The alpha spectrometry measurements of specific activity of 238Pu and 239Pu in urine from bioassay examinations of 1,013 workers employed at the radiochemical and plutonium production facilities of the Mayak Production Association and in autopsy specimens of lung, liver, and skeleton from 85 former nuclear workers who died between 1974-2009, are summarized.The accumulation fraction of 238Pu in the body and excreta has not changed with time in workers involved in production of weapons-grade plutonium production (e.g., the plutonium production facility and the former radiochemical facility). The accumulation fraction of 238Pu in individuals exposed to plutonium isotopes at the newer Spent Nuclear Fuel Reprocessing Plant ranged from 0.13% up to 27.5% based on the autopsy data. No statistically significant differences between 238Pu and 239Pu in distribution by the main organs of plutonium deposition were found in the Mayak workers. Based on the bioassay data,the fraction of 238Pu activity in urine is on average 38-69% of the total activity of 238Pu and 239Pu, which correlates with the isotopic composition in workplace air sampled at the Spent Nuclear Fuel Reprocessing Plant. In view of the higher specific activity of 238Pu, the contribution of 238Pu to the total internal dose, particularly in the skeleton and liver, might be expected to continue to increase, and continued surveillance is recommended.
Accelerated apoptosis and low bcl-2 expression associated with neuroendocrine differentiation predict shortened survival in operated large cell carcinoma of the lung.
In order to test the hypothesis that increased apoptotic activity is connected with neuroendocrine differentiation and low differentiation degree in large cell carcinoma (LCLC) and is regulated by bcl-2 family proteins, we analysed the extent of apoptosis and tumor necrosis and their relation to the expression of bcl-2, bax, bak and mcl-1 in 35 LCLCs, of which 20 were classified as large cell neuroendocrine lung carcinomas (LCNEC) and 15 as large cell non-neuroendocrine lung carcinomas (LCNNEC). The extent of apoptosis was determined by detecting and counting the relative and absolute numbers of apoptotic cells and bodies using in situ 3 -end labelling of the apoptotic DNA. The extent and intensity of expression of the bcl-2, bax, bak and mcl-1 proteins were studied by immunohistochemistry. Also the relative volume density of necrosis was evaluated and correlated with the other parameters. Finally, all the parameters were evaluated as prognostic markers and correlated with data on the survival of the patients. Relatively high apoptotic indices were seen in both tumor types (average for both 2.53%, range 0.09 27.01%). Significantly higher bcl-2 and bak indices were detected more often in LCNECs than in LCNNECs. Immunohistochemically detected bax, bcl-2 and bak expression was independent of apoptotic index in both tumor types, while there was a statistically significant positive association between mcl-1 expression and apoptotic index in LCNNEC but not in LCNEC. There was a statistically significant association between high apoptotic index and shortened survival in LCLC. However, no association was found between tumor stage and apoptosis. The patients with LCNEC and low bcl-2 protein expression had a significantly shorter survival time than those with high bcl-2 indices. There was also a clear association between shortened survival and necrotic LCNNEC. LCLCs show relatively high apoptotic activity, which is associated with shortened survival. The expression of bcl-2, bak and mcl- 1 is associated with neuroendocrine differentiation in LCLC. Finally, our results support some previous reports suggesting that bcl-2 expression in combination with some other markers involved in apoptosis and/or proliferation may be of prognostic value in cases of lung carcinoma with neuroendocrine differentiation.
Adrenal suppression in asthmatic children receiving low-dose inhaled budesonide: comparison between dry powder inhaler and pressurized metered-dose inhaler attached to a spacer.
BACKGROUND: Dry powder inhalers (DPI) have in recent years become a common mode for administration of inhaled corticosteroids for preventive therapy of asthma. Inhaled steroids delivered by DPI achieve increased lung deposition compared with pressurized metered-dose inhalers (pMDI), which is associated with increased therapeutic effect. This may be associated with increased systemic absorption. OBJECTIVE: The purpose of this study was to evaluate the prevalence of adrenal suppression in children using low-dose budesonide given by DPI, as compared with pMDI attached to a large-volume spacer device (pMDI + spacer). METHODS: In an open-labeled crossover study, 15 asthmatic children aged 5 to 15 years received 200 microg of inhaled budesonide twice daily by DPI (Turbuhaler, Astra, Draco AB, Lund, Sweden) and by pMDI + spacer, 1 month each, in a randomized order. Twenty-four-hour urine collections were performed at baseline and at the end of each of the 2 months of the study period, and urinary cortisol and creatinine were measured. RESULTS: Baseline urinary cortisol:creatinine was 0.038 +/- 0.012 microg/mg, similar in both groups. After 1 month of DPI therapy, urinary cortisol:creatinine was reduced by 27 +/- 16% to 0.028 +/- 0.012 microg/mg (P = 0.018). Urinary cortisol:creatinine after 1 month of pMDI + spacer therapy was similar to baseline 0.037 +/- 0.019 microg/mg (P = 0.78). CONCLUSIONS: Treatment of asthmatic children with budesonide 400 microg daily given via a DPI for 1 month was associated with hypothalamic-pituitary-adrenal axis suppression. This effect was not observed with the same dose of budesonide administered via pMDI + spacer. This indicates that systemic absorption might be reduced with pMDI + spacer therapy.
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Comment In: Ann Allergy Asthma Immunol. 2002 Dec;89(6):537-912487216
Annually, large tracts of forest in eastern Canada are sprayed aerially with insecticides (fenitrothion, aminocarb) in attempts to control an epidemic infestation by an indigenous forest pest, the spruce budworm (Choristoneura fumiferana, Clemens). The massive size of the spraying programs, the anecdotal reports of human exposure, and the potential for hazard to human health have led one province. New Brunswick, to initiate and fund specific environmental and laboratory studies which will provide adequate data upon which the government can base realistic legislation to protect both the forests and the population. These studies have included some unique field analyses of aerial spray drift conducted by a research group from the National Research Council; comparative subchronic studies in rats of fenitrothion and a new formulation; a nose-only inhalation study of this formulation in rats; field testing of the formulation for drift characteristics. Ongoing research involves the subchronic testing of the emulsifying agents being used routinely in the new formulation and studies of a low-drift additive which will stabilize the particle size of the spray. On the basis of the results to date, the government has been able to modify spraying techniques and to establish realistic buffer zones around human habitation.
KL-6 is a high-molecular-weight glycoprotein classified as a human MUC1 mucin. It was hypothesized that KL-6 could be detectable in the circulating blood and especially in airway secretions in lung diseases associated with mucus production such as chronic obstructive pulmonary disease (COPD). Additional aims of this study were to investigate whether the levels of KL-6 in plasma and sputum are related to ageing and smoking history.
The concentrations of KL-6 in plasma and induced sputum supernatants from young and/or middle aged/elderly non-smokers, smokers and patients with COPD were assayed by ELISA (n = 201). The subjects were classified into five groups according to age, smoking status and presence of COPD. In addition, KL-6 expression in control and diseased lung i.e. samples from patients with COPD (n = 28), were analyzed by immunohistochemistry and digital image analysis.
The plasma levels of KL-6 increased with age both in non-smokers and smokers. Among middle aged/elderly subjects, plasma KL-6 levels in all smokers regardless of COPD were significantly higher than in non-smokers, whereas sputum levels of KL-6 were significantly higher in COPD compared not only to non-smokers but also to smokers. KL-6 was more prominently expressed in the bronchiolar/alveolar epithelium in COPD than in the control lungs. Plasma and sputum KL-6 levels correlated inversely with obstruction and positively with smoking history and ageing. The linear multiple regression analysis confirmed that age and cigarette smoking had independent effects on plasma KL-6.
KL-6 increases with ageing and chronic smoking history, but prospective studies will be needed to elucidate the significance of KL-6 in chronic airway diseases.
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Tissue concentrations of antimony in lung, liver, and kidney tissue from a group of deceased smelter workers from northern Sweden have been compared with those of a group of persons without occupational exposure from a nearby area. Neutron activation analysis was used to determine the antimony concentration of lung tissue from exposed workers; these concentrations were 12-fold higher than those of referents (p less than 0.001). For lung tissue there was no tendency towards decreased antimony concentrations with time (up to 20 a) after the cessation of exposure, and this result indicates a long biological half-time. The highest values were found for workers who had worked for many years at the roasters and in the arsenic and selenium departments. There was no significant difference between the antimony concentration of the lung tissue from workers who had died of lung cancer and those of persons who died of other malignancies, cardiovascular disease, or other causes. This finding does not however rule out the possibility of a role for antimony in the etiology of lung cancer among smelter workers since multiple factors may have been operating. The antimony concentration of the liver tissue and the kidney cortex did not differ from the corresponding values of the reference group; this finding indicates either a short biological half-time or insignificance for the systemic distribution of antimony.
CX3CR1, a fractalkine receptor, mediates cell-adhesive and migratory functions in inflammation. Based on CX3CR1 expression observed in bronchial tissues of asthmatic subjects, we hypothesized that genetic variation at this locus may affect susceptibility to asthma. We carried out an association study and a haplotypic analysis with selected polymorphisms of the CX3CR1 in a familial asthmatic sample from a founder population. Genetic analyses performed by FBAT software showed five CX3CR1 single nucleotide polymorphisms (rs938203, rs2669849, rs1050592, T280M and V249I) with significant associations between their common alleles and asthma (P
Biologically active metals in human tissues. I. The effect of age and sex on the concentration of copper in aorta, heart, kidney, liver, lung, pancreas and skeletal muscle.
Autopsy specimens of aorta, heart, kidney, liver, lung, pancreas and skeletal muscle were collected from 86 accident victims. The copper concentration in each tissue was determined with atomic absorption spectrophotometry. The descending order of the tissues in respect to copper concentration was: liver, heart, kidney, pancreas, lung, muscle, and aorta. No significant difference was found in the copper levels of samples from male and female autopsies. When the effect of age on the average copper concentration was studied, liver and kidney showed a decreasing concentration up to maturity, the copper concentration in pancreas and skeletal muscle showed a continuous decline with increasing age, and there was no clear-cut effect of age on the copper concentration of heart, lung and aorta. According to the results the Finnish population does not differ, on the average, from other populations with respect to tissue copper concentrations.
The pulmonary cadmium (Cd) and chromium (Cr) contents from 45 decreased persons from Northern Finland were determined by plasma emission spectrometry (DCP-AES). These subjects did not have any malignant diseases or known occupational exposure to heavy metals. The pulmonary metal concentrations were compared with smoking history, pulmonary emphysema, age, and occupation. The mean Cd concentrations for the nonsmokers, smokers, and exsmokers were 0.4 (SD +/- 0.4), 3.0 (SD +/- 2.2), and 1.1 (SD +/- 1.0) micrograms/dry wt, and the corresponding values for Cr were 1.3 (SD +/- 0.9), 4.3 (SD +/- 3.3), and 4.8 (SD +/- 4.0) micrograms/g dry wt, respectively. The pulmonary Cr content increased with age and smoking time, but showed no connection with occupation. The Cd content was dependent only on smoking-related variables, increasing with the amount of tobacco smoked. The pulmonary Cd was seen to return to the level of nonsmokers in 21-22 years after cessation of smoking, whereas Cr showed no decreasing tendency with the time since smoking stopped.
Susceptibility to asthma depends on variation at an unknown number of genetic loci. To identify susceptibility genes on chromosome 7p, we adopted a hierarchical genotyping design, leading to the identification of a 133-kilobase risk-conferring segment containing two genes. One of these coded for an orphan G protein-coupled receptor named GPRA (G protein-coupled receptor for asthma susceptibility), which showed distinct distribution of protein isoforms between bronchial biopsies from healthy and asthmatic individuals. In three cohorts from Finland and Canada, single nucleotide polymorphism-tagged haplotypes associated with high serum immunoglobulin E or asthma. The murine ortholog of GPRA was up-regulated in a mouse model of ovalbumin-induced inflammation. Together, these data implicate GPRA in the pathogenesis of atopy and asthma.
