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Biomedical subjects

M Boeve

Publications and source records attributed to M Boeve.

10 recordsLinked to original sources

Nonlinear relations between house dust mite allergen levels and mite sensitization in farm and nonfarm children.

BACKGROUND: Low sensitization rates to common allergens have been observed in farm children, which might be due to high exposure to microbial agents. It is not known how microbial agents modify the association between specific allergen exposure and sensitization. OBJECTIVE: To examine the relations between house dust mite allergen exposure and mite sensitization in farm and nonfarm children and to assess the effects of microbial agents levels on this association. METHODS: Major mite allergens of Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1), endotoxin, beta(1,3)-glucans and fungal extracellular polysaccharides were measured in mattress dust of 402 children participating in a cross-sectional study in five European countries. Mite allergen (Der p 1 + Der f 1) levels were divided into tertiles with cut-offs 1.4 and 10.4 microg/g. Sensitization was assessed by measurement of allergen-specific immunoglobulin E against house dust mite. RESULTS: Prevalence ratios of mite sensitization for medium and high when compared with low mite allergen levels were 3.1 [1.7-5.7] and 1.4 [0.7-2.8] respectively. Highest mite sensitization rates at intermediate exposure levels were consistently observed across country (except for Sweden) and in both farm and nonfarm children. The shape of the dose-response curve was similar for above and below median mattress microbial agent levels, but the 'sensitization peak' appeared to be lower for above median levels. CONCLUSIONS: Our data suggest a bell-shaped dose-response relationship between mite allergen exposure and sensitization to mite allergens. In populations with high microbial agent levels and low sensitization rates, the curve is shifted down.

Adolescent↗

Exposure to microbial components and allergens in population studies: a comparison of two house dust collection methods applied by participants and fieldworkers.

Dust collection by study participants instead of fieldworkers would be a practical and cost-effective alternative in large-scale population studies estimating exposure to indoor allergens and microbial agents. We aimed to compare dust weights and biological agent levels in house dust samples taken by study participants with nylon socks, with those in samples taken by fieldworkers using the sampling nozzle of the Allergology Laboratory Copenhagen (ALK). In homes of 216 children, parents and fieldworkers collected house dust within the same year. Dust samples were analyzed for levels of allergens, endotoxin, (1-->3)-beta-D-glucans and fungal extracellular polysaccharides (EPS). Socks appeared to yield less dust from mattresses at relatively low dust amounts and more dust at high dust amounts than ALK samples. Correlations between the methods ranged from 0.47-0.64 for microbial agents and 0.64-0.87 for mite and pet allergens. Cat allergen levels were two-fold lower and endotoxin levels three-fold higher in socks than in ALK samples. Levels of allergens and microbial agents in sock samples taken by study participants are moderately to highly correlated to levels in ALK samples taken by fieldworkers. Absolute levels may differ, probably because of differences in the method rather than in the person who performed the sampling. Practical Implications Dust collection by participants is a reliable and practical option for allergen and microbial agent exposure assessment. Absolute levels of biological agents are not (always) comparable between studies using different dust collection methods, even when expressed per gram dust, because of potential differences in particle-size constitution of the collected dust.

Air Pollutants↗

[Diclofenamide].

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Animals↗

Bacterial and fungal agents in house dust and wheeze in children: the PARSIFAL study.

BACKGROUND: Growing up on a farm and an anthroposophic lifestyle are associated with a lower prevalence of allergic diseases in childhood. This might be related to increased inhalatory exposure to microbial agents. OBJECTIVE: To assess the association between microbial agents in house dust and atopic wheeze in farm children, Steiner school children and reference children. METHODS: Levels of bacterial endotoxin, fungal beta(1,3)-glucans and fungal extracellular polysaccharides (EPS) in mattress and living room floor dust were measured in a population of 270 atopic (=Phadiatop-positive) children with self-reported wheezing, including 168 current atopic wheezers, and 441 non-atopic, non-symptomatic controls. These children were selected from a cross-sectional study in five European countries. RESULTS: In the study population as a whole, average levels of mattress dust endotoxin, EPS and glucans were slightly (1.1-1.2-fold; P<0.10) higher in control children than in atopic wheezers. Atopic wheeze was related to mattress levels of endotoxin, EPS and glucans in farm and farm-reference children. However, when adjusting for group (farm vs. farm-reference children), the associations became non-significant whereas the group effect remained. No associations between atopic wheeze and microbial agents were observed in Steiner and Steiner-reference children. For current atopic wheeze, the farm effect became non-significant after adjustment for microbial agent levels. CONCLUSION: Not only bacterial endotoxin but also mould components might offer some protection against atopic wheeze in children. However, the protective effect of being raised on a farm was largely unexplained by the mattress microbial agent levels measured in this study.

Adolescent↗

Bacterial and fungal components in house dust of farm children, Rudolf Steiner school children and reference children--the PARSIFAL Study.

BACKGROUND: Growing up on a farm and an anthroposophic lifestyle are associated with a lower prevalence of allergic diseases in childhood. It has been suggested that the enhanced exposure to endotoxin is an important protective factor of farm environments. Little is known about exposure to other microbial components on farms and exposure in anthroposophic families. OBJECTIVE: To assess the levels and determinants of bacterial endotoxin, mould beta(1,3)-glucans and fungal extracellular polysaccharides (EPS) in house dust of farm children, Steiner school children and reference children. METHODS: Mattress and living room dust was collected in the homes of 229 farm children, 122 Steiner children and 60 and 67 of their respective reference children in five European countries. Stable dust was collected as well. All samples were analysed in one central laboratory. Determinants were assessed by questionnaire. RESULTS: Levels of endotoxin, EPS and glucans per gram of house dust in farm homes were 1.2- to 3.2-fold higher than levels in reference homes. For Steiner children, 1.1- to 1.6-fold higher levels were observed compared with their reference children. These differences were consistently found across countries, although mean levels varied considerably. Differences between groups and between countries were also significant after adjustment for home and family characteristics. CONCLUSION: Farm children are not only consistently exposed to higher levels of endotoxin, but also to higher levels of mould components. Steiner school children may also be exposed to higher levels of microbial agents, but differences with reference children are much less pronounced than for farm children. Further analyses are, however, required to assess the association between exposure to these various microbial agents and allergic and airway diseases in the PARSIFAL population.

Agriculture↗

Disruption of mouse SNM1 causes increased sensitivity to the DNA interstrand cross-linking agent mitomycin C.

DNA interstrand cross-links (ICLs) represent lethal DNA damage, because they block transcription, replication, and segregation of DNA. Because of their genotoxicity, agents inducing ICLs are often used in antitumor therapy. The repair of ICLs is complex and involves proteins belonging to nucleotide excision, recombination, and translesion DNA repair pathways in Escherichia coli, Saccharomyces cerevisiae, and mammals. We cloned and analyzed mammalian homologs of the S. cerevisiae gene SNM1 (PSO2), which is specifically involved in ICL repair. Human Snm1, a nuclear protein, was ubiquitously expressed at a very low level. We generated mouse SNM1(-/-) embryonic stem cells and showed that these cells were sensitive to mitomycin C. In contrast to S. cerevisiae snm1 mutants, they were not significantly sensitive to other ICL agents, probably due to redundancy in mammalian ICL repair and the existence of other SNM1 homologs. The sensitivity to mitomycin C was complemented by transfection of the human SNM1 cDNA and by targeting of a genomic cDNA-murine SNM1 fusion construct to the disrupted locus. We also generated mice deficient for murine SNM1. They were viable and fertile and showed no major abnormalities. However, they were sensitive to mitomycin C. The ICL sensitivity of the mammalian SNM1 mutant suggests that SNM1 function and, by implication, ICL repair are at least partially conserved between S. cerevisiae and mammals.

Amino Acid Sequence↗

Effect of heterozygous loss of p53 on benzo[a]pyrene-induced mutations and tumors in DNA repair-deficient XPA mice.

XPA-deficient mice have a complete deficiency in nucleotide excision repair, and as such they display a cancer predisposition after exposure to several carcinogens. Besides being sensitive to genotoxic agents applied to the skin, they are also susceptible to human carcinogens given orally, like benzo[a]pyrene (B[a]P). To study the role of the tumor suppressor gene p53 in DNA repair, gene mutation, and tumor induction, we crossed XPA-deficient mice with p53 knockout mice and lacZ (pUR288) gene marker mice. When treated orally (by gavage) with B[a]P, the XPA(-/-)/p53(+/-) double transgenic mice developed tumors much earlier and with higher frequency compared to their single transgenic counterparts. The major tumor type found in all genotypes was generalized lymphoma mainly residing in the spleen; several sarcomas were observed in p53(+/-) and XPA(-/-)/p53(+/-) mice. Next, we determined lacZ mutation frequencies in several (non)target tissues. It appeared that in the spleen (the major tumor target tissue) of XPA(-/-) and XPA(-/-)/p53(+/-) mice the lacZ mutation frequency was significantly elevated (80-100 x 10(-5)), and was two times higher as found in spleens of B[a]P-treated WT and p53(+/-) mice (P = 0.003). In nontumor target tissues like liver and lung, we found a moderate increase in the lacZ gene mutation frequency (30-40 x 10(-5)), which was independent of the genotype. The results obtained with the DNA-repair deficient XPA mice indicate that a significantly increased lacZ mutation frequency in a particular organ/tissue is an early marker for tumor development at later stages at the same site. However, the synergistic effect of a XPA(-/-)- and a p53(+/-)-deficiency in tumor development is not reflected by an absolute increase in the lacZ mutation frequency in the major tumor target tissue of XPA(-/-)/p53(+/-) or p53(+/-) mice compared to that of XPA(-/-) and WT mice, respectively.

Animals↗

Cloning and characterization of the gene encoding the primary sigma-factor of Campylobacter jejuni.

The rpoD gene encoding the primary sigma-factor of Campylobacter jejuni was amplified from genomic DNA with degenerate oligonucleotide primers. The complete gene encodes a polypeptide of 622 amino acids and has a deduced M(r) of 72.6 kDa. This polypeptide is 40% identical to the RpoD (sigma 70) protein of Escherichia coli and has 66% identity with the Helicobacter pylori RpoD protein. A C. jejuni sigma 70 promoter, not recognized by the E. coli sigma 70 factor, could be activated in this bacterium in the presence of the cloned C. jejuni RpoD protein.

Amino Acid Sequence↗

Identification of Campylobacter jejuni promoter sequences.

A promoterless lacZ shuttle vector, which allowed screening of promoters by beta-galactosidase activity in Campylobacter jejuni and Escherichia coli, was developed. Chromosomal DNA fragments from C. jejuni were cloned into this vector; 125 of 1,824 clones displayed promoter activity in C. jejuni. Eleven clones with strong promoter activity in C. jejuni were further characterized. Their nucleotide sequences were determined, and the transcriptional start sites of the putative promoters in C. jejuni were determined by primer extension. Only 6 of these 11 promoters were functional in E. coli. The 11 newly characterized and 10 previously characterized C. jejuni promoters were used to establish a consensus sequence for C. jejuni promoters. The 21 promoters were found to be very similar. They contain three conserved regions, located approximately 10, 16, and 35 bp upstream of the transcriptional start point. The -10 region resembles that of a typical sigma70 E. coli promoter, but the -35 region is completely different. In addition a -16 region typical for gram-positive bacteria was identified.

Base Sequence↗