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Biomedical subjects

J N Fink

Publications and source records attributed to J N Fink.

At least 55 records · Page 3Linked to original sources

Comparison of latex hypersensitivity among patients with neurologic defects.

BACKGROUND: Latex hypersensitivity has been described in discrete populations including health care workers and children with spina bifida (SB). OBJECTIVE: This study was designed to determine whether the SB population is a unique neuroimmunologic group manifesting this sensitivity. METHODS: Four groups of subjects were studied. These included: 36 patients with SB with or without clinical evidence of latex hypersensitivity, 50 patients with spinal cord injury (SCI), and 10 patients with cerebrovascular accidents (CVAs), all of whom were questioned regarding contact with and possible clinical allergic reactions to latex. Ten healthy control subjects were also studied. We used a latex sap extract, previously shown to react with latex-specific IgE in a biotin-avidin ELISA, to determine latex-specific IgE antibody titers and to compare the groups. RESULTS: Responses to questionnaires indicated that neither the patients with SCI nor the patients with CVA had histories suggestive of latex hypersensitivity. In contrast, 72% of the SB population had histories of clinical latex allergy. Comparisons of latex contact among the SB, SCI, CVA, and control groups revealed that the SB and SCI groups had similar latex exposure, whereas the other groups had less exposure. Both the SB and SCI groups had an average of two surgical procedures per year, which was greater than the average for the other groups. Comparisons of IgE latex antibody titers among the groups indicated that only the SB group had significant levels. The mean optical density values for each group were: 0.299 +/- 0.177 for patients with SB and positive skin prick test results, 0.072 +/- 0.066 for patients with SB and negative skin prick test results, 0.098 +/- 0.005 in patients with SCI, 0.073 +/- 0.038 in patients with CVA, and 0.053 +/- 0.034 in control subjects. The percentages of positive latex IgE antibody detection were 72% for SB, 4% for SCI, 0% for CVA, and 0% for control groups. CONCLUSIONS: The results suggest that the SB population is unique in demonstrating IgE responses to latex contact, which may be due to increased latex exposure or altered neuroimmunologic interactions.

Adolescent↗

Monoclonal antibody against a major latex allergen reacts with latex products and ammoniated natural latex.

Spina bifida patients have been shown to be a high-risk group for latex allergy. Of the several latex proteins identified from nonammoniated natural latex, a polypeptide with a molecular mass of about 23 kDa was shown to be one of the major allergens reacting with IgE in the sera from such patients. Using hybridoma technology, a monoclonal antibody (mAb) 1E2 against the 23-kDa latex allergen was produced. The presence of the 23-kDa or related allergens in finished latex products was evaluated using 1E2. Of the 16 extracts of finished latex products, 12 reacted with 1E2. The other four products are not used in health care. Since the majority of latex products used in health care are manufactured from ammoniated latex and ammoniation may alter latex proteins, we also investigated the effect of ammoniation on the 23-kDa allergen. Although ammoniation degraded latex proteins, the 23-kDa antigen could still be detected by using mAb 1E2 on immunoblot of ammoniated latex proteins. Furthermore, ammoniation resulted in the appearance of additional proteins in high molecular weight positions not present in nonammoniated natural latex, which retained the 23-kDa epitope. The 23-kDa allergen could also be detected on surgical gloves after extensive washing.

Allergens↗

Pigeon-serum-induced hypersensitivity pneumonitis in the dog.

Pigeon serum (PS) is one of the most common causes of hypersensitivity pneumonitis (HP). PS-induced HP was examined in a dog model. The dogs (n = 6) were immunized by i.m. injections of PS, followed by insufflation with aerosolized PS, while all control dogs (n = 3) received saline only. All animals insufflated with PS developed tachypnea 2-4 h after PS inhalation. After PS insufflation, a significant decrease in arterial oxygen tension (PaO2) was detected in sensitized dogs. No change in PaO2 was detected in sensitized dogs after saline or in the controls after PS insufflation. In intradermal skin tests with PS antigen, a positive skin reaction was found in 3/6 dogs in 30 min, and in 5/6 dogs in 6 and 48 h after the PS injections. Sensitized dogs showed a significant increase in PS-specific IgG in serum and lavage fluid (LF). In LF of sensitized dogs, an increase in the percentage of lymphocytes, eosinophils, and neutrophils was detected. Sensitized dogs developed chronic interstitial inflammation with lymphocytes, macrophages, plasma cells, and eosinophils in lungs. Granulomas with lymphocytes, histiocytes, and giant cells were detected in both the interstitium and the bronchiolar wall in the lungs of sensitized dogs. PaO2 was lowest in dogs showing the most severe interstitial inflammation in the lungs. The results indicate that dogs can be successfully used in immunologic and physiologic studies of PS-induced HP.

Alveolitis, Extrinsic Allergic↗

Comparison of latex antigens from surgical gloves, ammoniated and nonammoniated latex: effect of ammonia treatment on natural rubber latex proteins.

Immediate hypersensitivity to latex proteins from contact with natural rubber latex gloves has been increasingly reported, especially in health care workers. Proteins in the latex responsible for these reactions may potentially be extractable, adsorbed on glove powder, or remain unextractable. Because these gloves are manufactured from ammoniated natural rubber latex, our knowledge on the effect of ammonia on latex proteins is incomplete. Therefore, we have investigated the effect of ammoniation on the protein profile and antigenicity or allergenicity of natural rubber latex proteins (NAL). Results indicate that ammonia treatment leads to breakdown and even precipitation of certain latex proteins. However, the antigenicity or allergenicity of NAL is preserved in the degraded proteins that present as extractable latex antigens of gloves. In addition to the proteins present in glove extract and proteins adsorbed to glove powder, certain latex proteins (23, 10, and 8 kd) remain firmly bound to glove film as "unextractable" latex antigens that cannot be removed by washing. The unextractable latex antigens may represent the antigens precipitated by ammonia treatment and may be associated with latex allergy.

Ammonia↗

Hyperimmune serum modulates allergic response to spores in a murine model of allergic aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a disease in atopic asthmatics characterized by eosinophilia and elevated levels of immunoglobulin E (IgE) and IgG antibodies to the ubiquitous fungus Aspergillus fumigatus (Af). The role of specific antibodies in the disease process is not clear. In this study, BALB/c mice were injected with hyperimmune serum from syngeneic mice exposed to soluble antigen of Af. These mice were then exposed to either Af spores or soluble antigen. Total IgE, Af-specific IgG1 (enzyme-linked immunosorbent assay) in serum, and eosinophils (eosinophil peroxidase assay) in lungs and bone marrow were measured. Histologic sections of lungs were examined for cellular infiltration and morphologic changes. Results indicate a suppression of increase in levels of antibodies and eosinophilia in mice receiving immune serum and exposed to spores compared with controls receiving phosphate-buffered saline treatment. Spores being the primary source of exposure to Af in ABPA, these results are significant in understanding the role of preexisting specific antibodies in patients.

Animals↗

Latex-induced dermal and pulmonary hypersensitivity in rabbits.

BACKGROUND: Natural rubber latex (NRL) causes immediate, IgE-mast cell-mediated reactions in sensitized individuals, especially among health care workers and children with spina bifida. The immunopathogenesis of the reaction is obscure. METHODS: To study the immunologic mechanisms of NRL allergy, rabbits were sensitized with two nonammoniated and one ammoniated NRL antigens. Subcutaneous and intratracheal injections were used to immunize rabbits. Intradermal skin tests, IgG antibodies against NRL in serum and lung lavage fluid, and pulmonary histologic features were evaluated. RESULTS: One of nine sensitized rabbits died of anaphylaxis immediately after the third intratracheal injection with nonammoniated NRL. All sensitized rabbits, but not the controls, showed an immediate wheal and flare reaction in intradermal skin testing with NRL antigens. A positive skin reaction was detected 6 and 48 hours after the intradermal injections in four of five sensitized rabbits. A significant increase in NRL-specific IgG antibodies was detected in serum and lung lavage fluid of immunized rabbits. Lung histologic evaluation of NRL-sensitized rabbits showed a granulomatous interstitial and bronchial inflammation with a predominance of eosinophils and histiocytes in both intratracheally and subcutaneously sensitized rabbits. Vasculitis, hypertrophia, and contraction of pulmonary arteries could be detected in sensitized animals. CONCLUSION: The results of the first NRL rabbit model study indicate that eosinophils and IgE antibodies play a major role in the immunopathogenesis of NRL-induced allergy and anaphylaxis. A wide range of inflammatory responses detected in rabbits injected by subcutaneous route without intratracheal exposure suggests that NRL exposure may pose a risk for a subsequent systemic reaction.

Anaphylaxis↗

A double-blind study of the efficacy of nedocromil sodium in the management of asthma in patients using high doses of bronchodilators.

The effects of nedocromil sodium were assessed in 110 patients with asthma who experienced asthma symptoms despite the use of high doses of inhaled bronchodilators. During the baseline period, antiinflammatory agents were not permitted, and patients were treated with inhaled beta-agonists on an as-needed basis. Patients who required 12 or more puffs of albuterol and experienced continuing asthma symptoms for 7 of the 14 baseline days were randomized to treatment groups. Subjects received either nedocromil sodium (4 mg) or placebo four times a day for 10 weeks. Statistically significant (p < 0.05) between-treatment differences (weeks 3 to 10), favoring nedocromil sodium, were determined for the asthma summary score, daytime asthma severity, asthmatic cough, morning peak flow rates, reduction of as-needed bronchodilator use, physician's assessment of asthma severity, and patient and physician opinions of treatment effectiveness. By trial end (week 10), sleep difficulty caused by asthma decreased 29% in the nedocromil sodium group and 4% in the placebo group (p = 0.006). Nedocromil sodium was well tolerated and improved asthma control while reducing the inhaled bronchodilator load of these patients with moderately severe asthma.

Adolescent↗

The diagnosis of natural rubber latex allergy.

Allergy to latex is a rapidly emerging public health problem. Because our knowledge of the major allergens involved is incomplete, standardized in vivo and in vitro tests have not been available. Because of systemic reactions to skin prick testing, this method should be used only after results of other tests have been inconclusive. Risks and benefits of the test need to be explained to the patient, and until standard extracts of latex are available, skin tests should be performed under a research protocol. We anticipate that with greater knowledge of the relevant allergens, purification of these allergens with affinity chromatography, high-performance liquid chromatography, and monoclonal antibodies, a safe and reliable extract will be available in the near future for skin testing. Until then, the above guidelines can serve clinicians in their daily practice in the diagnosis of latex allergy.

Adult↗

Latex antigens induce IgE and eosinophils in mice.

Hypersensitivity to latex proteins has been reported with increasing frequency in recent years. Elevated levels of latex specific IgE have been detected in the majority of these patients. Severe anaphylaxis and death resulting from latex exposure has also been reported. Nevertheless, the immune mechanism of latex allergy is not fully understood. In this report, we describe a model of latex allergy developed in mice exposed to latex proteins. Animals exposed to latex proteins demonstrated enhanced levels of total IgE, peripheral blood and lung eosinophilia, and elevated levels of serum IL-4 and IL-5. mRNA transcripts of IL-4 and IL-5, but not IFN-gamma, could be demonstrated in spleen lymphocytes. Antibodies to latex belonging to all IgG subclasses were detected in the sera of mice exposed to latex antigens. The histology of the lung showed non-necrotizing granulomas and extensive interstitial chronic inflammatory infiltrates, particularly around bronchioles and small blood vessels. Although this model of latex allergy demonstrates a heterogeneous immunological response, the CD4-positive Th2 cell-mediated response predominated.

Animals↗

Immune responses to Aspergillus fumigatus and Pseudomonas aeruginosa antigens in cystic fibrosis and allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) in Cystic Fibrosis (CF) is well documented. Aspergillus fumigatus is the causative agent of ABPA, and Pseudomonas aeruginosa particularly the mucoid variety has been frequently isolated from the sputum of patients with CF. This study investigates the cellular and humoral immune response to both A fumigatus and P aeruginosa antigens in patients with CF and ABPA (CF/ABPA), CF only, and healthy controls. The A fumigatus and P aeruginosa antigen specific IgE and IgG in sera and peripheral blood mononuclear cell culture supernatants (PBMC sups), lymphoproliferation to antigens, and leukotriene B4 (LTB4) were measured. Results indicate significant elevated levels of A fumigatus specific IgG (A fumigatus-IgG) and Paeruginosa-IgE in serum. Significant Paeruginosa-IgG was measured in PBMC sups. The concanavalin A nonbinding A fumigatus antigen, previously shown to induce specific T-cell responses in vitro in patients with ABPA, elicited significant lymphoproliferative response in a greater proportion of patients with CF/ABPA and not in CF or controls, underlining the importance of this antigen in the diagnosis of ABPA. In contrast, a greater proportion of the CF group responded to P aeruginosa antigens compared with the controls and CF/ABPA. Hence, the CF and CF/ABPA groups respond to both P aeruginosa and A fumigatus antigens with the former group responding strongly to P aeruginosa and the latter to A fumigatus antigens.

Antigens, Bacterial↗

Investigations into the cellular immune responses in latex allergy.

Latex allergy is a hypersensitivity response to allergens in the natural latex products. Skin prick tests, which do not correlate very well with latex-specific immunoglobulin E (IgE), are yet the only reliable diagnostic tools for clinically determining hypersensitivity to latex. In this study, patients who were skin test (SPT) positive with (STP+/ANA+) or without (SPT+/ANA-) history of anaphylaxis formed the test groups. Healthy volunteers (SPT-/ANA-) served as controls. Lymphocyte proliferation in response to crude and purified latex antigens, serum immunoglobulin E-total, and latex-specific and in vitro immunoglobulin E (IgE) production in response to crude latex antigens were studied. Results indicate that both patient groups showed enhanced response to latex antigen by lymphoproliferation. In patient groups this response to the different antigens tested, or to crude versus purified antigens, was not statistically different. Serum total IgE (ng/ml) was elevated in patients (range, SPT+/ANA-, 40 to 1250; SPT+/ANA+, 40 to 4550) when compared with controls (40 to 450). Low levels (1 to 3 ng/ml) of IgE were detected in the peripheral blood mononuclear cell culture supernatants from the patient groups. These levels were < or = 1 ng/ml in the control group. Significant levels of IgE (log titer, mean +/- SD) specific to MFL1 and glove antigens were measured in serum from both SPT+/ANA- (MFL1, 1.85 +/- 0.23, p < 0.001; glove, 1.81 +/- 0.23, p < 0.001) and SPT+/ANA- (MFL1, 1.92 +/- 0.39, p < 0.007; glove 1.85 +/- 0.4, p < 0.006) and compared with results from the control group (MFL1, 1.50 +/- 0.1; glove, 1.38 +/- 0.19).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Aspergillus fumigatus antigen induced eosinophilia in mice is abrogated by anti-IL-5 antibody.

A murine model of allergic bronchopulmonary aspergillosis (ABPA), developed by exposure to Aspergillus fumigatus antigens, demonstrated eosinophilia of peripheral blood (PB), bone marrow (BM), and lung. The eosinophilia was abrogated by monoclonal anti-interleukin-5 (IL-5) antibody (TRFK-5) and not by an isotype control antibody (GL 113). Eosinophils in PB were enumerated from stained smears and their relative increase or decrease in cells from BM and lung was determined by an eosinophil peroxidase (EPO) assay (measured in optical density). Intraperitoneal injection of TRFK-5 in mice exposed to A. fumigatus antigen produced a significant reduction in eosinophils (PB 6.6 +/- 1.14% vs. 3.8 +/- 0.8%, P < .01) and EPO production in BM (0.935 +/- 0.03 vs. 0.615 +/- 0.02, P < .001). A similar reduction in EPO production in the lung (0.691 +/- 0.12 vs. 0.495 +/- 0.05, not significant) was also reflected in the histopathology for the different groups of mice. These findings confirming the role of IL-5 in eosinophilia, although not surprising, are significant in elucidating the immunopathogenesis of ABPA in the murine model. We conclude that in this model, eosinophilia may be due largely to the Th2 cytokine -IL-5 induced by A. fumigatus antigens.

Animals↗

Characterization of a monoclonal antibody against latex protein associated with latex allergy.

Several hybridomas were produced against antigens extracted from the latex sap of Hevea brasiliensis. One of the monoclonal antibodies (LA-E3) reacted with antigens demonstrating binding to patient sera on crossed enzyme immunoelectrophoresis. This monoclonal antibody reacted with 2 of 10 glove extracts studied and with both Malaysian and Indian latex plant extracts. The antigens purified with monoclonal antibody affinity chromatography demonstrated specific IgE in the sera of patients with latex allergy as determined by ELISA. This monoclonal antibody can thus be utilized to obtain reliable antigens useful in the diagnosis of latex sensitivity, although additional antigens will likely be necessary to enhance sensitivity and specificity.

Adolescent↗

Immunoglobulin E reactivity to latex antigens in the sera of patients from Finland and the United States.

BACKGROUND: Patients with latex sensitivity and latex antigens from the United States and Finland, two countries where allergic reactions to latex have been widely reported, were evaluated to determine the spectrum of immune responses. METHODS: Sera from 27 patients from Finland and 18 from the United States with latex allergy and control sera from nonsensitive individuals were studied for latex-specific IgE antibodies. Four antigen preparations were used: two extracted from gloves and one each extracted from rubber tree sap from Malaysia and India. All 45 patients had skin prick test results that were positive to latex antigens, and all sera were evaluated by enzyme-linked immunosorbent assay (ELISA) with the various antigens. RESULTS: There were considerable differences in the reactivity of patient sera with the different antigens. Only 50% of the sera from patients with latex allergy from Finland demonstrated significant levels of IgE to latex as determined by enzyme-linked immunosorbent assay. These patients showed more reactivity with rubber tree sap antigens than with glove antigens. However, 72% of the patients from the United States demonstrated antibodies to latex, and no marked differences were noted between the antigen extracts. CONCLUSIONS: The results indicate that reagents such as rubber tree sap, which contain multiple clinically significant antigenic components, should be included in evaluation of latex allergy and that differences in patient populations may result in serologic variances.

Adult↗

Skin and serologic testing in the diagnosis of latex allergy.

BACKGROUND: Latex hypersensitivity is associated with occupational allergy, contact urticaria, rhinitis, asthma, and anaphylaxis. However, standardized sensitive and specific latex extract for skin prick or serologic testing is not available in the United States. METHODS: We investigated the reliability of two latex extracts in 118 consecutive skin tests in patients with spina bifida, health care workers, and other patients with symptoms of latex allergy, and 10 control subjects. RESULTS: Forty-two of 86 patients with spina bifida, 11 of 15 health care workers with symptoms of latex allergy, 6 of 7 patients with symptoms of latex allergy, and 0 of 10 control subjects had demonstrable immediate wheal and flare responses to latex prick testing. In addition, 95 patients and 10 control subjects were tested concurrently for latex-specific IgE by ELISA. Of 55 patients with positive skin prick test results, 48 were reactive as determined by ELISA for IgE-specific latex antibody (sensitivity = 87%). Latex ELISA titers were significantly higher in patients with positive skin prick test results with a history of anaphylaxis to latex and in individuals without symptoms of latex allergy who had positive skin prick test results when compared with patients with negative skin prick test results. During the skin test procedure, nine patients had adverse reactions, including anaphylactic reactions in four. CONCLUSIONS: Skin prick and serum testing are reliable methods of diagnosing latex allergy. Serologic evaluation may be more desirable until allergen standardization is available.

Adult↗

Production and characterization of a monoclonal antibody to a major concanavalin A--nonbinding antigen of Aspergillus fumigatus.

A hybridoma secreting immunoglobulin G1 antibody was produced against Aspergillus fumigatus. In this study we used interleukin-4 as a growth factor to augment the survival and multiplication of immunoglobulin G1-secreting hybridomas. The antigen recognized by this monoclonal antibody is a low-molecular weight concanavalin A-nonbinding component of A. fumigatus. The monoclonal antibody affinity-purified antigen showed specific reactivity with serum from patients with allergic bronchopulmonary aspergillosis, whereas all allergic asthmatic patients with skin-test reactivity to A. fumigatus demonstrated only low levels of antibodies similar to those in normal control subjects. This antigen failed to show cross-reactivity with other fungal antigens. These results indicate that this monoclonal antibody can be used for the purification of specific antigens useful in the immunodiagnosis of allergic bronchopulmonary aspergillosis.

Animals↗