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Biomedical subjects

J J Pruzansky

Publications and source records attributed to J J Pruzansky.

At least 37 records · Page 2Linked to original sources
PubMed1981

Enrichment of human basophils.

A 3-step procedure is described in detail for producing 50% basophils in 50% yield from human blood. Leukocytes from dextran sedimented blood or preferably whole blood are sedimented on Hypaque-Ficoll, then on aqueous Hypaque, followed by adherence and elution from a column of glass beads. The cells appear normal and undergo specific histamine release after incubation with antigen. The procedure is relatively rapid and should allow further study of mechanisms of mediator release with more homogeneous populations of basophils. The first step also provides a 5 min separation of blood into a lymphocyte enriched mononuclear cell fraction and a granulocyte enriched fraction.

Basophils↗
PubMed1981

An agent that releases basophil and mast cell histamine but blocks cyclooxygenase and lipoxygenase metabolism of arachidonic acid inhibits immunoglobulin E-mediated asthma in rhesus monkeys.

An inhibitor of the lipoxygenase and cyclooxygenase pathways of arachidonic acid metabolism, BW755C, was evaluated with the rhesus monkey model of IgE-mediated asthma. BW755C was found to release histamine from human and rhesus peripheral blood leukocytes and rhesus bronchial lavage cells. BW755C did not induce a rhesus airway response but inhibited antigen-induced airway changes in pulmonary resistance and dynamic compliance. The results demonstrated that a lipoxygenase and cyclooxygenase inhibitor that is a histamine releaser may inhibit some pulmonary function abnormalities of an IgE-mediated response and suggested that histamine has a minor role as a stimulator of airway reaction in this model. This was supported by studies showing failure of the histamine H1 blocker pyrilamine maleate to inhibit the antigen-induced airway response. Although BW755C has been shown to be a lipoxygenase and cyclooxygenase inhibitor, it is not established that the inhibiting action of this agent on an antigen-induced airway response is due to an effect on arachidonate metabolism in the lung.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1981

Seasonal variation of IgE antibody specific for ragweed antigen E (IgE-a-AgE) from the basophil surface in patients with ragweed pollenosis.

Seasonal elevation in total serum IgE and IgE antibody specific for antigen E (IgE-a-AgE) are well recognized in patients with ragweed pollenosis. We found that the ratio of specific IgE-a-AgE to total IgE in plasma was the only measure predictive of the number of specific IgE-a-AgE molecules per basophil. Although both total and specific IgE rose with season, the ratio did not change, the number of IgE-a-AgE molecules per basophil did not change, and histamine release in response to AgE did not increase.

Antibody Specificity↗
PubMed1981

Human antibodies against trimellityl proteins: comparison of specificities of IgG, IgA and IgE classes.

The specificities of antibodies of different Ig classes against trimellityl (TM)-human serum albumin were examined by a radioimmunoassay inhibition technique. The antisera were from workers exposed to trimellitic anhydride who had 4 differing respiratory diseases. The studies demonstrated similarities between reactivities of antibodies of different Ig classes in these workers in that inhibition of antibody to TM-HSA required markedly less TM-HSA on a molar basis than TM-ovalbumin (OA) or sodium trimellitate (NaTM), the hapten for the trimellityl group. The results appears best explained by formation of new antigenic determinants on altered HSA molecules with the TM group forming a component of some of the new antigenic determinants. NaTM in high concentration could not completely inhibit the IgG antibodies of 2 sera suggesting either very low affinity for the hapten or that some of the antibodies might possibly be directed against new antigenic determinants formed from the reaction of TMA with HSA but that the TM group might not be a part of the antigenic specificity. The results of some studies also suggested that there were similar antigenic specificities on TM-HSA and TM-OA but of lesser concentration or lower affinity on the latter molecules. Passive transfer studies using a serum containing IgE antibodies against TM-HSA demonstrated that these human IgE antibodies will passively sensitize rhesus monkey skin. Neutralization of the cutaneous IgE antibodies occurred with TM-HSA but not with a great molar excess of NaTM in analogy with the in vitro studies.

Antibodies↗
PubMed1981

A double-antibody radioimmunoassay for specific IgE to ragweed antigen E.

A double-antibody radioimmunoassay has been developed for quantitating IgE-a-AgE in serum. The patient's IgE is complexed by rabbit anti-human IgE, which is then precipitated with GARG. Radiolabeled AgE is then added to the washed precipitate and is specifically bound by IgE-a-AgE. This assay is highly reproducible, and unlike specific IgE assays based on the RAST concept, it cannot be inhibited by specific antibody of other immunoglobulin classes (blocking antibody). In addition, the double-antibody method does not require the use of myeloma IgE, and its results correlate well with those of a previously developed polystyrene tube method.

Antibodies, Anti-Idiotypic↗
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

Immunoglobulin E-mediated asthma and hypersensitivity pneumonitis with precipitating anti-hapten antibodies due to diphenylmethane diisocyanate (MDI) exposure.

Two workers are presented who were exposed to diphenylmethane diisocyanate (MDI) while coating pipes with a polyurethane foam. After a latent period of exposure, worker A developed immediate-onset asthma and worker B developed a clinical picture of hypersensitivity pneumonitis for which he was hospitalized. The antibody response of these workers to a conjugate of MDI with human serum albumin (MDI-HSA) was measured by gel precipitation, total antibody binding of 125I MDI-HSA, and specific IgG and IgE antibody by polystyrene-tube radioimmunoassay (PTRAI). Worker B had precipitating antibody to MDI-HSA by double immunodiffusion in gel. Both workers had high levels of IgG antibody specific for MDI-HSA which had some cross-reactivity with a conjugate or toluene diisocyanate and HSA. Total serum antibody binding of 125I MDI-HSA was 15 microgram/ml in worker A and 900 microgram/ml in worker B. Both workers had serum IgE antibody specific for MDI-HSA as measured by two PTRIA techniques. These results indicate that a marked immunologic response to MDI is possible in exposed workers and that hypersensitivity pneumonitis can occur subsequent to the inhalation of a low-molecular-weight chemical in the industrail setting.

Adult↗
PubMed1980

A linear correlation between histamine release and degranulation of human basophils by specific antigen or the ionophore A23187.

Simultaneous kinetic measurements have been made of basophil degranulation and of histamine release. Both antigen and ionophore A23187 were studied. Cells from the same donor under the same conditions undergo both reactions at a similar rate. Regression analysis indicated a statistically highly significant correlation between these two parameters for activation by either antigen or ionophore. In addition, the mean slope of the regression lines approached unity indicating a close direct correspondence between the number of cells degranulated and the quantity of histamine released. At any time during histamine release almost all of the cells identifiable as basophils were confluently stained and only rarely were partly degranulated cells observed. These results suggest that: (1) histamine release is not synchronous for populations of basophils; (2) individual cells are fully activated to begin histamine release at different times during the release period and then release all or almost all of their histamine in a short time relative to the total release period; (3) some cells release essentially none of their histamine and the number of these cells varies among donors and experimental conditions accounting in large measure for the incompleteness of histamine release.

Anti-Bacterial Agents↗
PubMed1980

Detection of antibodies in human serum using trimellityl-erythrocytes: direct and indirect haemagglutination and haemolysis.

Utilizing trimellityl-erythrocytes (TM-E), antibodies were detected in sera of seven workers with trimellitic anhydride (TMA) induced airway syndromes by direct haemagglutination, indirect haemagglutination with anti-human IgG, IgA or IgM or by haemolysis. Detectable levels of antibody were obtained with all three methods. The most sensitive technique was indirect haemagglutination using anti-IgG. When added as an inhibitor, TM-human serum albumin produced a 10- to 800-fold reduction in titres. TM-ovalbumin of similar epitope density was less inhibitory and sodium trimellitate the least inhibitory on a molar basis. All of the assays using haptenized human red cells were also capable of detecting anti-TM antibodies in Rhesus monkeys whose airways had been exposed to TMA. These assays are useful for detecting anti-TM antibodies and may also be adapted to demonstrate antibodies induced against other inhaled haptens in sera of environmentally exposed individuals or in animal models of such exposure.

Animals↗
PubMed1980

Antibodies in hemodialysis patients against hapten-protein and hapten-erythrocytes.

Serum samples obtained from hemodialysis patients with immediate-type hypersensitivity reactions and hemodialysis patients with no reactions were analyzed for antibody activity against hapten-protein complexes prepared from PA and MDI. These chemicals, used in preparation of plastics, have been shown to be associated with immunologically mediated disease in other studies. IgE and IgG antibodies against P-HSA and MDI-HSA were detected in several sera, but symptomatic patients could not be differentiated from asymptomatic patients by antibody levels. Antibodies capable of agglutinating or hemolyzing P-E were also detected in some sera from hemodialysis patients. These studies demonstrate that although no clinical disease has yet been correlated with these antibodies, sufficient exposure of hemodialysis patients to protein-reactive chemicals occurs to elicit an immunologic response against hapten-protein or hapten-cells. Such antibodies may have immunopathogenetic significance in subjects systemically exposed to fluids which have been in contact with plastics.

Albumins↗
PubMed1979

Cytotoxicity of ionophore A23187 for basophils and other human blood cells.

The calcium ionophore A23187(A23) at concentrations exceeding 1 microgram/ml has been shown to be progressively cytotoxic for human blood basophils, neutrophils, lymphocytes, and erythrocytes. Toxicity to basophils was considered to be manifested by the increasing inability of 2-deoxyglucose (2DG) to inhibit histamine release (HR) at increasing concentrations of A23. The toxicity to neutrophils and lymphocytes was demonstrated by decreased lactate production (LP) after incubation with A23 of Ficoll-Hypaque fractions greatly enriched in each respective cell type. Red cells present in dextran-sedimented leukocytes were increasingly susceptible to lysis during washing subsequent to exposure to increasing concentrations of A23. A concentration of 4 microgram A23/ml, which is cytotoxic at 37 degrees C, produced optimal and noncytotoxic HR at 22 degrees C. It was possible to reduce A23 concentrations required for optimal HR by increasing Ca++ from 0.6 to 3 mM.

Anti-Bacterial Agents↗
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

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↗