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Biomedical subjects

P Wild

Publications and source records attributed to P Wild.

At least 19 recordsLinked to original sources

Lung cancer risk in hard-metal workers.

An industry-wide mortality study on the association between lung cancer and occupational exposure to cobalt and tungsten carbide was carried out in the French hard-metal industry. This case-control study was nested in the historical cohort of workers ever employed in this industry's 10 facilities, most of which are located in eastern France. Workers were followed up from 1968 to 1991. Occupational exposure was assessed using a job-exposure matrix that provided semiquantitative scores for 320 job periods. These scores were significantly correlated with the levels of cobalt measured in 744 historical air samples. In this cohort, which comprised 5,777 males and 1,682 females, the death rate from lung cancer was significant (63 deaths, standardized mortality ratio=1.30, 95% confidence interval (CI) 1.00-1.66) when compared with national death rates. Sixty-one cases and 180 controls were included in the study. When the exposures during the last 10 years were ignored, a twofold lung cancer risk was observed among workers simultaneously exposed to cobalt and tungsten carbide (odds ratio (OR)=1.93, 95% CI 1.03-3.62) adjusted for other cobalt exposure (OR=2.21, 95% CI 0.99-4.90). The odds ratios increased with cumulative exposure (first quartile, OR=1.00; second quartile, OR=2.64; third quartile, OR=2.59; fourth quartile, OR=4.13) and, to a lesser degree, with duration of exposure (one decade, OR=1.00; two decades, OR=1.61; three decades, OR=2.77; four decades, OR=2.03). Adjustments for smoking and for exposures to known or suspected carcinogens did not change the results, yet the odds ratio for smoking (3.38) was lower than expected, suggesting the possibility of some misclassification. Occupational risk was highest among smokers. This study supports the hypothesis that workers who manufacture hard metals have an increased mortality from lung cancer due to simultaneous exposure to cobalt and tungsten carbide.

Adult

Characterisation of two human dendritic cell-lines that express CD1a, take-up, process and present soluble antigens and induce MLR.

Dendritic cells (DC) are bone marrow derived cells present in diverse tissues and organs including the skin, mucosae and blood. DC have a capital role in the afferent pathway of the immune response because of its role in up-take, processing and presenting antigens to immune cells. Human DC are usually identified by the expression of surface CD1a and HLA-DR. Despite the significant recent developments for in vitro generation of DC derived from blood by using cytokines like GM-CSF and IL-4, the studies on DC and specially on human Langerhans cells (LC) have been hampered by the laborious isolation procedure and the small yield of cells obtained by the various methods of isolation used so far. Therefore, a priority has been a search for monoclonal dendritic cell-lines with LC characteristics in order to facilitate the research in this area. The present study reports on the generation of two stable, self-replicant, adherent, dendritic, CD1a+, HLA-DR , CD45RO , CD23/FcERII+ cell-lines that up-take and process soluble antigens but also inducing MLR and antigen-dependent T-cell response.

Antigen Presentation

Demographic evaluation of the fertility of aluminium industry workers: influence of exposure to heat and static magnetic fields.

A demographic analysis of the fertility of French aluminium industry workers was performed in order to evaluate the potential effects on male fertility of occupational exposure to heat and static magnetic fields occurring in certain workshops. Two groups of aluminium workers were studied: one group of 692 potroom workers exposed to heat and to static magnetic fields, and a control group of 588 workers from the same plants, who had not been exposed to these factors. The birthrate was significantly higher in the 'exposed' group than in the 'control' group. The relative birthrate ratio ('exposed' versus 'control') was 1.1 (P < 0.001). These results do not show any decrease in the fertility of potroom workers exposed to heat and static magnetic fields, when compared to other workers in the aluminium producing industry.

Aluminum

Respiratory symptoms and bronchial responsiveness in lifeguards exposed to nitrogen trichloride in indoor swimming pools.

OBJECTIVES: To measure the levels of exposure to nitrogen trichloride (NCl3) in the atmosphere of indoor swimming pools and to examine how they relate to irritant and chronic respiratory symptoms, indices of pulmonary function, and bronchial hyperresponsiveness to methacholine in lifeguards working in the pools. METHOD: 334 lifeguards (256 men; 78 women) recruited from 46 public swimming pools (n = 228) and 17 leisure centre swimming pools (n = 106) were examined. Concentrations of NCl3 were measured with area samplers. Symptoms were assessed by questionnaire and methacholine bronchial challenge (MBC) test by an abbreviated method. Subjects were labelled MBC+ if forced expiratory volume in one second (FEV1) fell by > or = 20%. The linear dose-response slope was calculated as the percentage fall in FEV1 at the last dose divided by the total dose given. RESULTS: 1262 samples were taken in the 63 pools. Mean NCl3 concentrations were greater in leisure than in public pools. A significant concentration-response relation was found between irritant eye, nasal, and throat symptoms-but not chronic respiratory symptoms-and exposure concentrations. Among women, the prevalence of MBC+ was twice as great as in men. Overall, no relation was found between bronchial hyperresponsiveness and exposure. CONCLUSIONS: The data show that lifeguards exposed to NCl3 in indoor swimming pools are at risk of developing irritant eye, nasal, and throat symptoms. Exposure to NCl3 does not seem to carry the risk of developing permanent bronchial hyperresponsiveness, but this association might have been influenced by self selection. The possibility that subjects exposed to NCl3 are at risk of developing transient bronchial hyperresponsiveness cannot be confidently ruled out.

Adult

[Mortality in the French paper and pulp industry].

BACKGROUND: The objective was to describe a possible cancer mortality risk in relation with the occupational exposure within an International study co-ordinated by the International Agency for Research on Cancer. METHODS: An epidemiological cohort study was set up to assess the mortality in four French pulp and paper companies. The four cohorts were followed up from January 1st 1968 to December 31st 1992. The causes of death were ascertained by matching with the national file of causes of death. RESULTS: The full cohort consisted in 5,529 men and 876 women. The total numbers of subjects deceased between 1968 and 1992 were respectively 708 and 34. Causes of death could be traced for 98%. The observed mortality was significantly lower than the expected for all causes of deaths (SMR = 0.86) as well for all deaths by cancer (SMR = 0.87). The analysis by departments showed an excess mortality by cancer of the pancreas in the wood preparation department (SMR = 3.14) as well as in the paper production department (SMR = 2.04). CONCLUSIONS: In absence of any prior hypothesis, it is difficult to assign an occupational origin to these observed excesses. The future results of the international study will enable us to interpret these results more precisely.

Cause of Death

Green fluorescent protein as a reporter for retrovirus and helper virus-free HSV-1 amplicon vector-mediated gene transfer into neural cells in culture and in vivo.

Green fluorescent protein (GFP) is an effective marker for retrovirus and herpes virus vector-mediated gene transfer into various central nervous system-derived cells, both proliferative and non-proliferative, in culture and in vivo. Retrovirus vectors were used to stably transduce several rat and human glioma lines, and a multipotent mouse neural progenitor line in culture. Implantation of selected pools of transduced glioma cells into rodent brain allowed clear visualization of the tumor and the invading tumor edge. Helper virus-free HSV-1 amplicon vectors successfully transferred gfp into non-dividing primary neural cells in culture and in the rat brain. This study describes the versatility of GFP for: (i) labelling of glioma cells in experimental brain tumor models and neural progenitor cells by retrovirus vectors, and (ii) efficient, non-toxic delivery of genes to post mitotic cells of the nervous system using helper-virus free HSV-1 amplicon vectors.

Animals

Reevaluation of the effect of lysoyzme on Escherichia coli employing ultrarapid freezing followed by cryoelectronmicroscopy or freeze substitution.

Lysozyme is able to lyse Gram-positive bacteria acting as muramidase on the peptidoglycan polymer. Gram-negative bacteria in vitro are not lysed by lysozyme. It was assumed that the peptido-glycan is protected by the outer membrane and thus that Gram-negative bacteria are not affected by lysozyme without the aid of other factors such as EDTA or complement which enable lysozyme to penetrate the outer membrane. Accidentally, Pellegrini et al. [(1992) J. Appl. Bacteriol., 72:180-187] found that lysozyme per se is able to kill some Gram-negative bacteria. On the basis of morphological and immunocytochemical findings obtained from chemically fixed bacteria, it was concluded that lysozyme does not lyse Gram-negative bacteria but affects the cytoplasm of for example, Escherichia coli, leading to its disintegration, whilst the membranes do not break down. In an attempt to clarify the action of lysozyme on E. coli, we employed cryotechniques including ultrarapid freezing, cryomicroscopy and freeze substitution, and immunolabeling. Bacteria that were immediately frozen after exposure to lysozyme remained morphologically intact. Individual bacteria plated on agar after exposure to lysozyme were mostly intact when frozen within a few seconds. However, inner and outer membranes of 80% of the bacteria were disrupted, whereas the cytoplasm of only a few bacteria showed signs of disintegration when bacteria were frozen with a delay of only 5 min of plating onto pure agar or agar containing growth medium. After a period of time of 15 min between plating onto agar and freezing, about 97% of the bacteria showed changes of disintegration of various extent. Immunolabeling showed that lysozyme binds to the outer cell membrane and may penetrate the membrane, reaching the periplasmic space and possibly the inner cell membrane. The ultrastructural findings and the results of antibacterial assays suggest that lysozyme is bactericidal for E. coli but is not able to induce disintegration. Disintegration is accomplished by changes of the environment starting at the cell membranes. The mechanism by which lysozyme penetrates the membrane, the way it acts to be bactericidal, and the way disintegration is initiated remain to be clarified.

Escherichia coli

Comparative reproduction of Cryptosporidium baileyi in embryonated eggs and in chickens.

At 2 days of age, each of 20 chickens was perorally or intracloacally infected with 3 x 10(5) oocysts of Cryptosporidium baileyi and maintained for 13 days post infection. In parallel, 20 embryonated chicken eggs were inoculated with 3 x 10(5) oocysts at day 10 of embryonation and were incubated for a further 7 days. The average reproduction rates in the two groups of chickens were x560 after peroral infection and x533 after intracloacal infection as compared with x256 in the eggs. Although the rate of reproduction of parasites seen in the eggs was only about 50% of that observed in chickens, large numbers of oocysts could be harvested (on average, 77 million per egg versus 161 and 168 million from chickens). Nearly the same number of oocysts could be obtained from two eggs as compared with one chicken. The use of embryonated eggs accommodates the sense of animal-protection regulations, is less expensive, and allows the isolation of oocysts under sterile conditions.

Animals

[Development of a job-exposure matrix in the heavy-metal industry in France].

A job exposure matrix (JEM) was developed by a committee of experts using the DELPHI method, in the French hard metal industry, in order to assess occupational exposures to cobalt along with tungsten carbide resulting from the industrial process. This JEM is part of a nested case-control study, carried out within the historical cohort of workers ever employed in these factories, aimed at assessing lung cancer risk. The committee included 8 experts: hygienists, chemical engineers, occupational physicians and epidemiologists. The JEM was developed in four stages: (i) visit of factories, (ii) definition of lines (job-periods) and columns (exposures) of the JEM, (iii) definition of coding procedures, (iv) coding the cells of the JEM. This last stage used a method derived from the DELPHI method. Throughout the study period 1945-1994. 320 job-periods and 21 agents were defined. A quantitative assignment (level 0 to level 9) along with a frequency code (1 to 3) was attempted for 4 agents, whereas only a qualitative assignment (non exposed/exposed, i.e. 0/l) was done for the other agents. An additional probability code (1 to 3) was assigned to all agents. This procedure led to 46 columns and 14,720 cells in the JEM. When applying the DELPHI method, the consensus of the committee was obtained for 85% of all cells after the first individual assignment of experts, 88% after the second individual assignment and 100% after the third assignment by the experts all together. In order to validate the JEM, these expert assignments will be brought together with the results of exposure measurements that were performed in some workplaces of these factories. The JEM will also be linked with the data base of the case-control study for the exposure assessment of cases and controls.

Case-Control Studies

Characterization of F18 fimbrial genes fedE and fedF involved in adhesion and length of enterotoxemic Escherichia coli strain 107/86.

Infection of susceptible weaned pigs with oedema disease strains of E. coli is associated with bacterial adhesion to the small intestine. F18 fimbria (previously named F107) was the first colonisation factor described on oedema disease strains, and its genetic determinant was cloned. In the present study, genes fedE and fedF were positioned in the F18 gene cluster, downstream of the major structural subunit gene fedA. Two fedE and two fedF mutants were identified that had lost their capacity to adhere to isolated porcine villi. Moreover, these mutants produced significantly longer fimbriae. In vitro adhesion tests, electron microscopy study, transcomplementation tests, and nucleotide sequence analysis indicated that proteins FedE and FedF are F18 minor subunits essential for fimbrial adhesion and effecting fimbrial length.

Bacterial Adhesion

Airflow obstruction in chalkpowder and sugar workers.

Our aim was to investigate the relationship between suspected occupational hazards and airflow obstruction in industrial workers. The study was a cross-sectional survey of 314 male workers from a chalkpowder plant (n = 158) and from a sugar refinery (n = 156). Occupational exposure to chalkpowder and sugar dust was assessed by individual job classification. Outcome variables included respiratory symptoms and routine spirometric parameters. Statistical analysis was done for each industry separately. Overall, mean pulmonary function parameters fell either within or above the normal range in both industries. However, analysis by job classification showed that in the chalkpowder plant, all indices of airway obstruction declined significantly with increasing dustiness. Additionally, workers in the dustiest workplace (chalk sacking) had significantly lower airflow parameters than workers from other workstations. In the sugar refinery, workers exposed to sugar dust in the sugar cube manufacture workstation had significantly lower forced expiratory volume in 1 s (FEV1) (p = 0.02) than the non-exposed ones. For both industries, the proportion of subjects complaining of cough and/or phlegm was greater among the most exposed subgroups than among the remaining workers but the differences were not statistically significant. In conclusion, coupling spirometry to job classification proved useful in disclosing a relationship between airflow obstruction and exposure to either chalkpowder or sugar dust in industrial workers.

Adult

Helper virus-free transfer of herpes simplex virus type 1 plasmid vectors into neural cells.

Herpes simplex virus type 1 (HSV-1) plasmid vectors have promise for genetic intervention in the brain, but several problems caused by the helper virus have compromised their utility. To develop a helper virus-free packaging system for these vectors, the DNA cleavage/packaging signals were deleted from a set of cosmids that represents the HSV-1 genome. Following cotransfection into cells, this modified cosmid set supported replication and packaging of vector DNA. However, in the absence of the DNA cleavage/packaging signals, the HSV-1 genome was not packaged, and consequently vector stocks were free of detectable helper virus. In the absence of helper virus, the vectors efficiently infected rat neural cells in culture or in the brain with minimal cytopathic effects. beta-galactosidase-positive cells were observed for at least 1 month in vivo, and vector DNA persisted for this period. This system may facilitate studies on neuronal physiology and potential therapeutic applications.

Animals

Airway responsiveness, respiratory symptoms, and exposures to soluble oil mist in mechanical workers.

OBJECTIVES: To assess the relation between measured levels of exposure to soluble oil mists in a plant manufacturing ball bearings, and both respiratory symptoms and airway responsiveness in the workforce. METHODS: 114 male workers exposed to oil mist and 55 unexposed male controls from nearby factories were studied. Soluble oil mist concentrations were measured with area samplers. Respiratory symptoms were assessed by questionnaire and measurement of airway responsiveness to methacholine with an abbreviated method. Subjects were labelled positive to methacholine airway challenge (MAC+) if forced expiratory volume in one second (FEV1) fell by > or = 20%. The linear dose-response slope was calculated as the percentage fall in FEV1 at the last dose divided by the total dose given. RESULTS: Geometric mean concentrations of oil mists ranged from 0.65 mg/m3 (GSD 1.29) to 2.20 mg/m3 (GSD 1.55) based on 92 measurements obtained from 1979-93. The prevalence of chronic cough or phlegm, bouts of bronchitis, and dyspnoea was greater among exposed workers than among controls (odds ratio (OR) 4.64, P = 0.002 for chronic cough and phlegm). After adjustment for smoking and age, dyspnoea was significantly related to an index of cumulative exposure to oil mist (OR 1.44, P = 0.006/10 y.mg/m3). The proportion of MAC+ subjects was similar in the two groups. However, after adjustment for baseline FEV1 and age, the dose-response slope was significantly steeper among exposed workers than among controls (P = 0.01), a finding indicating airway hyperresponsiveness in the exposed workers. Furthermore, the dose-response slope was significantly related to baseline FEV1, age, and, after adjustment for FEV1, the index of cumulative exposure to oil (P = 0.004). CONCLUSION: Subjects with exposure to soluble oil mist in the metal industry are at risk of developing both respiratory symptoms and airway hyperresponsiveness.

Aerosols

Mammalian parathyroids: morphological and functional implications.

Fixation with aldehydes is achieved either by immersion or perfusion. The parenchyma of parathyroid glands fixed by immersion consists of dark cells containing a lot of membranes of these organelles which are concerned with hormone secretion, light cells which are poor in these organelles, intermediate forms between the two, and multinuclear syncytial cells. They have been attributed to represent different functional stages of secretory activity, the dark cell being in an active form, the light cell in a resting form. Studies of the parathyroids of mice, rats, rabbits, cats, dogs, pigs, cattle, sheep, goats, and horses employing various fixation protocols clearly demonstrate that light cell variants and multinuclear syncytial cells are formed during improper immersion fixation as a result of membrane disintegration. Parathyroids fixed by perfusion or by immersion in an appropriate fixation medium comprise only one cell type which correspond to the dark chief cell. Parathyroid cells are polar cells bearing some of the rough endoplasmic reticulum in the basal pole, the rest of it, the Golgi complex, and secretory granules in the apical pole. The secretory product is released by exocytosis at the apicolateral domain of the plasma membrane into the intercellular space. Secretory activity can be altered experimentally, leading to drastic changes in the amount of cell membrane related to hormone synthesis, intracellular transport, exocytic release, and secretion coupled membrane retrieval. The sensitive reaction of parathyroid cells to both the mode of fixation and to fixation media demands careful evaluation of the fixation protocol. This and the polarity of parathyroid cells have to be borne in mind for estimating secretory activity on the basis of morphological criteria.

Animals

The biological significance of storage granules in rat parathyroid cells.

Both prosecretory and storage granules are concomitantly formed at the trans Golgi network including the innermost Golgi cisterna. Prosecretory granules develop into small secretory granules that release their contents by exocytosis finely regulated by a complex mechanism for maintaining calcium homeostasis. In the rat parathyroid cells, storage granules are large secretory granules storing parathyroid hormone for an emergency supply. The hormone is rapidly discharged by exocytosis when serum calcium concentration is decreased. The granules are constantly produced even under conditions of low serum calcium concentration in the regions of 8 mg/dl. The granule content is constantly hydrolyzed when not discharged, leading to a decreased core and finally to the formation of vacuolar bodies. The fate of the vacuolar bodies is unknown. Hypercalcemic conditions accelerate hydrolysis. The threshold value of calcium concentration required for the release of storage granule contents is between 8.0 and 7.5 mg/dl and that of calcium concentration for accelerating degradation of storage granules is about 11.5 mg/dl. Sympathetic stimulation causes storage granules to be discharged regardless of hypercalcemia or hypocalcemia. Parasympathetic stimulation accelerates hydrolysis. The degradation of storage granules seems to be closely associated with an intracellular regulatory mechanism for parathyroid hormone secretion.

Adrenergic beta-Agonists

Respiratory symptoms, ventilatory impairment, and bronchial reactivity in oil mist-exposed automobile workers.

Studies concerning the respiratory effects of oil mists are sparse and contradictory. The aim of this study was to determine the respective effects of occupational exposure to straight cutting oils and soluble mineral oils on the prevalence of respiratory symptoms, ventilatory impairment, and bronchial reactivity. The population study consisted of 308 male workers of a large French car-making plant, including 40 subjects chronically exposed to straight cutting oils (group S), 51 subjects chronically exposed to soluble mineral oils (group E), 139 subjects with chronic dual exposure to straight cutting oils and soluble mineral oils (group D), and 78 unexposed assembly workers used as a control group (group C). Worker evaluation included a standardized questionnaire, measurement of pulmonary function, and a methacholine challenge. Oil mist concentration at the work place was determined by gravimetric analysis. The arithmetic mean concentration was 2.6 +/- 1.8 mg/m3. The geometric mean concentration was 2.2 +/- 1.9 mg/m3. The prevalence of respiratory symptoms did not differ significantly among the four groups. However, the subjects exposed to straight cutting oils (group S + group D) had a significantly higher prevalence of chronic cough and/or phlegm than the others (group E + group O): 25.7% vs. 16.3% (p = 0.048). Furthermore, the prevalence of cough and/or phlegm increased significantly (p = 0.03) with increasing duration of exposure to straight cutting oils after adjustment on smoking categories. Lung function tests did not differ significantly among the four groups but we observed a significant decrease of forced expiratory volume in 1 sec (FEV1), forced expiratory flow during the middle half of forced vital capacity (FEF25-75), and maximal flow rate at 50% and 25% of exhaled forced vital capacity (V50 and V25) according to duration of exposure among smokers exposed to straight cutting oils, suggesting a synergistic effect of tobacco and insoluble oils. No effect of exposure to mineral oils on bronchial reactivity was demonstrated. It is concluded that despite low levels of pollution by oil mists, the present study has shown tenuous adverse chronic effects of straight cutting oils on respiratory symptoms and lung function. However, no adverse effect of soluble mineral oils was demonstrated. These results suggest that threshold limit values for mineral oils should be reassessed.

Adult