some extracts contained multiple highly immunoreactive proteins and IgE- and IgG-binding antigens that are not present in mosquito saliva, but few actual salivary antigens. In the four laboratory preparations, rank ordered from whole body, head and thorax, salivary gland to saliva extracts, the amount of salivary antigens significantly increased, while non-salivary proteins and antigens significantly decreased. CONCLUSIONS: Commercial mosquito extracts should be standardized. Purer mosquito extracts should be used in diagnosis and immunotherapy of mosquito allergy.

Aedes↗
PubMed1996

Effect of cimetidine on the pharmacokinetics and pharmacodynamics of chlorpheniramine and diphenhydramine in rabbits.

PURPOSE: The effects of concomitant administration of the H2-receptor antagonist cimetidine on the pharmacokinetics and pharmacodynamics of the H1-receptor antagonists chlorpheniramine and diphenhydramine were studied in rabbits. METHOD: A single dose of chlorpheniramine 10 mg (Group A) or diphenhydramine 10 mg (Group B) was given intravenously on three different study days as follows: 2 weeks before cimetidine administration, after giving cimetidine 100 mg/kg intravenously every 12 hours for one week, and two weeks after discontinuing the cimetidine. Serum chlorpheniramine and diphenhydramine concentrations were measured by HPLC. Histamine H1-blockade was assessed by measuring suppression of the histamine-induced wheals in the skin. RESULTS: The chlorpheniramine and diphenhydramine terminal elimination half-life values and area under the curve values were significantly increased, and the systemic clearance rates were significantly decreased, during concomitant administration of cimetidine. For each H1-receptor antagonist, pharmacokinetic parameters were similar before cimetidine was co-administered and two weeks after cimetidine was discontinued. Wheal suppression produced by chlorpheniramine or diphenhydramine was increased and prolonged when cimetidine was administered concomitantly. CONCLUSION: Any enhanced peripheral H1-blockade observed could be attributed, at least in part, to a pharmacokinetic interaction.

Alanine Transaminase↗
PubMed1996

Fel d 1 peptides: effect on skin tests and cytokine synthesis in cat-allergic human subjects.

We tested peptide immunotherapy in cat-allergic humans, using a formation of two synthetic peptides, IPC-1 and IPC-2, each of which is 27 amino acids long and contains T cell-reactive regions of Fel d 1, the major cat allergen. In this exploratory, randomized, double-blind, parallel-group study, 42 subjects received s.c. injections of treatment peptides 250 micrograms or placebo weekly for four consecutive weeks. Changes in immediate- and late-phase skin test reactivity, and in antigen-driven cytokine synthesis were assessed. Epicutaneous (end-point titration) and intradermal tests were performed with cat extract (ALK SQ Cat Hair) containing Fel d 1, before the first injection, then 2, 6 and 24 weeks after the fourth and last injection of peptides or placebo. IL-4, IL-10 and IFN-gamma expression by circulating peripheral blood mononuclear cells (PBMC) in response to cat extract was measured using short-term bulk culture of PBMC and short-term limiting dilution analysis. Subjects who received peptide immunotherapy did not tolerate significantly more cat extract containing Fel d 1 in the skin tests 2, 6 or 24 weeks after the last injection than they did at baseline, and their late-phase responses did not decrease significantly compared to baseline. Substantial IL-4, IL-10 and IFN-gamma responses were observed following primary culture of cat antigen-stimulated PBMC; however, the intensity of cytokine synthesis and the IFN-gamma: IL-4 ratio were unchanged in peptide- and placebo-treated groups 6 and 24 weeks after the last injection. A few hours after the injections, subjects receiving peptides reported more allergic rhinitis and asthma symptoms and more pruritus than those receiving placebo. We conclude that under the conditions tested, peptide immunotherapy did not reduce immediate- or late-phase skin reactivity to cat extract containing Fel d 1 or modify cat antigen-specific cytokine production significantly.

Adult↗
PubMed1996

Allergen-driven limiting dilution analysis of human IL-4 and IFN-gamma production in allergic rhinitis and clinically tolerant individuals.

Difficulties in detecting human IL-4 synthesis in antigen-driven primary culture have led to widespread reliance on less physiologic approaches to T cell activation. Although there is general agreement of a Th2-like bias, the precise defects in cytokine responsiveness remain controversial. Analysis of cytokine protein production by fresh, unselected cell populations in response to cognate, antigen-driven stimulation remains an important goal. Here, limiting dilution analysis (LDA) was used to evaluate antigen-stimulated cytokine gene expression by fresh peripheral blood mononuclear cells (PBMC). PBMC from 19 grass pollen sensitive, allergic rhinitis subjects and normal, non-atopic controls were evaluated 1 month after natural reimmunization (the peak of the local grass pollen season). Surprisingly, highly atopic subjects and clinically non-allergic individuals exhibited virtually equivalent antigen-specific, CD4-dependent cytokine production in response to short-term culture with these common environmental antigens. As anticipated, pronounced increases in Th2-like activity were evident in the circulating immune repertoire of grass pollen sensitive individuals, leading to a median ratio of antigen-stimulated IFN-gamma:IL-4 frequencies of 117:1 among normal subjects versus 4:1 among those with allergic rhinitis (Mann-Whitney U-test, P = 0. 00067). This Th2-like bias reflected both a lower frequency of IFN-gamma-producing cells and a markedly increased frequency of IL-4-producing cells in the circulating grass-pollen specific repertoire of atopic donors. The observation that every atopic and normal subject produced IFN-gamma (+/-IL-4) following antigen re-stimulation argues that the decision as to whether allergy or (clinical) tolerance results, hinges not on a genetically determined capacity of whether allergen-reactive T cells can be stimulated in any given individual by chronic exposure to ubiquitous environmental antigens, but on the nature of the cytokine response that comes to dominate that individual's response.

Humans↗
PubMed1996

Adverse central nervous system effects of older antihistamines in children.

Although older, potentially sedating, "first-generation" antihistamines (H1-receptor antagonists) are commonly used in childhood, their central nervous system (CNS) effects have not been well-documented in young subjects. We hypothesized that diphenhydramine and hydroxyzine would affect CNS function adversely in this population. Our objective was to evaluate the effects of these medications on central and peripheral histamine H1-receptors in children. Fifteen subjects with allergic rhinitis were tested before and 2-2.5 h after administration of diphenhydramine, hydroxyzine, or placebo in a double-blind, single-dose, three-way crossover study. Impairment of cognitive processing was assessed objectively by the latency of the P300 event-related potential (P300). Somnolence was assessed subjectively by a visual analog scale. Peripheral H1-blockade was assessed by suppression of the histamine-induced wheals and flares. At the central (Cz) and frontal (Fz) electrodes, diphenhydramine and hydroxyzine increased the P300 latency significantly (P < 0.05) compared to baseline. Hydroxyzine increased somnolence, as recorded on the visual analog scale, significantly compared to baseline (P < 0.05), with a similar trend for diphenhydramine (P = 0.07). Both antihistamines reduced histamine-induced wheals and flares significantly compared to baseline and compared to placebo. In children, diphenhydramine and hydroxyzine are effective H1-receptor antagonists, but both these medications cause CNS dysfunction, as evidenced by increased P300 latency, a measure of cognitive function, and by increased subjective somnolence.

Child↗
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↗