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Biomedical subjects

X Baur

Publications and source records attributed to X Baur.

At least 145 records · Page 8Linked to original sources
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↗
PubMed1995

Toluene diisocyanate induction of airway hyperresponsiveness at the threshold limit value (10 ppb) in rabbits.

Induction of acute lung injury and the development of airway hyperresponsiveness (AHR) by toluene diisocyanate (TDI) exposure was studied in a new rabbit model of occupational lung diseases. TDI in the range of the threshold limit value (TLV) of 10 ppb, as well as at 5 and 30 ppb, administered four times over a period of 1 h to three groups of eight rabbits, did not significantly alter airway resistance (RI), dynamic elastance (Edyn), slope of inspiratory pressure generation (delta Pes/tI), arterial pressure (Pa) or arterial blood gas tensions (PaO2, PaCO2). Airway responsiveness (AR) to aerosols of 2% acetylcholine (ACH) was measured before and after each TDI exposure. After TDI inhalation of 10 ppb over 4 h, the amplitude of the ACH-induced airway constrictor response indicated by the changes in Edyn rose significantly to almost twice the control response value (p < 0.005). Similar changes in the amplitude of RI and in the slope of delta Pes/tI were obtained. After inhalation of 5 ppb TDI, no changes in airway reactivity were observed. The responses of respiratory mechanical parameters to ACH rose to three to four times the control responses after exposure to 30 ppb TDI. In a control group of eight animals not undergoing TDI exposure, no significant changes of respiratory responses were obtained after inhalation of 0.2% ACH for 1 min. In summary, TDI atmospheres in the range of TLV increased AR to ACH within 4 h of exposure in this rabbit model. This augmented AR may indicate an increased risk for the development of isocyanate-induced obstructive lung diseases.

Acetylcholine↗
PubMed1995

A clinical and immunological study on 92 workers occupationally exposed to anhydrides.

This study aimed at investigating sensitizing and hazardous effects of a new acid anhydride, pyromellitic dianhydride (PMDA), in addition to those of phthalic anhydride, maleic anhydride and trimellitic anhydride, in a group of 92 exposed workers in two German chemical plants. Of the 92 workers, 56 reported work-related complaints with a predominance of phlegm and dyspnoea in those exposed to anhydride dust for less than 1 year. Haemorrhagic rhinitis occurred only after a prolonged exposure of more than 15 years. Specific IgE antibodies to anhydride-HSA conjugates could be detected in 15 exposed subjects, 12 of whom had work-related symptoms. The IgE-positive group had significantly more impaired lung function parameters than the IgE-negative group. The proportion of IgE-positive subjects was highest in the groups with dyspnoea (5/18), cough (6/24) and rhinitis (11/44) whereas only 1 of 11 workers with haemorrhagic rhinitis had such antibodies. A follow-up study of 23 affected workers was performed after 10 months to assess clinical symptoms, lung function and IgE antibody levels. This follow-up study showed the absence of obstructive ventilation patterns in three out of six subjects in addition to cessation of symptoms in most initially affected workers who were no longer exposed. On the other hand, 14 workers under continuous exposure had comparable pathological findings on re-examination. Our results confirm that anhydrides including the lesser known PMDA, behave as respiratory irritants and as immediate-type sensitizers. They predominantly induced reversible symptoms in workers whose exposure stopped after a working period of about 0.7 years. Abnormal lung function parameters normalized in nearly 50% of these subjects.

Adult↗
PubMed1995

Ethylene oxide as a major factor in DNA and RNA evolution.

Gaseous ethylene oxide (EO) is genotoxic in a wide variety of biological systems and carcinogenic in rats and mice. The major product of EO reaction with DNA is 7-(2-hydroxyethyl)guanine. In the organism, EO originates through biotransformation of ethylene. Ethylene in higher plants has been found to be a key factor in the control of a number of developmental processes including senescence, abscission and ripening. Ethylene oxide can participate in the transition of pyrimidine bases from C to T or U and from U to C. Thus, EO may provide a key approach to the study of DNA and RNA evolution. The studies here suggest a role for EO in modulating multiple messenger pathways in DNA and RNA functions. Perhaps surprisingly, it exerts two quite different activities, expressed in diverse cells. On the one hand, EO causes mutagenesis and carcinogenesis if available in excess. On the other, at low concentrations it can mediate repair of DNA at replication and RNA at transcription and translation. The report provides substantial evidence that EO can also play a very important role in the DNA and RNA evolution of whole biological systems. This important effect of EO needs to be understood more completely.

Animals↗
PubMed1995

Hypersensitivity pneumonitis (extrinsic allergic alveolitis) induced by isocyanates.

BACKGROUND: Chemical-induced hypersensitivity pneumonitis has been so far rarely described. The purpose of this study was to find out whether hypersensitivity pneumonitis is a common disorder in isocyanate workers. METHODS: Company physicians' case histories of 1780 isocyanate workers were evaluated. In 16 subjects suspected of having isocyanate-induced hypersensitivity pneumonitis, chest x-ray films were made; levels of IgE and IgG antibodies to isocyanate-human serum albumin were estimated; conjugates and isocyanate challenge tests, bronchoalveolar lavage fluid analyses, and/or lung histologic investigations were performed. RESULTS: Each of the 14 study patients who had hypersensitivity pneumonitis had work-related dyspnea and fever occurring several hours after the start of work with isocyanates. Typical clinical findings were the reduction of lung diffusing capacity (n = 10), reticular or nodular lung patterns in the x-ray film (n = 9), and serum IgG antibodies specific to isocyanate-human serum albumin conjugates (n = 10). Restrictive ventilation patterns in the inhalation challenge tests (n = 5), lymphocytic and/or neutrophilic alveolitis seen in bronchoalveolar lavage fluid analyses (n = 7), and lymphohistiocytic patterns mostly associated with mild fibrosis in lung histology (n = 5) confirmed the diagnosis. CONCLUSIONS: Occupational exposure to isocyanate vapors and aerosols induces typical hypersensitivity pneumonitis in at least 1% of the isocyanate workers with symptoms. Diphenylmethane diisocyanate was found to be the main cause of this disorder.

Adolescent↗