Lung retention of cerium in humans.

A retrospective study was conducted to evaluate lung retention of particles containing cerium in subjects with and without previous occupational exposure to mineral dusts. Analytical transmission electron microscopy was performed on 459 samples of bronchoalveolar lavage (BAL) fluid and 75 samples of lung tissue. Study of the distribution of mineralogical species in human samples showed that particles containing cerium were encountered in less than 10% of subjects. The proportion of subjects with particles containing cerium in their biological samples was not different between controls and subjects with previous occupational exposure to fibrous or nonfibrous mineral dusts. This was considered as the background level of lung retention of cerium in the general population. By contrast, determination of the absolute concentration of particles containing cerium in BAL fluid and lung tissue samples showed that 1.2% (from BAL fluid) and 1.5% (from lung tissue) of subjects with previous exposure to mineral particles had high lung retention of particles containing cerium. This study is believed to be the first one in which lung retention of cerium was estimated in the general population.     

High allele loss rates at I7q I2-q2I in breast and ovarian tumors from BRCAI-linked families

Loss of heterozygosity (LOH) was evaluated in 174 breast and ovarian tumors derived from 94 families with at least 3 first-degree relatives affected with either of these cancers. By linkage analysis 26 families were identified as having a high posterior probability of being due to BRCAI (the breadovarian cancer susceptibility locus on 17q 12–21) with lod scores varying from 0.5 1 to 9.49. Tumor genotypes were determined at at least 2 constitutionally heterozygous markers flanking BRCA I in a total of 58 tumors from these families. These tumors were derived from 52 patients, the BRCAI mutation carrier status of which was evidenced by DNA sequencing in 20, and inferred by reconstructing haplotypes in the remainder. LOH was detected in 50 (86%) tumors. and invariably involved the wild-type allele. Where informative, this allele was of paternal origin in 33 cases and of maternal origin in I0 cases. These results strongly suggest that BRCA I is a tumor suppressor gene and that LOH is greatly favored to fully inactivate it. © 1995 Wiley-Liss, Inc.     

Leaching of chrysotile asbestos in human lungs: Correlation with in vitro studies using rabbit alveolar macrophages

The chemical microanalysis of chrysotile fibers obtained from human lungs and from chrysotile phagocytosed in vitro by rabbit alveolar macrophages (AM) was carried out with the use of an energy dispersive spectrometer mounted on a scanning electron microscope (SEM). This microanalysis was compared to natural fibers in order to investigate the chemical stability of chrysotile in biologic residence. The Mg versus Si content was estimated by the ratio of the peaks intensity Si:Mg. Lung samples were obtained from workmen with definite asbestos exposure, and chrysotile asbestos was extracted by chemical digestion. Phagocytosed chrysotile fibers were obtained after incubating standard chrysotile (A UICC) with rabbit alveolar macrophages for 24 hours or 5 days. Both chrysotile fibers from human lungs and from in vitro incubation with AM have shown an increase of the Si:Mg ratio in respect to standard fibers. Moreover, the results have shown that the magnesium leakage was not constant along the fiber axis and was different from one fiber to another.     

In vitro reactivity of alveolar macrophages and red blood cells with asbestos fibres treated with oxalic acid, sulfur dioxide and benzo-3,4-pyrene

The effects of 3 UICC asbestos fibres (A chrysotile, crocidolite, amosite) were observed in vitro on red blood cells (RBC) and alveolar macrophages (AM). THe reactivity of the fibres after leaching with 0.1 N oxalic acid or adsorption of SO2 or benzo-3,4-pyrene (BP) was studied. The haemolytic activity of crocidolite and amosite was very low. A cytotoxic effect on AM occurred when the fibres were present in high concentration (100 microgram/ml), this was characterized by a release of both cytoplasmic (LDH) and lysosomal (beta-galactosidase) enzymes. The leached fibres were more haemolytic than the unleached ones, and more beta-galactosidase (beta-Gal) than lactic dehydrogenase (LDH) was released from the AM. In contrast to the amphiboles, chrysotile fibres were highly haemolytic and induced a selective release of beta-Gal from AM. Leached fibres were less haemolytic and were cytotoxic for AM (both enzymes were released). Their in vitro reactivity was similar to that observed with quartz. The results showed that SO2 changed the reactivity very little. BP sorption on acid-leached chrysotile decreased the LDH release from AM. The difference in the in vitro reactivity related to the chemical state of asbestos fibres might explain the difference in their in vivo reactivity (latency, degree of fibrosis). This point is discussed.     

Effect of chrysotile and crocidolite on the morphology and growth of rat pleural mesothelial cells

The effects of the UICC asbestos fibers chrysotile A and crocidolite on the morphology and growth of rat pleural mesothelial cells were examined. The response was different according to the fiber used. Within 4 hr of treatment with 5, 10, 20, or 50 micrograms/ml of chrysotile fibers, cell morphology showed intense vacuolization, in both logarithmic and confluent cells. Following treatment of growing cells with 20 or 50 micrograms/ml of chrysotile fibers, cell spreading was also observed. Four hours after treatment of cells with 5, 10, or 20 micrograms/ml of crocidolite fibers, no such changes were seen. Vacuolization appeared later and was much less marked than for chrysotile fibers. The mesothelial cell population-doubling time of about 30 hr was not significantly altered by addition of 5 to 20 micrograms/ml of crocidolite fibers, but a concentration of 50 micrograms/ml lengthened doubling time to about 90 hr. Treatment with 5 or 10 micrograms/ml chrysotile fibers usually prolonged this time, but 20 or 50 micrograms/ml caused cell lysis. After 48 hr of incubation with both types of fiber, the proportion of mitosis was the same as in control cultures, whatever the fiber concentration, and asbestos fibers were often seen inside dividing cells.     

Particle size study of nine metered dose inhalers, and their deposition probabilities in the airways

This study deals with the particle size measurement of nine aerosol metered dose inhalers. Calibration was made possible by the use of a laser particle velocimeter (aerodynamic Particle Sizer from TSI). The count median aerodynamic diameters (CMAD) show little variation, from 0.63 to 0.73 micron, with standard deviations (sigma g) between 1.2 and 1.8. Aerodynamic diameter aerosol diagram analysis showed multimodal mass distribution for all the tested dose inhalers. Calculations for the airway deposition probabilities (extrathoracic, tracheobronchial and alveolar) refer to the studies made by W. Stahlhofen and co-workers. As most aerosol metered dose inhalers have a predominantly bronchial therapeutic destination, the deposition at the bronchial level could be enhanced with the following parameters: inspired volume of 1500 ml, inspiratory time of 2 sec, aerosol mass median aerodynamic diameter (MMAD) of 7.5 microns, with a monodispersed distribution. The respective influences of the excipients and propellents used for the aerosolization of these dose metered inhalers are also discussed.     

Spontaneous hemolytic activity of rat alveolar lining material

During assays of the complement hemolytic activity in lavage fluids (LF) from humans and various laboratory animals (hamsters, rabbits, rats, guinea pigs), we have observed that rat bronchoalveolar lavages had a spontaneous, complement-independent, hemolytic activity to sheep red blood cells (SRBC). Rat lavage fluids were able to lyse sheep and autologous red blood cells at 2 degrees C as well as at 37 degrees C. Together with these observations, the inverse relationship that existed between the LF hemolytic activity and the calcium concentration in the incubation medium suggested that lysis could be due to the presence of large amounts of lysophospholipids in rat lavage fluid. However, thin layer chromatography did not reveal any abnormal amount in lysoderivative, whereas the free fatty acid (FFA) content was very high. Pure palmitic acid, at a concentration similar to that observed in LF from rat, was able to lyse SRBC (8.5 micrograms lysed 50% of 10(8) SRBC); lytic activity decreased when Ca++ or bovine serum albumin was added to the incubation mixture. FFA through their detergent effect, appear to account for the hemolytic activity of the rat alveolar lining material.     

Parenchymal, bronchiolar, and bronchial measurements in centrilobular emphysema: Relation to weight of right ventricle

Measurements of lung parenchyma, membranous bronchioles, and bronchial mucous gland hyperplasia were made on lungs from eight cases of pure centrilobular emphysema (CLE) and on five normal lungs. The lungs were fixed in formalin and inflated under partial vacuum at a standard transpulmonary pressure of +30 cm. H₂O. The results obtained from the upper halves and the lower halves of the lungs were compared. The circulatory effects of the disease were measured by weighing the heart ventricles, by studying the small pulmonary arteries in microscopical sections, and by post-mortem arteriography. Whereas the parenchymal and internal surface areas destroyed by the emphysematous spaces were relatively moderate and localized, right ventricular hypertrophy was noted in most of the cases. In these cases bronchiolar stenoses were found scattered throughout the whole lung and there was a reduction in the number of these bronchioles, mainly in the upper halves of the lungs. In CLE ventilatory disturbances were caused not only by the centriacinar dilated spaces delaying gas diffusion, but also by scattered bronchiolar stenoses situated at the termination of the conducting air passages. The stenoses seemed the more important cause. It was shown statistically that chronic arterial pulmonary hypertension and right ventricular hypertrophy were mainly the result of functional disturbances, especially hypoxia and abnormalities of VA/Q produced by the two structural changes situated at the end of the small airways.     

Ultrastructural examination of broncho-alveolar lavage for diagnosis of pulmonary histiocytosis X: Preliminary report on 4 cases.

Fibreoptic broncho-alveolar lavage was used in four patients; the diagnosis of histiocytosis X had been established by lung biopsy in three and was suggested on clinical grounds in the remaining patient. Characteristic cells with an ultrastructural cytoplasmic marker (X body) were found in the washes of all four patients. In the patient without biopsy confirmation, the findings in the broncho-aleolar washes supplied the corroborating evidence for the diagnosis. From this preliminary study the technique seems able to provide a diagnosis in pulmonary histiocytosis X without the need for an open lung biopsy.