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PubMed1993

[Diagnostic possibilities in drug allergies].

Drug allergies can be subclassified into three subgroups, which differ in their pathophysiology and require different diagnostic steps: (1.) classical drug allergies, which are directed to the drug itself, a reactive compound of the drug, or some contamination of it; (2.) pseudo-allergic reactions, which are caused by non-immune mediated degranulation of mast cells and basophils, and (3.) autoimmune reactions, in which the drug elicits an immune reaction to autologous structures. A very detailed (criminalistic) history has the highest priority for clarification of a suspected drug allergy. In addition, skin tests, serological tests and the lymphocyte transformation test may be useful. It is necessary to differentiate between tests which imitate the drug elicited allergic reaction (i.e. Coombs test in drug induced hemolytic anemia) and tests which only indicate sensitization. The detection of IgG antibodies to drugs bound to various carriers (nitrocellulose, sepharose) is controversial and the meaning of a positive result is unclear. Therefore, this test cannot be recommended for the routine diagnosis of drug allergy. Special emphasis is placed on the value of the lymphocyte transformation test, which is more often positive than other test procedures and may sometimes strengthen the suspicion that a disease may be caused by a drug. Nevertheless, this test requires cautious interpretation as it may be falsely positive as well as falsely negative.

Basophils↗

PubMed1998

Histamine release from bronchoalveolar lavage cells from asthmatic subjects after allergen challenge and relationship to the late asthmatic response.

BACKGROUND: Metachromatic cells obtained from asthmatic subjects demonstrate increased spontaneous and stimulated histamine release in vitro. Their ability to synthesize and store proinflammatory cytokines has focused renewed interest on their role in asthma. OBJECTIVE: The late asthmatic response provides a useful model of clinical asthma. The aim of the study was to examine metachromatic cell derived mediators and histamine releasability in vitro after in vivo allergen exposure in atopic subjects with and without asthma and relate them to the type of physiological response observed. METHODS: Bronchoalveolar lavage (BAL) cells were obtained 4 h after challenge from asthmatics exhibiting a single early response (EAR, n = 5), a dual response (LAR, n = 7), unchallenged (basal, n = 5), atopic non-asthmatic (ANA, n = 6) and non-atopic non-asthmatics (normal, n = 5). BAL histamine and tryptase concentrations and in vitro histamine release (HR) after stimulation with anti-IgE, allergen, A23187, conconavalin A and substance P were compared. RESULTS: Metachromatic cell numbers were lower in normal controls compared with all asthmatic groups and in LAR compared with EAR. Metachromatic cell derived mediators were higher in asthmatic compared with normal subjects. Spontaneous HR in LAR (20.5 +/- 5.0%) was lower than EAR (29.5 +/- 3.9%) and ANA (30.2 +/- 1.4%) (P < 0.05). No differences were seen in stimulated HR between EAR and LAR. HR in ANA stimulated with anti-IgE was greater than LAR (P < 0.05). HR in ANA stimulated with anti-IgE was greater than LAR (P < 0.05). After stimulation with ionophore A23187 (1 microM), release was greater in LAR compared with basal (P < 0.05) and no different at 5 microM. All subject groups responded to substance P (SP) but was significantly more in the asthmatic subjects compared to normal controls (P < 0.05). Allergen challenge did not modify the response of asthmatic subjects to SP. CONCLUSION: Functional differences in metachromatic cell reactivity are present in atopic subjects 4h after in vivo allergen exposure which relate to the physiological response observed after this time and suggest that there is ongoing metachromatic cell degranulation subjects who subsequently develop LAR.

Adolescent↗

PubMed1983

[Comparative diagnostic value of laboratory tests in infectious allergic myocarditis].

A comparative assessment of a series of laboratory tests has been made in 206 patients with infectious-allergic myocarditis. Routine laboratory parameters were shown to be of little informative value. Neutrophil alkaline phosphatase activity, the index of neutrophil damage with respect to soluble cardiac antigen, basophil and eosinophil degranulation, and absolute blood basophil and eosinophil quantity were found to be the most meaningful criteria for the assessment of the activity of inflammatory and allergic processes in patients with infectious-allergic myocarditis.

Acid Phosphatase↗

PubMed1994

[Drug allergy].

Drug allergies can cause a great variety of symptoms and can thus imitate various diseases, like in previous times the lues. Drug allergies can be classified into three subgroups, which differ in their pathophysiology and require different diagnostic steps: firstly, classical drug allergies which are directed to the drug itself, a reactive compound of it or some contamination of the drug; secondly, pseudoallergic reactions which are caused by nonimmune mediated degranulation of mast cells and basophils; and thirdly, autoimmune reactions in which the drug elicits an immune reaction to autologous structures. A very detailed (criminalistic) history has the highest priority for the clarification of a suspected drug-allergic reaction; in addition, skin tests, serological tests and the lymphocyte transformation test might be useful. One should differentiate between tests which imitate the drug-elicited allergic reaction (i.e. Coombs test in drug induced hemolytic anemia) and tests which solely indicate a sensitization, these tests should be interpreted accordingly.

Drug Eruptions↗

PubMed1998

Hepatic alterations and induction of micronuclei in rainbow trout (Oncorhynchus mykiss) exposed to a textile industry effluent.

Rainbow trout, Oncorhynchus mykiss, were exposed to a sublethal dose of a wool shrinkproofing effluent for 15, 30, 45 and 60 days. Liver and blood samples were taken after the exposure time together with samples of control handled fish. A light and electron microscope study was carried out to evaluate the histopathological lesions induced in the liver of treated fish. The genotoxic potential of the effluent was assessed by piscine micronucleus test. Vacuolation of liver bile preductular cells was observed in all exposed fish; abnormal lipid accumulation and basophilic foci were seen in the liver of one 30-days- and 45-days-exposed fish, respectively. These specific alterations could be related to a pre-carcinogenic process. On the contrary, other lesions also described in all treated fish such as dilatation, vesiculation and degranulation of the rough endoplasmic reticulum, altered mitochondria, increase in myelin bodies and lysosomes and presence of phagosomes in wandering macrophages might be considered as non-specific alterations, similar to those described in fish exposed to different pollutants. Frequencies of micronucleated peripheral erythrocytes showed a significant increase following 30-days exposure.

Animals↗

PubMed1991

Detection of circulating histamine releasing autoantibodies with functional properties of anti-IgE in chronic urticaria.

Circulating histamine releasing factor(s) have been demonstrated previously in chronic urticaria by an immediate weal-and-flare response to intradermal autologous serum injection. We have studied 25 chronic urticaria patients by in vivo skin testing with autologous sera and an in vitro histamine release assay using mixed leukocytes of healthy donors, to define the nature and functional properties of the serum factor(s). Twenty showed a weal response to autologous serum (mean +/- s.e.m., 37.3 +/- 6.8 mm3). Weal formation was confined to ultrafiltered serum fractions greater than 100 kD in nine of nine patients. There was no response in 10 healthy controls of five patients with symptomatic dermographism. Fourteen chronic urticaria sera elicited histamine release greater than 10% (mean +/- s.e.m., 44.3% +/- 6.7) above basal levels from leukocytes of at least one of seven healthy donors. This in vitro response was also confined to ultrafiltered serum fractions greater than 100 kD in seven of seven sera and was present in IgG fractions of six of seven chronic urticaria sera that showed histamine releasing activity. Functional studies indicated that this histamine releasing autoantibody had the properties of anti-IgE: chronic urticaria sera 'desensitized' basophil leukocytes to subsequent challenge with other chronic urticaria sera and to goat anti-human IgE antibody; human myeloma IgE inhibited histamine release from leukocytes in response to chronic urticaria sera; removal of surface-bound IgE by lactic acid 'stripping' reduced histamine release in response to chronic urticaria sera and anti-IgE and subsequent passive sensitization with IgE myeloma serum partially restored it. Stainable peripheral blood basophils/mm3 in chronic urticaria patients were significantly reduced (mean +/- s.e.m, 7.9 +/- 2.0) when compared to healthy controls (39.6 +/- 4.4), P less than 0.001. These results suggest that histamine releasing autoantibodies are important in the pathogenesis of chronic urticaria by stimulating or facilitating degranulation of basophils and cutaneous mast cells through cross-linking cell surface IgE receptors.

Adult↗

PubMed2000

Nasal and bronchial responses to flour-inhalation in subjects with occupationally induced allergy affecting the airway.

OBJECTIVES: The aim of the study was to follow the similarities and differences, of cellular and mediator changes and mucosal/vascular permeability in the upper and lower airway after specific and nonspecific bronchial provocation, in bakers with diagnosed occupationally induced allergy affecting the airway. In addition, the authors try to find whether there is a relationship between cellular changes in nasal and bronchoalveolar lavage, and bronchial hyperreactivity. METHODS: The study participants were 10 bakers with occupational bronchial asthma and allergic rhinitis. All patients were sensitized to investigated allergen-flour. Nasal- and bronchoalveolar lavage techniques were used to evaluate the changes of the cellular and mediator response (tryptase, eosinophil cationic protein, ECP) and albumin level after specific (flour) and placebo provocation. In addition. bronchial hyperreactivity for histamine, and forced expiratory volume in 1 s (FEV1) were measured after the challenge. RESULTS: There was a significant increase in the percentage of eosinophils, basophils and albumin in nasal and bronchoalveolar lavage of occupationally sensitized bakers. A statistically significant increase in the percentage of neutrophils in bronchoalveolar lavage was observed only 24 h after the allergen challenge. The level of tryptase in nasal lavage was significantly higher during the early allergic response. The levels of ECP in both nasal and bronchoalveolar lavage were significantly increased during the late allergic response. There were also severe bronchial reactions and increase of bronchial hyperreactivity for histamine in occupationally sensitized bakers in the late phase of allergic reaction. CONCLUSION: Eosinophils and basophils proved to be the predominant cells in nasal and bronchoalveolar lavage of patients with occupationally induced bronchial asthma and rhinitis. The prolonged increase of albumin level seems also to be a good predictor of protracted nasal and bronchial inflammation. The results obtained confirmed that tryptase and ECP are good markers for monitoring mast cell and eosinophil degranulation during the allergic reaction. Increase of airway responsiveness reflects an eosinophil and basophil contribution to airway allergic response.

Adult↗

PubMed1998

Histamine content and secretion in basophils and mast cells.

Biochemical determinations of the histamine content and secretion from basophils and mast cells have been available for some time, and much of the complex anatomy of these cellular populations and their release reactions has been documented using the electron microscope. The ultrastructural analyses led to the description of vesicular transport between secretory granules and the plasma membrane as a mechanism for secretion from basophils and mast cells--a process termed piecemeal degranulation. Proof of concepts incorporated in a general degranulation model put forth in 1975 (DVORAK, H.F. and DVORAK, A.M.) requires high magnification imaging of a granule constituent in trafficking vesicles in the process of a stimulated release reaction in which the constituent release is monitored biochemically. Development and application of a new enzyme-affinity method to detect histamine at high magnifications in well-preserved ultrastructural samples have provided the necessary means to establish proof that appropriate secretagogues can stimulate the vesicular transport of histamine in basophils and mast cells during release reactions monitored biochemically. The background information necessary to the understanding of this result is presented here, as well as the development and verification of the diamine oxidase-gold method to image histamine in human mast cell granules as the test system. Also presented are applications using this technology to examine histamine stores and secretion in vitro, in vivo, and ex vivo in human basophils and mast cells and in mouse mast cells. Specifically examined are histamine stores developing in maturing mast cells induced to develop de novo from cultured human cord blood cells, secretagogue-stimulated release and recovery of histamine stores from isolated, purified human lung mast cells ex vivo, cytokine-stimulated degranulation of human skin mast cells and their histamine stores in vivo, piecemeal degranulation of human gut mast cells and their histamine stores in inflammatory bowel disease in vivo, piecemeal degranulation of mouse skin mast cells and their histamine stores in inflammatory eye disease in an interleukin-4 transgenic mouse model in vivo, and the stimulated secretion and recovery of histamine from human basophils ex vivo.

Animals↗

PubMed1993

[Drug allergies].

Drug allergies can be classified into three subgroups which differ in their pathophysiology and require different diagnostic steps: 1. classical drug allergies, which are directed against the drug itself, a reactive metabolite or some contaminant of the drug, 2. pseudoallergic reactions, which are caused by non-immune mediated degranulation of mast cells and basophils, and 3. autoimmune reactions, in which the drug elicits an immune reaction to autologous structures. A very detailed accurate history is of the greatest importance in the clarification of a suspected drug allergic reaction, as well as experience with the drug. In addition, skin tests, serological tests and the lymphocyte transformation test may be useful. One should differentiate between tests which imitate the drug-elicited allergic reaction (i.e., Coombs test in drug-induced hemolytic anemia) and tests which solely indicate a sensitization and the tests must be interpreted accordingly.

Antibody Formation↗

PubMed1986

The effect of some immunomodulating agents on the sensitization phase of experimental contact allergic reactions.

In an experimental model which allows comparison of the macroscopic changes with the differentiated dermal inflammatory cell infiltrate of the allergic contact reaction to oxazolone in guinea pigs, the effects of single doses of the cytostatic agents cyclophosphamide, methotrexate and azathioprine and the anti-lymphocyte agent cyclosporin A administered prior to sensitization were studied. All the agents tested increased the degree of erythema and edema of reactions compared to controls. The dermal inflammatory mononuclear cell response showed little significant increase and would not seem to explain the enhancement of reactions. The number of basophils in reactions was not significantly different from controls, and there is no evidence for early arrival, degranulation and destruction of basophils prior to our first routine assessment at 24 h. The number of mast cells in the reactions was also unchanged. A role for the latter two cells involving degranulation without changes in the number of cells could provide a possible explanation for the augmentation of the vascular response. A mechanism for the effect of cyclophosphamide other than T-suppressor lymphocyte susceptibility based on selective cytostatic effects on precursor cells may need to be considered.

Animals↗

PubMed1990

Nimodipine versus terfenadine in the treatment of physical stimulus-induced urticaria.

Basophil and mastocyte degranulation is calcium-dependent. Calcium-antagonists can inhibit synthesis of and release in vitro some mediators in various types of cells. Both immunologically stimulated and non-immunologically stimulated release of material from basophils isolated from normal and allergic subjects can be antagonized by calcium blockers. The present study was aimed at testing the therapeutic effects and side effects of nimodipine therapy, a new dihydropyridine anti-calcium derivative for physical stimulus-induced urticaria, in comparison with a standard H1-antihistamine therapy. The study was done in 32 outpatients who had physical stimulus-induced urticaria: 20 patients received nimodipine three times a day in a daily dose of 180 mg, 12 patients were treated with terfenadine in a dose of 120 mg. In the majority of patients treated with both nimodipine and terfenadine, satisfactory clinical results were obtained after 3 weeks of therapy. There were, however significant (P less than 0.05) differences in responses. Complete clearance after 3 weeks was noted in 50% patients treated with nimodipine, whereas only 16% of patients on terfenadine were completely clear, and some showed only slight improvement. The treatment was easily manageable, and with few side effects.

Benzhydryl Compounds↗

PubMed2003

Induction of mucosal tolerance with recombinant Hev b 1 and recombinant Hev b 3 for prevention of latex allergy in BALB/c mice.

The prevalence of type I allergy to Hevea brasiliensis latex is particularly high among individuals with frequent exposure to latex products, such as health-care workers (HCW) and patients with spina bifida (SB). Treatment of latex allergy seems problematic as preventive measures, such as allergen avoidance, are not always possible and conventional immunotherapy with standardized latex extracts is not performed routinely. Thus, the aim of the present study was to establish a mouse model of latex allergy using two major latex allergens for HCWs and SB patients, Hev b 1 and Hev b 3, for sensitization. Prophylactic measures on the basis of mucosal tolerance induction with the recombinant allergens were tested in this model. Female BALB/c mice immunized intraperitoneally with recombinant (r)Hev b 1 or rHev b 3 displayed strong immune responses in vivo and in vitro. Intranasal treatment with rHev b 1 and rHev b 3 prior to sensitization led to reduced allergen-specific IgG1/IgE levels and significantly suppressed allergen-induced basophil degranulation. Moreover, lymphocyte proliferation and cytokine production (IL-4, IL-5, IFN-gamma) in vitro were significantly suppressed after pretreatment with both allergens. Suppressive cytokines, such as interleukin (IL)-10 and transforming growth factor (TGF)-beta, remained unchanged after the intranasal pretreatment, indicating mechanism of anergy rather than active immunosuppression. Taken together, these results suggest that mucosal tolerance induction with recombinant allergens could present a promising prevention strategy against latex allergy.

Allergens↗

PubMed2001

Constitutive hyperhistaminaemia: a possible mechanism for recurrent anaphylaxis.

The process underlying anaphylaxis involves an uncontrolled elevation in blood levels of mediators, including histamine. Usually, these abnormal levels are attributed to the degranulation of basophils and mast cells. Few reports have assessed the contribution of defects in histamine pharmacodynamics to allergic responses. In this report we describe a patient with recurrent anaphylaxis who was initially suspected to have enhanced histamine intolerance. We evaluated urine and blood samples collected from this patient and from control individuals using an ELISA test. Our data clearly show constitutive hyperhistaminaemia and a markedly impaired urinary histamine clearance ratio in the index patient. It is suggested that this defect facilitates anaphylaxis.

Anaphylaxis↗

PubMed1988

[Antihistaminic or anti-degranulating activity of pregnancy serum].

From observation of women who had anaphylactic accidents to hymenoptera venoms, with positive histamine release, we have noticed that these same patients lose their histamine release during pregnancy. Measurement of histamine release to pollens confirms the existence of a histaminase, which develops from the third month of the pregnancy and which is the origin of the loss of histamine release. This study makes eliminates a possible anti-degranulation ability of pregnancy sera.

Amine Oxidase (Copper-Containing)↗

PubMed1992

Aggregation of IgE-receptor complexes on rat basophilic leukemia cells does not change the intrinsic affinity but can alter the kinetics of the ligand-IgE interaction.

The aggregation of IgE anchored to high-affinity Fc epsilon receptors on rat basophilic leukemia (RBL) cells by multivalent antigens initiates transmembrane signaling and ultimately cellular degranulation. Previous studies have shown that the rate of dissociation of bivalent and multivalent DNP ligands from RBL cells sensitized with anti-DNP IgE decreases with increasing ligand incubation times. One mechanism proposed for this effect is that when IgE molecules are aggregated, a conformational change occurs that results in an increase in the intrinsic affinity of IgE for antigen. This possibility was tested by measuring the equilibrium constant for the binding of monovalent DNP-lysine to anti-DNP IgE under two conditions, where the cell-bound IgE is dispersed and where it has been aggregated into visible patches on the cell surface using anti-IgE and a secondary antibody. No difference in the equilibrium constant in these two cases was observed. We also measured the rate of dissociation of a monovalent ligand from cell surface IgE under these two conditions. Whereas the affinity for monovalent ligand is not altered by IgE aggregation, we observe that the rate of ligand dissociation from IgE in clusters is slower than the rate of ligand dissociation from unaggregated IgE. These results are discussed in terms of recent theoretical developments concerning effects of receptor density on ligand binding to cell surfaces.

Animals↗

PubMed1997

Biologic allergen assay for in vivo test allergens with an in vitro model of the murine type I reaction.

BACKGROUND: The determination of the biologic activity of allergenic extracts in human beings is limited for ethical and practical reasons. The establishment of a simplified in vitro model, which mimics a main event of the type I reaction, should provide true benefit for manufactures, researchers, and clinicians. OBJECTIVE: This study was designed to develop and evaluate a mediator release assay based on rat bosophil leukemia cells for the purpose of investigating allergenic extracts. METHODS: Rat basophil leukemia cells were passively sensitized with murine IgE raised against allergens and stimulated by serial dilutions of allergenic extracts in a dose-related manner. The allergen-specific degranulation was monitored by measuring the release of beta-hexosaminidase. RESULTS: The investigation of standardized commercial allergen products for in vivo diagnostics (birch pollen, cat dander, and bee venom) allowed a quantitative description of differences in biologic activity in accordance with the declared activity units. The Fel d 1 content was determined in 17 cat dander extracts and correlated well with the results of a two-site binding ELISA (r = 0.93, log/log). Extremely low allergen amounts in the range of 10 to 100 pg/ml could be easily detected. Moreover, the cross-reactivity pattern of patients allergic to birch pollen could be reproduced with extracts of hazel, alder, apple, and celery. CONCLUSION: The assay is suitable for supplementing quality control of allergenic extracts and for the determination of biologic activity of final allergen products. As a research tool, it allows the study of IgE cross-linking properties of modified and recombinant allergens at an early stage before they are tested in human beings.

Allergens↗

PubMed1998

Ultrastructural analysis of human skin biopsy specimens from patients receiving recombinant human stem cell factor: subcutaneous injection of rhSCF induces dermal mast cell degranulation and granulocyte recruitment at the injection site.

We performed an ultrastructural analysis of 10 skin biopsy specimens that had been obtained from three women who were undergoing daily subcutaneous dosing with recombinant methionyl-human stem cell factor (rhSCF) as part of a phase I clinical trial. The biopsy specimens were obtained at sites of subcutaneous administration of rhSCF, within approximately 1 to 2 hours of rhSCF injection, and, at the same time, at contralateral control sites that had not been directly injected with rhSCF. We previously reported that subcutaneous dosing with rhSCF in these subjects induced the local development of a wheal and flare response, which was associated with evidence of mast cell degranulation, as well as a systemic increase in numbers of cutaneous mast cells. The present electron microscopic analysis revealed that all biopsies of swollen, erythematous rhSCF-injected sites exhibited anaphylactic degranulation of both mature and immature mast cells, an acute inflammatory response characterized by the migration of neutrophils, basophils (some of which exhibited evidence of piecemeal degranulation), and eosinophils through blood vessel walls into the perivascular and extravascular spaces, and edema and fibrin deposition within the interstitium. By contrast, the control biopsies contained no evidence of mast cell degranulation or acute inflammation. However, both control and rhSCF-injected sites exhibited mast cells that were undergoing granule building and maturation. Thus at the doses tested in these subjects, subcutaneous injection of rhSCF induced anaphylactic-type degranulation of dermal mast cells at the injection site, with an acute inflammatory response that was associated with the recruitment of granulocytes. By contrast, mast cells at sites distant from those directly injected with rhSCF exhibited no evidence of enhanced secretion.

Anaphylaxis↗

PubMed1978

[Microcirculatory hemostasis and its changes in cardiovascular diseases].

The indices of microcirculatory hemostasis were studied in 955 persons, 200 of whom were healthy while 755 had diseases of the heart and vessels. The results were compared with blood fibrinolytic and coagulation activity and with the functional condition of the basophil-mast cell apparatus. A reverse trend in the functional shifts of microcirculatory and plasmo-coagulative hemostasis in the reaction of emergency adaptation was established. Delayed formation and increased resistance of platelet aggregates with simultaneous decrease in the number of platelets in circulation were revealed in cardiovascular diseases during a remission, which reflects intensified expenditure of the platelets or their aggregation energy in the microcirculatory channel. The administration of exogenous heparin, just like the period of basophil degranulation in stresses of various origin, is attended with distinct platelet hyperfunction which allows small doses of heparin to be used for the prevention of diapedetic hemorrhages in hypertensive disease.

Adrenocorticotropic Hormone↗