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Biomedical subjects

X Baur

Publications and source records attributed to X Baur.

At least 37 records · Page 2Linked to original sources
PubMed1996

Role of substance P and neurokinin A in toluene diisocyanate-induced increased airway responsiveness in rabbits.

The aim of the present study was to examine the role of neuropeptides, especially substance P (SP) and neurokinin A (NKA), in toluene diisocyanate (TDI)-induced airway hyperresponsiveness (AHR) to acetylcholine aerosols. Thirty parts per billion of TDI in air administered over 4 hours caused a significant increase in the airway constrictive response to acetylcholine (ACH) aerosols in rabbits (DeltaRI: 245 +/- 30%, p < 0.005) without altering basic values of respiratory, cardiovascular or blood gas parameters. Inhalation of the aerosolized neuropeptides SP and NKA resulted in a similar increase in airway responsiveness (AR) to ACH as exposure to 30 ppb TDI. To determine whether neuropeptides contribute to TDI-induced AHR, we studied their effects after systemic treatment with capsaicin as well as after infusion of specific synthetic antagonists for SP and NK2 (NKA) receptors. CAPS treatment performed on 4 consecutive days as well as antagonists' infusion only moderately (p > 0.05) decreased airway responses to ACH. CAPS application prevented the TDI-induced increase in AR to ACH in all rabbits. The increase in airway resistance to ACH did not significantly change after TDI exposure (98 +/- 22% of the control response before TDI, p > 0.05). Simultaneous infusion of specific synthetic SP and NK2 receptor antagonists also abolished the TDI-induced increase in airway responses to ACH in all animals investigated (p > 0.05). The results of this study demonstrate that neuropeptides, especially the tachykinins SP and NKA, are important mediators in TDI-induced AHR in rabbits.

Acetylcholine↗
PubMed1996

Lymphocyte proliferation response to extracts from different latex materials and to the purified latex allergen Hev b 1 (rubber elongation factor).

BACKGROUND: Type I allergy to latex is a growing problem, especially among health care workers. A detailed study of the peripheral blood cell responses to latex allergens has not been reported. METHODS: Peripheral blood mononuclear cells of patients and healthy subjects were isolated and stimulated with protein extracts from latex sap and latex gloves and the purified latex allergen Hev b 1 (rubber elongation factor) at different concentrations to determine the antigen-specific proliferation response. The examined patients were sensitized to latex by occupational exposure (n = 23) and had rhinitis, conjunctivitis, contact urticaria, and/or asthma. Two control groups of nonsensitized subjects were studied: one occupationally exposed to latex (n = 8), and the second, not exposed to latex (n = 8). RESULTS: In general, only latex-exposed subjects responded to the different latex antigen preparations. Lymphocyte proliferation responses to latex sap extract were found in 65% of latex-sensitized subjects and in 37.5% of the latex-exposed healthy subjects. Latex glove extract induced a significant proliferative responses in 47.8% of latex-sensitized patients and in 25% of the latex-exposed individuals. Hev b 1 induced lymphocyte proliferation responses in 52% of the latex-sensitized patients and in 25% of the latex-exposed subjects indicating that Hev b 1 is relevant antigen in these latex-sensitized and latex-exposed groups. Peripheral blood mononuclear cells of 39.1% of the latex-sensitized subjects responded to all three allergen preparations (latex sap and latex glove extract, as well as Hev b 1). We could find no correlation between latex-specific IgE level and latex-induced lymphocyte proliferation response. CONCLUSION: Our data indicate that the 14 kd protein Hev b 1 is a relevant allergen in health care workers. It can be detected by specific IgE antibodies to Hev b 1, as well as in lymphocyte proliferation assay. In addition, our study suggests that antigen-specific proliferation response to latex is associated with exposure to latex, but not with the level of specific latex IgE. This may be useful for the evaluation and prediction of latex hypersensitivity development.

Adult↗
PubMed1996

Heating inactivates the enzymatic activity and partially inactivates the allergenic activity of Asp o 2.

BACKGROUND: Sensitization to various flours and flour additives in the baking industry has been known for some time. However, most studies refer to allergens in their native state. OBJECTIVE: The aim of our study was to find out how high temperatures during the baking process influence enzymatic and allergenic activities of the common flour additive alpha-amylase (Asp o 2), a relevant allergen for bakers derived from Aspergillus oryzae. METHODS: In order to assess the allergenicity of Asp o 2 during the baking process, four to 11 correspondingly sensitized bakers were investigated by Enzyme Allergo-Sorbent Test (EAST) with native Asp o 2 and Asp o 2 heated to 80, 90, 95, 99.8 or 200 degrees C. Furthermore, the enzymatic activity was assayed in simulated baking processes at the above mentioned temperatures. RESULTS: Elevated temperatures resulted in a gradual loss of IgE antibodies' recognition of Asp o 2 in two commercially available enzyme products. The enzymatic activity decreased more rapidly. Heating the enzyme to 200 degrees C abolished both the enzymatic and the allergenic activity of the enzyme. CONCLUSION: Based on these results, alpha-amylase in flour additives partially retains its allergenicity. This finding could be relevant for consumers.

Allergens↗
PubMed1996

Characterization of soybean allergens causing sensitization of occupationally exposed bakers.

Fourteen bakers suffering from workplace-related respiratory symptoms and sensitized to soybean were studied. Twelve of them were also allergic to wheat flour, 10 to rye flour, and five to alpha-amylase of Aspergillus oryzae (Asp o 2). IgE estimation by RAST strongly indicated that the trypsin inhibitor and lipoxidase are major allergens of soybean. Various allergenic components could be characterized by immunoblotting after two-dimensional electrophoresis. Our RAST and immunoblotting results show an interindividually different allergic response to inhalative soybean constituents, and that the trypsin inhibitor (20 kDa, pI approximately 4.5) is an important inhalative soybean allergen recognized by IgE antibodies in the sera of 86% of the examined sensitized bakers.

Adolescent↗
PubMed1996

The influence of ammonium persulfate on guinea pig tracheal muscle tone: release of nitric oxide.

Clinical studies have shown that oxidizing substances like hydrogen peroxide (H2O2) and ammonium persulfate used in the hair cosmetic industry may cause airway diseases. In in vitro experiments with isolated guinea pig tracheae ammonium persulfate solutions induced an initial transient relaxation of smooth muscles. This relaxation could be measured by a decrease in isometric pressure in the cannulated trachea instilled with ammonium persulfate at a hydrostatic pressure of 2.5 kPa. In control experiments, saline caused an initial pressure decrease of less than 10% within one minute. In contrast, instillation of different ammonium persulfate solutions (9.10(-5) to 9.10(-2) M) effectively dilated tracheae and resulted in a concentration-dependent drop in intratracheal pressure to 1.53 +/- 0.62 kPa (61% of the instillation pressure). The effect of ammonium persulfate on smooth muscles is obviously mediated by nitric oxide because the relaxation could be blocked by inhibitors of nitric oxide synthase (L-NMMA 40 microM and L-NAME 200 microM). The precursor of nitric oxide, L-arginine (1 mM), the D-isomers of the inhibitors and a mixture of L-arginine and L-NAME did not affect the ammonium persulfate-induced initial intratracheal pressure decrease. The results allow us to conclude that acutely elicited tracheal muscle dilatation by ammonium persulfate is mediated by nitric oxide. However, it is possible that a continuous use of oxidizing substances may lead to epithelial damage and, therefore, reduce the production of nitric oxide, thus facilitating constrictory responses.

Acetylcholine↗
PubMed1996

Asthmatic reactions after nasal allergen provocation.

Three bronchoconstrictive responses associated with acute rhinitis and occurring in two patients were observed among 400 nasal allergen challenges. Causative substances were birch pollen, Dermatophagoides pteronyssinus and HSA-conjugated pyromellitic dianhydride. Both subjects showed bronchial hyperreactivity and immediate-type sensitization to these allergens. It is concluded that bronchoobstruction nearly occurs in nasal allergen challenges. The underline pathophysiological mechanism remains unclear.

Acute Disease↗
PubMed1996

Lung function testing: the dilemma of predicted values in relation to the individual variability.

Quantitated lung function parameters are usually interpreted in relation to so-called "normal ranges' obtained from healthy study groups. The aim of this paper is the critical review of formulas and the evaluation of intraindividual variation in modern lung function testing. To which extent is the total variation of lung function parameters in cross-sectional studies (usually serving as basis for the normal range) attributed to the intraindividual variation between repeated measurements? This question raises a further question: are lung function values in the normal range really normal? To assess spirometric and body plethysmographic parameters 26 healthy subjects from three medical centers underwent 30-72 measurements over a period of 2 months for the determination of variations due to (1) intraindividual variation over time and (2) interindividual variation. For each subject, predicted values of different lung function parameters published by Quanjer et al. [Eur Respir J 1993; 6:5-40.1], of intrathoracic gas volume by Ulmer et al. [Die Lungenfunktion; Stuttgart, Thieme, 1991] and of total airway resistance by Ruehle and Matthys [Pneumologie 1976;153:223] were applied. When converted into percent predicted and adjusted for differences in medical centers, the intraindividual standard deviation was estimated to be about half of the interindividual standard deviation. We conclude that the normal range of lung function parameters derived from the standard deviation within populations is too wide for the assessment of individual values. Interpretation of individual lung function measurements should primarily be based on the "individual normal range' derived from former lung function measurements of the individual and only secondly on the "predicted value'.

Adult↗
PubMed1996

Systemic sclerosis in German uranium miners under special consideration of autoantibody subsets and HLA class II alleles.

Systemic sclerosis (scleroderma) is a connective tissue disease with a wide range of clinical manifestations, with high or low degrees of skin and internal organ involvement together with different antinuclear antibody (ANA) specificities. Several studies provide evidence that males, who are rarely affected by systemic sclerosis, have an increased risk when working in mines. Therefore we reinvestigated 21 male subjects and 6 cases of deceased male patients who had been engaged in East German uranium mines and had shown evidence of this disease in medical examinations. Dermatological investigations, evaluation of chest X-rays and autoantibody estimation were performed. PCR-sequence-specific oligonucleotide typing was used to study the genetic association of HLA-D alleles with autoantibodies typical for scleroderma in these uranium miners suffering from systemic sclerosis and in patients with idiopathic systemic sclerosis. The determined HLA phenotype frequencies and the following statistical analysis (Fisher's exact test (2-sided)) revealed that in comparison with randomly selected controls, alleles DRB1*0300 (DR3) and DQB1*0201 (DQ2) were distinctly increased in the group of affected uranium miners, especially in those with anti-Scl-70 positivity. In contrast, we did not observe significant differences between affected and unaffected miners. Comparing anti-Scl-70-positive affected uranium miners with anti-Scl-70-positive idiopathic systemic sclerosis cases. DRB1*0300 as well as DQB1*0201 were also significantly enhanced in the former group. ACA-positive systemic sclerosis miners had significantly elevated frequencies in DRB1*0100 (DR1) and DRB1*0800 (DR8) only in comparison with unaffected miners and unexposed controls. Our genetic and immunological data lead to the assumption that a different set of HLA-D alleles in combination with exogenous factors is involved in the induction of anti-Scl-70 antibodies in uranium miners that might influence their susceptibility to the disease, whereas the same occupational exposure seems to have no influence on the induction of ACA antibodies.

Adult↗
PubMed1996

Molecular analysis of HLA-DPB1 alleles in idiopathic systemic sclerosis patients and uranium miners with systemic sclerosis.

According to clinical mainifestation and autoantibody pattern [anti-Scl-70, anti-centromere antibodies (ACAs)], systemic sclerosis is a connective tissue disease with heterogenous subgroups. PCR-sequence-specific-oligonucleotide typing was used to study the genetic association of HLA-DPB1 alleles in 54 patients with idiopathic systemic sclerosis, 26 uranium miners with systemic sclerosis and 70 unrelated healthy control subjects. Systemic sclerosis patients with and without former employment in mines were divided into two subgroups according to their scleroderma-typical autoantibody specificities--anti-Scl-70 positive and ACA positive--and third subgroup comprising the rest. Statistical analysis revealed a significantly increased frequency of DPB1*1301(p=0.0001, corrected p=0.011) in idiopathic anti-Scl-70-positive systemic sclerosis cases when compared with unexposed controls. In the same group, we observed an enhanced frequency of DPB1*0601 and *1701 alleles. Since these three alleles carry the information for a glutamic acid residue in position 69 of DPB1, we tested the association of this residue with anti-Scl-70 expression. A strong association between anti-Scl-70 positivity in idiopathic systemic sclerosis patients and amino acid residue 69 of DPB1 was observed when compared with anti-Scl-70-negative idiopathic systemic sclerosis patients (p=0.0009) or unrelated controls (p=0.0007). ACA expression was not associated with the presence of any DPB1 allele tested. The data show that anti-Scl-70 expression in idiopathic systemic sclerosis patients is linked with DPB1*1301 whereas anti-Scl-70-positive miners do not show such a DPB1 association. Futhermore, the data indicate that glutamate 69 of DPB1 might be involved in the susceptibility to idiopathic anti-Scl-70 expression.

Alleles↗
PubMed1996

EAST and CAP specificity for the evaluation of IgE and IgG antibodies to diisocyanate-HSA conjugates.

Sera of 54 symptomatic workers showing sensitization to isocyanate-human serum albumin (HSA) conjugates were subjected to parallel enzyme allergosorbent test (EAST) and CAP measurements to determine IgE antibodies to diphenyl-methane diisocyanate-HSA, toluene diisocyanate-HSA and hexamethylene diisocyanate-HSA. Results of both methods correlated rather well with each other. In comparison to the EAST results, the CAP values were twice as high, and 4, 17 and 13% more frequently positive findings were obtained with the three different antigens. Autoinhibition performed with both methods proved the specificity of IgE binding in 92% of sera in EAST and in 89% of sera in CAP if values of > or = 0.35 kU/l were considered. The total IgE level in sera influenced the antibody results. Four of 20 sera studied by autoinhibition had a total IgE of > 700 kU/l, and two of them did not show significant autoinhibition with all conjugates by CAP and one serum by EAST. In addition, three of these sera showed an elevated binding to control HSA only (0.31-0.5 kU/l), and two revealed only a slightly increased IgE binding when compared with the HSA control (ratio of isocyanate-HSA to HSA, < 2). Only 2 of the 16 sera with a total IgE level of < 700 kU/l yielded a noninhibitory positive CAP result, whereas all positive EAST values of these sera could be significantly blocked by autoinhibition. Therefore, we suggest regarding EAST and CAP IgE results to isocyanate-HSA as positive if they exceed HSA control by 100% and are above 0.35 kU/l. Weak positive CAP results (< or = kU/l), especially of sera with total IgE > 700 kU/l, should by confirmed by inhibition experiments. Twelve of 40 symptomatic isocyanate workers exhibited borderline or weakly increased IgG values for diisocyanate-HSA conjugates in the CAP system and IgG-EAST. HSA tested in EAST as a reference showed nearly the same results as the isocyanate-HSA conjugates. In the 23 inhibition experiments, IgG-binding specificity was not confirmed. These findings imply IgG measurement to be of no diagnostic value in isocyanate-induced airway disorders.

Binding, Competitive↗
PubMed1996

[Respiratory and cardiovascular effects of acetylcholine provocation after inhalation exposure to various occupational pollutants--studies in the rabbit].

Airway hyperresponsiveness, manifested by increased flow resistance and resulting drop in oxygen partial pressure when conducting provocation tests, is considered an early sign of a developing obstructive airway disease, an example of which is a professionally conditioned asthma. We conducted a detailed study exploring the interrelation between the respiratory mechanical parameters and the partial pressures of oxygen and carbon dioxide (PaO2, PaCO2). Reproducibility tests for the studied cardiovascular, ventilatory and respiratory mechanical parameters at rest and under various conditions of stress (external stenoses, inhalation of hypercapnic and hypoxic gas mixtures, infusion of an acetylcholine solution) showed good reproducibility of the measured data with variation coefficients < 10%. In blood gas analyses we also found comparable variation coefficients. Four groups of experimental animals were exposed for different periods of time to various working place substances (coolants, ammonium peroxodisulfate, hair bleaches [blondizing agents], isocyanates). After the exposure we checked on the bronchial sensitivity to aerosols of 0.2% and 2% acetylcholine solutions. Concomitant with an increased response of dynamic elastance, we found an increased drop in oxygen partial pressure and an almost constant carbon dioxide partial pressure, dependent on the working place substance used and on its concentration. In untreated controls the inhalation of acetylcholine resulted in bronchoconstriction and drop in oxygen partial pressure only on provocation with 2% acetylcholine. However, in the groups exposed to coolants and ammonium peroxodisulfate there was a significant drop in oxygen partial pressure already on provocation with 0.2% acetylcholine, as well as a noticeable bronchial respiratory response. The drop in oxygen partial pressure increases further after provocation with 2% acetylcholine, whereas the oxygen partial pressure dropped to a maximum of one-third of its original level by more than 10%. Placing the drop in oxygen partial pressure provoked by acetylcholine in relation to the increase in dynamic elastance, this can be well expressed by a logarithmic formula (y = -6.2. In (x) + 0.72, r = 0.96) that does not change significantly after exposure to working place substances (y = -7.0. In (x) + 3.33, r = 0.93). The close correlation of both parameters suggests that study of the oxygen partial pressures to determine the airway hyperresponsiveness should be considered important, since a marked drop in oxygen partial pressure is seen even if obstructive respiratory response is only slightly increased (slight increase in dynamic elastance). The reason for the behaviour of the blood gases is probably an increased ventilation-perfusion imbalance due to inhomogenous peripheral bronchial reactions. In the hyperresponsive animals the reactions were merely enhanced without demonstrating any differences.

Acetylcholine↗
PubMed1996

Allergenic and antigenic determinants of latex allergen Hev b 1: peptide mapping of epitopes recognized by human, murine and rabbit antibodies.

BACKGROUND: The rubber elongation factor in Hevea rubber (Hev b 1) is one of the most important latex allergen and is leading cause of latex type 1 hypersensitivity in children with spina bifida. OBJECTIVE: The aim of this study was to define the allergenic and antigenic epitopes of Hev b 1. METHODS: The immunoglobulin- (Ig)E and IgG antibody binding sites on Hev b 1 allergen were delineated by enzyme linked immunosorbent assay (ELISA) using synthetic overlapping peptides covering the whole Hev b 1 sequence. In order to improve the binding capacity and specificity all peptides were biotinylated at the N-terminal end via a 6-aminohexanoic acid as spacer and then adsorbed to streptavidin pre-coated microtitre plates. Fine mapping to define the essential amino acid residues for the antibody binding was achieved by using overlapping peptides with one amino acid offset. RESULTS: It was demonstrated that the IgE epitopes were located in different regions of Hev b 1 including the C-terminal segment (121-137) and the segments with amino acid residues of 30-49 and 46-64. Two monoclonal antibodies (MoAbs) II2F3 and II4G9 raised against purified Hev b 1 recognized the C-terminal segment only. The results of epitope mapping with three rabbit antisera revealed that five positive peptides, including the epitope peptides 31-49, 46-64 and 121-137, were involved in the antibody-binding sites. Fine mapping on the segments 46-64 and 121-137 showed that the two MoAbs reacted with the peptide 125-134 in the C-terminal region, whereas the peptide with amino acids 124-134 was essential for recognition by human IgE antibodies. Epitopes to rabbit polyclonal IgG and human IgE were also found to be involved in the amino acid residues of 47-59. CONCLUSION: Our results indicate that the most allergenic/antigenic portions of Hev b 1 allergen are the C-terminal region and the region with amino acid residues of 31-64. In both regions, the minimal IgE-binding epitope is almost identical with the IgG-binding epitope.

Allergens↗
PubMed1995

Cellular and mediator profile in bronchoalveolar lavage of guinea pigs after toluene diisocyanate (TDI) exposure.

Toluene diisocyanate (TDI) is a volatile, highly reactive chemical widely used as a polymerizing agent in the production of polyurethane foams, lacquers, adhesives, and other items. Repeated airway exposures in the workplace to TDI may cause a concentration-dependent risk of developing chronic airway disorders. Different pathomechanisms are involved. IgE-mediated sensitization and irritative effects were clearly demonstrated in exposed subjects as well as in animals. In this study we examined the cellular and mediator composition in bronchoalveolar lavage fluid (BALF) of guinea pigs (eight in each group) exposed to TDI (10, 20, or 30 ppb) on 5 consecutive days for 2 hours each. Increased numbers of eosinophils and significantly elevated levels of LTB4 and LTC4/LTD4/LTE4 were obtained in BALF of all exposed animals when compared to nonexposed control animals. PGD2 and TXB2 remained unaltered in BALF. Stimulation of BALF cells of exposed and control animals with Ca-ionophore A23187 and arachidonic acid induced an increased generation of LTB4. Furthermore, BALF cells of the exposed animal groups generated immunoreactive LTC4/LTD4/LTE4, whereas controls did not show peptido-leukotriene formation in the presence and absence of stimuli. Our data clearly demonstrate an influx of eosinophils into the airways associated with mediator release and higher cellular responsiveness after TDI exposure.

Animals↗