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Biomedical subjects

M A Shaughnessy

Publications and source records attributed to M A Shaughnessy.

At least 55 records · Page 3Linked to original sources
PubMed1989

Diphenylmethane diisocyanate hypersensitivity pneumonitis: a serologic evaluation.

We describe the clinical and immunologic evaluation of a steel plant maintenance supervisor who had clinical symptoms consistent with hypersensitivity pneumonitis. No antigen was obvious but after a thorough occupational history and review of the industrial hygiene data, the most likely antigen appeared to be diphenylmethane diisocyanate. Precipitating antibodies were not detected in the worker's serum; however, significant antibody levels of IgG specific for diphenylmethane diisocyanate-human serum albumin were detected by other immunoassays. This case highlights the importance of a thorough occupational history and an aggressive laboratory immunologic evaluation in identifying the offending agent in a worker with hypersensitivity pneumonitis. Hypersensitivity pneumonitis due to an inhaled reactive chemical may be present without precipitins demonstrated in vitro due to the nature of the haptenized chemical protein conjugate or the concentration of IgG antibody.

Alveolitis, Extrinsic Allergic↗
PubMed1989

Baker's asthma: report of an unusual case.

Using immunologic techniques recently available, we report the evaluation of baker's asthma due to wheat flour and demonstrate the usefulness of these techniques in occupational asthma. The diagnosis of baker's asthma was very important in this case, as even a trial of avoidance of work exposure was not possible because of the social and economic factors involved. A commercial wheat extract was obtained and the wheat flour actually used at the work site was extracted. Prick skin testing with each of these extracts resulted in positive wheal and flare responses. Enzyme linked immunosorbent assay and inhibition assays were performed to assess the worker's antibody response to wheat flour and wheat extracts. Significant specific IgE and IgG levels to the wheat flour and wheat extracts were detected in the worker's serum. Because of unique psychosocial and educational factors, this worker was unable to change occupations. Even with respiratory protection, she continued to be symptomatic. She is currently controlled on bronchodilators and inhaled steroids.

Antibody Specificity↗
PubMed1988

Estimation of IgE antibody with a nonisotopic technique with no interference of isotypic antibodies.

A modified ELISA was developed to estimate antigen-specific IgE antibody. IgE against ragweed antigen E (AgE) was the model system, and paired pre- and postimmunotherapy sera were evaluated because the latter had been demonstrated to contain significant amounts of IgG antibody. Patients' serum IgE was bound to the surface of wells of a polystyrene microtiter plate previously coated with monoclonal murine antihuman IgE. After washing, AgE conjugated with alkaline phosphatase was added and was specifically bound by IgE. Optical density was recorded after addition of enzyme substrate to the wells and was proportional to the concentration of IgE directed against ragweed AgE in the serum samples. In contrast to many other assay techniques for antigen-specific IgE, interference by specific antibody of other classes cannot occur with this method. Results correlated well with those of a previously described solid-phase radioimmunoassay that required myeloma IgE.

Allergens↗
PubMed1988

Prospective immunologic and clinical study of a population exposed to hexamethylene diisocyanate.

We have prospectively evaluated 150 workers exposed to hexamethylene diisocyanate (HDI) and its trimer (THDI) during an 18-month period. The evaluation consisted of periodic serum antibody studies and a questionnaire that was designed to attempt to identify symptoms compatible with work-related syndromes of allergic rhinitis, allergic conjunctivitis, hypersensitivity pneumonitis, asthma, or irritant reactions. The study population was divided into seven groups on the basis of job classification. The groups differed in exposure levels but were similar in terms of age, sex, smoking history, and duration of work with isocyanates. IgE and IgG against HDI and THDI conjugated to human serum albumin (HSA) (HDI-HSA and THDI-HSA) were determined by ELISA. There were no instances of immunologically induced disease among the 21% of workers in this sample with antibody; however, there is insufficient evidence at this time to make judgments about the relationship between antibody and clinical disease. The antibody was generally low-level IgG that may be a sensitive indicator to detect exposure to certain reactive chemicals. The level of antibody was not different among job classes or between smokers and nonsmokers. Moreover, there was no correlation between antibody level and exposure duration in these workers whose exposure levels are all well below National Institute for Occupational Safety and Health recommendations. Further evaluation will extend these observations.

Antibodies↗
PubMed1987

The safety and activity of polymerized ragweed: a double-blind, placebo-controlled trial in 81 patients with ragweed rhinitis.

Eighty-one patients with ragweed pollinosis were recruited for a double-blind, histamine placebo-controlled study of the safety, immunogenicity, and efficacy of 15 weekly injections of polymerized ragweed (PRW) immunotherapy totaling 1359 allergy units. Patients were paired on the basis of cutaneous end point titration to RAST standardized extracts of giant and short ragweed. One patient of each pair was randomized to receive PRW, and the other patient, a caramelized glucose histamine placebo. Symptom and medication score diaries were completed by 68 patients. All 68 patients received the full maintenance dose. No patient dropped out because of adverse reactions, and there were no systemic reactions. Except for one patient receiving placebo who developed mildly elevated liver function tests, there were no clinically significant changes in routine laboratory tests associated with injections. By Student's test on log-transformed values, blocking antibody rose significantly in the patients receiving PRW but was unchanged in those receiving placebo. By Wilcoxon paired signed-rank test, the symptom and medication scores in the patients receiving PRW were significantly lower than scores in the patients receiving placebo. This study demonstrates the safety, immunogenicity, and activity of PRW in the treatment of ragweed pollinosis.

Adult↗
PubMed1987

Evaluation and management of corticotropin allergy.

Subsequent use of an adrenocorticotropic hormone (ACTH) preparation may be considered in some instances in a patient who has demonstrated a suspected or proven allergic reaction to corticotropin on prior administration. We describe a patient with multiple sclerosis with a history of anaphylaxis to porcine ACTH in whom another course of treatment with ACTH was being considered. The patient had immediate cutaneous reactivity to porcine ACTH but not to the synthetic ACTH peptide, cosyntropin. With a test-dose schedule, we were able to uneventfully administer cosyntropin to the patient. The presence of serum IgE antibody directed against porcine ACTH and absence of IgE antibody against cosyntropin were demonstrated by ELISA technique, corroborating the skin test results. These studies are consistent with previous evidence that immediate hypersensitivity reactions to corticotropin are IgE mediated and support the value of skin testing in the clinical evaluation and management of known or suspected corticotropin hypersensitivity.

Adrenocorticotropic Hormone↗
PubMed1986

Soluble copolymer of wasp venom with human albumin for venom immunotherapy.

Polymerization of allergens decreases allergenicity while retaining immunogenicity, as we have demonstrated for ragweed, grass, and tree pollens. We have also polymerized bee venom with human albumin to form soluble, high-molecular-weight copolymers that are immunogenic in rabbits. We now have prepared a soluble wasp venom-albumin polymer (WVAP), molecular weight greater than or equal to 240,000 daltons, by glutaraldehyde treatment and Sephacryl S-300 column fractionation. Rabbits immunized with WVAP produced IgG to both WVAP and wasp venom (WV), as measured by ELISA. IgG against WVAP was totally inhibitable by a mixture of WV and albumin, demonstrating both retention of native antigens and absence of new antigenic determinants in WVAP. IgG against WV in serum from patients receiving maintenance doses of WV immunotherapy was inhibited by WVAP. In summary, we have synthesized a soluble, high-molecular-weight copolymer of WV that retains the immunogenicity of native WV, contains no new antigenic determinants, and has potential value in the treatment of patients with WV anaphylaxis.

Animals↗
PubMed1986

A double-blind placebo-controlled trial of polymerized whole grass administered in an accelerated dosage schedule for immunotherapy of grass pollinosis.

Forty-four patients were entered into a study of the efficacy and safety of individually polymerized grass (IPG) immunotherapy with an accelerated dosage schedule. Patients were paired on the basis of cutaneous end point titrations to timothy, orchard, and Bermuda grass-pollen extracts. In a double-blind manner, one patient in each pair was treated in nine weekly visits with 13 injections that totaled 24,000 PNU of each grass to which the patient had cutaneous reactivity. The other patient in each pair received caramelized glucose histamine placebo. Symptom and medication score sheets were completed by 33 patients each day of the grass season. Blocking antibody rose significantly in the IPG-treated group but was unchanged in the placebo-treated group. By Wilcoxon paired signed-rank test, the symptom medication scores in the IPG-treated group were significantly lower than those in the placebo-treated group. There were no systemic reactions and no clinically significant changes in routine laboratory tests in either group. In summation, this study demonstrates the safety, immunogenicity, and efficacy of IPG therapy in an accelerated dosage schedule for treatment of grass pollinosis.

Adult↗
PubMed1986

Safety and immunogenicity of immunotherapy with polymerized tree, grass, and ragweed in patients with multiple inhalant sensitivities.

Immunotherapy with polymerized ragweed (PRW) and individually polymerized grasses (IPG) previously has been demonstrated to be safe and effective. We conducted this trial in order to assess safety and immunogenicity of individually polymerized trees (IPT) and to assess safety of concomitantly administering IPT, IPG, and PRW in patients with multiple inhalant sensitivities. Sixteen patients with typical tree pollinosis were recruited; all but one had grass pollinosis, and all had ragweed pollinosis. Patients were treated in 12 weekly visits with allergens to which they were sensitive, 48,850 PNU of IPT; 2668 AU (50,000 PNU) of PRW; and 48,850 PNU of IPG. There were no systemic reactions and no changes in laboratory parameters, including renal and hepatic functions with injections. Blood was drawn for immunologic studies before and after the injection series. There were significant rises in IgG titers by ELISA to each tree allergen administered, oak, elm, and box elder. There were significant rises in total antibody binding of ragweed AgE and rye grass group I in patients treated with PRW and IPG, respectively. Changes in IgE to oak, elm, box elder, AgE, and rye grass group I were minimal. In summary, IPT is safe, immunogenic, and can be administered concomitantly with PRW and IPG in patients with multiple inhalant sensitivities.

Blood Proteins↗
PubMed1986

Modified antigens in the treatment of allergic disease.

In summary, effects at improvement upon conventional immunotherapy by antigen modification have taken three major directions. First, methods designed primarily to impede allergen release from the site of deposition have been only modestly successful. An example is alum-precipitated extracts which require somewhat fewer injections. Second, attempts to suppress specific IgE production have been unsuccessful in human trials, although antigen-specific IgG levels have increased in a manner similar to that produced by conventional allergen immunotherapy. The third major avenue of antigen modification, to reduce allergenicity while retaining immunogenicity, appears, at present, to be the most promising. Clinical studies of polymerized allergens summarized above have shown that patients can be given a course of polymerized allergen immunotherapy in a few weeks, while a course involving a comparable quantity of unmodified allergen would require years. With the use of polymerized pollen extracts, degree of symptom reduction, persistence of benefit, and magnitude of IgG-blocking antibody induction are comparable to that achieved with unmodified allergens, while the incidence of systemic reactions is greatly reduced. The development of polymerized allergens appears to represent a significant advance which may be expected to expand the clinical utility of allergen immunotherapy.

Allergens↗
PubMed1986

Comparison of cutaneous and bronchial reactivity to leukotriene D4 in humans.

To establish whether a relationship exists between cutaneous and bronchial reactivity to leukotriene D4 (LTD4), endpoint cutaneous reactivity and bronchial reactivity were determined in six patients with asthma, six patients with seasonal allergic rhinitis, and six nonatopic men. In all subjects, increasing doses of LTD4 produced decreases in specific airway conductance (SGaw) and flow at 30% of vital capacity measured from a partial forced expiratory maneuver (V30P). Intracutaneous injections of LTD4 and histamine resulted in immediate wheal and erythema reactions in all patients. Serial 10-fold dilutions of LTD4 and histamine were injected to establish the lowest dose capable of producing a 4 mm wheal with erythema. Endpoint cutaneous reactivity to LTD4 ranged from 1 mumol to 100 pmol in controls and from 100 nmol to 1 fmol in patients with asthma, but statistically significant differences between groups were not apparent even with inclusion of six additional subjects. No meaningful correlations were found between the quantity of LTD4 producing the threshold cutaneous reaction and the dose of inhaled LTD4 that produced a 35% decrease in SGaw and 30% decrease in V30P. In contrast to the bronchi, where subjects in all three groups were 264 to 840 times more sensitive to LTD4 than to methacholine, 11/18 subjects (3/6 with asthma) were less sensitive to LTD4 than to histamine in terms of endpoint cutaneous reactivity. However, seven of 18 subjects who were more sensitive to LTD4 than to histamine had relative potencies ranging from 5 to 500,000.

Asthma↗
PubMed1986

A comparison of the immune response to immunotherapy with polymerized grass allergen and monomeric grass allergen.

This study compares the immune response of ten patients treated with polymerized grass (PG) immunotherapy with that of 12 patients treated with conventional monomer grass (MG) immunotherapy. The patients treated with PG immunotherapy received a mean cumulative dose of 44,840 protein nitrogen units (PNU), and those treated with MG immunotherapy received a mean cumulative dose of 46,083 PNU. Total antibody binding of perennial rye grass groups I, II, and III (RGGI, RGGII, and RGGIII) was measured in the serum of each individual. In addition, IgG titers to partially purified extracts of Bermuda, timothy, and orchard grass were also determined. A significant increase in the total antibody binding of RGGI, as well as an increase in the mean IgG titer to Bermuda, timothy, and orchard grass was demonstrated after treatment in the patients who had received PG immunotherapy. The mean total antibody binding of RGGII and RGGIII also increased in these patients, although not significantly. No significant difference in the mean total antibody binding of RGGI, RGGII, or RGGIII nor in the mean IgG titer to the three grass extracts was found in the sera of the two groups of patients. This study demonstrates a comparable immune response between immunotherapy with PG and MG, and retention of antigenic determinants during the polymerization process.

Allergens↗
PubMed1985

Immunotherapy: parameters of assessment.

Allergen immunotherapy has proved safe and effective for selected aeroallergens that can be studied under controlled conditions. Various mechanisms of action have been proposed with limited evidence for their role in the protection resulting from immunotherapy. The exception is blocking antibody, which was discovered 50 years ago. In eight successive studies sponsored or carried out by one institution in which clinical efficacy was demonstrated, the serum level of IgE antibody was unchanged or slightly increased. All eight studies showed a significant rise in the serum level of IgG antibody, and this response is the logical immunologic explanation for clinical efficacy. For aeroallergens that cannot be avoided or subjected to clinical efficacy studies, demonstrations of safety and of significant IgG antibody response constitute the appropriate method of assessment.

Aerosols↗
PubMed1985

Modified forms of allergen immunotherapy.

There have been many attempts to modify allergens and thus to improve upon conventional immunotherapy, which has been proved effective but has several drawbacks. These include the risk of systemic reactions and the time and cost involved. The modifications have taken three major approaches. One approach, to impede allergen release from the site of deposition, has met with limited success. An example is alum precipitation, which has modestly reduced the number of injections and incidence of systemic reactions. A second approach, to suppress specific IgE production and to induce specific tolerance, has not been successful in man. The third approach, to reduce allergenicity while retaining immunogenicity of allergens, has been the most successful and appears to have the most promise. One example is polymerized allergens, which have been shown to be safe, efficacious, and immunogenic in multiple clinical trials. Other examples include allergoids and glutaraldehyde-treated, tyrosine-adsorbed allergens.

Allergens↗
PubMed1985

Characterization of an antigen in acute anaphylactic dialysis reactions: ethylene oxide-altered human serum albumin.

Anaphylactic reactions to dialysis have been associated with antibody to human serum albumin (HSA) that has been reacted with ethylene oxide (ETO). ETO, an agent used to sterilize dialyzers, is a potent alkylator of proteins. We have studied the antigenic characteristics of ETO-HSA. By use of immunoelectrophoresis we have demonstrated differences in electrophoretic mobility between HSA and ETO-HSA. By gel chromatography we have observed an apparent increase in the molecular weight of ETO-HSA as compared to HSA. Antigenic activity of ETO-HSA as determined by the technique of Lidd and Farr is found in all molecular weight fractions. Cutaneous reactivity to ETO-HSA can be transferred to subhuman primates. That reactivity is lost if the sera are heated to 56 degrees C for 4 hours. Antibody activity to ETO-HSA cannot be inhibited by ETO-glycine or HSA but can partially be inhibited by ETO-polylysine or ETO-ovalbumin. This suggests that antibody is directed against a new antigenic determinant on the ETO-protein moiety, probably an ETO-amino acid determinant like lysine.

Anaphylaxis↗
PubMed1985

Allergenicity, immunogenicity, and safety of immunotherapy with various molecular weight ranges of polymerized ragweed.

Since the observation had been made that allergenicity of polymerized ragweed (PRW) varies inversely with molecular weight over ranges we had studied previously, we conducted this study to determine the utility of immunotherapy with PRW molecular weight greater than 20,000,000 alone or as part of a final product pool. Twenty-one patients with ragweed pollinosis were randomized into three groups on the basis of ragweed skin test titration. Each patient received 500 micrograms AgE (50,000 PNU) of one of the following molecular-weight ranges: PRW A greater than 500,000; PRW B 200,000 to 20,000,000; and PRW C greater than 20,000,000. There was no difference between PRW A, B, and C by intradermal end point titration, by incidence of large local reactions, by amount of erythema or induration from injections, or by rise in blocking antibody that was significant in each group. There were no systemic reactions nor any changes in clinical laboratory parameters. In summary, each of the molecular-weight ranges of PRW studied was similarly allergenic, immunogenic, and safe to administer, and thus PRW greater than 20,000,000 can be used for immunotherapy as a part of the final product pool. This has the advantages of increasing yields and of simplifying the fractionation by eliminating one chromatographic process.

Analysis of Variance↗