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Biomedical subjects

J N Fink

Publications and source records attributed to J N Fink.

At least 109 records · Page 6Linked to original sources

Enzyme profile and immunochemical characterization of Aspergillus fumigatus antigens.

We have compared the immunochemical characteristics of culture-filtrate antigens (Ag) from Aspergillus fumigatus extracted in our laboratory with commercially available Ags. A total of 20 different preparations were studied for protein and carbohydrate content, presence of endotoxins, mycotoxins, and hemolytic toxins. These extracts were analyzed by two-dimensional electrophoresis for protein components. The immunogenicity of the preparations was determined by rocket electrophoresis with rabbit anti-A. fumigatus sera and by agar gel diffusion with sera from patients with allergic bronchopulmonary aspergillosis, aspergilloma, and normal control subjects. In order to have dependable immunologic results, the Ags must be sufficiently pure and reproducible. Until such time as pure and standardized Ags are available, the crude Ags used should be characterized to the extent that adequate reproducibility between preparations can be ascertained. The enzyme profile of the Ag preparations provides a fair indication of the quality of antigenic components, and together with other immunochemical parameters, it will be of use in determining the suitability of the extracts in immunodiagnosis. Immunochemical results demonstrate that commercial Ags contain less proteins and carbohydrates and fewer enzymes than the homemade antigens. In addition, fewer patients demonstrated specific precipitins against commercial Ags than with homemade Ags. This study once again confirms the need for pure standardized Ags for studying the immunologic response in patients with Aspergillus-induced diseases. Until such preparations are readily available, partially purified or crude Ags with known immunochemical properties and enzyme profile may be the choice for immunodiagnosis.

Antigens, Fungal↗

A partially purified glycoprotein antigen from Aspergillus fumigatus.

Culture filtrate antigens of Aspergillus fumigatus were fractionated by isoelectric focusing using a pH gradient of 4-6.5. Three fractions, namely, 18, 19 and 20 were pooled and subjected to immunochemical analysis. It contained a concanavalin A binding glycoprotein. Antibody raised against this component was used to prepare an affinity column of IgG-Sepharose and was used to purify crude culture filtrate antigens. This component produced three precipitin arcs in crossed immunoelectrophoresis using anti-A. fumigatus rabbit serum. This fraction has an isoelectric point of 6.5 and showed three components in two-dimensional electrophoresis with approximate molecular weights of 20, 40 and 80 kilo daltons. This antigen reacted with patient sera in the biotin-avidin linked immunosorbent assay and showed high levels of anti-A. fumigatus IgG and IgE antibodies in allergic bronchopulmonary aspergillosis and IgG antibodies in aspergilloma. Both controls and Aspergillus skin test positive asthmatics showed only low levels of specific antibodies. Because of the purity of this antigen, its potential use as a standardized antigen in the detection of antibody is discussed.

Animals↗

Immunoglobulin G4 in pigeon breeder's disease.

Immunoglobulin G4 has previously been implicated in the pathogenesis of pigeon breeder's disease (PBD), a form of hypersensitivity pneumonitis associated with inhalation of pigeon antigens. We investigated the presence of IgG4 antibody to antigens in pigeon dropping extracts (PDE) in the lungs of pigeon breeders. Seven of these subjects had symptoms of PBD and eight others had no symptoms. IgG4 antibody to PDE was compared with IgG3 levels because both were relatively minor subclasses, but IgG3 is not considered reaginic whereas IgG4 is. An increase in IgG4 antibody relative to IgG3 would therefore be considered a selective increase and suggest a role for this subclass in the development of PBD. Our results, however, indicated that pigeon breeders without symptoms had significantly higher levels of serum IgG4 and that there were no significant differences with regard to the lavage fluid levels of IgG4, IgG3, or total IgG antibody in the two groups of subjects. A tendency of higher IgG4 antibody levels was found in lavage fluid from subjects without symptoms. These results do not support the hypothesis that IgG4 may act as a reaginic trigger in the development of PBD symptoms.

Adult↗

Study of two controlled-release theophylline preparations.

Two sustained-release theophylline preparations, one a 12-hour and the other a 24-hour product, were compared in 20 subjects with stable asthma. All patients had good control of symptoms, and the calculated pharmacokinetic parameters were comparable for both drugs. The 24-hour sustained-release preparation can thus be utilized in the therapy of asthma.

Adolescent↗

Allergenic properties of rat urine and pelt extracts.

We studied the relative diagnostic efficacy of skin tests and RAST assays in laboratory animal allergy in 16 rat-sensitive animal workers with the use of epithelial extract and urinary antigens from three inbred rat strains. RAST inhibition was used to evaluate possible urinary antigen-strain specificity. The urinary antigens were more reliable skin test and RAST reagents than were epithelial extracts; data from urinary antigen testing correlated better with historical data. RAST inhibition did not detect strain specificity among the urinary antigens. Antigens in rat urine appear to be of better diagnostic value than do epithelial extracts.

Adult↗

Immunotherapy of asthma.

Immunotherapy of allergic diseases can be effective. The injection of allergen into the sensitized host induces a number of cellular and humoral changes associated with clinical improvement. Although studies demonstrating clear efficacy are available for immunotherapy for allergic rhinitis, additional information is needed for complete evaluation of immunotherapy in asthma.

Allergens↗

Serum antibodies and their role in antibody-dependent cell-mediated cytotoxicity in aspergillosis.

A total of 22 sera from patients with aspergilloma and allergic bronchopulmonary aspergillosis (ABPA) were examined concomitantly for specific antibody against Aspergillus fumigatus antigen and for their activity in antibody-dependent cell-mediated cytotoxicity (ADCC) against Aspergillus antigen-coated target cells. These sera demonstrated significant precipitin bands in agar gel double diffusion test (78% of ABPA and 75% of aspergilloma sera), while in indirect immunofluorescence studies all sera showed positive reactivity with a titer distribution of 1:40 to 1:160 and 1:40 to 1:320, respectively, for ABPA and aspergilloma sera. In enzyme-linked immunosorbent assay all sera demonstrated titers varying from 1:200 to 1:6400. Several sera also displayed marked cytotoxic reactions against A. fumigatus antigen-coated SB target cells in ADCC assays using normal lymphocytes as effector cells (35% of aspergilloma and 25% of ABPA sera). These findings suggest a role for ADCC activity in patients with Aspergillus infections.

Antibodies, Fungal↗

Allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) occurs as a complication of asthma. It presents as an infiltrative pulmonary disorder with respiratory and systemic symptoms, eosinophilia, elevated total serum IgE, and skin sensitizing, as well as precipitating antibodies to Aspergillus fumigatus. Sputum cultures are not always positive for the organism. If unchecked, the disease may lead to bronchiectasis and ultimately pulmonary fibrosis. Therapy consists mainly of corticosteroids.

Adrenal Cortex Hormones↗

Antigen-induced enhancement of bronchial reactivity.

Bronchial hyperreactivity as determined by the airway response to methacholine was evaluated pre- and post-antigen challenge in three patients with specific antigen sensitivity. No significant change in pulmonary function was noticed after inhalation of antigen alone. However, transient but significant increase in methacholine responsiveness followed the antigen challenge. The studies indicate a need for a nonspecific inhalation challenge following a negative antigen challenge when clinically indicated.

Adult↗

Hemolytic plaque inhibition by synthetic antigenic peptides of sperm whale myoglobin.

We have investigated the systemic antibody response to sperm whale myoglobin (SWMb) antigenic sites in three strains of inbred mice using an inhibition of plaque assay. Sperm whale myoglobin was attached to sheep red blood cells (SRBC) via rabbit anti-SRBC Fab' fragments. Inhibition of lysis was obtained with synthetic peptides representing the purported five antigenic sites but not with a peptide whose sequence was unrelated to SWMb and synthetic peptides of SWMb from outside the antigenic sites gave minimal or no inhibition. The results of our studies show that the pattern of response to the five antigenic sites differs in each strain, but that almost total inhibition is obtained in all strains with these five sites. The antigenic dominance of these sites supports the concept of discrete antigenic sites on soluble proteins. They also suggest a reason for contrary reports in the literature based on hybridoma technology.

Animals↗