The new Hev b 7.02 iso-allergen from Hevea brasiliensis is an important allergen for health care workers and spina bifida patients.
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Allergens↗
Biomedical subjects
T Brüning
Publications and source records attributed to T Brüning.
Genotoxic risk assessment in white blood cells of occupationally exposed workers before and after alteration of the polycyclic aromatic hydrocarbon (PAH) profile in the production material: comparison with PAH air and urinary metabolite levels.
OBJECTIVE: Workers in various industries can be exposed to polycyclic aromatic hydrocarbons (PAHs). The relationship between biomarkers of genotoxic risk, PAH compounds in air (ambient monitoring) and PAH metabolites in urine (internal exposure) were studied in 17 workers exposed to PAHs in a fireproof-material producing plant before and 3 months after the PAH profile was altered in the binding pitch. METHODS: Two biomarkers of exposure, specific DNA adducts of (+/-)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) and non-specific DNA adduct of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) were determined in white blood cells (WBCs). In addition, DNA strand breaks were analysed in lymphocytes by single-cell gel electrophoresis in a genotoxic risk assessment. Sixteen PAH compounds in air were determined by personal air sampling, and hydroxylated metabolites of phenanthrene, pyrene and naphthalene were determined in urine. RESULTS: After substitution of the binding pitch the concentrations of benzo[a]pyrene in air decreased (P<0.01). No changes could be observed for pyrene, while levels of phenanthrene (P=0.0013) and naphthalene (P=0.0346) in air increased. Consequently, median DNA adduct rates of anti-BPDE decreased after alteration of the production material (from 0.9 to <0.5 adducts/10(8) nucleotides). No changes in the excretion of 1-hydroxypyrene in urine could be determined, whereas increased levels of 1-, 2+9-, 3- and 4-hydroxyphenanthrene (P<0.0001) and 1-naphthol and 2-naphthol (P=0.0072) were found in urine. In addition, a statistically significant increase in DNA strand break frequencies (P<0.01) and elevated 8-oxodGuo adduct levels (P=0.7819, not statistically significant) were found in the WBCs of exposed workers 3 months after the PAH profile in the binding pitch had been altered. CONCLUSION: The results presented here show that the increased concentration of naphthalene and/or phenanthrene in the air at the work place could induce the formation of DNA strand breaks and alkali-labile sites in WBCs of exposed workers.
Adult↗
DNA strand breaks in the lymphocytes of workers exposed to diisocyanates: indications of individual differences in susceptibility after low-dose and short-term exposure.
Diisocyanates are chemically reactive and induce asthma, but data on genotoxic effects of diisocyanates in humans are limited. The investigation presented here used short term diisocyanate chamber exposure to study DNA strand breaks in lymphocytes of 10 healthy individuals and of 42 workers, with airway symptoms, who had previously been exposed to diisocyanates. The alkaline version of the Comet assay was used to analyse DNA strand breaks in lymphocytes. In addition, blood samples of 10 further control individuals without any exposure to diisocyanates were studied. Substances studied were 4,4'-methylenediphenyldiisocyanate (MDI, n=25), 2,4-toluenediisocynate and 2,6-toluenediisocyanate (TDI, n=5), and 1,6-hexamethylenediisocyanate (HDI, n=12), at concentrations between 5 and 30 ppb for 2 h. Lymphocytes isolated from the subjects before exposure and 30 min and 19 h after were used to evaluate DNA damage. No significant changes in DNA strand-break frequencies were measured, as Olive tail moment (OTM), either between groups or before and after diisocyanate exposure. OTM was similar in subjects with an asthmatic reaction (MDI, n=5; TDI, n=1; HDI, n=1) and in subjects without such a reaction. However, a small and susceptible group (about 10% of the individuals studied) could be identified with higher frequencies of DNA strand breaks in lymphocytes after chamber exposure. The occurrence of DNA damage in this group may be based on indirect mechanisms such as oxidative stress or apoptosis.
Adult↗
Immune-mediated rippling muscle disease.
The authors report a 44-year-old man with rippling muscle disease (RMD) who does not have a mutation in the caveolin-3 gene. Immunohistochemistry of the muscle biopsy revealed a marked reduction of caveolin-3 and a mosaic pattern of dysferlin immunostaining. Ultrastructural studies showed a loss of caveolae and alterations of the triad. Autoantibodies were directed against the sarcolemma, triad, and several unknown muscle proteins.
Adult↗
[Lung cancer screening revisited -- are we merely combing a giraffe?].
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Humans↗
[Occupational allergies to papain].
Occupational exposure against dusts of plant, bacterial, mould, and animal enzymes is long known to be associated with a high risk of specific sensitization. The present evaluation of literature data confirms that this is also true for papain. This frequently used industrial protease is derived from papaya (Carica papaya). Several cases of specific airway sensitization caused by papain are verified by a number of case reports and cross sectional studies. As symptoms, results of skin prick tests, detection of specific IgE-antibodies and results of specific bronchoprovocation tests are consistent, an immunologic mechanism can be assumed.
Humans↗
The use of biomarkers of exposure of N,N-dimethylformamide in health risk assessment and occupational hygiene in the polyacrylic fibre industry.
BACKGROUND: N,N-dimethylformamide (DMF) was recently prioritised for field studies by the National Toxicology Program based on the potency of its reproductive toxic effects. AIMS: To measure accurately exposure to DMF in occupational settings. METHODS: In 35 healthy workers employed in the polyacrylic fibre industry, N-methylformamide (NMF) and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) in urine, and N-methylcarbamoylated haemoglobin (NMHb) in blood were measured. Workplace documentation and questionnaire information were used to categorise workers in groups exposed to low, medium, and high concentrations of DMF. RESULTS: All three biomarkers can be used to identify occupational exposure to DMF. However, only the analysis of NMHb could accurately distinguish between workers exposed to different concentrations of DMF. The median concentrations were determined to be 55.1, 122.8, and 152.6 nmol/g globin in workers exposed to low, medium, and high concentrations of DMF, respectively. It was possible by the use of NMHb to identify all working tasks with increased exposure to DMF. While fibre crimpers were found to be least exposed to DMF, persons washing, dyeing, or towing the fibres were found to be highly exposed to DMF. In addition, NMHb measurements were capable of uncovering working tasks, which previously were not associated with increased exposure to DMF; for example, the person preparing the fibre forming solution. CONCLUSIONS: Measurement of NMHb in blood is recommended rather than measurement of NMF and AMCC in urine to accurately assess exposure to DMF in health risk assessment. However, NMF and AMCC are useful biomarkers for occupational hygiene intervention. Further investigations regarding toxicity of DMF should focus on highly exposed persons in the polyacrylic fibre industry. Additional measurements in occupational settings other than the polyacrylic fibre industry are also recommended, since the population at risk and the production volume of DMF are high.
Acetylcysteine↗
Challenges to environmental toxicology and epidemiology: where do we stand and which way do we go?
Modern toxicology investigates a wide array of both old and new health hazards. Priority setting is needed to select agents for research from the plethora of exposure circumstances. The changing societies and a growing fraction of the aged have to be taken into consideration. A precise exposure assessment is of importance for risk estimation and regulation. Toxicology contributes to the exploration of pathomechanisms to specify the exposure metrics for risk estimation. Combined effects of co-existing agents are not yet sufficiently understood. Animal experiments allow a separate administration of agents which can not be disentangled by epidemiological means, but their value is limited for low exposure levels in many of today's settings. As an experimental science, toxicology has to keep pace with the rapidly growing knowledge about the language of the genome and the changing paradigms in cancer development. During the pioneer era of assembling a working draft of the human genome, toxicogenomics has been developed. Gene and pathway complexity have to be considered when investigating gene-environment interactions. For a best conduct of studies, modern toxicology needs a close liaison with many other disciplines like epidemiology and bioinformatics.
Animals↗
Comparison of wheat and rye flour skin prick test solutions for diagnosis of baker's asthma.
BACKGROUND: Skin prick tests (SPTs) play an important role in the diagnosis of baker's asthma and in the investigation of sensitization frequencies in field studies. It was the aim of our study to compare different SPT solutions for wheat and rye flour sensitization and to assess the validity of test results. METHODS: Skin prick tests with wheat and rye flour were performed in parallel with extracts from different companies and compared with the results of bronchial challenge tests with both flours (69 rye flour and 51 wheat flour challenge tests). Additionally, specific immunoglobulin E (sIgE) to wheat and rye flour were tested. SPT solutions were analysed for protein content and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: Skin prick test solutions for diagnosis of wheat and rye flour sensitization from three companies differed in protein concentrations and composition with the consequence of widely differing SPT results. Sensitivity of SPTs in comparison with allergen-specific bronchial challenge as a gold standard was between 40 and 67%, specificity was between 86 and 100%, the positive predictive value (PPV) ranged from 81 to 100% and the negative predictive value (NPV) from 44 to 70%. These numbers were only marginally affected by using a combination of challenge test result and sIgE value as a more specific gold standard. CONCLUSION: Improvement and standardization of SPT extracts for wheat and rye flour is highly recommended.
Adult↗
[Compensation of low profusion coalworkers' pneumoconiosis. New occupational disease, new convention or leave it as it is?].
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Compensation and Redress↗
[Occupational allergies to xylanases].
The exposure against enzyme dusts have long been known to cause occupational allergies. In the 1960s an increasing number of occupational allergies in the detergent industry were observed. In this context the high sensitization potential of enzyme dusts attracted attention. The present evaluation of literature data confirms that this is also true for xylanases. These frequently used industrial enzymes belong to the hemicellulases and are mostly of fungal origin. Several cases of specific airway sensitization caused by xylanases or other hemicellulases are verified by a number of case reports and cross sectional studies. As symptoms, results of skin prick tests, detection of specific IgE-antibodies and results of specific bronchoprovocation tests are consistent, an immunologic mechanism can be assumed.
Drug Hypersensitivity↗
Characterization of B- and T-cell responses and HLA-DR4 binding motifs of the latex allergen Hev b 6.01 (prohevein) and its post-transcriptionally formed proteins Hev b 6.02 and Hev b 6.03.
BACKGROUND: Multiple immunoglobulin E (IgE)-binding proteins in natural rubber latex extracts have been identified. In the case of Hev b 6 a differentiation was made between the precursor protein prohevein (Hev b 6.01) and its two post-transcriptionally formed proteins, the N-terminal hevein (Hev b 6.02) and the C-terminal domain (Hev b 6.03). All three components act as independent allergens. The aim of this study was a detailed analysis of the T-cell responses and the IgE-binding capacity of Hev b 6.01, Hev b 6.02 and Hev b 6.03 by using these allergens as recombinant maltose-binding fusion (MBP) proteins and the usage of synthetic modified hevein peptides. METHODS: Latex-allergic health care workers (HCWs) suffering from rhinitis, conjunctivitis, contact urticaria and/or asthma with increased specific IgE-antibodies to latex were tested for their IgE-binding capacity and T-cell reactivity (by proliferation response) to the recombinant MBP-rHev b 6.01, MBP-rHev b 6.02, MBP-rHev b 6.03, to native Hev b 6.02, to modified hevein peptides and wheat germ agglutinin (WGA). For testing of the human leucocyte antigen (HLA) class II restriction of MBP-rHev b 6.01 induced peripheral blood mononuclear cell (PBMC) responses, monoclonal antibodies against HLA-DR, HLA-DP or HLA-DQ were added. RESULTS: Seventeen of 18 (94%) serum samples from latex-allergic HCWs had increased levels of specific IgE to MBP-rHev b 6.01, 16 (89%) to MBP-rHev b 6.02 and 13 (72%) to MBP-rHev b 6.03. A significant difference existed between the specific IgE-values of MBP-rHev b 6.02 and MBP-rHev b 6.03 (P < 0.01). Proliferation responses of PBMC of the same 18 latex-allergic patients were positive for MBP-rHev b 6.01 and MBP-rHev b 6.03 in 83 and 67% of the tested PBMC suspension, whereas the proliferation responses induced with MBP-rHev b 6.02 or native Hev b 6.02 were very low (5.6 and 22.2%). Sera from nine additional latex-allergic patients showed specific IgE binding to the native Hev b 6.02, but none of these sera showed specific IgE binding to the modified Hev b 6.02-peptides [whereby all eight cysteine residues were substituted by serine (C --> S) or by alanine (C --> A)]. Proliferation responses induced by the modified Hev b 6.02 peptides were not significantly different from that induced by Hev b 6.02. Potential HLA-DR4Dw4(DRB1*0401)-restricted T-cell epitopes of Hev b 6.01 predicted by two computer algorithms were only found in the Hev b 6.03-part of Hev b 6.01. CONCLUSION: In the Hev b 6.01 precursor the regions responsible for IgE binding and those for inducing the T-cell proliferation responses are settled in different parts of the protein. The Hev b 6.02 domain is responsible for IgE binding and carries discontinuous B-cell epitopes whereas Hev b 6.03 is a better inducer of a proliferation response and contains HLA-DR4-binding motifs.
Adult↗
Changes in low molecular weight DNA fragmentation in white blood cells after diisocyanate exposure of workers.
The pathogenesis of diisocyanate-induced asthma is still largely unknown. Recently, it has been shown that thiol-redox homeostasis of human airway epithelial cells may be altered after in vitro exposure to diisocyanates. In the present study, low molecular weight (LMW) DNA fragmentation patterns in white blood cells (WBCs) were assessed on 16 industrial workers with work-related asthma, before and after chamber challenges with one of three commonly used diisocyanates in concentrations up to 30 ppb. LMW-DNA fragmentation changes were evaluated after 15 h incubation of WBCs embedded in agarose plugs in lysis buffer with or without hydrogen peroxide (H2O2). Increased LMW-DNA fragmentation occurred in WBCs taken at 30 min or 19 h after the end of the chamber challenge in both subjects with positive and in 8 of 14 subjects with negative challenges. In contrast, no change in LMW-DNA fragmentation was seen in WBCs taken at the same time intervals from 11 non-exposed controls. There was no association between changes in DNA fragmentation patterns and possible confounding factors such as age, smoking status, atopy, medication, duration of occupational exposure and period since exposure cessation. These results indicate that diisocyanate exposure can induce DNA fragmentation. Similarities in the increased amounts of WBC LMW-DNA fragments following diisocyanate exposure with the DNA fragmentation after plugs lysis in buffer with H2O2 support the hypothesis that diisocyanates change the intracellular redox steady-state. Whether this effect plays any role in isocyanate-induced asthma has to be investigated in larger epidemiological studies.
Administration, Inhalation↗
Molecular cloning, purification, and IgE-binding of a recombinant class I chitinase from Hevea brasiliensis leaves (rHev b 11.0102).
BACKGROUND: Class I chitinase in natural rubber latex (NRL) has been assumed to be an important allergen, especially concerning its cross-reactivity with fruits like avocado and banana. OBJECTIVES: The present study aimed to produce a recombinant latex class I chitinase from Hevea brasiliensis leaves and to study its immunoglobulin (Ig)E-binding reactivity. METHODS: A class I chitinase-specific complementary DNA from H. brasiliensis leaves was synthesized, subcloned, sequenced and overexpressed in fusion with the maltose-binding protein (MBP) in Escherichia coli. The IgE-binding reactivity of this protein was studied by the Pharmacia CAP System and by immunoblot experiments using sera from latex-allergic patients. RESULTS: The rHev b 11.0102 was found to have a length of 295 amino acid residues and contains an N-terminal hevein-like domain with a 56% homology to hevein. Analysis by the CAP method revealed the presence of rHev b 11.0102-specific IgE antibodies in 17 of 58 sera (29%) of IgE-mediated latex-allergic subjects tested. Immunoblot analysis of the MBP-rHev b 11.0102 fusion protein and the MBP carrier protein as a negative control confirmed the IgE-reactivity of rHev b 11.0102. CONCLUSION: Due to its IgE-reactivity rHev b 11.0102 represents an allergen of intermediate prevalence in NRL. Its property to cross-react with certain fruits makes it an important supplement in the diagnostic panel of recombinant NRL allergens.
Adolescent↗
[Airways and lung disease by metal working fluids].
Metal working fluids (MWF) are used in the manufacturing process to cool and lubricate machined parts. MWF contain the coolant, mostly water-oil emulsions with soluble semi-synthetic or synthetic oils, but also emulsifiers and additives. Reaction products and both bacterial and fungal contamination occur during use. In the present review we listed literature data of dose-effect-relationships with a focus on biological substances. Most studies describe obstructive airways disease due to irritant effects of MWF. Immunoglobulin E mediated airways disease or hypersensitivity pneumonitis have rarely been described. There is no doubt that MWF exert adverse effects on human airways, but there is few data concerning dose-effect relationships. The role of bacterial and fungal contamination or endotoxin exposure cannot be defined by the available information. However, there is some evidence that biological components in MWF may represent the most hazardous substances.
Airway Obstruction↗
[Occupational allergies to cellulases].
In the 1960s an increasing number of occupational allergies in the detergent industry against the proteolytic enzyme Subtilisin were observed. In this context the high sensitization potential of enzyme dusts attracted attention. The present evaluation of literature data confirms that this is also true for cellulases. These enzymes--mostly of fungal origin--are frequently used in biotechnology. Several cases of specific airway sensitization caused by cellulases are verified by a number of studies. As symptoms, results of skin prick tests, detection of specific IgE-antibodies and results of specific bronchoprovocation tests are consistent, an immunologic mechanism seems to be confirmed.
Cellulase↗
[Immediate type allergies due to metal compounds: platinum salts].
Immediate type allergies due to metal compounds containing chromium, nickel, cobalt and platinum are rare. However, allergies to platinum salts represent a major health hazard in few precious metal refineries and catalyst productions. Sensitization can be shown with a highly specific and sensitive skin prick test. A dose-response relationship has clearly been established by prospective longitudinal studies, however the definition of a valid threshold limit is difficult due to the high variability of exposure. Smoking is a predicting factor, whereas atopy is not. Prognosis depends on the duration of symptomatic exposure in high exposure areas. Secondary prevention (medical surveillance) is effective in the prevention of persistent symptoms and bronchial hyperresponsiveness.
Humans↗
[Immediate type allergies due to metal - nickel].
Occupational allergies of the immediate type due to metals, which are predominantly caused by nickel, platinum, chromium and cobalt, are rather rare. The present paper reviews the results of the evaluation of literature data concerning the occupational airway sensitization due to nickel, which is used in many different industrial fields - especially in the electroplating industry. Cases of specific airway sensizitation caused by nickel are verified by a number of studies, predominantly case histories. In conclusion, there is sufficient evidence that nickel may cause IgE-mediated hypersensitivity with typical symptoms.
Adult↗