Search PubMed⌕ Search

Biomedical subjects

A W Wheeler

Publications and source records attributed to A W Wheeler.

48 records · Page 3Linked to original sources
PubMed1976

The IgG subclasses of antibodies to grass pollen allergens produced in hay fever patients during hyposensitization.

Total IgG, IgG subclass and IgE antibodies specific for grass pollen allergens were measured by the red cell linked antigen-antiglobulin reaction (RCLAAR) in a serum samples from nineteen patients who had undergone a course of hyposensitization. Increases in both specific IgG and IgE antibodies were seen after treatment in most patients. In the IgG subclasses the predominant response was for IgG1 and IgG4 antibodies. Attempts were made to correlate the antibody responses with the clinical response and the results are discussed with reference to the possible mechanisms of hyposensitization.

Antigen-Antibody Reactions↗
PubMed1976

Antigenic properties of polymers formed by beta-lactam antibiotics.

Purified polymers have been isolated from 6-aminopenicillanic acid and from semi-synthetic penicillins and cephalosporins. All the polymers were shown to react with rabbit antibody of penicillins and cephalosporins. All the polymers were shown to react with rabbit antibody of penicilloyl specificity, as demonstrated by passive cutaneous anaphylaxis in guinea pigs, and the reactions were shown to be penicilloyl-specific by hapten inhibition experiments. The cephalosporin-derived polymers in addition reacted with rabbit antibodies raised to the corresponding cephalosporin conjugates of bovine gamma-globulin. Using direct skin tests, passive cutaneous anaphylaxis and an in vitro assay, no evidence was obtained that the polymers induced the formation of specific antibodies in baboons, guinea pigs and rabbits, but in baboons the induction of cell-mediated immunity, demonstrable by delayed skin test reactions, was shown.

Ampicillin↗
PubMed1976

Chemical modification of crude timothy grass pollen extract. I. Antigenicity and immunogenicity changes following amino group modification.

Glutaraldehyde modification was found to reduce the allergenic potency of crude timothy pollen extracts yet even highly substituted materials retained the capability of inducing the formation of allergen-specific antibody in animals. Experiments showed that these antibodies were capable of blocking skin test reactions to native timothy allergens in pollen-sensitive human volunteers. The value of glutaraldehyde-modified allergen extracts for use in desensitization vaccine therapy is discussed.

Aldehydes↗
PubMed1976

Chemical modification of crude timothy grass pollen extract. II. Class and specificity of antibodies induced by chemically modified timothy grass pollen extract.

The effects have been studied of three different chemical modifications of timothy grass pollen extract on various immunological properties. The ability to induce IgG antibody with specificity for native antigen was least affected by glutaraldehyde treatment; IgE antibody production was reduced to a similar extent by all three modifications; there was no increase in IgM production; delayed reactions were reduced. New antigenic determinants were introduced by all the modifications, but the effect was minimal following glutaraldehyde treatment. The significance of these results and the potential application of modified allergen in hyposensitisation therapy are discussed.

Acetoacetates↗
PubMedDate not supplied

Standardisation of glutaraldehyde-modified tyrosine-adsorbed tree pollen vaccines containing the Th1-inducing adjuvant, monophosphoryl lipid A (MPL).

BACKGROUND: a new range of allergy vaccines has been developed by the introduction of a relatively new Th1-inducing adjuvant known as 3-deacylated monophosphoryl lipid A (MPL). MPL adjuvant is of natural origin, derived from the lipopolysaccharide of Salmonella minnesota R595. This adjuvant is incorporated in a glutaraldehyde-modified pollen extract adsorbed to L-tyrosine (Pollinex Quattro). A major potential benefit provided by MPL adjuvant is the promotion of a Th1 response which enhances the efficacy of allergy vaccination and can consequently allow a reduction in the number of injections required for treatment. The standardisation of Pollinex Quattro tree pollen allergy vaccine is described and we include details of some innovative analytical procedures. METHODS AND RESULTS: an essential feature of the analytical strategy is the assay of the MPL adjuvant using a recently developed HPLC technique. The adjuvant has a complex chemical structure and the analysis is illustrated in detail. We give a full picture of the vaccine standardisation by describing biochemical and immunological characterisation of the allergen extract, together with some brief manufacturing details. CONCLUSIONS: a high overall level of standardisation is illustrated by a number of different tests applied to all stages of vaccine manufacture. Tree pollen allergen potency is measured following the pollen extraction, chemical modification and formulation as a tyrosine adsorbate. Good batch-to-batch reproducibility is shown. The HPLC assay for MPL adjuvant showed high quality resolution which did not vary when measuring raw material or when incorporated in the vaccine and the technically complex assay is shown to be reliable.

Adjuvants, Immunologic↗
PubMedDate not supplied

Immunological properties of allergen chemically modified with synthetic copolymer of N-vinylpyrrolidone and maleic anhydride.

Several conjugates of model allergen ovalbumin (OA) and the copolymer of N-vinyl pyrrolidone and maleic anhydride (VMA) modified with epsilon-aminocaproic acid (Acp) were prepared in different OA/Acp-VMA ratios. All conjugates were separated by ultrafiltration and analyzed by HPLC. Their compositions were determined by amino acid analysis and UV spectrometry. To detect immunogenicity, all conjugates were injected intraperitoneally into (CBAxC57BL/6)F1 mice three times in 3-week intervals in OA doses equivalent to 0.5, 10, and 100 micrograms/mouse. Only the conjugate containing 20%OA (OA(20%)-Acp-VMA) did not induce significant quantities of anti-OA IgE, but did induce anti-OA IgG antibodies in dose-dependent manner comparable to that of unmodified OA. Mixtures of OA and Acp-VMA or OA modified only with VMA without Acp activation with Acp induced dose-dependent anti-OA IgE and IgG antibody formation comparable to that of OA. Using passive cutaneous anaphylaxis, RAST inhibition and leukocyte histamine release, a significant reduction of allergenicity was noted using OA(20%)-Acp-VMA. This conjugate stimulated activation of the OA-specific T-cell hybrid 3DO-548 comparable to that of unconjugated OA. During experimental allergen-specific hyposensitization with OA(20%)-Acp-VMA, suppression of anti-OA IgE response and elevation of anti-OA IgG responses were noted when compared with unmodified OA. Selective blockade of B-cell epitopes of allergen may occur using the carrier Acp-VMA to reduce allergenicity while not affecting T-cell epitopes, thereby preserving immunogenicity. This approach of chemical modification of allergen suggests new opportunities in the creation of preparations for allergen-specific immunotherapy.

Allergens↗
PubMedDate not supplied

Comparison of the efficacy and safety of two preseasonal regimens of glutaraldehyde modified, tyrosine-adsorbed parietaria pollen extract over a period of three years in monosensitive patients.

The purpose of this study was to evaluate the clinical efficacy over a period of three years (1988-90) of two preseasonal dosage regimens of a Parietaria allergoid (Bencard Tyrosine Parietaria) in patients who were only sensitive to this pollen. Fifty patients were included (14 men and 36 women, age: mean, 28 years; range, 14-47 years). Twenty five patients (group A) were treated each january with the basic course of Bencard Tyrosine Parietaria. This consisted of injecting subcutaneously 0.5 ml from each of three vials, with one week between each injection. A further injection using the vial with the highest dose was given one week later. Each january and february, twenty five patients (group B) were treated with the basic course of Bencard Tyrosine Parietaria, repeating the last dose five times, with one week between each injection. Immunotherapy with a tyrosine-adsorbed Parietaria judaica allergoid is an effective method for mitigating nasal (p < 0.0001), bronchial (p < 0.005), conjunctival (p < 0.001) and palatal itching symptoms (p < 0.0001) in patients who are sensitive to this pollen. Sensitivity to Parietaria pollen, as verified by skin test and nasal challenge, decreased during immunotherapy (p < 0.001). Histamine release by peripheral blood basophils decreased during the course of the study, falling from 43.5 ng/ml to 12.3 ng/ml in group A and from 42.9 ng/ml to 10.0 ng/ml in group B; during the second and third years, IgG levels were increased one and four months after starting treatment with the extract, while this was not the case after ten months; IgE levels were also increased. Finally, overall tolerance to this immunotherapy product was good in almost all patients.

Adolescent↗