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Biomedical subjects

M A Shaughnessy

Publications and source records attributed to M A Shaughnessy.

At least 37 records · Page 2Linked to original sources
PubMed1994

Risk factors for immunologically mediated respiratory disease from hexahydrophthalic anhydride.

Our objective was to identify risk factors for development of immunologically mediated respiratory disease in workers exposed to hexahydrophthalic anhydride. We performed a medical and immunologic survey study of 57 workers in a workplace molding operation utilizing hexahydrophthalic anhydride. The main outcome measurements were the development of a respiratory disease due to specific IgE antibody (asthma and/or rhinitis) or specific IgG antibody (hypersensitivity pneumonitis or hemorrhagic rhinitis). Of the 57 workers, 7 had both IgE- and IgG-mediated disease, whereas 9 had only IgE-mediated disease. Although neither smoking, age, nor race were risk factors for development of immunologically mediated disease, exposure level and specific antibody were. In conclusion, development of immunologically mediated respiratory disease due to hexahydrophthalic anhydride is most closely associated with exposure level and development of specific IgE or IgG antibodies.

Adult↗
PubMed1994

Immunologic cross-reactivity of acid anhydrides with immunoglobulin E against trimellityl-human serum albumin.

The purpose of this study was to determine whether workers sensitized by one acid anhydride, trimellitic anhydride (TMA), would possibly react immunologically to two other acid anhydrides, phthalic anhydride (PA) or maleic anhydride (MA). We studied serum samples from four workers with TMA asthma and immunoglobin E (IgE) against TMA conjugated to human serum albumin (TM-HSA). In enzyme-linked immunosorbent assay (ELISA) cross-inhibition studies, TM-HSA inhibited IgE binding to TM-HSA, but when 100 times more P-HSA or M-HSA was used, no significant inhibition occurred. However, in ELISA studies of P-HSA and M-HSA, we saw binding of specific serum IgE. Finally, in passive transfer studies in rhesus monkeys with serum from an individual with antibodies to all three acid anhydrides, the following titers were obtained: TM-HSA (1:32), P-HSA (1:8), M-HSA (negative). We conclude that cross-inhibition studies may not be the best method for determining whether an individual sensitized to one antigen will react to a related antigen. The determination of biologic reactivity in a rhesus monkey model of passive cutaneous transfer makes it likely that biologic reactivity would also occur in a human sensitized to TMA and then exposed to another anhydride such as PA.

Animals↗
PubMed1993

Prepolymers of hexamethylene diisocyanate as a cause of occupational asthma.

BACKGROUND: Occupational asthma (OA) caused by products that contain hexamethylene diisocyanate (HDI) has been ascribed to the highly volatile monomer of HDI. Most two-component paints are now made up primarily of nonvolatile prepolymers of HDI (30% to 60%) with only trace amounts (< 0.1%) of the monomer. The respective role of the two chemical forms of HDI in causing OA has never been investigated. METHODS: Twenty workers who were consecutively referred for possible OA that resulted from exposure to spray paints underwent inhalation challenges on separate days with pure HDI monomer and the commercial formulation of HDI prepolymers to which they had been exposed at work. RESULTS: Specific inhalation challenges elicited a positive asthmatic reaction in 10 of the 20 subjects. Among these subjects, four had positive bronchial reactions (two early, one late, and one dual) to both the monomer and the prepolymers. Four other subjects had asthmatic reactions (two early, one late, and one dual) after exposure to the prepolymers but not after exposure to the monomer. The discordance in bronchial response elicited by the monomer and the prepolymers could not be due to differences in the level of baseline nonspecific bronchial reactivity or in HDI concentrations during the tests. One subject showed an atypical progressive reaction after exposure to the monomer but not after exposure to the prepolymer. In this case, the discordant response could be explained by differences in HDI concentration. CONCLUSION: These observations show that, although they are nonvolatile, the prepolymers of HDI can induce OA and that asthmatic reactions as a result of exposure to prepolymers but not the monomer is not a rare occurrence.

Adult↗
PubMed1993

Hypersensitivity pneumonitis-like reaction among workers exposed to diphenylmethane [correction to piphenylmethane] diisocyanate (MDI).

Isocyanates are well documented as a cause of occupational asthma. A hypersensitivity pneumonitis type of reaction has also been reported but only in a few isolated cases. We investigated nine subjects who complained of respiratory and general symptoms related to workplace exposure. All the subjects had worked in a plant where a resin based on diphenylmethane diisocyanate (MDI) is used in the manufacture of woodchip boards. They underwent inhalation challenges using the MDI resin for progressively increasing periods of time on separate days. In eight subjects, exposure to subirritant amounts of MDI induced a pattern of reaction consistent with hypersensitivity pneumonitis, i.e., significant falls in both FEV1 and FVC associated with a rise in body temperature (> 38 degrees C) and an increase in blood neutrophils (> +2,500/mm3). Bronchoalveolar lavage, performed in two subjects 24 h after the end of challenge exposure, revealed an increase in lymphocytes and neutrophils. Specific immunoglobulin G (IgG) and IgE antibodies to MDI human serum albumin (HSA) conjugates were present in all subjects. We conclude that the MDI resin caused an hypersensitivity pneumonitis type of reaction in at least eight (4.7%) of the 167 potentially exposed workers employed in the plant. These findings indicate that in some workplaces, a hypersensitivity pneumonitis type of reaction may be a more frequent consequence of isocyanate exposure than is usually thought.

Adult↗
PubMed1993

A clinical and immunologic study of workers with trimellitic-anhydride-induced immunologic lung disease after transfer to low exposure jobs.

The objective of the study was to determine the clinical and immunologic status of trimellitic anhydride (TMA) workers who have had immunologic lung diseases and who have been moved to lower exposure jobs. Twenty-nine consecutive workers with TMA-induced immunologic lung diseases who had been moved to low exposure jobs for more than 1 yr were studied retrospectively. Pulmonary symptoms were obtained by physician-administered questionnaire. Immunologic studies were performed using radioimmunoassay. Spirometry and chest film were obtained. Workers with late asthma (LA) (n = 3), late respiratory systemic syndrome (LRSS) (n = 8), or both LRSS and asthma rhinitis (A/R) (n = 6) had improved symptoms, improved pulmonary functions, and lower total antibody against TM-HSA. Five of the 12 workers with A/R had improved symptoms, improved pulmonary functions, and lower IgE against TM-HSA, whereas seven continued to have moderate to severe symptoms, abnormal pulmonary functions, and elevated IgE against TM-HSA. There were no chest film findings in any group that were definitely attributed to TMA. Although TMA workers with LA or LRSS improve when moved to lower exposure jobs, only half of workers with A/R improve; elevated IgE against TM-HSA appears to be a marker for the subpopulation of workers with A/R that does not improve.

Adult↗
PubMed1993

Hemorrhagic rhinitis. An immunologic disease due to hexahydrophthalic anhydride.

This is a descriptive study of six men who had been occupationally exposed to heated epoxy resin containing hexahydrophthalic anhydride (HHPA) who presented with rhinitis, nasal mucosal erosions, and significant epistaxis; three also had asthma. When they were removed from exposure to HHPA, the rhinitis symptoms, nasal erosions, and epistaxis resolved spontaneous. All six had high titers of IgG and IgE against HHP-HSA as determined by an enzyme-linked immunosorbent assay (ELISA). Other asymptomatic workers with similar HHPA exposure had ver low or negative titers of IgG and IgE against HHP-HSA. We conclude that these results are very suggestive of an immunologic mechanism being responsible for the rhinitis, nasal mucosal erosions, and epistaxis that occurred in the six described HHPA workers.

Adult↗
PubMed1993

Exposure to TMXDI (meta) aliphatic isocyanate and TMI (meta) unsaturated aliphatic isocyanate. Clinical and immunological evaluation of 96 workers.

We evaluated 96 workers employed at facilities that manufacture or use TMXDI (meta) aliphatic isocyanate and TMI (meta) unsaturated aliphatic isocyanate. We used immunoglobulin (Ig) and IgG serum antibody enzyme-linked immunosorbent assay (ELISA) studies and a questionnaire designed to identify symptoms compatible with work-related syndromes such as asthma and hypersensitivity pneumonitis. There were no workers with immunologically induced disease due to TMI isocyanate or TMXDI isocyanate nor were there any workers whose questionnaires suggested new onset of asthma. Approximately 40% of workers experienced some irritant symptoms, mostly upper respiratory or ocular. One worker had low level IgE antibody against TMXDI-HSA but had no work-related respiratory symptoms. Very low-level IgG against TMI-HSA or TMXDI-HSA was present in 7% of workers, all of whom were in the high-exposure category.

Air Pollutants, Occupational↗
PubMed1993

Immunologic specificity of IgG against trimellityl-human serum albumin in serum samples of workers exposed to trimellitic anhydride.

The specificity of immunoglobulin G (IgG) against trimellityl-human serum albumin (TM-HSA) in serum samples from 11 workers exposed to trimellitic anhydride (TMA) was characterized in this study. Levels of IgG against TM-HSA and HSA-conjugates of other acid anhydrides, phthalic anhydride (PA), maleic anhydride (MA), hexahydrophthalic anhydride (HHPA) and tetrachlorophthalic anhydride (TCPA) were estimated by enzyme-linked immunosorbent assay index. Inhibition studies using each of 5 HSA acid anhydride conjugates were performed on all 11 serum samples with IgG against TM-HSA, and on the three serum samples with highest IgG binding to P-HSA and M-HSA. The only conjugate capable of inhibiting TM-HSA was TM-HSA. Both P-HSA and TM-HSA were able to inhibit IgG bound to P-HSA, and all other anhydride conjugates were able to inhibit IgG bound to M-HSA to some degree. When using TM-HSA and the other anhydride-HSA conjugates to inhibit IgG against TM-HSA, cross-reactivity was not apparent. However, when using those same conjugates to inhibit IgG against P-HSA or M-HSA, cross-reactivity could be demonstrated in some serum samples. Thus TMA workers may have antibody that has some affinity for other anhydride-HSA conjugates, but this antibody cannot be demonstrated by inhibition studies of IgG against TM-HSA when using other acid anhydride-HSA conjugates. Further studies are needed to define the biologic relevance of these immunologic observations.

Adult↗
PubMed1992

Biological activity of paramyxovirus fusion proteins: factors influencing formation of syncytia.

The fusion (F) and hemagglutinin-neuraminidase (HN) glycoproteins of the paramyxovirus simian virus 5 (SV5) were expressed individually or coexpressed in CV-1 cells by using SV40-based vectors and recombinant vaccinia viruses. The extent of detectable fusion in a syncytium formation assay was found to be affected by the expression system used. In addition, when HN was coexpressed with F, it was found that the expression vector system influenced the contribution of HN in forming syncytia. The abilities of the SV5, human parainfluenza virus type 3, and Newcastle disease virus F glycoproteins to cause fusion, when expressed alone or coexpressed with HN, were directly compared by using the SV40-based vector system in CV-1 cells. The F proteins exhibited various degrees of fusion activity independent of HN expression, but the formation of syncytia could be enhanced to different extents by the coexpression of the homotypic HN protein.

Cell Line↗
PubMed1992

IgG subclass antibody against trimellitic anhydride in workers with and without immunologic lung diseases.

In a retrospective comparison of two worker cohorts with elevated total antibody against trimellitic anhydride (TMA) conjugated to human serum albumin (TM-HSA), IgG subclass antibodies against TMA were studied in 19 workers with and 12 workers without TMA-induced immunologic lung disease. The main outcome measures were ELISA index of IgG1, IgG2, IgG3, and IgG4 against TM-HSA. There were no statistically significant differences in levels of any IgG subclass between these two groups. Neither were there any statistically significant differences when workers without lung disease were compared with subgroups of workers with lung disease, such as late respiratory systemic syndrome (n = 8), asthma/rhinitis (n = 6), or both (n = 5). In TMA workers with elevated total antibody against TM-HSA, IgG subclasses against TM-HSA in workers with TMA-induced immunologic lung disease were not different from workers without disease.

Adult↗
PubMed1991

Antibodies to toluene diisocyanate in patients with and without dialysis anaphylaxis.

In a majority of patients with anaphylaxis to dialysis, ethylene oxide has been identified as an etiologic agent. In a significant minority of patients sustaining such reactions, the antigen remains unidentified. Conflicting results have been published with regard to isocyanates as a possible antigen. The authors studied 19 hemodialysis patients with anaphylaxis in whom IgE against ethylene oxide-human serum albumin (ETO-HSA) was not identified (Group 1) and 25 peritoneal dialysis patients without anaphylaxis (Group 2). IgE against toluene diisocyanate-human serum albumin (TDI-HSA) was found in one patient in Group 1, and a similar incidence of IgG against TDI-HSA in Group 1 (16%) and Group 2 (12%) was noted. The results do not suggest that IgE against TDI-HSA is an important cause of dialysis anaphylaxis.

Anaphylaxis↗
PubMed1991

Anaphylaxis during intrauterine insemination secondary to bovine serum albumin.

A case of anaphylaxis is reported after IUI with sperm processed in Tyrode's solution supplemented with BSA. The patient had a positive prick cutaneous test to BSA and also had specific IgE antibody against it. Repeat IUI using the patient's own blood serum instead of BSA for processing the sperm proceeded without incident. Clinicians should be aware of this rare, but not inconsequential, adverse effect of using xenogeneic proteins during IUI and other assisted reproductive techniques.

Adult↗
PubMed1990

Clinical and immunologic evaluation of 37 workers exposed to gaseous formaldehyde.

Thirty-seven workers exposed to formaldehyde (F) were evaluated to determine whether any of their respiratory or ocular symptoms were mediated by an immunologic response to F. Because there has never been a case of defined immunologically mediated respiratory or ocular disease as a result of exposure to gaseous F, we used clinical and immunologic criteria developed for immunologic respiratory diseases that result from inhalational exposure to trimellitic anhydride. A clinical assessment included review of a medical summary of history, physical examination, chest x-ray films, and pulmonary function studies. Serologic assessment was made with an ELISA for IgE and IgG to F human serum albumin. The final evaluation for immunologically mediated disease was based on both the clinical and serologic assessments. None of the workers had IgE or IgG antibody to F-human serum albumin or an immunologically mediated respiratory or ocular disease caused by F; however, some of the workers appeared to experience irritant symptoms caused by workplace exposure to F or other irritant chemicals.

Adult↗
PubMed1990

Human IgE, IgG and IgA antibody responses to T101, a murine monoclonal antibody against human lymphocytes: implications for pathogenesis, risk and avoidance of adverse immunologic reactions.

To study immune responses that may play a role in immediate-type allergic reactions (ITAR) and serum-sickness-like reactions that have been reported with administration of monoclonal antibodies (MAb), we measured by enzyme-linked immunosorbent assay serum levels of IgE, IgG, and IgA human antimurine antibody (HAMA) to T101, a murine IgG2a antibody that has been used in the treatment of cutaneous T cell lymphoma (CTCL) and chronic lymphocytic leukemia (CLL). None of 8 patients (4 with CLL, 4 CTCL) pretreated with T101 had elevated titers of any HAMA class tested as compared to normal control sera. All CTCL patients who had elevated total serum IgE levels, but normal total serum levels of other antibody classes, had significant rises in IgE, IgG, and IgA HAMA to T101 after intravenous MAb infusion. However, the CLL patients who were hypogammaglobulinemic failed to develop significant rises in HAMA. Three patients (2 CLL, 1 CTCL) had ITAR (e.g., urticaria, angioedema, bronchospasm) associated with infusion of T101; prophylactic medication regimens based upon the control of radiographic contrast media reactions were used with apparent benefit in subsequent infusions in these patients. All 8 patients had negative immediate intradermal skin tests (1 microgram/ml) to T101 prior to its infusion. Our data confirm that (1) non-IgE-mediated mechanisms cause ITAR from this MAb, possibly by a mechanism inherent in the action of this MAb against lymphocytes, and (2) that isotypic antibody responses to MAb vary with the type of malignancy being treated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Safety and immunogenicity of immunotherapy with accelerated dosage schedules of polymerized grass and ragweed in patients with dual inhalant sensitivity.

Immunotherapy with individually polymerized grasses (IPG) and immunotherapy with polymerized ragweed (PRW) have been demonstrated to be immunogenic and safe and to result in lowering of symptom-medication scores compared to placebo. We conducted this study to evaluate the immunogenicity and safety of immunotherapy with concomitantly administered accelerated dosage schedules of IPG and PRW in 12 patients with dual inhalant sensitivities. Patients were treated in nine weekly visits with IPG, comprising 71,950 PNU; they were treated in 11 weekly visits with PRW comprising 2955 allergy units. Eleven additional patients who had been previously treated with IPG received only PRW. There were no systemic reactions and no clinically significant changes in routine laboratory parameters, including hepatic and renal functions, with injections. There were significant rises in IgG titers by ELISA to each grass-pollen allergen administered, orchard, timothy, and Bermuda, and in total antibody binding of antigen E. Changes in IgE against orchard, timothy, Bermuda, and antigen E were minor. Thus, IPG and PRW administered concomitantly in accelerated dosage schedules are safe and immunogenic in patients with dual inhalant sensitivities.

Adult↗
PubMed1989

IgG antibody against formaldehyde human serum proteins: a comparison with other IgG antibodies against inhalant proteins and reactive chemicals.

Immune responses to formaldehyde (F) have been recorded for seven decades. More recently, sensitive assays for antibody against F-human serum albumin (HSA) have been reported. IgG antibody against F-HSA has been said to correlate with symptoms against F-HSA. We report on 61 serum samples analyzed for IgG antibodies against F-HSA. IgG antibodies against F-HSA were most prevalent in subjects who had received intravenous F. In no case (either presumed symptomatic to F or with IgG antibody against F-HSA) was there a correlation of serologic results with symptoms. We also reviewed inhalation disease caused by chemicals and proteins acting as immunogens and report that at this time there is no evidence that gaseous F meets the criteria for causation of inhalational IgG-mediated lung disease by clinical or serologic studies. Very high IgG antibody levels occur in respiratory immunologic inhalational disease, and the absence of these high IgG levels against F is strong evidence against F or F proteins being an inhalational antigen of significance.

Allergens↗
PubMed1989

Analysis of the relationship between cleavability of a paramyxovirus fusion protein and length of the connecting peptide.

The relationship between the length of the connecting peptide in a paramyxovirus F0 protein and cleavage of F0 into the F1 and F2 subunits has been examined by constructing a series of mutant F proteins via site-directed mutagenesis of a cDNA clone encoding the simian virus 5 F protein. The mutant F proteins had one to five arginine residues deleted from the connecting peptide. The minimum number of arginine residues required for cleavage-activation of the simian virus 5 F0 protein by host cell proteases was found to be four. F proteins with two or three arginine residues in the connecting peptide were not cleaved by host cell proteases but could be cleaved by exogenously added trypsin. The mutant F protein possessing a connecting peptide consisting of one arginine residue was not cleaved by trypsin. The altered F proteins were all transported to the infected-cell plasma membrane as shown by cell surface immunofluorescence or cell surface trypsinization. However, the only mutant F protein found to be biologically active as detected by syncytium formation was the F protein which has four arginine residues at the cleavage site. The results presented here suggest that in the paramyxovirus F protein the number of basic amino acid residues in the connecting peptide is important for cleavage of the precursor protein by host cell proteases but is not the only structural feature involved. In addition, the data indicate that cleavage of F0 into F1 and F2 does not necessarily result in biological activity and that the connecting peptide may affect the local conformation of the F polypeptide.

Amino Acid Sequence↗