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Biomedical subjects

Jordan N Fink

Publications and source records attributed to Jordan N Fink.

At least 19 recordsLinked to original sources

Gastro-intestinal exposure to latex antigens induce allergic responses in mice.

BACKGROUND: Natural rubber latex (NRL) has emerged as a major cause of respiratory allergy among specific exposed groups of individuals. Since latex allergens are dispersed in the environment it is conceivable that latex proteins are both inhaled and ingested. The mechanism of latex allergy and the immune responses following reexposure of latex allergens by the intranasal route was studied in a murine model of latex allergy developed by intragastric sensitization with NRL. METHODS: BALB/c mice were sensitized intragastrically ('ig'), intranasally ('in') or 'ig' followed by 'in' challenge with NRL allergens. The cellular and humoral immune responses, lung function and histological changes were determined. RESULTS: Peripheral blood eosinophilia was observed in the 'ig' and 'ig/in'-NRL-sensitized animals in comparison to normal controls (p < 0.05). The 'ig' group showed a marked increase over control mice in serum total IgE, NRL-specific IgG and IgG subclasses (p < 0.05). Increased levels of IL-4, IL-5, IL-10, and IL-13 were detected in 'ig'-NRL-sensitized mice. Intranasal exposure with NRL after 'ig' sensitization further enhanced the cytokine levels. A tendency towards enhanced stimulation was determined in 'ig'-sensitized mice; a significant difference was shown in the 'ig/in'-group (p < 0.05). Increased airway hyperreactivity was found in 'ig'-NRL-sensitized-mice (15.1 +/- 2.5 vs. 8.9 +/- 1.7 cm H2O x ml(-1) x s, p < 0.05). Mucus secretion from jejunal epithelium and eosinophilic infiltration into the jejunal lamina propria were observed in the 'ig'-NRL-sensitized-mice. CONCLUSIONS: The results demonstrate that intragastric NRL sensitization did not induce specific tolerance, and additional intranasal exposure with latex allergens resulted in systemic allergic manifestations in the murine model.

Administration, Intranasal↗

Airbag asthma: a case report and review of the literature.

BACKGROUND: Although airbags are a significant development in automobile safety, they have brought with them new medical problems. OBJECTIVE: To describe a case of new-onset asthma occurring after exposure to a deployed airbag's contents. METHODS: A 47-year-old man had a 2.5-year history of chest tightness, decreased exercise tolerance, and nocturnal and activity-associated cough beginning after a head-on motor vehicle collision when he was driving an automobile equipped with dual driver-passenger airbags. The collision activated both airbags, with the driver's side airbag breaking open, filling the automobile with particulates. The driver remained in the car for 3 minutes and developed acute shortness of breath and chest tightness for the first time in his life. He had a smoking history of 1 pack-year 20 years earlier. Before that time he could exercise frequently, running for 30 minutes almost daily without difficulty. After the collision, he had respiratory symptoms at rest and after exercise, requiring daily control and rescue medication. Subsequently, he developed bronchospasm following exposure to nonspecific agents, which he had never previously experienced. RESULTS: Skin test reactivity was detectable only to dust mite. Methacholine challenge results were markedly positive at 8 weeks and 2.5 years after the incident. Video laryngoscopy revealed normal vocal cord appearance and function. CONCLUSIONS: Our patient represents the first case, to our knowledge, of new-onset, persistent, irritant-induced asthma following airbag deployment. Physicians should be aware of its possibility after airbag exposure, since prompt institution of aggressive therapy may improve patient outcome and dampen or prevent persistent disease.

Accidents, Traffic↗

Latex allergen IgE assays in the assessment of Veterans Affairs health care workers.

BACKGROUND: A previous multicenter study of Veterans Affairs health care workers evaluated hospital participants for latex hypersensitivity. Well-defined groups from that study allowed us to explore the diagnostic utility of newer antilatex allergen IgE immunoassays in the present study. OBJECTIVES: To determine whether an enhanced CAP (ENHCAP) assay or an enzyme-linked immunosorbent assay (ELISA) identifies latex glove symptomatic individuals with antilatex allergen IgE that had not been detected by the CAP assay used in the original study and to determine the specificity of the ENHCAP assay. METHODS: The ELISA measured IgE antibody to Malaysian nonammoniated natural rubber latex extract (MNA), Hev b1, Hev b5, and Hev b6. Four patient groups were tested: confirmed latex glove allergic, latex glove symptomatic, latex glove sensitized/asymptomatic, and latex glove nonallergic. RESULTS: The ENHCAP assay and the MNA ELISA were highly concordant with the original CAP assay. In the subgroup with latex glove symptoms that were previously negative by the CAP assay, the ENHCAP assay value was elevated in 7 (11%) of 64 samples, only 3 of which were class 2 or higher. The MNA ELISA result was positive in only 4 (6%) of these 64 samples, and 3 of these were fractionally above the cutoff value for this assay. CONCLUSIONS: The ENHCAP assay and the MNA ELISA identified a few additional positive individuals in the group that was latex glove symptomatic and originally CAP assay negative. The ENHCAP assay and the MNA ELISA produced only a modest improvement in diagnostic sensitivity over that of the original CAP assay.

Antigens, Plant↗

Specific IgE response to purified and recombinant allergens in latex allergy.

BACKGROUND: In recent years, allergy to natural rubber latex has emerged as a major allergy among certain occupational groups and patients with underlying diseases. The sensitization and development of latex allergy has been attributed to exposure to products containing residual latex proteins. Although improved manufacturing procedures resulted in a considerable reduction of new cases, the potential risk for some patient groups is still great. In addition the prevalent cross-reactivity of latex proteins with other food allergens poses a major concern. A number of purified allergens and a few commercial kits are currently available, but no concerted effort was undertaken to evaluate them. METHODS: We studied 11 purified latex allergens, Hev b 1 to Hev b 10, and Hev b 13 along with several crude allergen extracts and two commercial ImmunoCAP assays to evaluate specific IgE antibody in the sera from latex allergic patients and controls. Health care workers and spina bifida patients with clinical symptoms of latex allergy, spina bifida patients without latex allergy, and non-atopic health care workers have been studied. RESULTS: The results suggest that Hev b 2, 5, 6, and 13 together identified over 80 percent health care workers with latex allergy, while Hev b 6 along with Hev b 1 or 3 detected specific IgE antibody in all sera studied from patients with spina bifida and latex allergy. The ImmunoCAP results using both Hev b 5 amplified and non-amplified closely agreed with the clinical diagnosis of latex allergy in health care workers and in spina bifida. CONCLUSION: Although the purified allergens and crude extracts reacted diversely with IgE from different patient groups, the results indicated that use of certain combinations of purified recombinant antigens will be useful in commercial kits or in in-house assays for detecting specific IgE antibody in the sera. The results suggest that a combination of Hev b 2, 3, 5, 6, and 13 together detected specific IgE in 80% of the sera from latex allergic patients. Both ImmunoCAPs correctly identified over 95% of latex allergic patients, however, showed reactivity with a few normal control subjects.

Journal Article↗

Needs and opportunities for research in hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) develops after inhalation of many different environmental antigens, causing variable clinical symptoms that often make diagnosis uncertain. The prevalence of HP is higher than recognized, especially its chronic form. Mechanisms of disease are still incompletely known. Strategies to improve detection and diagnosis are needed, and treatment options, principally avoidance, are limited. A workshop recommended: a population-based study to more accurately document the incidence and prevalence of HP; better classification of disease stages, including natural history; evaluation of diagnostic tests and biomarkers used to detect disease; better correlation of computerized tomography lung imaging and pathologic changes; more study of inflammatory and immune mechanisms; and improvement of animal models that are more relevant for human disease.

Adult↗

Allergy and "toxic mold syndrome".

BACKGROUND: "Toxic mold syndrome" is a controversial diagnosis associated with exposure to mold-contaminated environments. Molds are known to induce asthma and allergic rhinitis through IgE-mediated mechanisms, to cause hypersensitivity pneumonitis through other immune mechanisms, and to cause life-threatening primary and secondary infections in immunocompromised patients. Mold metabolites may be irritants and may be involved in "sick building syndrome." Patients with environmental mold exposure have presented with atypical constitutional and systemic symptoms, associating those symptoms with the contaminated environment. OBJECTIVE: To characterize the clinical features and possible etiology of symptoms in patients with chief complaints related to mold exposure. METHODS: Review of patients presenting to an allergy and asthma center with the chief complaint of toxic mold exposure. Symptoms were recorded, and physical examinations, skin prick/puncture tests, and intracutaneous tests were performed. RESULTS: A total of 65 individuals aged 1 1/2 to 52 years were studied. Symptoms included rhinitis (62%), cough (52%), headache (34%), respiratory symptoms (34%), central nervous system symptoms (25%), and fatigue (23%). Physical examination revealed pale nasal mucosa, pharyngeal "cobblestoning," and rhinorrhea. Fifty-three percent (33/62) of the patients had skin reactions to molds. CONCLUSIONS: Mold-exposed patients can present with a variety of IgE- and non-IgE-mediated symptoms. Mycotoxins, irritation by spores, or metabolites may be culprits in non-IgE presentations; environmental assays have not been perfected. Symptoms attributable to the toxic effects of molds and not attributable to IgE or other immune mechanisms need further evaluation as to pathogenesis. Allergic, rather than toxic, responses seemed to be the major cause of symptoms in the studied group.

Adolescent↗

Toxic mold syndrome.

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Air Pollution, Indoor↗

Role of C-terminal cysteine residues of Aspergillus fumigatus allergen Asp f 4 in immunoglobulin E binding.

Among the several allergens cloned and expressed from Aspergillus fumigatus, Asp f 4 is a major one associated with allergic bronchopulmonary aspergillosis (ABPA). The structure-function relationship of allergens is important in understanding the immunopathogenesis, diagnosis, and treatment of allergic diseases. These include the epitopes, conformational or linear, deletion of the N or C terminus or both N and C termini, and glycosylation or nonglycosylation, all of which affect immune responses. Similarly, the role of cysteine residues present in allergens may yield useful information regarding the conformational structure of allergens and the immunoglobulin E (IgE) epitope interaction. Such information may help in developing new strategies towards immunotherapy. In order to define the role of cysteine in the interaction of the antibody with Asp f 4, we have constructed mutants by selectively deleting cysteine residues from the C-terminal region of the Asp f 4. Immunological evaluation of these engineered recombinant constructs was conducted by using sera from patients with ABPA, Aspergillus skin test-positive asthmatics, and healthy controls. The results demonstrate strong IgE binding with Asp f 4 and two truncated mutants, Asp f 4(1-234) (amino acids [aa] 1 to 234) and Asp f 4(1-241) (aa 1 to 241), while another mutant, Asp f 4(1-196) (aa 1 to 196), showed reactivity with fewer patients. The result suggests that deletion of cysteines and the alteration of IgE epitopes at the C-terminal end resulted in conformational changes, which may have a potential role in the immunomodulation of the disease.

Allergens↗

Modulation of airway inflammation by immunostimulatory CpG oligodeoxynucleotides in a murine model of allergic aspergillosis.

Allergic aspergillosis is a Th2 T-lymphocyte-mediated pulmonary complication in patients with atopic asthma and cystic fibrosis. Therefore, any therapeutic strategy that selectively inhibits Th2 T-cell activation may be useful in downregulating allergic lung inflammation in asthma. In the present study, we developed a CpG oligodeoxynucleotide (ODN)-based immune intervention of allergic inflammation in a mouse model of allergic aspergillosis. Four different groups of mice were used in a short-term immunization protocol. Three experimental groups of animals (groups 1 to 3) were sensitized with Aspergillus fumigatus antigens. Animals in group 1 were immunized with A. fumigatus antigen alone, while those in group 2 were treated with CpG-ODN 1 day before the first antigen immunization, and the animals in group 3 received the first CpG-ODN administration between the antigen treatments. The animals in group 4 served as controls and were given phosphate-buffered saline. Allergen-specific serum immunoglobulins and total immunoglobulin E in different groups of animals were measured by enzyme-linked immunosorbent assay, while airway remodeling and cytokine production were studied by immunohistochemistry. The results demonstrated that CpG-ODN administration either before (group 2) or between (group 3) antigen treatments resulted in reduced total immunoglobulin E levels and peripheral blood eosinophil numbers compared to A. fumigatus allergen-sensitized group 1 animals. Similarly, treatment with CpG-ODN also downregulated inflammatory cell infiltration, goblet cell hyperplasia, and basement membrane thickening compared to A. fumigatus-sensitized mice. The distinct reduction in peripheral blood eosinophilia and airway remodeling in CpG-ODN-treated mice emphasized its usefulness as an immunomodulating agent for allergic fungal diseases.

Allergens↗

Toxic and other non-IgE-mediated effects of fungal exposures.

There are more than 100000 recognized species of fungi, comprising 25% of the biomass of the earth. Allergic, IgE-induced, manifestations of airborne fungi are common, whereas non-IgE manifestations are rare. Recently, much focus has been placed on the non-IgE-mediated effects of various molds, including hypersensitivity pneumonitis, infectious disease, and mycotoxicoses. Hypersensitivity pneumonitis is a clinical syndrome associated with systemic and interstitial lung disease that occurs in susceptible individuals following fungal inhalation. Most fungi are not pathogenic to man; however, certain fungi are capable of infecting immunocompetent individuals. Although mycotoxins and exposure to mycotoxins ("toxic mold syndrome") are implicated in causing numerous, nonspecific, systemic symptoms, currently, there is no scientific evidence to support the allegation that human health is affected by inhaled mycotoxins. However, if mold is discovered in a home, school, or office setting, the source should be investigated and appropriate remediation undertaken to minimize structural damage and potential allergic sensitization.

Air Microbiology↗

Latex hypersensitivity in Department of Veterans Affairs health care workers: glove use, symptoms, and sensitization.

BACKGROUND: This report of the prevalence of latex glove allergy in 3 Department of Veterans Affairs (VA) medical centers was a collaboration of the VA, the Centers for Disease Control and Prevention, and the National Institute for Occupational Safety and Health. OBJECTIVE: To enroll and evaluate personnel from across the entire hospital workforce for latex hypersensitivity and to determine the type and extent of latex glove use. METHODS: A questionnaire was administered that covered demographics, job category, latex glove use, and current latex glove allergic symptoms. Skin testing to aeroallergens was performed to evaluate the presence of atopy. Blood was drawn for analyses of serum antilatex IgE antibody by CAP assay. RESULTS: Of 1,959 subjects, 158 (8.1%) had latex glove-allergic symptoms, a positive latex CAP assay result, or both. In 1,003 subjects who reported latex glove use, 915 (91.4%) used nonpowdered gloves. A total of 133 subjects reported latex glove allergic symptoms, and 36 subjects had positive CAP assay results. Latex sensitization was correlated with atopy, race, and latex glove exposure. Latex symptoms were correlated with atopy, a positive CAP assay result, and latex glove exposure. Of the 133 subjects with latex glove allergic symptoms, only 11 had positive CAP assay results, giving a prevalence of confirmed latex glove allergy of 0.6%. CONCLUSIONS: Symptoms attributed to latex gloves and/or latex sensitization occurred in 8.1% of the employee population, with exposure, race, and atopy being the major risk factors. Few symptomatic individuals were sensitized to latex (0.6%). This low rate of confirmed latex glove allergy may have been related to nonpowdered glove use.

Adult↗

Occupational lung disease related to cytophaga endotoxin exposure in a nylon plant.

Workers at a nylon plant developed pulmonary disease with systemic symptoms. Differentiating between humidifier fever and hypersensitivity pneumonitis (HP) is challenging. Cytophaga, an endotoxin-producing bacteria, was isolated from the plant air-conditioning system. A number of workers had systemic and pulmonary symptoms. Precipitins to Cytophaga endotoxin were identified. Several workers underwent lung biopsies demonstrating HP. Inhalation challenges with purified Cytophaga endotoxin were performed on three pairs of subjects: group 1, or employees with clinical features and biopsy consistent with HP; group 2, asymptomatic exposed workers with precipitins; and group 3, nonexposed healthy individuals. All subjects had fever and leukocytosis after inhalation challenge. Acute and/or late pulmonary function changes occurred in groups 1 and 2. Group 3 only had acute and transient pulmonary function changes. Cytophaga bacterial endotoxin is capable of inducing HP as well as humidifier fever.

Alveolitis, Extrinsic Allergic↗

C-terminal cysteine residues determine the IgE binding of Aspergillus fumigatus allergen Asp f 2.

The knowledge of the structure function relationship of the allergen is essential to design allergenic variants with reduced IgE binding capacity but intact T cell reactivity. Asp f 2 is a major allergen from the fungus Aspergillus fumigatus and >90% of A. fumigatus-sensitized individuals displayed IgE binding to Asp f 2. In the present study, we evaluated the involvement of C-terminal cysteine residues in IgE binding conformation of Asp f 2. The deletion mutants were constructed by adding three C-terminal cysteines of the native Asp f 2 one at a time to the non-IgE binding Asp f 2 (68-203). The point mutants of Asp f 2 (68-268) with C204A and C257A substitutions were constructed to study the role of C-terminal cysteines in IgE binding. Immunological evaluation of reduced and alkylated Asp f 2 and its mutants were conducted to determine the contribution of free sulfhydryl groups as well as the disulfide bonds in allergen Ab interaction. Four-fold increase in IgE Ab binding of Asp f 2 (68-267) compared with Asp f 2 (68-266) and complete loss in IgE binding of C204A mutant of Asp f 2 (68-268) indicate the involvement of C(204) and C(267) in IgE binding conformation of Asp f 2. A significant reduction in IgE binding of wild and mutated Asp f 2 after reduction and alkylation emphasizes the importance of cysteine disulfide bonds in epitope Ab interaction. The hypoallergenic variants may be explored further to develop safe immunotherapeutic strategy for allergic disorders.

Allergens↗

IgE binding conformational epitopes of Asp f 3, a major allergen of Aspergillus fumigatus.

sp f 3 has been identified as one of the major allergens of Aspergillus fumigatus associated with the sensitization and immune responses in allergic bronchopulmonary aspergillosis (ABPA). In order to understand the structure/function relationship of Asp f 3, we studied synthetic peptides and constructed mutants deleted of specific IgE binding regions. The mutated allergens were obtained by expressing the genes and studied by ELISA for their reactivity with IgE from patients with ABPA. Seven linear IgE binding regions spanning the whole Asp f 3 molecule were demonstrated. The results demonstrated strong binding of IgE from ABPA patients with Asp f 3 and one mutant, Asp f 3(1-150), but not with other mutant constructs. The results identified 12 amino acids at the N-terminal end and 8 amino acids (143-150) at the C-terminal end as significant in the conformational constraints for IgE binding. The Fourier transfer spectra showed comparable beta-sheet structure of Asp f 3(1-150) and Asp f 3, indicating the role of secondary structure in IgE binding. The primary and secondary structures may help understanding of the functional role the allergens play in the disease and may have implications in immunodiagnosis and probably immunotherapy.

Allergens↗

The long-term outcome in acute, subacute, and chronic forms of pigeon breeder's disease hypersensitivity pneumonitis.

BACKGROUND: Pigeon breeder's disease (PBD) is an avian-induced hypersensitivity pneumonitis. The limited data that exist on the long-term outcome for the disease are conflicting. OBJECTIVE: We sought to determine the long-term outcome of patients with PBD to evaluate the course of the disease. METHODS: Review a case series of 18 pigeon breeders that were followed from 4 to 26 years after initial diagnosis. RESULTS: Fourteen breeders reduced their bird contact significantly; four kept their birds. In eight patients with the acute form of the disease, pulmonary function either did not change from normal or improved to normal. Of five patients with subacute disease, four had persistent symptoms. All had mildly abnormal spirometry with either restrictive or obstructive changes which persisted. Five patients with chronic disease exhibited daily dyspnea. They had severe abnormalities of lung function at diagnosis. Of these patients, three improved and two deteriorated. Chest radiographs were of little value in predicting outcome. CONCLUSIONS: Patients with the acute form of PBD have the best prognosis, compared with those with subacute and chronic forms. Although some improvement could be seen in most individuals, recovery may still not be complete. Those with the chronic form are at particular risk for morbidity.

Acute Disease↗

Alkaline serine proteinase from Aspergillus fumigatus has synergistic effects on Asp-f-2-induced immune response in mice.

BACKGROUND: Exposure to Aspergillus fumigatus allergens results in the sensitization and the development of allergic bronchopulmonary aspergillosis in susceptible individuals. Aspergillus antigen consists of a number of chemically diverse components and their cumulative or synergistic effect may result in disease. When mice were challenged with individual recombinant allergens, there was only reduced inflammation and immunological responses compared to the whole antigen. Various enzymes identified from A. fumigatus have been thought to cause airway damage. In the present study, we evaluated the effect of exposure to Asp f 13, an alkaline serine proteinase, and Asp f 2 in mice. METHODS: BALB/c mice were challenged intranasally with Asp f 2 and Asp f 13 alone and in combination. The antibody response, pulmonary inflammation, and airway hyperreactivity were studied. RESULTS: Results demonstrated no major difference in antibody response and airway responses among the different groups. The inflammatory responses in the lungs, however, showed marked differences in the various groups. CONCLUSION: In spite of the similar immunological responses in the different groups of mice studied, the results demonstrate enhanced inflammation in the lungs of mice exposed to a combination of both allergens. Allergens with proteinase activity have been found to be involved in airway inflammation and remodeling, which may also apply for Aspergillus-induced allergy.

Animals↗