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X Baur

Publications and source records attributed to X Baur.

At least 91 records · Page 5Linked to original sources

Pathomechanisms and pathophysiology of isocyanate-induced diseases--summary of present knowledge.

During recent years in Western countries, diisocyanates are one of the main causes of occupational asthma. The mechanism of diisocyanate-induced asthma is still unknown but recent evidence suggests immunological mechanisms, including cell-mediated immune responses. Immune responses to isocyanates may result in different illnesses, cell- and/or antibody-mediated entities. In addition, irritative, toxic, and mutagenic effects may occur. This review summarizes current knowledge of the pathomechanisms, including immunological and nonimmunological (mutagenic and genotoxic) aspects of isocyanate disorders.

Alveolitis, Extrinsic Allergic↗

Prevention of occupational asthma including medical surveillance.

The high figures of occupational asthma worldwide necessitate the intensification of appropriate primary, secondary, and tertiary preventive measures. Based on new scientific data on dose-response relationships as well as our own experience and ethical aspects, we focus on medical surveillance within the framework of secondary prevention. We propose that medical surveillance programs be mandatory for workplaces/occupations with an asthma incidence of > or = 200% than that of the general population. Medical surveillance programs are recommended if asthma frequency is elevated but below 200%. A stepwise approach of monitoring workers at risk for developing occupational asthma including a screening by questionnaire and a personal interview and diagnosis confirmation is presented. In addition, we briefly comment on the management of affected subjects.

Asthma↗

Reduction of latex aeroallergens and latex-specific IgE antibodies in sensitized workers after removal of powdered natural rubber latex gloves in a hospital.

BACKGROUND: Respiratory symptoms of natural rubber latex (NRL) allergy in health care workers (HCWs) have been reported in rooms with a detectable allergen load. Preventive measures have been proposed to reduce the risk of NRL sensitization. OBJECTIVES: Eliminating powdered NRL gloves from the workplace and giving NRL-free material to sensitized workers has been among proposed preventive measures. To appraise the success of such procedures among HCWs, a prospective study was carried out. METHODS: Sensitization of HCWs to NRL was determined by skin prick tests and measurements of specific IgE antibodies. NRL allergen concentrations in room air were measured before and after substitution of powdered NRL gloves with powder-free or synthetic gloves in different departments of a hospital and determined by a competitive inhibition immunoassay. RESULTS: The prevalence of HCWs with positive skin prick test responses and NRL-specific IgE-positive HCWs was 8% (n = 7) among the 90 examined staff members before the intervention started. All 7 reported glove-related allergic symptoms. Six of 7 sensitized subjects had a significant decrease of latex-specific IgE antibody concentrations during follow-up examinations in April and September 1997 (P <.003). Within 24 hours after substitution took place, NRL aeroallergen levels (up to 49.9 ng/m3) fell below the detection limit in areas with synthetic gloves or powder-free NRL gloves alike. Use of asthma medication and antiallergic drugs could be discontinued by 2 HCWs with NRL-related respiratory tract symptoms. CONCLUSIONS: Our results demonstrate that elimination of powdered NRL gloves is a useful device in reducing aerogen NRL allergen loads below the detection limit and permitting sensitized or allergic personnel to remain on the job.

Adult↗

Allergy to Aspergillus-derived enzymes in the baking industry: identification of beta-xylosidase from Aspergillus niger as a new allergen (Asp n 14).

BACKGROUND: Aspergillus-derived enzymes are used in dough improvers in bakeries. Some of these enzymes are identified as causing IgE-mediated sensitization in up to 25% of bakers with workplace-related symptoms. OBJECTIVE: The aim of this study was to compare the frequency of sensitization to Aspergillus xylanase, cellulase, and glucoamylase with the sensitization to alpha-amylase (Asp o 2) and to identify IgE-reactive proteins in enzyme preparations. METHODS: Sensitization to Aspergillus-derived enzymes and cross-reactivity were retrospectively studied by enzyme allergosorbent test (EAST) and EAST-inhibition experiments. IgE-reactive proteins were detected by electrophoretic separation and immunoblotting. Liquid chromatography with electrospray ionization mass spectrometry and Edman degradation of tryptic protein fragments were used for the biochemical identification of an unknown IgE-binding protein. RESULTS: Twenty-three percent of 171 tested bakers had specific IgE to alpha-amylase, 8% reacted to glucoamylase, 13% reacted to cellulase, and 11% reacted to xylanase. Xylanase and cellulase preparations, each containing at least 6 different proteins, showed cross-reactivity in the range of 80%. The main IgE-binding protein in the xylanase preparation recognized in 7 of 8 xylanase-positive subjects was a protein of about 105 kd. This protein was identified as beta-xylosidase by peptide mass spectrometric fingerprinting. The identification was confirmed by matching 12 peptide sequences obtained by N-terminal and mass spectrometric sequencing to this protein. CONCLUSIONS: Beta-Xylosidase from Aspergillus niger is an occupational allergen present in currently used baking additives, which causes sensitization in at least 4% of symptomatic bakers. According to the International Union of Immunological Societies nomenclature, we suggest the term Asp n 14 for this allergen.

Adult↗

Identification of hevein (Hev b 6.02) in Hevea latex as a major cross-reacting allergen with avocado fruit in patients with latex allergy.

BACKGROUND: Recent studies demonstrated that allergy to natural rubber latex is frequently associated with hypersensitivity to avocado fruit. The responsible cross-sensitizing allergen has not been identified. OBJECTIVE: The purpose of this study was to investigate the cross-reactivity of a latex major allergen, hevein, with avocado proteins. METHODS: Serum samples from 118 health care workers (HCWs) allergic to latex (HCW group) and 78 patients with spina bifida (SB) allergic to latex (SB group) were included in this study. Anti-hevein and anti-avocado IgE antibodies were measured by enzyme-linked allergosorbent assay. Cross-reactivity of hevein to avocado proteins was assessed by inhibition of the IgE binding in individual patients' sera containing IgE antibodies to both hevein and avocado. RESULTS: The prevalence of seropositive IgE antibodies to avocado was found to be strongly associated with the presence of hevein-specific IgE antibodies in subjects of both groups (P < .001). Sixty-seven of 91 (73%) subjects from the HCW group and all 19 subjects in the SB group with positive IgE antibodies to hevein also had elevated IgE values to avocado. Competitive RAST inhibition with 42 sera showed that IgE binding to avocado could be completely inhibited in 27 (64%) sera by preincubation with hevein. By contrast, the degrees of inhibition of IgE to hevein by avocado extract ranged from 0% to 36% (n = 16). These results indicate that sensitization to avocado in most patients allergic to latex is caused exclusively by IgE-binding epitopes present in hevein. Results of immunoblots and immunoblot inhibition with 11 serum samples confirmed that a 30-kd protein in avocado was the major IgE-binding component; the IgE-binding reactivity to this protein could be inhibited by hevein in all sera tested. CONCLUSION: Hevein is the major cross-reacting allergen with avocado in subjects with latex allergy.

Adolescent↗

Can a threshold limit value for natural rubber latex airborne allergens be defined?

BACKGROUND: Recent studies have shown that systemic or respiratory occupational responses to latex can be induced by inhalation of latex aeroallergens. OBJECTIVE: Our objectives were to study the relationship between exposure to different latex aeroallergen levels and type I allergic reactions in subjects with occupational contact with latex and to assess a threshold value for latex airborne allergens required for sensitization and symptom elicitation. METHODS: We screened 145 subjects working in 32 hospitals or operating rooms with different latex aeroallergen levels. The quantified latex aeroallergen concentrations in the 32 rooms were compared with latex-related allergic symptoms. RESULTS: Different latex aeroallergen concentrations could be detected in rooms where powdered latex gloves were used and no effective ventilation systems were installed. In environments with latex aeroallergen levels of 0.6 ng/m3 or greater, the reported workplace-related symptoms were significantly increased (p < 0.02). All 22 subjects with latex-specific IgE antibodies worked in rooms contaminated with latex aeroallergens (p < 0.05). CONCLUSIONS: Our results demonstrate that symptoms and presence of latex-specific IgE antibodies in subjects are significantly associated with measurable levels of latex aeroallergens. A latex aeroallergen level of 0.6 ng/m3 is a critical threshold, especially for health care workers who are sensitized to natural rubber latex.

Air Pollutants, Occupational↗

Baker's asthma: still among the most frequent occupational respiratory disorders.

BACKGROUND: Baker's asthma and rhinitis are among the most frequent occupational respiratory disorders. OBJECTIVE: The aim of the study was to evaluate the frequency of work-related symptoms and the clinical relevance of sensitization to allergens in screened and symptomatic bakers. METHODS: Eighty-nine bakers participating in a screening study and 104 bakers filing a claim for compensation were examined with regard to occupational and clinical case history, lung function parameters, and sensitization to bakery allergens by skin prick tests, specific IgE analyses, and inhalative challenge tests. RESULTS: A high prevalence of respiratory disorders, abnormal lung function parameters, and sensitization to bakery allergens exists. Most frequently, bakers with workplace-related respiratory symptoms showed sensitization to wheat flour (64%), rye flour (52%), soy bean flour (25%), and alpha-amylase (21%). The correlation between these sensitizations and asthma case history and inhalative challenge test responses was significant. However, approximately 29% of the bakers with respiratory symptoms showed no sensitization to these bakery allergens, whereas 32% of the sensitized bakers in the screening group had no workplace-related symptoms. Atopic status defined by skin prick test sensitization to common allergens or elevated total IgE levels was found to be a risk factor for the development of sensitization to bakery allergens and respiratory symptoms. On the other hand, there is evidence for an increased frequency of elevated total IgE as the result of occupational allergen exposure because respective findings were observed in bakers without symptoms. CONCLUSION: Sensitization to bakery allergens seems to be the main cause of baker's asthma and rhinitis but cannot explain the asthma case history in each case. Further methods are required to objectively assume irritative pathomechanisms. Our findings indicate the necessity for an improved primary prevention of exposure to inhalative noxae in bakeries.

Allergens↗

Latex allergens.

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Allergens↗

Molecular analysis of DRB and DQB1 alleles in German spina bifida patients with and without IgE responsiveness to the latex major allergen Hev b 1.

BACKGROUND AND OBJECTIVE: Spina bifida patients are at a high risk of developing latex allergy. Recently, we found a relationship between the IgE responsiveness to latex allergen hevein and human leucocyte antigen (HLA) alleles DRB1*04(DR4) as well as DQB1*0302(DQ8). This study was carried out to investigate the association between HLA class II alleles and the specific IgE response to latex allergen Hev b 1 in spina bifida patients. METHODS: Blood samples from 103 unrelated German spina bifida patients exposed to latex products and from 90 unsensitized controls were examined. Genomic DNA isolation followed by HLA-D-specifc polymerase chain reaction (PCR) amplification was used to perform HLA typing of allelic polymorphisms in exon 2 of DQB1 and of DRB1,3,4,5 with sequence-specific oligonucleotide probes (SSOPs). RESULTS: Fifty-one out of 103 spina bifida patients were found to have anti-latex IgE antibodies; 40 had also anti-Hev b 1 antibodies. Further, we observed that 80% of the Hev b 1 responders underwent five or more surgeries whereas 55% of the Hev b 1 non-responders and 75% of the latex-non-responders underwent less than five surgical interventions. From the latex-sensitized group 33% showed an elevated phenotype frequency of DRB1*0701(DR7) when compared with unsensitized patients (12%, P = 0.0095, Pc = NS) and with controls (17%; P = 0.035, Pc = ns). Fifteen out of 40 Hev b 1 responders also exhibited an elevated DR7 frequency when compared with latex-sensitive but Hev b 1-negative patients (38% vs 18%, P = NS) or with unsensitized controls (38% vs 17%, P = 0.013, Pc = NS). CONCLUSIONS: Although we found that the DRB1*0701 (DR7) phenotype frequency was elevated in SB patients with latex- as well as with Hev b 1-IgE responsiveness, the analyses of the other class II alleles clearly demonstrate that the HLA-D region does not play a major role in the pathogenetic way of sensitization to Hev b 1.

Adolescent↗

Analysis of T-cell reactive regions and HLA-DR4 binding motifs on the latex allergen Hev b 1 (rubber elongation factor).

BACKGROUND: The rubber elongation factor in Hevea rubber (Hev b 1) is one of the important latex-allergenic proteins inducing the production of specific IgE antibodies in latex-exposed subjects. In addition, Hev b 1 induces lymphocyte proliferation responses. A study about detailed T-cell epitope analysis of major latex allergens has not been published yet. OBJECTIVE: The aim of this study was to define the T-cell reactive regions on the latex allergen Hev b 1. METHODS: Nine overlapping peptides with 19 or 17 amino acid lengths representing the complete sequence of Hev b 1 were used for T-cell epitope mapping. Peripheral blood mononuclear cells (PBMCs) of latex-sensitized patients and healthy subjects were isolated and stimulated with the synthetic peptides to determine the specific proliferation response. The examined patients were sensitized to latex by occupational exposure (n=14) and suffered from rhinitis, conjunctivitis, contact urticaria and/or asthma. Two control groups of non-sensitized subjects were studied, one occupationally exposed to latex (n=4), the other one not exposed to latex (n=4). RESULTS: Positive proliferation response induced by one or more peptides was detected in 10 of the latex-sensitized patients and in two of the latex-exposed non-sensitized subjects. Each patient exhibited an individual epitope reactivity pattern. The whole protein was found to be immunogenic, but the intensity of lymphocyte responses induced by the peptides was different. The majority of the patients' PBMCs (more than 66%) responded to the peptides 31-49 and 91-109. Using the peptide selection of Stille's algorithms, three epitopes were predicted covering region 38-74 and two others covering region 82-104; the two peptides 31-49 and 91-109 are part of these regions. A strong HLA-DR4Dw4 (DRB1*0401)-binding motif according to published DR4w4 binding motifs was predicted in the region of 102-110 including peptide 91-109 to which the majority of tested HLA-DR4-positive patients responded. CONCLUSIONS: Our data indicate that the whole 14 kDa protein Hev b 1 is immunogenic having regions that demonstrate individual and varying PBMC stimulation. Experimental data of T-cell reactive regions based on PBMC-stimulation complement the information on T-cell epitope prediction. In addition, the Hev b 1 molecule contains a HLA-DR4Dw4 (DRB1*0401)-binding motif.

Adult↗

Exposure-response relationships of occupational inhalative allergens.

Only a few threshold limit values exist at present for allergens in the workplace known to cause bronchial asthma. This contrasts with the great number of occupational asthma cases observed in industrialized countries. Recently published studies provide clear evidence for exposure intensity response relationships of occupational allergens of plant, microbiological, animal or man-made origin. If allergen exposure levels fall short of determined limit values, they are not associated with an increased risk of occupational asthma. Corresponding data are available for wheat flour (1-2.4 mg/m3), fungal alpha-amylase (0.25 ng/m3), natural rubber latex (0.6 ng/m3), western red cedar (0.4 mg/m3) and rat allergens (0.7 microg/m3). It is suggested to stipulate legally binding threshold limit values (TLV/TWA) on this basis in order to induce more effective primary preventive measures. If no reliable data on the health risk of an occupational airborne noxa exist, the lowest reasonably practicable exposure level has to be achieved. Appropriate secondary preventive measures have to be initiated in all workplaces contaminated with airborne allergens. Verified exposure-response relationships provide the basis for risk assessment and for targeted interventions to reduce the incidence of occupational asthma also in consideration of cost benefit aspects. 'Occupational asthma is a disease characterized by variable airflow limitation and/or airway hyperresponsiveness due to causes in a working environment. These causes can give rise to asthma through immunological or non-immunological mechanisms. Up to 15% of all asthma cases are of occupational origin or have at least a significant causal occupational factor. According to the New Zealand part of the European Respiratory Health Survey, an increased risk of asthma prevalence was found for several occupations such as laboratory technicians, food producers, chemical workers, plastic and rubber workers. The Spain part of this study comprising 2646 Spanish subjects showed an asthma risk to be attributed to occupational exposures between 5 and 6.7%. Main asthma-inducing agents in the workplace are flour, grain and feed dust, animal dander/urinary proteins and isocyanates. Further, several inhalative irritants such as chlorine, acid or alkaline aerosols play a pivotal role. Many low molecular weight chemicals have irritative as well as allergenic effects on the airways, e. g. isocyanates and acid anhydrides. In addition to chronic or repetitive exposures, also singular accidental exposure to high concentrations of irritative or toxic airborne substances can cause occupational asthma. This condition is frequently called reactive airways dysfunction.

Allergens↗

Cloning, expression and characterization of the major latex allergen prohevein.

BACKGROUND: About 70-80% of latex allergic health care workers are sensitized to prohevein (Hev b 6.01), a 20 kDa cysteine-rich chitin-binding protein of Hevea latex. OBJECTIVE: This study reports on the bacterial cloning, expression and immunochemical characterization of rHev b 6.01. METHODS: Prohevein was expressed in the periplasmatic space of Escherichia coli as maltose binding protein (MBP) fusion protein and purified to homogeneity after factor Xa cleavage. The IgE binding capacity of both rHev b 6.01 and prohevein isolated from fresh Hevea latex was compared by immunoblotting experiments using sera of latex-allergic patients. The diagnostic value of rHev b 6.01 was analysed by enzyme allergosorbent test (EAST). RESULTS: Two different cDNA clones of rHev b 6.01 were established. The deduced amino acid sequence of both clones revealed two and three amino acid differences in the C-terminal domain of prohevein compared with the original database entry. Purified rHev b 6.01 bound with high affinity to chitin as its natural counterpart isolated from natural latex. In IgE-immunblotting using sera of affected subjects binding intensity to both proteins was comparable indicating a very high antigenic similarity. The diagnostic value of MBP-prohevein was tested in EAST using sera of 33 latex-allergic subjects. The in vitro test showed high sensitivity and specificity and proved the diagnostic value of uncleaved MBP-prohevein. CONCLUSIONS: The production of recombinant latex key allergens with defined quality like prohevein is a straightforward strategy for the development of standardized in vitro test systems.

ATP-Binding Cassette Transporters↗

Baker's asthma due to the enzyme xylanase -- a new occupational allergen.

The asthmatic baker showed IgE-mediated sensitization to xylanase of Aspergillus niger used as a baking additive. Inhalative challenge with approximately 0.5 microg of the enzyme resulted in an immediate-type asthmatic reaction. This case, as well as a preliminary screening of symptomatic bakers, shows that xylanase is a further relevant type I-sensitizer in the baking industry.

Administration, Intranasal↗

[Occupational medicine aspects of nasal diseases].

BACKGROUND: With respect to occupational and environmental exposure risks and corresponding diseases, upper and lower airways show similarities and common aspects, e.g., in allergic reactions to inhalant allergens as well as in disorders caused by chemical irritants, toxic or cancerogenic substances. In addition to special occupational medical preventive examinations, an otolaryngologist is involved in the diagnosis, assessment, and therapy of occupational ENT diseases. RESULTS AND CONCLUSIONS: A significant proportion of ENT illnesses is work-related or represents an occupational disease. Factual figures are presented. A detailed occupational history of ENT patients should be prepared. If required, the factory physician or the expert in occupational medicine should be contacted to assist in appropriate preventive measures. In case of a confirmed diagnosis, the disease has to be reported.

Humans↗

Results of wearing test with two different latex gloves with and without the use of skin-protection cream.

A total of 109 subjects reporting symptoms indicating type I hypersensitivity reactions to natural rubber latex (NRL) gloves was included in this study, and 66 of them had latex-specific IgE antibodies. They underwent provocation tests by wearing two types of NRL gloves with high (n=103) and low (n=75) allergen contents. The first glove type caused positive skin reactions in 30% of IgE-positive and in 3% of IgE-negative subjects. After application of a commercially available skin protection (barrier) cream, the frequencies of positive skin responses in wearing tests increased to 41% and 7%, respectively. The gloves with low allergen content did not cause hypersensitivity without skin-protection cream but induced responses in 5% of IgE-positive subjects when this cream was applied. Corresponding findings were obtained in intraindividual comparisons of test results, which were possible in 69 cases. Of all wearing-test responders, 92% had latex-specific IgE antibodies. Our results demonstrate that high allergen contents in latex gloves frequently elicit skin responses in NRL-sensitized subjects, and that skin-protection creams may favor the uptake of allergens from gloves, thus increasing allergic reactions. The stipulation of a legally binding threshold limit value (TLV) for allergens in NRL products is urgently needed. This TLV should not be set above 2 microg allergen/g rubber.

Adult↗

Characterized allergens causing bakers' asthma.

Although airborne allergens in bakeries and confectioneries cause one of the most common forms of occupational asthma, namely, bakers' asthma, only a few of them are known in detail so far. Here we summarize current knowledge of bakery allergens and describe our own two-dimensional (2-D) immunoelectrophoresis studies of wheat-flour allergens as well as the allergenic baking enzyme Asp o 2. Out of approximately 700 soluble wheat polypeptides, 70 show IgE binding; the following wheat-flour allergens could be identified and characterized: members of the alpha-amylase inhibitor family (14-18 kDa), acyl-CoA oxidase (26 kDa), peroxidase (36 kDa), and fructose-bisphosphate aldolase (37 kDa). However, the great majority of the soluble wheat-flour allergens, mainly located in the 27-, 55-, and 70-kDa areas of the 2-D immunoblots with pI values of 5.8-6.8, 5.9-6.5, and 5.5-6.1, respectively, are not known at present. Asp o 2, to which approximately 25% of all bakers with respiratory symptoms are sensitized, is a well-characterized starch-cleaving enzyme. We conclude that great effort is still needed to describe all major wheat-flour allergens. As shown by Asp o 2, knowledge of the causative allergens and their characteristics enables us to initiate very effective preventive measures such as the introduction of granulated allergenic products.

Allergens↗