Rings of intrapulmonary bronchi isolated from rabbits producing anti-horseradish peroxidase IgE antibodies contracted when exposed to antigen. The contractile response had a lag period of about 1 min, reached a peak at 6 min and then subsided. Bronchi from rabbits with detectable levels of specific IgG (in addition to IgE) antibodies did not differ in response from those with undetectable specific IgG levels. Histamine also contracted rabbit intrapulmonary bronchi with an EC50 of 10ωM (SD 1.29). The response to antigen was completely inhibited with chlorpheniramine (30 ωM). In contrast to intrapulmonary bronchi, responsiveness of mainstem bronchi to antigen was observed only occasionally, whereas histamine was equipotent on both mainstem and intrapulmonary bronchi. Thus, the amount of antigen-induced mediator release may be less in the mainstem bronchi. Acetyl glyceryl ether phosphorylcholine, in concentrations up to 10 ωM, did not contract either mainstem or intrapulmonary bronchi. This study indicates that histamine is the major mediator of (and acetyl glyceryl ether phosphorylcholine does not significantly participate in) antigen-induced contraction of isolated bronchi from IgE-producing rabbits. The results provide a likely mechanism for the increase in pulmonary resistance observed in IgE anaphylaxis in this species.

Thesis (M.S.P.H.)--University of Michigan, 1941.

Thesis (M.S.P.H.)--University of Michigan, 1941.

No description available.

Thesis (Ph.D.) -- Flinders University, School of Medicine, Dept. of Immunology, Allergy and Arthritis. / Typescript (photocopy). Includes bibliographical references. Also available online.

This research aims to assess the practice pattern of Canadian emergency physicians for management of anaphylaxis and investigate the clinical predictors for biphasic reactions in children with anaphylaxis. We conducted two studies: a national survey and a multicenter Health Records (HR) review of emergency department visits. Of the 608 physicians surveyed, 340 (56%) responded. Overall, 211(62%) of the physicians correctly agreed that both hypothetical scenarios in the survey were consistent with anaphylaxis, and 206(61%) chose to administer epinephrine. In our HR review, we found five independent predictors of biphasic reactions: age 6-9 years (OR 3.60; 95% CI 1.5-8.58), time from onset of the anaphylactic reaction to ED presentation >90 minutes (OR 2.58; 95% CI 1.47-4.53), wide pulse pressure at triage (OR 2.92; 95% CI 1.69-5.04), treatment of the reaction with >1 dose of epinephrine (OR 2.7; 95% CI 1.12-6.55), and administration of inhaled salbutamol in ED (OR 2.39; 95% CI 1.24-4.62).

No description available.

The objective of this study was to determine whether neutrophils play a significant role in anaphylaxis or in the response to the anaphylactic mediator platelet activating factor (PAF) in the rabbit. Vinblastine and anti-neutrophil antibodies were compared as neutrophil depleting agents, and 0.35 mg/kg vinblastine was selected as optimal for efficiency and specificity of depletion. Anaphylaxis was induced in sensitized rabbits by intravenous antigen challenge. Neutrophil depletion to 399 ± 101 cells/mm³ blood (14 ± 3%) did not significantly inhibit the physiologic and hematologic events associated with anaphylaxis except tachycardia. However, vinblastine pretreatment significantly reduced tachycardia and the right ventricular pressure increase and abolished the increase in pulmonary resistance caused by intravenous PAF. We conclude that although neutrophils do not play a significant role in IgE-anaphylaxis, they are important in the PAF-induced increases in right ventricular pressure and pulmonary resistance. PAF may not be a major mediator of these two physiologic alterations in IgE-anaphylaxis.

No description available.

Fullerenes are carbon nanospheres that can be solublized by the addition of polar chemical groups to the carbon cage, forming fullerene derivatives. One specifically derivatized fullerene compound, termed C70-Tetragylocolate (C70-TGA), has been shown to stabilize mast cell responses in vitro thus we hypothesized it may have an effect on mast cell-driven diseases such as asthma and systemic anaphylaxis. To observe the effects of C70-TGA on systemic anaphylaxis, mice were subjected to a model of passive systemic anaphylaxis. In this model, mice were injected with DNP-specific IgE 16 hours prior to challenge, then treated with C70-TGA. Immediately prior to DNP challenge, mice were subjected to a second injection of C70-TGA. Following DNP challenge, body temperature was recorded and blood was collected for quantitation of histamine levels. Treatment with C70-TGA significantly reduced body temperature drop associated with systemic anaphylaxis and serum histamine levels. To observe the effects of C70-TGA on chronic features of asthma in vivo, we utilized a heavily MC influenced model of asthma pathogenesis. Mice were sensitized by intraperitoneal (i.p.) injection of ovalbumin (OVA) in saline, challenged intranasally (i.n.) with OVA, and one of two treatment strategies was pursued. In one, C70-TGA was given i.n. throughout disease development. In the other, C70-TGA was given following an initial set of challenges to allow disease to develop prior to treatment; mice were then re-challenged with OVA to assess the effect on established disease. We found that C70-TGA treatment significantly reduced airway inflammation and eosinophilia and dramatically reduced bronchoconstriction in either model. Cytokines IL-4 and IL-5 and serum IgE levels are significantly reduced in C70-TGA treated animals. Interestingly, we also saw an increase in the anti-inflammatory eicosanoid 11, 12-epoxyeicosatreinoic acid (11,12-EET) in the BAL fluid, suggesting the involvement of this mediator in C70-TGA inhibition. Further experiments utilizing an inhibitor of 11,12-EET formation (6-(2-Propargyloxyphenyl)hexanoic acid) and a structural analog of 14,15-EET (14,15-EE-5(Z)-E) in vivo indicate that these mediators are closely associated with C70-TGA mediated inhibition as their inhibition reverses the anti-inflammatory effects of C70-TGA. Importantly, mice did not exhibit any acute toxicity following C70-TGA treatment and liver and kidney function were normal. Collectively, these results show that the fullerene C70 derivative C70-TGA is capable of dampening severe allergic responses including systemic anaphylaxis, airway inflammation, and bronchoconstriction. The mechanism of inhibition is through the upregulation of the anti-inflammatory EETs, which may dampen mast cell degranulation in vivo, thus contributing to the inhibitory effect of C70-TGA on allergic disease.