[Etiology, epidemiology, biology. Occupational respiratory cancers]. / Cancers respiratoires professionnels.

Lung cancer and pleural mesothelioma are the most common occupational cancers. Recent epidemiological studies have estimated that the fraction attributable to occupational factors varies from 13 to 29% for lung cancer in men and is about 85% for pleural mesothelioma in men. Previous occupational exposure to asbestos is the most common occupational exposure in these cancers. Mesothelioma immediately leads the clinician to look for past asbestos exposure. In contrast, the search for an occupational exposure that should be routine in all cases of lung cancer, is generally more difficult because of the number of occupational aetiological factors and the absence of criteria that allow distinction of an occupational cancer from a tobacco related one. Therefore attention should be paid to the identification of occupational exposure in order to set up primary prevention programmes to prevent exposure still present in the working environment and, on the other hand, to identify the subjects entitled to the acknowledgement of occupational disease and/or to obtain the compensation available to asbestos victims.

[Occupational respiratory cancers]. / Cancers respiratoires professionnels.

Lung cancer and pleural mesothelioma are the most common occupational cancers. Recent epidemiological studies have estimated that the fraction attributable to occupational factors varies from 13 to 29% for lung cancer in men and is about 85% for pleural mesothelioma in men. Previous occupational exposure to asbestos is the most common occupational exposure in these cancers. Mesothelioma immediately leads the clinician to look for past asbestos exposure. In contrast, the search for an occupational exposure that should be routine in all cases of lung cancer, is generally more difficult because of the number of occupational aetiological factors and the absence of criteria that allow distinction of an occupational cancer from a tobacco related one. Therefore attention should be paid to the identification of occupational exposure in order to set up primary prevention programmes to prevent exposure still present in the working environment and, on the other hand, to identify the subjects entitled to the acknowledgement of occupational disease and/or to obtain the compensation available to asbestos victims.

Reactive airways dysfunction syndrome caused by bromochlorodifluoromethane from fire extinguishers.

Although the neurological and cardiovascular effects of Freons have been extensively described, the respiratory effects have been less well documented. We report four cases of occupational asthma following accidental exposure to bromochlorodifluoromethane (Halon 1211) due to release of the contents of a fire extinguisher. All subjects developed an irritative reaction of the upper airways and lower respiratory symptoms immediately after exposure. Non-specific bronchial hyperreactivity was present for at least two months in all subjects and was still present more than two years after exposure in one case. The diagnosis of reactive airways dysfunction syndrome can be adopted in at least three of these four cases.

Healthy worker effect and changes in respiratory symptoms and lung function in hairdressing apprentices.

AIMS: To compare the prevalence and incidence of respiratory symptoms and lung function values between hairdressing apprentices and office apprentices. METHODS: A total of 322 hairdressing apprentices and 277 office apprentices (controls) were studied. Two cross sectional surveys were conducted in 1994 and 1996/97 with longitudinal follow up for a subgroup of apprentices (191 hairdressing apprentices and 189 office apprentices). RESULTS: In the initial phase, the prevalence of respiratory symptoms was significantly lower among hairdressing apprentices than among office apprentices. Lung function test results showed significantly higher values for hairdressing apprentices. Non-specific bronchial reactivity was similar in the two groups. In the final phase, results for respiratory symptoms were similar. The incidence of respiratory symptoms was not significantly different between hairdressing apprentices and office apprentices. Subjects who dropped out had lower values for FVC and FEV1 in the initial phase than those who completed the final phase. There was a significant deterioration of FEV1 and FEF25-75% in hairdressing apprentices compared to office apprentices. There was a link between atopy and the incidence of most of the respiratory symptoms (day/night cough, wheezing, dyspnoea, mucosal hyperresponsiveness) and between smoking and the incidence of bronchial hyperreactivity. There was no significant correlation between change in lung function tests and specific hairdressing activities reported at the end of the apprenticeship or with environmental working conditions in hairdressing salons. CONCLUSIONS: Although a healthy worker effect can be suspected, results showed a significant deterioration of baseline values of lung function tests in the hairdressing apprentice group. However, no clear link was shown between change in lung function tests and specific parameters of occupational activities.

Estimation of the incidence of pleural mesothelioma according to death certificates in France.

BACKGROUND: The number of cases of pleural mesothelioma in France has varied substantially according to methods of assessment. MATERIALS AND METHODS: We collected information from certifying physicians about 316 subjects who died between 1 July 1992 and 30 June 1993 in three regions of France with a cause of death coded as ICD-9 category 163. The ICD codes selected as the cause of death for 178 deaths between 1 January 1987 and 31 December 1992 histologically confirmed and diagnosed as pleural mesothelioma by an expert committee were examined. Finally, we used this information to estimate the number of deaths from pleural mesothelioma in France in 1992. RESULTS: In Part I, 45% (men: 54%; women: 28%) of the cases coded as ICD-9 section 163 were definitely or probably mesothelioma; 18% (men: 16%; women: 21%) possibly mesothelioma; and 37% (men: 30%; women: 51%) other tumors, primarily adenocarcinoma metastases. In Part II, 74% of the confirmed pleural mesotheliomas were coded in category 163 (men: 75%; women: 70%). Extrapolation nationwide indicated that 902 deaths were coded as ICD-9 163 in 1992: 521 cases involved definite or probable mesothelioma and 724 definite, probable, and possible cases. CONCLUSIONS: The analysis of this sample suggests that estimating the number of mesothelioma cases from the cause-of-death statistics may overestimate their incidence, but that death certificates appeared to report the diagnosis of histologically confirmed mesothelioma accurately.

Role of urokinase in the activation of macrophage-associated TGF-beta in silica-induced lung fibrosis.

Since tumor growth factor beta (TGF-beta) and its receptor are ubiquitously expressed and because latent TGF-beta cannot bind to the cell surface receptor, the ability of a cell to activate latent TGF-beta upon secretion represents an important regulatory mechanism of TGF-beta action. In vivo, the protease plasmin is considered to be one of the main enzymes operative in the proteolytic cleavage of the latency-associated peptide moiety from TGF-beta, which converts it into the biologically active form. The TGF-beta response was characterized in alveolar macrophages during pulmonary inflammation (d 3) and fibrosis (d 120) induced by a single intratracheal instillation of silica particles (5 mg/mouse). To appreciate the role of urokinase-type plasminogen activator (uPA) in the activation of TGF-beta, the production of total, active and latent TGF-beta by explanted alveolar macrophages was compared in uPA-deficient (uPA-/-) mice and their normal counterparts (uPA+/+). At d 3 and 120 after silica treatment, a significant increase in cell-associated PA activity was found in uPA+/+ mice compared to that of saline controls. As expected, this response was almost totally absent in uPA-/- mice. Alveolar macrophages from uPA+/+ controls were found to release TGF-beta mainly expressed in a biologically active form. In response to silica treatment, inflammatory cells were found to upregulate, especially at the fibrotic stage, their secretion of total and bioactive TGF-beta. No significant difference was found between uPA-/- and uPA+/+ silica-treated animals for the expression of total, active, or latent TGF-beta. Although it has previously been reported that macrophage surface activation of TGF-beta is dependent on both plasmin generation and uPA cell surface receptor, no evidence was found to support this hypothesis in the present study.

Modulation by palmitoyl-carnitine of calcium activated, phospholipid-dependent protein kinase activity and inhibition of melanoma cell growth.

Phospholipid-sensitive, Ca++-dependent protein kinase activity was investigated in the cytosol of melanoma cells. A protein kinase system was partially purified, and enzyme activity was found to be modulated by palmitoyl-carnitine. In order to link the actions of palmitoyl-carnitine on phospholipid-sensitive protein kinase activity and the already reported role of protein kinase C in cell division, we studied the action of palmitoyl-carnitine on melanoma cell growth by measuring colony forming ability in a soft agar culture system. Palmitoyl-carnitine was found to inhibit cell growth in a dose-dependent manner. These findings suggest that palmitoyl-carnitine (or long-chain acylcarnitine), a naturally occurring metabolite, may play a key role in the onset of cell division. We suggest that the action of palmitoyl-carnitine on phospholipid-dependent protein kinase activity is in part related to the molecular events linking protein kinase C activity and the ionic events in the initiation of cell growth.

Hyperthermia inhibition of tumor cells growth in the presence of ruthenium red.

Ruthenium red (RR) is taken up by DS sarcoma cells as a linear function of its concentration. Higher temperatures produce a higher uptake. This increased uptake is coincident with an augmentation of Trypan blue inclusion. A diminution of calcium transport in the presence of RR is observed at hyperthermia, and its uptake is not linear but presents a plateau for all temperatures and concentrations. RR-cell membrane interaction seems to produce two different effects: an early blocking of calcium transport, and a later change of the physicochemical characteristics of the plasma membrane. On the colony forming ability of CA1 cell RR shows clearly an intrinsic toxic effect, and when present during hyperthermia a low but significant enhancement of tumor cells mortality.

Effects of methylazoxymethanol given at different stages of postnatal life on development of the rat brain. Comparison with those of thyroid deficiency.

Newborn rats were treated at different stages of their development with low doses of methylazoxymethanol acetate. The postnatal increase of the DNA content of the cerebrum did not differ from that of controls. In the cerebellum, the DNA content was transitorily reduced, but later, the external granular layer became thicker and DNA deposition increased in comparison with controls; finally, the cerebellar DNA returned to a normal value. Morphological abnormalities of the cerebellum, abnormal orientation of migrating cells, scattering of Purkinje cell bodies within the internal granule cells and specially striking abnormalities of the morphology and orientation of Purkinje cell dendrites were noted in rats treated with MAM from birth to day 3. The effects of the Purkinje cell morphogenesis persisted but were much less marked when MAM was given from 4 to 7 or from 8 to 11 days. Neonatal thyroid deficiency, as MAM-treatment between days 0 and 3, leads to an abnormal position of Purkinje cell bodies within the cerebellar cortex; it also leads to morphological abnormalities of their dendritic arborization which closely resemble those observed after MAM-treatment during the second postnatal week. It also alters the cell formation in the cerebellum. Thyroid deficiency probably exerts its effect on cell formation earlier than previous biochemical studied have shown. On another hand, the morphological abnormalities of Purkinje cell arborizations in the thyroid-deficient animals may be partly due to the perturbations of cell formation which persist later in the cerebellum.

Effects of undernutrition on cell formation in the rat brain and specially on cellular composition of the cerebellum.

In 35-day-old rats which were undernourished by quantitative restriction of the mother's diet from the 6th day of gestation, the wet weight and the DNA content of the cerebellum were slightly more decreased than those of the cerebrum. Cell growth (estimated from the DNA concentration and form the ratios of RNA and protein to DNA) was significantly affected by food deprivation only in the cerebellum. In the cerebullar cortex, the number of Purkinje, Golgi and stellate cells were unchanged. The numbers of other cell tyes were affected to various extents: there were significantly less granules and basket cells per Purkinje cell, and a still more marked hypoplasia of glia involving the glial cells of the molecular layer, as well as the astrocytes of the internal granular layer and the Bergmann cells of the Purkinje cell layer. Finally, the total number of glial cells within the cortex was decreased by 44% against 13% for neurones. These effects of undernutrition on cell acquisition within the brain, and on the cellular composition of the cerebellum, contrast with those of thyroid deficiency.

Thyroid hormone and cell formation in the developing rat cerebellum.

Effects of neonatal hyperthyroidism on cell formation in the developing rat cerebellum were reinvestigated. Administration at birth of excessive doses of thyroxine or triiodothyronine led to an early stimulation of cell acquisition, followed by a permanent deficit of cells in the cerebellum. The corrective effects of physiological doses of thyroxine on the troubles of the histological and biochemical development of the cerebellum in thyroid-deficient animals were also studied. As early as 6 days, cell maturation and formation were already retarded in animals treated with propylthiouracil, but, as previously reported, cell formation was prolonged and the final number of cells was normal. Administration to thyroid-deficient animals of progressively increasing doses of thyroxine, nearly equal to the amounts of hormone secreted by the thyroid gland of the developing normal rat, returned the evolution of the cerebellar wet weight and of the cerebellar DNA to normal, as well as the histological maturation of the cerebellum, even if it did not entirely correct the retardation of body growth. These results are consistent with the view that thyroid hormone early stimulates maturation of the cerebellar germinative cells and subsequently interacts with cell formation in the cerebellum, and that this action is physiological.

[Effect of cortisol on the cellular proliferation and maturation in the cerebrum and the cerebellum of the rat: Importance of the age of the animals at the beginning of treatment]. / Effets du cortisol sur la prolifération et la maturation cellulaires dans le cerveau et le cervelet du Rat: Importance de l'âge des animaux au début du traitement

Young rats were given either a single subcutaneous injection (1 mg at 0, 1, 4 or 8 days), or four consecutive daily injections (0.2 mg/day between 0 and 3 days; 0.4 mg/day between 4 and 7 days; 0.6 mg/day between 8 and 11 days) of cortisol acetate in order to test the influence of age on the action of corticosteroids on the biochemical maturation of the cerebrum and cerebellum in terms of their DNA, RNA, and protein contents. The results showed that: 1 The diminution of the DNA content at 35 days was greater in the cerebellum (- 16 to - 32%) than in the cerebrum (- 9 to 20%); the DNA content of the cerebrum was more affected by treatment at birth, whereas that of the cerebellum was more affected by the delayed treatments. Results were different when expressed in terms of reduction of the normal increase: the gain of DNA decreased more in the cerebrum (-70%) than in the cerebellum (-40%); but the most delayed treatment induced a greater effect in both organs. These abnormalities were not always accompanied by a significant decrease of the body weight. 2 Generally, the treatments led to an increase of the mean cell territory, expressed either in terms of decrease of the DNA concentration, or in terms of increase of the organ weight/DNA ratio. Moreover, the increase of the RNA/DNA and the protein/DNA ratios constituted an indication of an accelerated cellular maturation.