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Biomedical subjects

I M Suszko

Publications and source records attributed to I M Suszko.

At least 37 records · Page 2Linked to original sources
PubMed1979

The immune response of patients with ragweed hay fever treated with polymerized ragweed antigens.

This report describes the immune response of patients with ragweed hay fever treated with polymerized ragweed antigens (PRW). Their IgG antibody responses to crude ragweed extract, antigen E, antigen K, and antigen Ra3 were determined by a solid-phase radioimmunoassay. The results indicate that PRW contains an array of clinically important antigens that are available for immunologic processing and result in an immune response in patients treated with this new form of immunotherapy for ragweed hay fever.

Analysis of Variance↗
PubMed1979

Reduced allergenicity of high molecular weight ragweed polymers.

Polymerized ragweed antigens of different molecular weight ranges were studied to determine if the degree of allergenicity was dependent on molecular size of the polymers. In this study, allergenicity is defined as the ability to elict IgE-mediated skin reactivity. Ragweed antigen treated with glutaraldehyde was fractionated into one preparation with a molecular weight range of 200,000 to 20,000,000 and another with molecular weights less than 200,000. Except for the difference in molecular sizes of the two molecular sizes of the two preparations, all ragweed polymers had been treated in an identical fashion. The low molecular weight fraction had cutaneous endpoint reactivity greater than 10(5) to 10(8) times that of the high molecular weight materials. In these and other studies, immunogenicity defined as the ability to induce an IgG antibody response was retained by the high molecular weight material. The results are consitent with the hypothesis that allergenicity decreases as the molecular weight of the polymerized allergen increases.

Allergens↗
PubMed1978

Quantitation of IgE antibody specific for ragweed and grass allergens: binding of radiolabeled allergens by solid-phase bound IgE.

IgE antibody specific for multiple allergens extracted from grass and ragweed pollens was measured by radioimmunoassay. The assay depends on the interaction between IgE antibody bound to a polystyrene solid phase, , 125I-labeled grass allergens (GA), and ragweed allergens (RW). The binding of 125I RW by serum IgE antibody from 37 allergic patients ranged from 0.2 ng to 75 ng RW protein (P) bound per ml. This binding of 125I RW by patient's IgE was paralleled by their IgE binding of 125I antigen E (AgE), a purified allergen from ragweed pollen (r = 0.90, p less than 0.001). Inhibition of patient's IgE binding of 125I RW by highly purified AgE ranged from 25% to 85% indicating individual differences in patient's IgE response to inhaled ragweed pollen. The binding of 125I GA by serum IgE antibody from 7 grass-sensitive patients ranged from 0.6 ng GA P bound per ml to 15 ng. This assay should be useful in the study of IgE responses to environmental agents containing multiple allergens and has the advantage that other antibody classes cannot interfere with the interaction between IgE antibody and labeled allergens.

Allergens↗
PubMed1978

Comparison of immune reactivity to polyvalent monomeric and polymeric ragweed antigens.

The proteins of an aqueous extract of ragweed pollen (RW) were precipitated at 90% saturation with (NH4)2SO4, solubilized, and sieved through Sephadex G-15. The excluded fraction, termed the monomeric form (MRW), was cross-linked with glutaraldehyde to form polymerized ragweed (PRW). As compared with MRW, PRW is more immunogenic in rabbits in the production of antibody against RW antigen E (AgE). MRW and PRW resulted in equal peak reaginic responses in rabbits but the duration of reagin production was longer after immunization with MRW than with PRW. Both MRW and PRW have exposed antigenic determinants of AgE but PRW had approximately 1/3 the number as shown by neutralization of human antibody against RW AgE. PRW had 100-to 1,000-fold less human cutaneous reactivity than MRW. PRW may be a more easily effective therapeutic agent for human RW immunotherapy than currently used aqueous extracts and may be more readily obtainable than polymerized AgE.

Antibody Formation↗
PubMed1978

The in vivo transfer of antigen-induced airway reactions by bronchial lumen cells.

Rhesus monkeys with airway responses to aerosol challenge with Ascaris antigen constitute a primate model of inhalant asthma. Previous studies have shown that bronchial lavage cells from airway-reactive animals will release histamine or a slow-reactive substance of anaphylaxis after challenge with antigen. Because these bronchial lumen cells are the first cells in contact with inhaled antigen, they may play a role in induction of antigen-induced airway responses. To evaluate this possibility, bronchial lumen lavage cells from animals with airway reactivity were transferred to the bronchial lumens of animals with negative airway responses to antigen challenge. The transfer of the bronchial lumen cells resulted in transient airway reactivity of the recipients to aerosol antigen challenge. It is suggested that the mast cells which constitute a component of the bronchial lumen cells may be the active cell alone, or in combination with other cells, which results in this primate immunoglobulin E-mediated airway response and its transfer to nonreactivie recipients.

Animals↗
PubMed1977

Polymerization of mixtures of grass allergens.

Mixed grass pollen allergens were precipitated from crude grass extract by 90% saturation with ammonium sulfate. The precipitate was dissolved and polymerized with glutaraldehyde. Polymerized allergens with a molecular weight range of 200,000 to 4,000,000 were isolated. The resultant grass allergen polymers had reduced allergenicity but were capable of absorbing out IgG antibody from sera of 2 patients treated with crude grass allergens. This alteration of allergenicity was intended to reduce the ability of allergens to react with IgE-sensitized cells rather than to modify or destroy antigenic determinants. Prior exposure of allergens to phenol used as a preservative inhibited the polymerization process probably by blocking combining sites with which glutaraldehyde reacts.

Allergens↗
PubMed1977

Ultrastructural identification of mast cells obtained from human bronchial lumens.

We have investigated the morphology of mast cells in human bronchial lavage fluid. Under light microscopy, these cells were seen to contain discrete metachromatically positive granules that were indistinguishable from those present in mast cells and basophils from other sources. With electron microscopy, the bronchial mast cells were shown to be mononucleated and to contain granules which primarily consisted of particulate materials. Complex structures such as scrolls and crystalloids were also found in the granules. In order to delineate the relationship between bronchial mast cells and mast cells from other anatomic sites, we studied the ultrastructure of tissue mast cells from bronchial, lung parenchymal, and bone marrow biopsy specimens, and that of basophils from peripheral blood. There were similarities as well as differences in these cells from different sources--in their size, shape, lobes of nuclei, nuclear chromatin distribution, and structure of special, presumably histamine-containing, cytoplasmic granules. Based on the electron microscopic data, we believe the intralumenal cells previously described in human beings can be classified as mast cells. The presence of viable, immunoreactive mast cells in the lumen of bronchi may have a significance in relation to respiratory allergic reactions, especially the immediate-type respiratory response.

Basophils↗
PubMed1977

Sequential immunologic stimuli to the respiratory tract: a paradox in the degree of potentiation of airway responses depending on the sequence of reverse passive and active immunologic stimulation.

Immunologic stimuli to the airway of rhesus monkeys were given by aerosol challenge with ascaris antigen or anti-IgE. Both of these stimuli produce immediate-type airway responses. When 2 sequential aerosol challenges were given during the same experiment, the response following the second stimulus was always less than or equal to the first response following any combination of stimuli except the anti-IgE-ascaris sequence. The second response following the latter challenge was always greater than or equal to the first response. The possibility that this exception was the result of anti-IgE priming mediator releasing cells for antigen was not supported by in vitro experiments. It is suggested that the results obtained with the anti-IgE-ascaris sequence may relate to the presence of intralumenal mast cells in the bronchi and the molecular weights of the 2 immunologic stimuli.

Animals↗
PubMed1977

Living histamine-containing cells from the bronchial lumens of humans. Description and comparison of histamine content with cells of rhesus monkeys.

Cell populations obtained by bronchial lavage from human subjects were examined for the presence of cells related to the mast cell-basophil series. Such bronchial lumen histamine-containing cells (BLHCC) were identified. The BLHCC stained with toluidine blue may be identified by bright field or dark field microscopy. The BLHCC are alive as evidenced by ability to release histamine (H) after exposure to anti-IgE or calcium ionophore. Although H release from peripheral blood leukocytes by these two agents is potentiated by the presence of D2O, H release from BLHCC of the same subjects by anti-IgE or calcium ionophore was not potentiated by D2O. In studies comparing bronchial cell populations of humans and rhesus monkeys with peripheral blood leukocyte populations of the same subjects, the histamine content of the bronchial cell population was much higher in rhesus monkeys. IgE/Alb ratios of respiratory secretions and serum of the same human subjects were of the same order of magnitude in contrast to previous comparisons done on these fluids in rhesus monkeys.

Animals↗
PubMed1977

Immediate-type hypersensitivity to keyhole limpet haemocyanin in the dog.

A model of immediate-type hypersensitivity (ITH) in the dog using keyhole limpet haemocyanin (KLH) as the antigen was studied. Long-lasting ITH was induced in fifteen of sixteen dogs by the i.v. (Kepron & Tse, 1975), intradermal (Rockey, Schwartzmann & Halliwell, 1971), inhalation (Patterson & Kelley, 1974) and i.d. plus inhalation (Rockey et al., 1971) routes. This ITH was demonstrated by direct skin reactivity, acute respiratory reactions and peripheral blood leucocyte and respiratory cell histamine release. The reaginic antibodies considered to mediate these reactions were larger than canine IgG, heat labile, 2-mercaptoethanol sensitive, and are probably canine IgE. In addition to cutaneous and respiratory reactions, these reagins were shown to mediate systemic reactions. In the course of these studies, an unexpected finding was the occurrence of ITH to KLH in three dogs which had had no prior experimental exposure to KLH. This ITH was of sufficient intensity to be associated with acute airway reactions to the inhaled antigen.

Animals↗
PubMed1976

Comparison of polymerized and unpolymerized antigen E for immunotherapy of ragweed allergy.

Polymerization of ragweed antigen into high-molecular-weight polymers could improve immunotherapy for ragweed pollinosis by reducing side effects while retaining immunogenicity. To study this thesis, 23 ragweed-sensitive patients were treated with either ordinary ragweed antigen E or ragweed antingen E polymerized by glutaraldehyde. Four patients received the polymerized antigen, and six controls ordinary antigen according to the standard immunotherapy schedule; two groups of three patients received either form by a "doubling-dose" schedule. Seven subjects received the polymerized antigen by a schedule in which each successive dose was tripled. Serum antigen E binding capacity (blocking antibody) increased significantly in all subjects (P less than 0.001 by Student-test). Patients treated with polymerized antigen had fewer local and generalized reactions than those receiving the monomeric preparation. Polymerized ragweed antigen permits more rapid immunization of atopic persons, with fewer side effects than standard monomeric preparations.

Adult↗
PubMed1976

Polymerized ragweed antigen E. IV. The analysis of the stability of molecular size and antigenic reactivity of the polymer.

Ragweed antigen E polymerized by treatment with glutaraldehyde offers a potentially improved method for immunotherapy of human IgE-mediated pollinosis because studies have demonstrated that the polymer retains antigenic reactivity but has decreased ability to release histamine when these functions are compared on a weight basis. The potential clinical usefulness of the polymer is dependent both on stability of the polymer and on retention of antigenic reactivity. The method used for the analysis of the stability of the polymer under conditions of storage was the comparison of gel filtration fractionation profiles. No depolymerization was demonstrated during storage conditions for 2 mo, and only minimal evidence of additional polymerization (less than 8%) or depolymerization (less than 7%) was observed after 6 mo of storage. There was no difference in the per cent of polymerized antigen E precipitated by rabbit antiserum after storage as compared with control samples.

Antigens↗
PubMed1976

Effect of D2O on phytohemagglutinin-induced lymphocyte proliferation.

The effect of D2O on phytohemagglutinin (PHA)-induced proliferation of human lymphocytes in vitro was examined. A significant dose-dependent inhibition of the lymphocyte reactivity by D2O was observed. This inhibition did not require the simultaneous presence of D2O and PHA in the cultures. Both cytotoxic and cytostatic mechanisms for this inhibition are implicated.

Deuterium↗
PubMed1976

Reagin-mediated asthma in rhesus monkeys and relation to bronchial cell histamine release and airway reactivity to carbocholine.

Rhesus monkeys with persistent immediate-type cutaneous and respiratory responses (RR) to ascaris antigen (AA) were compared with rhesus monkeys with skin reactivity and no respiratory responses, and animals with no skin reactivity and no respiratory responses to inhaled antigen (NR). The RR group could not be distinguished from the nonresponding (NR) group by the cutaneous skin test titers, serum, or respiratory secretion IgE concentration. Leukocyte histamine (H) release due to anti-IgE was similar with peripheral blood leukocytes and bronchial lumen mast cells (MC) from RR and NR animals. The RR group of animals could be distinguished from the NR group by their degree of sensitivity to inhaled carbocholine and H release from respiratory MC exposed to AA. The RR group demonstrates consistent, persistent respiratory responses suitable for immunologic, pharmacologic, and physiologic studies. Finally, it was found that the IgE concentration in respiratory secretions of rhesus monkeys was comparatively higher than in serum, evidence for IgE as a secretory Ig in the respiratory tract of this species.

Aerosols↗
PubMed1976

IgE-mediated histamine and SRS-A release from respiratory cells and peripheral blood leukocytes of rhesus monkeys.

Peripheral blood leukocytes (PBL) and free respiratory cells (RC) of the mast cell-basophil type were obtained from normal rhesus monkeys or rhesus monkeys with defined immediate-type hypersensitivity to ascaris antigen (AA). PBL or RC from the latter were exposed to AA and the former were exposed to anti-IgE. Histamine (H) release and release of a slow reacting substance of anaphylaxis (SRS-A) occurred following exposure of the appropriate cells to AA or anti-IgE. The release of both H and SRS-A from PBL was potentiated by D2O. D2O did not potentiate release of SRS-A or H from RC due to anti-IgE to the same extent. Although potentiation of H release from RC due to AA was observed in the presence of D2O in some individual animals, this could not be demonstrated by statistical analysis of group results. We could not demonstrate potentiation of SRS-A release from RC due to anti-IgE or AA. The results suggest the possibility that there may be differences in antigen reactive cells of the respiratory tree and peripheral blood and biochemical studies may be of use in demonstrating these differences.

Animals↗
PubMed1976

Histamine-containing cells in bronchial lavage fluid. I. Ultrastructural characterization and comparison with mast cells in three types of tissues of rhesus monkeys.

We have studied the ultrastructure of histamine-containing cells in the bronchial lavage of normal rhesus monkeys. These cells were recognized by the similarities of their specific cytoplasmic granules to those in tissue mast cells and basophilic leukocytes of other species. According to cell shape, two forms of bronchial lavage histamine-containing cells (BL-HCC) were observed. One was round and small, and the other pleomorphic and large. However, the subcellular structures, especially the specific cytoplasmic granules, were identical for both forms of HCC. With available evidence, we now consider both types of BL-HCC to be one cell species. The difference in cell shape may be an inherent variation within this cell population, or a reflection of the maturity of individual cells. Most BL-HCC had long slender pseudopods, and the majority of them were mononucleated. Some HCC appeared binucleated; multinucleated cells were not encountered. The ultrastructure of mast cells, in tissue fragments biopsied from three sites, was in many ways similar to that of BL-HCC, but there were clear morphological dissimilarities between these two cell groups. It is unlikely that tissue mast cells are the direct precursors of BL-HCC. Attempts to compare BL-HCC with blood basophilic leukocytes were unsuccessful due to the failure to detect the latter in monkey peripheral blood with electron microscopy in the present study. The possible origin of BL-HCC is discussed.

Animals↗
PubMed1976

In vitro production of IgE by human peripheral blood lymphocytes: effect of cholera toxin and beta adrenergic stimulation.

Peripheral blood lymphocytes from two human donors with elevated serum IgE concentrations were maintained in short term tissue culture preparations. Repeated culture preparations demonstrated that IgE was produced in vitro in amounts that could be measured by the double antibody radioimmunoassay technique. The amount of IgE produced by replicate cultures of cells from a single bleeding of the donor was similar when the cultures were simultaneously prepared. In contrast, IgE production by the same donor's lymphocytes varied when the culture preparations were initiated from separate bleedings. The results of simultaneous cultures of a single bleeding were sufficiently consistent to provide a means of testing the effect of pharmacologic agents on the in vitro production of IgE. Cholera toxin effected a marked reduction in production of IgE by lymphocytes of both cell donors. Isoproterenol showed marked inhibition of IgE production at 10(-3) M but cell viability studies suggested that this may have been due to decreased cell viability. At lower, nontoxic concentrations of isoproterenol (10(-4) M-10(-6) M) slight but definite inhibition of in vitro IgE production was evident. This inhibition was more pronounced subsequent to the first 24 hr of exposure of the cells to isoproterenol.

Cell Survival↗