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Biomedical subjects

C R Zeiss

Publications and source records attributed to C R Zeiss.

At least 55 records · Page 3Linked to original sources

Antibodies to purified protein derivative in different immunoglobulin classes in the diagnosis of tuberculosis in man.

The sera of patients with active tuberculosis (TB) and sera from control groups were assayed for IgG, IgA, secretory IgA, IgM and IgE antibody activity to purified protein derivative (PPD) using the enzyme-linked immunosorbent assay. Patients with active TB clearly had higher levels of IgG antibody activity to PPD antigen than did healthy patients who were skin test positive or negative. There was a clear separation between the diseased and healthy groups. Similar, but not as marked increases were seen in IgA and secretory IgA antibody activity in diseased patients. No correlation between the presence of disease and antibody levels were found with IgM, and no IgE antibodies were found. The method presented is a rapid reproducible assay using commercially available materials, and may offer a clinically useful test for the diagnosis of TB.

Antibodies↗

Syndromes in workers exposed to trimellitic anhydride. A longitudinal clinical and immunologic study.

A longitudinal study of workers involved in the manufacture of trimellitic anhydride has been in progress since 1977. Trimellitic anhydride is a low-molecular-weight, reactive chemical used in the manufacture of plastics. Initial studies done in 1976 defined three syndromes due to inhalation of trimellitic anhydride: asthma-rhinitis, a late respiratory systemic syndrome, and an irritant response. Also, serologic techniques were developed to measure total antibody and IgE antibody to trimellityl human serum albumin. From 1977 to 1981, 64 workers were assessed. Six workers presented with asthma-rhinitis, high levels of IgE antibody, and skin test reactivity to trimellityl human serum albumin; five workers developed the late respiratory systemic syndrome; and one worker had both immunologic syndromes. These serologic measurements detected or were predictive of an immunologic respiratory illness and were useful in monitoring workers involved in the manufacture of trimellitic anhydride.

Asthma↗

The enzyme-linked immunosorbent assay method for IgG antibody to purified protein derivative in cerebrospinal fluid of patients with tuberculous meningitis.

Three patients with culture-proven Mycobacterium tuberculosis meningitis were studied. Analysis of cerebrospinal fluid with an enzyme-linked immunosorbent assay (ELISA) method measuring IgG antibody to purified protein derivative rapidly yielded positive results, whereas results of acid-fast smears were negative and cultures took several weeks before growth appeared. We did serial studies of cerebrospinal fluid and sera from one patient. Initially, greater amounts of IgG antibody to purified protein derivative were present in the cerebrospinal fluid than in the serum. The antibody level in the cerebrospinal fluid paralleled the patient's clinical course, cerebrospinal fluid cell count, protein level, and glucose level. Cerebrospinal fluid samples from 33 hospitalized control patients were negative for antibody to purified protein derivative. The ELISA method measuring IgG antibody to purified protein derivative should be evaluated as a means of early diagnosis and management of patients with suspected tuberculous meningitis.

Enzyme-Linked Immunosorbent Assay↗

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↗

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↗

Clinical and immunologic evaluation of trimellitic anhydride workers in multiple industrial settings.

This article described our clinical and immunologic experience in assessing workers exposed to trimellitic anhydride (TMA) in three industrial settings. Since 1977 we have had engaged in a prospective study of workers involved at the site of manufacture of TMA. These studies demonstrate that serologic measurements of total antibody to trimellityl human serum albumin (TM-HSA) and IgE antibody to TM-HSA are predictive of the development of an immunologically mediated respiratory illness and are useful in monitoring workers removed from TMA exposure, in identifying asymptomatic workers who may be at risk in the future, and in defining the nature of sensitization of the work force. In a different industrial setting, we have been able to study workers who mixed previously manufactured TMA powder with epoxy resins. This study indicated that clinical assessments by a plant physician with a standardized questionnaire, along with serologic tests, could establish the presence or absence of an immunologic respiratory illness caused by the inhalation of TMA dust. In a third industrial situation, workers were exposed to both TMA and phthalic anhydride (PA). Here workers were interviewed by a local physician with minimal experience with TMA-related respiratory illness. In this situation a more detailed questionnaire was utilized, along with serologic tests utilizing the enzyme-linked immunosorbent assay to establish the presence of a TMA- or PA-related syndrome. Immunologic studies demonstrated in workers exposed to both TMA and PA that the antibody responses elicited showed little crossreactivity between antibodies directed against TM-HSA or PA-HSA.

Antibodies↗

Immunology and immunopathology of trimellitic anhydride pulmonary reactions.

Inhaled trimellitic anhydride (TMA) reacts with airway proteins to produce trimellityl (TM) proteins. THe TM-proteins result in both systemic and local immune responses, of which various proteins present in the airway can be used for markers. Thus TM-human serum albumin (HSA), TM-IgG, and TM-IgA can be used as hapten-protein complexes for immunologic studies in sera of humans exposed to TMA by inhalation. Various immunologic assays have been established to measure antibodies against TM-proteins and have various purposes. With TM-HSA as a model antigen, total serum antibody may be measured by the ammonium sulfate technique of coprecipitation of TM-125I HSA. By solid-phase radioimmunoassays, IgE, IgG, IgA, and IgM antibodies can be measured. Lymphocyte reactivity can be measured by 3H thymidine uptake of TM-protein-stimulated lymphocytes. Biological effects of IgE antibody can be measured by allergy skin tests and leukocyte histamine release with TM-proteins such as TM-HSA. The reaction of TMA with proteins results in alteration of those proteins that include changes in charge and physical conformation, the latter resulting in an apparent change in molecular size. These changes may relate to the observations that human antibody is not merely directed against the hapten in the hapten-human protein complex but also against new antigenic determinants formed by the TM-protein complex. Correlations have been made with certain human immunologic responses and lung disease after TMA inhalation, as follows: IgE antibody against TM-proteins correlates with TMA-induced rhinitis, conjunctivitis, and asthma; high levels of total antibody, IgG, and IgA antibody appear to correlate with the late respiratory systemic syndrome, probably a variant of hypersensitivity pneumonitis; workers exposed to TMA fumes (rather than TMA powder) have the highest levels of antibody, and this may correlate with occurrence of the hemorrhagic pneumonitis seen in this group of workers; patients with no symptoms or mild irritative symptoms have the lowest or no antibody levels. The immunopathogenetic relationships may be better understood with the further development of animal models to TMA lung disease now available.

Antibody Formation↗

Clinical and immunologic evaluation of trimellitic anhydride-and phthalic anhydride-exposed workers using a questionnaire with comparative analysis of enzyme-linked immunosorbent and radioimmunoassay studies.

Twenty workers exposed to trimellitic anhydride (TMA) powder an phthalic anhydride (PA) fumes concurrently were evaluated by questionnaire and serum antibody studies. The study group was divided into high-an low-exposure groups on the basis of job descriptions and intensity of daily exposure. The questionnaire, which was designed to identify symptoms compatible with TMA-associated rhinitis, asthma, late respiratory systemic syndrome, and irritant responses, was administered to 18 of 20 workers. Total antibody binding was determined by the ammonium sulfate assay, and specific IgG and IgE binding was measured with an enzyme-linked immunosorbent assay (ELISA) to both PA-human serum albumin (PA-HSA) and TMA-human serum albumin (TM-HSA) conjugates. Specific IgE to TM-HSA was measured with the polystyrene-tube radioimmunoassay (PTRIA). The questionnaire identified nonirritant, immunologic symptoms caused by TMA primarily in the high-exposure group. Specific IgG, IgE, and total antibody binding to TM-HSA and PA-HSA were found exclusively in the high-exposure workers. One worker was identified with PA-associated rhinitis, high total antibody binding, and specific IgG and IgE to PA-HSA by means of the ELISA. The ELISA was as sensitive as the PTRIA in detecting the presence of specific IgE to TM-HSA. The present study demonstrates that an itemized questionnaire, combined with ELISA IgG and IgE determinations, may be a sensitive method for identifying workers who have or are at risk for developing TMA-induced respiratory symptoms.

Asthma↗

Progressive cutaneous protothecosis.

The diagnosis of severe progressive cutaneous protothecosis in a 34-year-old woman was made by skin biopsy and culture. Analysis of host defense mechanisms revealed a persistent defect in the ability of the patient's PMN to kill the infecting organism. Specific IgG and IgE antibody was demonstrated. Serum levels of complement and immunoglobulins were normal or elevated. The patient was not anergic and peripheral blood lymphocytes responded to nonspecific mitogens. Treatment with amphotericin B and tetracycline resulted in resolution of skin lesions and negative cultures.

Adult↗

Detection of immunoglobulin G antibody to purified protein derivative in patients with tuberculosis by radioimmunoassay and enzyme-linked immunosorbent assay.

Sera from patients with active tuberculosis and sera from appropriate control individuals were assayed for immunoglobulin G antibody activity to purified protein derivative by a polystyrene tube radioimmunoassay and an enzyme-linked immunosorbent assay. Both assays showed a marked increase in immunoglobulin G antibody activity in patients with active tuberculosis. There was no overlap between the values for the patient group and the values for the purified protein derivative skin test-positive control individuals. The replication of these assays was excellent, and both could provide quantitative measurements of immunoglobulin G antibody activity to purified protein derivative antigen within 24 h. These techniques have potential as rapid diagnostic aids in evaluating patients with suspected active tuberculosis.

Antibodies, Anti-Idiotypic↗

Immune response of dogs and rabbits to intrabronchial trimellitic anhydride.

8 dogs and 7 rabbits were immunized intrabronchially with trimellitic anhydride (TMA) using three different immunizing doses. An immune response occurred in both animal species. Predominantly IgG with lower levels of IgM and IgA antibodies against trimellityl-erythrocytes (TM-E) were detected on both dogs and rabbits. Antibody binding of TM125I dog serum albumin (TM125I-DSA) occurred in most dogs and of TM125I rabbit serum albumin (TM125I-RSA) in 1 out of 7 rabbits. Lymphocyte reactivity was present in all 8 dogs. Death occurred in the 2 dogs immunized with the low dose (0.1 mg/kg) of TMA, in 2 of the 4 dogs immunized with the moderate dose (1.0 mg/kg), and in neither of the 2 dogs immunized repeatedly with the high dose (10.0 mg/kg). No correlation of deaths could be made with serum levels of anti-TM-E antibody or anti-TM125I-DSA antibody binding, or lymphocyte reactivity. The deaths occurred early in the TMA immunizations. All antibody levels in the diseased animals were less than those seen in human workers with TMA-related respiratory disease. Autopsy findings in the 4 dogs showed hemorrhagic pneumonitis possibly analogous to the pulmonary lesions seen in the hemorrhagic pneumonitis of some workers exposed to TMA fumes. TMA as used in these experiments was not toxic to dogs as the high doses of TMA (10.0 mg/kg) did not lead to death which did occur at the lower doses. No deaths occurred in the 7 rabbits immunized with 1.0 mg TMA/kg. The immune responses and pathological findings in dogs encourage further work in the development of animal models of TMA immunologic lung disease.

Animals↗

Occupational hypersensitivity pneumonitis after exposure to diphenylmethane diisocyanate.

A foundry worker developed dyspnea and a restrictive breathing defect after being exposed to diphenylmethane diisocyanate (MD) at work. His symptoms and lung function impairment subsided a few weeks after he left work. Specific inhalation challenges with the offending agent induced general malaise together with a significant increase in body temperature and leukocyte count as well as a significant decrease in forced vital capacity and transfer factor. Total antibody activity to a MDI human serum albumin (MDI-HSA) conjugate was detected by ammonium sulfate precipitation. Specific IgG antibodies were demonstrated by the enzyme-linked immunoabsorbent (ELISA) technique. Thus, it was found that MDI exposure can cause hypersensitivity pneumonitis and induce the production of specific antibodies.

Adult↗

Quantification of ultrastructural variations in enriched blood basophils: correlation of morphological changes and antigen-induced histamine release.

Highly purified preparations of human basophils have been studied ultrastructurally to delineate quantifiably those alterations associated with immunologically-induced histamine release. Of six characteristic variations of basophil morphology, totally degranulated cells, those with some exteriorized granules and those with some extracellular vesicles were almost exclusively associated with antigen challenge. Of these, total degranulation without extracellular granules or vesicles was most frequent. A correlation was found between percentage histamine released and percentage totally degranulated cells present in the samples incubated with antigen. In addition, increased plasma membrane folding and irregularity were more prevalent in stimulated samples than in controls and their mean frequency was related quantifiably to the percentage of histamine released in each group. Cells with empty vesicles or electronlucent intracellular granules or both occurred to the same extent in experimental and control aliquots. The possible of histamine release is discussed.

Antigens, Fungal↗

An animal model of occupational immunologic asthma due to diphenylmethane diisocyanate, with multiple systemic immunologic responses.

Inhalation of MDI in the plastics industry may produce hypersensitivity pneumonitis or immediate-type asthma in workers. A suspension of MDI was given intrabronchially to dogs to determine whether any of the clinical and immunologic human responses could be duplicated, Results showed that dogs produce a systemic immune response to MDI-DSA. Serum MDI-125I-DSA binding was shown by the ammonium sulfate binding technique. Antibody activity of IgG, IgA, and IgM antibody classes was shown by a solid-phase enzyme-linked immunoassay. Precipitating antibodies were detected in he dog serum against MDI-DSA. Immediate-type skin reactivity to MDI-DSA consistent with a canine IgE response occurred. The skin reactivity appeared to correlate with an immediate-type airway response characterized by an increase in pulmonary resistance after intrabronchial MDI. There was transient peripheral blood lymphocyte reactivity to MDI-DSA. The results indicate that a large animal model of human immune response to MDI is available for various immunopathogenic studies.

Airway Resistance↗

Trimellitic anhydride Toxicity. A cause of acute multisystem failure.

A person exposed to trimellitic anhydride (TMA) an epoxy resin widely used in industry, experienced respiratory failure, anemia, and gastrointestinal bleeding. A lung biopsy specimen demonstrated intra-alveolar hemorrhage and damage to alveolar lining cells. The patient and six co-workers were examined. Results indicated the presence of hemolytic antibodies directed against TMA-haptenized erythrocytes, IgG, IgA, and IgM antibodies directed against TMA-erythrocyte complexes, and antibodies against TMA-human serum albumin. Antibody levels in the patient were greater than in the co-workers. The elevated antibody levels demonstrate the antigenic potential of TMA. However, the cause of the pulmonary and hematologic damage remains uncertain and may represent either immunologic or direct toxic effects of TMA. In patients with multisystem failure of this nature, occupational hazards should be added to the differential diagnosis.

Adult↗

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↗

Comparison of the radioallergosorbent test and a quantitative solid-phase radioimmunoassay for the detection of ragweed-specific immunoglobulin E antibody in patients undergoing immunotherapy.

Commercially available radioallergosorbent test (RAST) was compared with a quantitative solid-phase polystyrene tube radioimmunoassay (PTRIA) for the detection of ragweed-specific IgE antibody in sera of patients undergoing ragweed immunotherapy. Both assays showed good replication over a wide range of IgE antibody activity. The RAST was limited in the ability to discriminate between sera with high levels of specific IgE antibody. In addition, RAST gave falsely low values of IgE antibody activity in the presence of high levels of blocking antibody.

Animals↗