Cigarette smoking can induce CYP1A1 in the lung. Induction requires the aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor nuclear translocator (ARNT) proteins. Lung samples from seven of 75 Finnish patients who smoked until the time of surgery exhibited absent or low levels of CYP1A1 protein, mRNA and enzymatic activity, suggesting that these individuals might be genetically non or poorly inducible for CYP1A1. All seven lung samples expressed normal levels of AHR mRNA and ARNT mRNA, indicating that they did not carry inactivating polymorphisms in the 5' upstream regulatory regions of these genes. Sequencing of cDNAs encompassing the complete coding regions of AHR and ARNT identified a previously known codon 554 polymorphism in AHR, which was present in the homozygous state in one individual. This polymorphism, which leads to an amino acid substitution, has previously been reported either to have no effect or to enhance CYP1A1 induction. Previously unreported silent single nucleotide polymorphisms were identified in codon 44 of AHR and codon 189 of ARNT. 1500 bp of genomic sequence from the 5' upstream regulatory sequence of the CYP1A1 gene was also sequenced in the non-inducible individuals. A nucleotide substitution polymorphism at position -459 was detected in the heterozygous state in two individuals. This polymorphic site does not reside in any known regulatory sequence. The complete CYP1A1 coding sequence and intron/exon boundaries were then sequenced. None of the non or poorly inducible individuals exhibited any polymorphisms, either homozygous or heterozygous compared to representative inducible individuals or the previously published CYP1A1 sequence. Thus, no polymorphisms in the AHR, ARNT or CYP1A1 genes were identified that could be responsible for the non/low inducibility phenotype observed.
OBJECTIVES: To assess the possible presence in patients with rheumatoid arthritis (RA) of autoantibodies recognising citrullinated peptides derived from type I and II collagens. METHODS: Firstly, the binding of four pairs of synthetic peptides (arginine-containing and artificially citrullinated forms) related to different regions of human type II collagen were tested with sera from 120 patients with RA and 81 controls. Secondly, two similar pairs of peptides related to the carboxy terminal telopeptides of the alpha1 and alpha2 chains of human type I collagen were tested. RESULTS: 42-53% of the RA sera showed increased binding of arginine peptides related to type II collagen. However, 12 RA sera bound the citrullinated form of the alpha1(II) telopeptide more strongly than the corresponding arginine peptide. 20 RA sera bound the citrullinated carboxytelopeptide from the alpha1 chain of type I collagen (alpha1(I) telopeptide) more strongly than the respective arginine peptide. The correlation between the autoantibodies to type I and II collagen telopeptides was r(s) = 0.576, p
Primary prevention carried out today can reduce the disease incidence in the future decades. The present disease panorama is the consequence of past asbestos exposure mainly before the 1970s. The peak incidence of asbestos-induced diseases will be reached around 2010 in Finland. The number of asbestos-related premature deaths is at present annually about 150 which exceeds the figure of fatal work accidents. Asbestos-related cancer will increase still for 15-20 years and reach its maximum, about 300 cases, in 2010, and will start to decrease after that. More than 20,000 asbestos-exposed workers have participated in the medical screening and follow-up. The termination of exposure, antismoking campaigns, improved diagnostics and careful attention to compensation issues, as well as other potentials for prevention, were the central issue of the Asbestos Program of the Finnish Institute of Occupational Health. An important objective of research work is to improve early diagnostics, and thereby treatment prospects, in case of asbestos-induced cancers.
Concentrations of asbestos bodies (AB) were assessed by optical microscopy of 10 ml iron-stained samples and compared with the exposure history acquired by personal interview for 156 patients. Concentrations equalling or exceeding 1 AB/ml were found in 85% of patients who had been heavily exposed to asbestos and only 7% of those who were unlikely to have been exposed. Elevated AB concentrations were observed among primary asbestos, shipyard and construction workers. Smoking was not found to affect the AB concentrations. The use of Papanicolaou-stained cytological Millipore preparations during routine screening was a less sensitive method for the assessment of AB concentrations than that involving iron-stained preparations. The expression of AB concentration as AB/ml or AB/million cells were found to be equally useful indicators of exposure. The correlation between AB concentration and exposure history was greater than in earlier studies on workers exposed to chrysotile. Concentrations exceeding 1 AB/ml were indicative of a nontrivial exposure to asbestos. Despite the observed correlation between AB concentration and exposure history, the individual variability of AB counts, methodological differences and laboratory-bound reference values are important in the interpretation of AB concentrations in bronchoalveolar lavage (BAL) fluid at individual level.
In Finland, unlike other countries, anthophyllite asbestos has been widely used due to its domestic production in 1918-1975. In this particular context, the aim of the present study was to analyse the relationship between asbestos bodies (ABs) in bronchoalveolar lavage (BAL) fluid and the concentration of ABs and the different amphibole asbestos fibres in lung tissue. Sixty five BAL lung tissue sample pairs from patients with pulmonary disease were analysed. The concentration of ABs in BAL fluid and lung tissue was determined with optical microscopy, and the concentration, type and dimensions of asbestos fibres in lung tissue with scanning electron microscopy. There was a significant correlation between the concentrations of ABs in BAL fluid and in lung tissue (r = 0.72; p
In a series of 65 surgically treated lung cancer patients, past exposure to asbestos was evaluated by personal interviews, and by scanning electron microscopy analyses of the mineral fibers in lung tissue. Lung tissue samples of 17 autopsied male office workers were analyzed as referents. According to occupational history, 37% of the lung cancer patients had definite or probable, 31% possible, and 32% unlikely exposure to asbestos. The fiber concentration in the lung tissue ranged from
The aim of the study was to determine the pulmonary concentrations of mineral fibers in the Finnish male urban population and to evaluate the analysis of pulmonary fiber burden by scanning electron microscopy (SEM) as an indicator of past fiber exposure.
The pulmonary concentration of mineral fibers was determined by SEM and compared with occupational history for a series of 300 autopsies of urban men aged 33 to 69 years.
The concentration of fibers (f) longer than 1 micron ranged from
The aim of the study was to investigate the asbestos-associated risk of lung cancer according to histological type of cancer, lobe of origin, pulmonary concentration, and type of amphibole fibers and also to estimate the etiologic fraction of asbestos for lung cancer.
The pulmonary concentration of asbestos fibers in 113 surgically treated male lung cancer patients and 297 autopsy cases among men serving as referents was determined by scanning electron microscopy. The age- and smoking-adjusted odds ratios of lung cancer were calculated according to pulmonary fiber concentration for all lung cancer types, squamous-cell carcinoma, and adenocarcinoma and for the lower-lobe and the upper- and middle-lobe cancers.
The risk of lung cancer was increased according to the pulmonary concentration of asbestos fibers (f) of 1.0 to 4.99 x 10(6) f.g-1 [odds ratio (OR) 1.7] and > or = 5.0 x 10(6) f.g-1 (OR 5.3). The odds ratios associated with fiber concentrations of > or = 1.0 x 10(6) f.g-1 were higher for adenocarcinoma (OR 4.0) than for squamous-cell carcinoma (OR 1.6). The asbestos-associated risk was higher for lower lobe tumors than for upper lobe tumors. The risk estimates for anthophyllite and crocidolite-amosite fibers were similar, except for the risk of squamous-cell carcinoma. An etiologic fraction of 19% was calculated for asbestos among male surgical lung cancer patients in the greater Helsinki area.
Past exposure to asbestos is a significant factor in the etiology of lung cancer in southern Finland. The asbestos-associated risk seems to be higher for pulmonary adenocarcinoma and lower-lobe tumors than for squamous-cell carcinoma and upper-lobe tumors.
