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Biomedical subjects

J Bignon

Publications and source records attributed to J Bignon.

At least 37 records · Page 2Linked to original sources
PubMed1995

Human malignant mesothelial cells: variability of ultrastructural features in established and nude mice transplanted cell lines.

The aim of this study was to determine, by transmission electron microscopy, the differentiation features of 21 human malignant mesothelioma cell lines (HMCLs) established from 13 specimens of 12 confirmed human malignant mesotheliomas, and of tumours induced in nude mice injected with 16 HMCLs. Fifty per cent of HMCLs showed typical mesothelial differentiation (long and slender microvilli, desmosomes, perinuclear intermediate filaments); 29 per cent did not show differentiation; and the remainder were poorly differentiated. Three human tumour specimens gave several different HMCLs; the cell lines obtained from a given tumour exhibited variable mesothelial differentiation. Eleven HMCLs were compared with the native tumour. Four were similar to the tumour and seven were less well differentiated, in most cases in relation to their microvilli. With six HMCLs, tumours induced in nude mice were less well differentiated than the corresponding cell lines, whereas with four HMCLs, tumours were equally or better differentiated. However, in most nude mice tumours, typical mesothelial microvilli were present. These results show that cell lines established from malignant mesothelioma may exhibit dedifferentiated features. However, while the variability in ultrastructural differentiation may result from the culture microenvironment, it could also be related to the state of differentiation, of the native tumour sample and to tumour cell heterogeneity.

Animals↗
PubMed1995

Proposal of a tiered approach to assessing and classifying the health risk of exposure to fibres.

The basis of a preventative health policy for humans against potential risks from chemical products is based on risk assessment leading to the classification and labeling of substances. However, the different existing classifications do not give an homogeneous framework that can be used in every country. Therefore, a tiered approach to assessing and classifying the health risk of exposure to fibres is proposed based on the EU Directive on carcinogens. The aim of this paper is to propose an algorithm for the risk assessment of existing and future fibres. Clearly chemically defined respirable fibres should be classified according to an algorithm based on a step-by-step procedure: a priori criteria, screening tests, long-term inhalation tests and epidemiological data (for commercial fibres). Then fibre-containing products should be labelled according to the classification of each type of fibre it contains, on one hand, and the ability of the product to release fibre in the air, on the other. The different tests listed in this algorithm, extensively discussed during the Workshop, are presented in detail in the following paper.

Carcinogenicity Tests↗
PubMed1995

Lack of evidence for a role of HLA-DP in unexplained recurrent spontaneous abortion.

Using the "Polymerase Chain Reaction-Sequence Specific Oligoprobes" (PCR-SSOp) technique, we studied the HLA-DPB locus in both partners of 59 couples with a history of three spontaneous abortions, and of 38 control couples in order to determine the role of this centromeric region of the major histocompatibility complex (MHC) in the immune reaction needed for a favorable course of pregnancy. As no particular phenotypes were noted, and also neither excessive HLA-DP homozygosity in sterile women nor excessive HLA-DP allele sharing between sterile partners, this MHC class II sub-region would seem to play no role either directly or by linkage disequilibrium, in the development of normal pregnancy.

Abortion, Habitual↗
PubMed1995

CYP2D6 genotype and lung cancer risk according to histologic type and tobacco exposure.

Polymorphism for CYP2D6 was determined genetically as part of a hospital-based case-control study. The cases were males with a histologically confirmed lung cancer diagnosis, < 75 years old, and no previous cancer diagnosis. Male controls were matched for age, hospital and residence area. This study includes 301 cases and 310 controls. A DNA bank was established for 547 patients (89.5%), and genotypes for CYP2D6 were differentiated by the Heim and Meyer method for the DNA samples of 249 cases and 271 controls. Among the cases, the frequencies of homozygous for the wild-type (EM), heterozygous (HEM) and homozygous for the mutant alleles (PM) were 62%, 32% and 7%; among the controls: 57%, 37% and 6%. Using EM as the reference, and adjusting for age, hospital and residence, we estimated the odds ratios for the HEM group and the PM group at 0.8 (95% CI [0.5-1.2]) and 1.1 (95% CI [0.5-2.4]) respectively. The PM frequency among the cases of adenocarcinoma was twice as high as among the controls (OR = 1.8, 95% CI [0.7-4.9]). This result was not observed among squamous and small cell carcinoma (OR = 0.7, 95% CI [0.3-1.8]). Twelve different case-control studies on CYP2D6 and lung cancer have so far been performed; the ORs they estimate range from 0.1 to 2.0, with a median value of approximately 0.6. This result lends some support to the hypothesis that belonging to the PM group is associated with a slight protective effect against lung cancer, but does not take into account the possibility that results may vary according to histologic type. In this context, the suggestion of a positive relationship between CYP2D6 and adenocarcinoma seems to us to merit investigation.

Adult↗
PubMed1995

Ciliary abnormalities in bronchial epithelium of smokers, ex-smokers, and nonsmokers.

Although respiratory changes induced by tobacco smoke have been extensively described, no study has focused on ciliary abnormalities associated with chronic smoking. Ciliary ultrastructure was studied in 37 adults with chronic sputum production (CSP) consisting of 13 current smokers (Group 1), 5 ex-smokers (Group 2), and 19 nonsmokers (Group 3). Five healthy nonsmokers constituted the control group (Group 4). Clinical and radiologic data and respiratory function tests were recorded. Acute respiratory infection was diagnosed by culture of tracheobronchial secretions obtained during bronchoscopy. Bronchial ciliated cells were obtained and processed for transmission electron microscopy. Within each group, the percentages of abnormal cilia were similar in patients with either chronic bronchitis or bronchiectasis and in patients with or without acute infection. The percentage of axonemal ultrastructural abnormalities (AUA) was higher in smokers (16.5% +/- 2.7%) and ex-smokers (17.5% +/- 7%) than in nonsmokers (5.2% +/- 1%) or control subjects (0.7% +/- 0.2%) (p < 0.0002). The AUA were polymorphic, characteristic of acquired ultrastructural changes. These results suggest that chronic smoking may induce an increased number of abnormal cilia which could participate in impairment of tracheobronchial clearance and which appears to be independent of the etiology of CSP.

Adult↗
PubMed1995

[Longitudinal study of radiologic anomalies in subjects working in asbestos-insulated buildings].

The respiratory effects of environmental pollution by asbestos was examined in a cohort of subjects working inside university buildings partly insulated with asbestos containing materials (University of Jussieu in Paris). The present study concerned 727 subjects having undergone two standard radiographic examinations (postero-anterior and oblique chest x-ray) in the period 1981-1992. The first examination was realized between 01/01/81 and 31/12/85 and the second examination took place between 01/01/86 and 31/12/92. The subjects were classified into three groups according to their exposure status: the group G1 consisted of 161 workers occupationally exposed to asbestos; the group G2 comprised 416 subjects working for at least 15 yr in asbestos-insulated buildings without known occupational exposure to asbestos; the group G3 consisted of 150 workers working for at least 15 yr in the university with no known exposure to asbestos. Whatever the radiological abnormalities considered, no significant difference was observed between G2 and G3 in cross-sectional analyses of the two phases. The group G1 exhibited a significantly higher prevalence of pleural thickening compared to the other exposure groups after adjustment for confounding variables. Detailed examination of oblique x-ray allowed to confirm that pleural thickening were largely due to extrapleural fat. Concerning the changes in pleural abnormalities between the two phases of the study, no difference was observed between G2 and G3. This study was unable to show any excess of radiographic chest abnormalities among subjects working in asbestos-insulated buildings compared to non-exposed subjects. However, the participation in the second phase of examination was 51.2%. The study is still on-going. Therefore, it would be necessary to continue to follow-up the subjects because respiratory disorders could occur after a long latent period.

Adult↗
PubMed1994

Intrapleural treatment with recombinant gamma-interferon in early stage malignant pleural mesothelioma.

BACKGROUND: This report presents the results of a prospective multi-institutional study of intrapleural treatment with gamma-interferon in patients with Butchart's Stages I and II epithelial or mixed malignant pleural mesothelioma. METHODS: Interferon was administered at a dose of 40 million units twice a week for 8 weeks intrapleurally via a catheter or an implantable port. Thoracoscopic or surgical biopsy was performed if computed tomography scan 2 weeks after the end of treatment demonstrated a reduction in tumor size. Survival was calculated after a follow-up of at least 18 months. Prognostic factors were identified by univariate and multivariate analyses (Cox model). RESULTS: Eighty-nine patients were included over 46 months. Eight histologically confirmed complete responses and nine partial responses with at least a 50% reduction in tumor size were obtained. The overall response rate was 20%. Most responses were achieved in patients with early stage disease. The response rate for patients with Stage I disease was 45%. Tolerance of interferon was good. Treatment was performed on an outpatient basis. The main side effects were hyperthermia, liver toxicity, neutropenia, and catheter-related infection. CONCLUSIONS: Gamma-interferon is effective mainly in Stage I mesothelioma, especially if the tumor is confined to the parietal or diaphragmatic pleura (Stage IA).

Aged↗
PubMed1994

Intrapleural production of interleukin 6 during mesothelioma and its modulation by gamma-interferon treatment.

In vivo production of monokines was analyzed in 17 human malignant pleural mesotheliomas. High concentrations of interleukin 6 (IL-6) were detected in pleural effusions, contrasting with low levels of IL-1 beta and tumor necrosis factor alpha. This production arose from malignant cells, as shown by immunochemical analysis of pleural cells and by production of IL-6 by mesothelial cell lines. Intrapleural administration of recombinant human gamma-interferon to six patients led to a marked decrease in intrapleural IL-6 concentrations in all cases. This treatment was associated with in situ activation of macrophages and cytotoxic T-lymphocytes, as indicated by increased intrapleural neopterin and soluble CD8 concentrations. In vitro gamma-interferon had no effect on the production of IL-6 by mesothelial cell lines but decreased the growth of 3 of 6 mesothelioma cell lines. These results indicate that systemic manifestations of malignant mesothelioma, including fever, cachexia, and thrombocytosis may be related to the production of IL-6 by malignant cells, and that local gamma-interferon infusion may reduce this production by stimulating antitumoral immunity and/or by directly decreasing the proliferation of malignant cells.

Biopterins↗
PubMed1994

Retention of asbestos bodies in the lungs of welders.

Examination of asbestos bodies (AB) retained in the lungs is a useful way of assessing past occupational exposure to this material. AB retention has been extensively studied in workers directly exposed to asbestos, but less so in those end users, such as welders, who use asbestos-containing products. We therefore retrospectively studied AB retention in 211 welders, for whom biological testing procedures had been requested by a chest physician, between 1988 and 1991. Optical microscopy of AB was performed on samples of sputum (40 subjects), bronchoalveolar lavage fluid (BAL) (147 subjects), and lung tissue obtained after thoracotomy (38 subjects). Information on previous jobs and exposure was obtained using a questionnaire (the mean duration of welding activities was 16.6 years). Eighty-two subjects (38.9%) had elevated lung retention of AB in all the samples studied. Significant AB retention occurred in only 30% of sputum samples, but in 40.1% of BAL samples and 39.5% of lung tissue samples. The duration of welding activities correlated with the density of AB in BAL or lung tissue (r = 0.31, p < 0.01 and r = 0.49, p < 0.05, respectively). On the basis of the questionnaire, only two of the welders with significant AB retention had other occupational exposure to asbestos. Our findings suggest that welding activities may increase lung retention of AB, and consequently might produce higher risks of fibrotic and/or malignant pulmonary diseases. These potential risks need to be brought to the attention of doctors; a longitudinal follow-up may also be warranted in such populations, even after individuals have ceased their welding jobs.

Asbestos↗
PubMed1994

Pleural mesothelioma: a descriptive analysis based on a case-control study and mortality data in Ile de France, 1987-1990.

Incidence rates of pleural mesothelioma in Ile de France were examined for the period 1987-1990, on the basis of information collected in a case-control study. This study was designed to include all new cases of pleural mesothelioma occurring in the region. On the other hand, mortality rates from pleural malignancies in the same region were examined on the basis of death certificates recorded by INSERM for the same period. A large difference was found between the two types of data. Average annual incidence rates were 7.5 per million among men and 1.6 per million among women. Average annual mortality rates due to primary pleural malignancies were 25.2 per million in males and 8.9 per million in females. This study confirms discordances between incidence and mortality data for pleural malignancies already reported in several countries. However, contrasting with some previous reports, the annual mortality rate from pleural malignancies was higher than the incidence rate of mesothelioma in this study. This emphasizes the usefulness of a specific investigation to explain such discordances, prior to comparison of data from one country to another.

Adult↗
PubMed1994

Pleural plaques, asbestos exposure, and asbestos bodies in bronchoalveolar lavage fluid.

The profiles of occupational asbestos exposure were investigated in a series of 66 hospital patients in whom pleural plaques constituted the only asbestos-induced abnormality. The relationship between a radiological semiquantitative score of pleural plaques and indices of asbestos exposure was also examined. On the basis of a standardized occupational questionnaire, four classes of asbestos exposure were distinguished in our study population: no evidence of exposure, low-level exposure, sporadic exposure at higher levels, and a remaining group of individuals with substantial exposure. Asbestos body count in bronchoalveolar lavage fluid (BALF) was used as an objective indicator of cumulative lung retention of asbestos. Our results support the data indicating that pleural plaques may occur in subjects with low-level or sporadic asbestos exposure. Although it is admitted that pleural plaques are strongly associated with past asbestos exposure, our data suggest that the stage of pleural plaques was not correlated to the level, frequency, duration of exposure nor to the amount of asbestos bodies in the BALF in subjects free of any lung parenchymal abnormalities on high resolution computerized tomography.

Adult↗
PubMed1994

Expression of cytochrome P450 in rat pleural mesothelial cells in secondary cultures.

Cultured rat pleural mesothelial cells (RPMC) isolated from male Sprague-Dawley rats have been shown to metabolize polycyclic aromatic hydrocarbons to more oxygenated metabolites. This capacity, which is maintained with passages, suggested the presence of monooxygenase enzymes. In order to clarify the enzymatic pathway, we investigated the expression of cytochromes P450 (CYP) in cultured RPMC by Western and Northern blot analyses. Cells were cultured in Ham's F10 medium supplemented with 10% fetal calf serum. The CYP expression was studied from passage 9 to 16 on different cell strains treated for 48 hours with P450 inducers. CYP1A1 apoprotein expression was very low in untreated cells, but was markedly induced after treatment with 1 microM 3-methylcholanthrene or 22 microM beta-naphthoflavone. CYP1A1 mRNA was not detected in untreated cells and appeared after 3-methylcholanthrene treatment. CYP2E1 apoprotein was constitutively expressed in cultured RPMC, and markedly increased by 170 mM ethanol, and 0.1 microM or 1 microM dexamethasone treatments. Unexpectedly, whereas the amount CYP2E1 mRNA was not modified by ethanol treatment, dexamethasone has a marked inductive effect on CYP2E1 mRNA level. The CYP expression pattern was found similar in RPMC issued from different rats, and not dependent on passage number. The CYP expression and the detection of NADPH-P450 reductase, and of epoxide hydrolase, ascertained that RPMC contain the overall enzymatic pathway required for the biotransformation and activation of procarcinogen compounds, such as polycyclic aromatic hydrocarbons and nitrosamines. Both expression and regulation properties are maintained in long-term cultures of RPMC.

Animals↗
PubMed1994

Initial characterization of human thymocyte sialidase activity: evidence that this enzymatic system is not altered during the course of T-cell maturation.

1. The sialidase activity of human thymocyte was examined by a fluorogenic assay. 2. These studies revealed that human thymocyte sialidase activity is essentially acid-active and membrane-bound since 59.6% and 33% of the total activity was recovered in the lysosome-enriched and microsomal fractions, respectively. 3. A weak activity was also detected in the cytosolic fraction. 4. However, the acidic optimum pH of this soluble sialidase was at variance with the general concept of mammalian soluble sialidases which are known to be optimally active at more neutral pH. 5. This acidic soluble sialidase seems to be a general characteristic of the human T-cell lineage since examination of mature circulating T-cells revealed that they contain a soluble sialidase activity similar to that observed in thymocytes. 6. Analysis of mature and immature thymocyte subpopulation obtained by differential PNA agglutination indicated that this enzymatic system was not altered during the course of thymic maturation. 7. These results suggest that unlike in T-cell activation where changes in the level of sialidase activity were shown to influence the extent of cell surface sialylation and thereby the cell physiology, this enzymatic system seems not to be involved in the fluctuation of cell surface sialic acid content observed during thymic maturation.

Agglutination↗
PubMed1994

Immunocytochemical characterization of cell lines from human malignant mesothelioma: characterization of human mesothelioma cell lines by immunocytochemistry with a panel of monoclonal antibodies.

A panel of nine monoclonal antibodies was used to characterize human mesothelioma cell lines that we established from human malignant mesothelioma. The antigens detected were cytokeratin, vimentin, epithelial membrane antigen, carcinoembryonic antigen, Leu-M1 (CD15), desmin, factor VIII-related antigen (von Willebrand factor antigen), OV632, and ME1, a specific monoclonal antibody directed against human malignant mesothelioma. The technique used was the alkaline phosphatase anti-alkaline phosphatase method. All 30 cell lines, either epithelial, sarcomatous, or mixed, showed strong reactivity with cytokeratin and vimentin antibodies. None of the cell lines demonstrated any reactivity with carcinoembryonic antigen, Leu-M1, or factor VIII antibodies; moreover, all of 22 cell lines studied were positive for ME1 antibody and 10 of 12 cell lines studied were positive for OV632. Some interesting features were noted: only two of the 30 cell lines presented a weak positive staining with epithelial membrane antigen, and nine of 19 cell lines tested demonstrated a cytoplasmic staining pattern with desmin antibody. These results show that established human mesothelioma cell lines still possess the immunocytochemical characteristics that are basically consistent with the immunohistochemical features described in tumor tissues of malignant mesothelioma. These characteristics can be used to identify the mesothelioma cells grown from human malignant mesothelioma. Hence, the mesothelioma cell lines will provide a useful tool for the investigation of the cell biology of the tumor and the mechanisms of mesothelial cell transformation, as well as the in vitro evaluation of the effects of some drugs in order to develop new therapies for malignant mesothelioma.

Actins↗
PubMed1994

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.

Adult↗
PubMed1994

Pleural mesothelioma and exposure to asbestos: evaluation from work histories and analysis of asbestos bodies in bronchoalveolar lavage fluid or lung tissue in 131 patients.

Exposure to asbestos was evaluated in 131 patients with pleural malignant mesothelioma in the Paris area between 1986 and 1992 using data from a detailed specific questionnaire and light microscopy analysis of the retention of asbestos bodies in bronchoalveolar lavage fluid or lung tissue. Probable or definite exposure to significant levels of asbestos dust was identified in only 48 (36.6%) subjects, and significant asbestos body counts (above 1 asbestos body/ml in bronchoalveolar lavage fluid or 1000 asbestos bodies/g of dry lung tissue) were found in only 45 (34.3%) subjects. Overall 50 subjects had experienced exposure to only low levels of asbestos or no exposure at all and showed no significant retention of asbestos bodies in the biological sample analysed. Previous studies have shown that light microscopy may be useful in the identification of subjects with previous exposure to asbestos. In this study, apart from cases with obvious exposure to asbestos, a large group of subjects seemed to have a history of exposure or lung retention of asbestos bodies suggestive of very low levels of cumulative exposure, similar to those described in the general population.

Adult↗