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Biomedical subjects

I M Suszko

Publications and source records attributed to I M Suszko.

At least 19 recordsLinked to original sources
PubMed1985

Polymerized soluble venom--human serum albumin.

Extensive previous studies have demonstrated that attempts to produce polymers of Hymenoptera venoms for human immunotherapy resulted in insoluble precipitates that could be injected with safety but with very limited immunogenicity in allergic patients. We now report soluble polymers prepared by conjugating bee venom with human serum albumin with glutaraldehyde. The bee venom-albumin polymer (BVAP) preparation was fractionated on Sephacryl S-300 to have a molecular weight range higher than catalase. 125I-labeled bee venom phospholipase A was almost completely incorporated into BVAP. Rabbit antibody responses to bee venom and bee venom phospholipase A were induced by BVAP. Human antisera against bee venom were absorbed by BVAP. No new antigenic determinants on BVAP were present as evidenced by absorption of antisera against BVAP by bee venom and albumin. BVAP has potential immunotherapeutic value in patients with anaphylactic sensitivity to bee venom.

Animals↗
PubMed1984

Persistence of efficacy after a brief course of polymerized ragweed allergen: a controlled study.

Immunotherapy with PRW has been demonstrated to be safe and effective. To determine whether the efficacy would remain in successive ragweed seasons without further therapy, a trial was conducted comparing PRW to histamine placebo therapy in patients that had received courses of PRW previously. Those patients were also compared to previously untreated ragweed-sensitive patients. In a double-blind fashion, 21 previously treated patients were treated before the 1982 ragweed season with four injections of PRW therapy, whereas 21 previously treated patients were treated with four injections of placebo therapy. An additional control group of 21 previously untreated ragweed-sensitive patients received no injections. Daily symptom and medication score sheets were completed by patients each day of the ragweed season. Blocking antibody rose elevenfold with treatment (p less than 0.0001) in the PRW group. There was a statistically significant difference in symptom score mean between untreated patients (1007 +/- 174) and previously treated patients whether they received supplemental injections (554 +/- 180) (p less than 0.01) or whether they did not (650 +/- 168) (p less than 0.03). In summary the efficacy of 15 injections of PRW immunotherapy persists at least several years without need for supplemental immunotherapy.

Clinical Trials as Topic↗
PubMed1984

Polymerization of individual species of tree pollen allergens.

This report describes the preparation of individual tree pollen allergen polymers in contrast to our previous description of the polymerization of a mixture of tree pollens.. These individual polymers may be used for immunotherapy as indicated by the IgE-mediated reactivity of each patient. A modified chromatographic fractionation process was used which results in tree polymers with skin reactivity 1,000- to 10,000-fold less from monomers and with a defined lower molecular weight limit. The modified preparative methodology results in polymer preparations as safe but with greater ease of production than polymers prepared with previous methodologies.

Allergens↗
PubMed1983

Polymerization of individual species of grass pollen allergens.

Six grass pollen allergens have been individually polymerized. We had previously polymerized mixed grass pollen allergens. However, since every patient does not react to every grass, we sought to polymerize individual grasses that could subsequently be mixed into a preparation based on a patient's skin reactivity. As demonstrated by Sepharose 4-B chromatography of individual grass monomers and polymers, all six grasses were polymerized. Polymerized grass preparations as compared with monomer preparations demonstrated a 10(3)- to 10(5)-fold reduction in allergenicity as determined by cutaneous end point titer. That grass polymer contains the great majority of clinically important allergenic determinants was demonstrated by the ability of polymer to inhibit 78% IgE binding against crude grass in a pool of untreated grass-sensitive patients. Its antigenic similarity to crude grasses is further shown by the ability of polymer to inhibit 85% of IgG binding against crude grass in a pool of patients treated with usual crude grass extracts.

Binding, Competitive↗
PubMed1983

Evaluation and standardization of polymerized ragweed extracts by chromatography, radioimmunoassay inhibition, and end point cutaneous titration.

The standardization procedures for polymerized ragweed (PRW) must evaluate activity of PRW with assessments that differ from those used for standard unmodified extracts. This is because PRW allergens are different from conventional ragweed extracts in that they are much greater in average molecular weight and much lower in allergenicity for equivalent immunogenicity. We have evaluated seven samples of PRW for three parameters: allergenicity as determined by cutaneous end point titration, molecular weight distribution as determined by Sephadex G-200 chromatography, and availability of antigen E (AgE) determinants as measured by the ability of an extract to inhibit AgE binding to antibody by using a modification of the Farr technique. The skin test titers and molecular weight profiles provide information as to the safety of a PRW preparation and antigen-binding inhibitory activity gives information about allergenicity and immunogenicity. Appropriate limits may be set for each of these parameters to standardize PRW for clinical use.

Allergens↗
PubMed1983

A double-blind histamine placebo-controlled trial of polymerized whole grass for immunotherapy of grass allergy.

Twenty-six patients were recruited for a study of the safety and efficacy of immunotherapy with IPG. They were randomly assigned to two groups based on skin test titrations to grass allergens. One group was treated in a double-blind fashion before the 1982 grass season with 12 weekly injections totaling approximately 48,000 PNU, and the other group was treated with 12 weekly injections of caramelized glucose histamine placebo. Daily symptom and medication score sheets were completed by all patients each day of the grass season. Blocking antibody rose ninefold in the IPG group (p less than 0.007) but was unchanged in the placebo group. There was no significant change in IgE against rye grass group I in either the IPG or the placebo group. Symptom-score mean in the IPG group was 217 +/- 71 (S.E.M.), statistically lower (p less than 0.02) than the mean in the placebo group 496 +/- 117 (S.E.M.). There were no systemic reactions and only minor local reactions. There was no change in routine laboratory tests in either group. Although two prior studies with grass allergen immunotherapy reported efficacy, these studies did not use symptom-score analysis. This is the first double-blind, histamine placebo-controlled study of grass immunotherapy that demonstrates efficacy by symptom-score index evaluation. IPG is a safe, clinically effective, and potentially cost-effective therapy for grass pollinosis.

Clinical Trials as Topic↗
PubMed1982

The immune response in humans and rabbits to monomeric and polymeric grass allergens.

The antigenicity of polymerized grass (PG) and monomer grass (MG) was studied. As compared with MG, PG produces a similar immunologic response in rabbits as demonstrated by a tanned red blood cell (TRBC) passive hemagglutination assay or by total serum binding of perennial rye grass Group I antigens (RGGI). Six patients with allergic rhinitis sensitive to several grass pollens received an average of 60,000 protein nitrogen units (PNU) or PG. The initial dose was 100 PNU ans a maintenance dosage of 8500 PNU was obtained after six injections without systemic reactions in any of the patients. Serum binding of RGGI increased significantly in the PG-treated patients and this increase was quantitatively similar to that measured in a second group of six atopic patients previously treated for 1 year with a total of 100,000 PNU of a standard grass extract mixture. PG, like polymerized ragweed (PRW), has a reduced allergenicity while retaining immunogenicity. These data suggest that PG as compared to standard aqueous grass extract mixtures represents an improved form of immunotherapy for the atopic patients.

Allergens↗
PubMed1982

A double-blind, placebo-controlled trial of polymerized whole ragweed for immunotherapy of ragweed allergy.

Immunotherapy with polymerized ragweed (PRW) has been demonstrated to be safe and effective when compared with monomeric ragweed or untreated controls. To further establish the efficacy of PRW, a trial was conducted comparing PRW, placebo, and no treatment in ragweed-sensitive individuals. In a double-blind manner, 21 patients were treated before the 1981 ragweed season with 15 weekly injections of PRW totaling about 50,000 PNU and 1200 microgram antigen E, while 19 patients were treated with 15 weekly injections of a caramelized glucose and histamine placebo. An additional control group received no injections. Blood was drawn for IgE against ragweed antigen E (IgE-a-AgE) and for blocking antibody against AgE before treatment, after treatment (before season), and after season. In the untreated patients, blood was drawn before season and after season. Daily symptom score sheets were completed by patients each day of the ragweed season. Blocking antibody rose more than 40-fold with treatment (p = 0.0001) in the PRW group but was unchanged in the placebo group with treatment. IgE-a-AgE rose with PRW therapy. Clinical efficacy of PRW was again confirmed in this study. Symptom score mean in the PRW group was statistically lower than the mean in the placebo group (p = 0.022) and in the untreated group (p = 0.018). There were no systemic reactions and only minor local reactions during treatment. In summary, PRW is an improved form of immunotherapy.

Adult↗
PubMed1981

Characterization of hapten-human serum albumins and their complexes with specific human antisera.

Human antisera against trimellityl-human serum albumin or diphenylmethane diisocyanate-human serum albumin were fractionated by Sephadex G200. The fractions containing IgG were pooled and reacted with trimellityl 125I-human serum albumin or diphenylmethane diisocyanate-125I-human serum albumin, and these mixtures were again fractionated through Sephadex G200. The resultant chromatographic profiles showed two peaks. The first peak contained hapten-human serum albumin-antibody as demonstrated by the precipitability of radioactivity with anti-human IgG. During these studies it was found that trimellityl-human serum albumin or diphenylmethane diisocyanate-human serum albumin have different elution profiles and electrophoretic mobilities than human serum albumin. Trimellityl-human serum albumin elutes earlier and migrates farther toward the anode than either diphenylmethane diisocyanate-human serum albumin or human serum albumin. Diphenylmethane diisocyanate-human serum albumin elutes earlier and migrates farther toward the anode than human serum albumin. These results may be explained by swelling of the trimellityl-human serum albumin molecule due to the additional negative charges of the trimellityl carboxyl groups and loss of positive charges at basic amino acid binding sites of trimellityl. The lesser changes in diphenylmethane diisocyanate-human serum albumin may result from only the delection of positive charges on basic amino acids of human serum albumin since diphenylmethane diisocyanate contributes no additional charge.

Antigen-Antibody Reactions↗
PubMed1981

Further studies on the safety of polymerized antigens for immunotherapy.

Six patients receiving immunotherapy with standard aqueous extracts for the treatment of atopic disease were selected from the patient population of Northwestern University Allergy Clinics for continued immunotherapy with polymerized antigens. These six patients could not tolerate quantities of conventional aqueous extracts considered maintenance doses because of immediate-type local or systemic allergic reactions or both to immunotherapy. These six patients were treated with separate preparations of polymerized ragweed (PRW) and polymerized grass (PG), and each of the six patients was rapidly advanced to previously unobtainable maintenance doses of PRW and PG without local or systemic reactions. Treatment with other aeroallergen standard extracts was continued to maintenance dosage without further systemic reactions. In patients highly sensitive to ragweed and grass aqueous extracts, the substitution of these extracts with PRW and PG allows these patients to receive therapeutic immunotherapy injections with decreased risk of immediate-type local and systemic reactions.

Adult↗
PubMed1981

Polymerized tree pollen antigens.

Aqueous extracts of tree pollen were partially purified and polymerized with methods previously established for preparation of ragweed and grass polymers. The polymerized tree preparations were antigenic as demonstrated by ability to elicit immediate-type skin reactivity in humans and to induce an immune response in rabbits. The polymerized tree antigen was 100- to 10,000-fold less skin reactive than monomer tree antigen in tree pollen-sensitive patients but both preparations had similar antigenicity in rabbits. These results demonstrate that polymerized tree antigens can be prepared and should have the therapeutic potential already demonstrated for polymerized ragweed preparations.

Animals↗
PubMed1980

Polymerized insoluble bee venom.

Using a polymerization process previously used for ragweed allergens, honeybee venom was polymerized. Instead of soluble polymers, an insoluble precipitate, polymerized insoluble bee venom (PIBV), is the result. A major allergen of honeybee venom, 125I phospholipase A (PL-A) incorporated into PIBV, was shown to have decreased dissemination from subcutaneous injection sites. After thorough mixing, samples of PIBV can be withdrawn from a vial with a syringe with no more than 10% error. Approximately 90% of PL-A was incorporated with PIBV. The soluble PL-A was removed during subsequent washing of the PIBV and this soluble PL-A was shown to be polymerized mainly to high-molecular weight PL-AS. PIBV (20 mg) injected in each of six rabbits resulted in formation of precipitating antibody in all rabbits. The rabbit antisera bound 125I PL-A and reacted with PL-A in whole been venom. These physical and immunologic characteristics of PIBV suggest further study of its potential for human use.

Absorption↗
PubMed1980

Heterogeneity of bronchial lumen mast cells which are homogeneous by electron microscopy.

Bronchial lumen mast cells were obtained by bronchial lavage from rhesus monkeys and fractionated on a discontinuous metrizamide gradient. Those cells identified as pleomorphic by standard microscopy sedimented in the higher concentrations of metrizamide, while the round cells were dispersed through all gradient fractions. Electron microscopic studies of the pleomorphic and round cells demonstrated that these were morphologically identifiable as mast cells. Although all the cells appear to be mast cells, they are heterogenous in that mast cells in the higher concentrations of metrizamide had higher concentrations of histamine. By contrast, the mast cells in the lower concentrations of metrizamide had greater biologic activity as indicated by greater release of histamine following an immunologic stimulus. The heterogeneity of bronchial lumen mast cells shown by light microscopy, histamine content, and histamine releasibility may be due to the presence of subpopulations of mast cells or changes in a single cell line reflecting differential maturation.

Animals↗