Paul P. VanArsdel

The effect of hyposensitization on the in vitro histamine release by specific antigen

Abstract Whole blood from 14 untreated allergic patients was incubated with various concentrations of specific antigen and the amount of histamine released into the plasma was measured chemically. During the course of specific hyposensitization of these patients, a total of 30 similar studies were carried out, and the pattern of histamine release was compared with the pre-treatment data for each patient. Studies on 2 patients showed that treatment was associated with a suppression of histamine release which was practically complete at all antigen concentrations. In the remainder, suppression of histamine release occurred only at low antigen concentrations, and was more effective as treatment progressed. However, surprisingly little change occurred at an antigen concentration of 4 μg protein nitrogen per 100 ml. blood, even though more suppression was often seen at the highest concentration (40 μg PN per 100 ml. blood). Some of our observations are explained by the production of serum blocking antibody during treatment, but other changes are more consistent with an alteration in cellular reactivity during hyposensitization.

A quantitative study on the in vitro release of histamine from leukocytes of atopic persons

Abstract Blood from forty-one persons with atopic disease was incubated with various concentrations of specific antigen. The amount of histamine released into the plasma was measured chemically. Histamine was released by concentrations of pollen extract as low as 0.01 meg. protein nitrogen per liter of blood; more histamine was released by greater amounts of antigen until a maximum level was reached at antigen concentrations of from 4 to 20 meg. P.N. per liter of blood. Histamine release tended to be suppressed by high concentrations of antigen unless massive amounts were used (4,000 meg. P.N. per liter of blood), at which point nonspecific release occurred. The degree of skin reactivity of the subjects studied was related inversely to the antigen concentration producing maximal histamine release. The rate of histamine release was apparently linear, maximum release being approached only after at least thirty minutes of incubation of blood with the specific antigen.

In vitro Histamine Release from Rat Mast Cells by Chemical and Physical Agents.

Summary Release of histamine from suspensions of rat peritoneal mast cells under various conditions has been measured directly by a microchemical technic. Compound 48/80 released histamine in a concentration as low as 2 × 10-7M and was the most potent substance investigated. Several other substances released histamine; the effects of compound 1935L, protamine, n-octylamine and stilbamidine were evaluated at several concentrations and compared with those of 48/80. Stilbamidine was considerably less potent than the others. As expected, certain physical changes released histamine, and low temperatures prevented 48/80 histamine release. Qualitative variations in response of these mast cells to different releasers suggested that mechanisms of histamine release vary considerably among the chemical agents now being investigated.

Some biochemical characteristics of allergic histamine release from leukocytes of ragweed-sensitive subjects

Abstract The experiments reported in this article show that allergic histamine release from leukocytes of atopic subjects (ragweed sensitivity) can be blocked by the chelating agents, EDTA, citrate, and oxalate. The concentrations which are anticoagulant also inhibit histamine release. This finding is interpreted as showing a requirement for calcium ions in the release reaction. Of a number of other compounds tested for their inhibitory effect on histamine release, only iodoacetate and phenol were found to be consistently inhibitory. Phenylbutazone and phthlate exhibited mild inhibitory properties. The mechanism by which these compounds inhibit has not been elucidated. Allergic histamine release is abolished when the reaction is run at 45° C., and it is reduced at temperatures below 37° C.

Specific response of human lymphocytes to pollen antigen in tissue culture

Abstract Human peripheral lymphocytes of 27 timothy-sensitive individuals were cultured for ten days in the presence of 15 μg protein nitrogen per milliliter of timothy pollen antigen. Approximately 25 per cent transformation to blastlike cells occurred, compared with 2.5 per cent in the absence of antigen and 2.2 per cent for cells of nonsensitive individuals cultured with antigen. The response was not significantly changed with hyposensitization treatment. No evidence for specific skin-sensitizing antibody production was found, and none of the three immunoglobulins was detected free or on the cultured cells.

Antigenic Histamine Release from Passively Sensitized Human Leukocytes

With histamine release as an indicator, consistent passive sensitization of normal human leukocytes to specific anligen could be achieved with human serum, fresh or stored at -70 � C, from allergic individuals. With certain sera, dilution slowed the rate of sensitization but increased eventual histamine release.

Allergy and adverse drug reactions

This review begins with a classification of adverse drug reactions and a summary of those features that distinguish allergic from toxic and idiosyncratic reactions. Factors that influence the risk of developing drug allergy are then reviewed, followed by a discussion of the known and suspected immunologic mechanisms responsible for the development of drug allergy. The next section-on the types of clinical reactions-begins with the reactions that are mediated, or suspected of being mediated, by antibodies of the immunoglobulin E class. These are followed by a description of reactions involving single organ systems and those involving several systems. The next section reviews the cutaneous reactions that are sometimes due to drug allergy, and those that may be mistakenly blamed on drug allergy. This is followed by a discussion of pseudoallergic drug reactions-caused by toxicity or side effects of some drugs. The review concludes with a discussion of the prevention and treatment of reactions that are allergic or commonly suspected of being allergic.

Role of cell-mediated immunity in Hymenoptera allergy

Currently there is little information regarding the immunologic mechanisms responsible for large local reaction (LLR) after Hymenoptera stings. To investigate this question, we measured in vitro lymphocyte proliferation and delayed skin reactivity to venom antigens in 10 subjects with LLR (six with LLR only and four with LLR and systemic reactions), seven subjects with systemic reactions, and eight nonallergic controls. The lymphocyte response to venoms in the LLR group was greater than that in either the systemic reactor group (p less than 0.05) or the control group (p less than 0.001). In contrast, lymphoproliferative responses to Candida albicans, streptokinase-streptodornase, and phytohemagglutinin were comparable in the three groups. Forty percent of the LLR group had positive delayed skin tests to venom antigens, and none of the patients in the systemic reactor group had such responses. These findings suggest that cellular immune mechanisms play a role in the pathogenesis of LLR after Hymenoptera stings.

Penicillin allergy in children: The role of immunological tests in its diagnosis

Abstract Of 160 hospitalized children who were thought to be allergic to penicillin, only 17 had positive immunologic tests. Of these, 16 had positive skin tests and only 10 had significant titers of hemagglutinating antibodies. Three children had acute, explosive reactions, 4 had accelerated reactions, and 11 had late-onset reactions. In the 143 children with negative immunological tests, the diagnosis of penicillin allergy was often questionable on clinical grounds alone. Whatever the clinical features, negative tests have helped to establish the safety of subsequent penicillin treatment for many of these children.

Blood groups and secretion of blood group substances: Comparison of allergic with nonallergic persons in a pacific northwest college population

Abstract The blood group distribution of 5,657 mixed-white college students from the Pacific Northwest was found to be 42.4 per cent O, 43.4 per cent A, 10.6 per cent B, and 3.6 per cent AB. Seventy-nine per cent of 1,125 group A persons were A 1 . Eighty-three per cent of 4,387 students were Rh-positive, and 24.1 per cent of 3,144 were nonsecretors of blood group substance. There were no significant differences in such distributions within this population between allergie (hay fever and asthma) and nonallergic persons.