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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

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

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

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

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

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

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

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

HIV-1 in human alveolar macrophages from infected patients is latent in vivo but replicates after in vitro stimulation.

It has been demonstrated that alveolar macrophages (AM) are permissive for human immunodeficiency virus (HIV-1) after in vitro infection. However, data concerning in vivo infection of AM by HIV-1 still conflict. Therefore, we investigated AM collected by bronchoalveolar lavage from 15 HIV-1-infected patients. HIV-1 p24 and Gp120 antigens and viral RNA were not detected by immunocytochemistry and in situ hybridization, respectively, using 35S-labeled 3 kb Pol-Env, 0.350 kb Gag, and 0.150 kb U5 LTR cRNA probes. In contrast, when using polymerase chain reaction on DNA extracted from purified AM, HIV-1 DNA was detected in the seven patients tested. After short-term culture of alveolar cells from three HIV-1-infected patients and in vitro stimulation with granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha), HIV-1 replication was observed in most of the AM. These results demonstrate that AM are latently infected by HIV-1 in vivo but are not a site for viral replication. In contrast, HIV-1 replication occurs when AM are withdrawn from their local environment, enhanced by GM-CSF and TNF-alpha stimulation. This suggests either a negative control or an inadequate stimulation of HIV-1 replication in the alveolar environment.

Cell Line

Biopersistence of nonfibrous mineral particles in the respiratory tracts of subjects following occupational exposure.

Transmission electron microscopy analysis (TEMA) was used to analyze the bronchoalveolar lavage fluid (BALF) of 262 subjects occupationally exposed (OE) to nonfibrous mineral particles (NFMP) and 42 controls not occupationally exposed to mineral dusts. OE subjects were divided into three groups according to the lapse of time since last exposure: < or = 1 year and < 10 years (E2), > or = 10 years (E3). The total BALF mineral particle concentration was significantly higher in OE patients than in controls and was closely related to the time lapse since last exposure to NFMP (median values for OE, 7.7 x 10(5) particles/ml; E1, 9 x 10(5) particles/ml; E2, 5 x 10(5) particles/ml; E3, 4.3 x 10(5) particles/ml; controls, 2 x 10(5) particles/ml). No statistical difference was observed for age and smoking habits between OE and control subjects. Concentrations of crystalline silica and metals (exogenous iron, aluminum, metallic alloys and other metals) were significantly higher in OE subjects than in controls, and even though these mineral concentrations decreased with increasing time since last occupational exposure, they still remained higher in the E3 group than in controls. Crystalline silica and metals were thus identified as biopersistent NFMP in the human lung using BALF ATEM method. This method is a useful tool in assessing occupational exposure to NFMP, even when a long period has elapsed since last exposure, and may be used in studying etiology of some respiratory diseases.

Adult

The occupational physician's point of view: the model of man-made vitreous fibers.

This article gives a detailed description of the procedure the occupational physician uses in interpreting the available scientific data to provide useful information for prevention of pulmonary diseases related to man-made mineral fibers, particularly lung cancer and mesothelioma. As it is difficult to reach definite conclusions from human data on the toxicity of specific fibers, an experimental approach is needed. Concerning animal data, we emphasize that adequate inhalation studies are the "gold standard" for extrapolating to humans. However, experiments using intracavitary injection or cells in vitro may represent indicative tests for a possible carcinogenic effect. Such tests should be used to assess the intrinsic carcinogenicity of fibers, but they must be confirmed by adequate inhalation models. Despite the present uncertainties, a proposal is made that could make it possible to classify fibers according to their toxicologic potential, grading them in accordance with physicochemical parameters, in vitro testing, and animal experiments. This procedure may be applicable to nonvitreous fibers and to organic fibers.

Air Pollutants

[Resistance of Streptococcus pneumoniae to penicillin. "Bacteriological" resistance/"clinical" resistance].

From January 1988 to December 1992, 143 Streptococcus pneumoniae strains have been isolated at a significant level from 136 patients hospitalized in the pulmonary care unit of CHI Créteil. The clinical presentations were: 83 pneumonia (P), 48 acute bronchitis (B) and 12 colonizations (C). Fourteen strains were found to be penicillin resistant (MIC > 0.125 mg. l-1): 11 P, 2 B, 1 C. Two patients were lost of view after the beginning of the treatment: a pneumonia (Serotype 23F, MIC = 2 mg. l-1) and a bronchitis (Serotype 23F, MIC = 2 mg. l-1). Treatment was pristinamycine for one and amoxicilline alone or associated to clavulanic acid for the other 13. We observed the failure of the treatment in two. A pneumonia (Serotype 23, MIC = 2 mg. l-1) was treated before hospitalization by josamycine (3 days), then cefpodoxime (4 days) and amoxicillin-clavulanic acid (1.5 gr/d during 7 days). Healing was obtained with the increase to 3 gr/d. The other failure was a pneumonia without improvement after 11 days with 3 gr/d of amoxicilline. The treatment was stopped during 5 days and a protected brushing was performed. A Streptococcus Pneumoniae (Serotype 23F, MIC = 8 mg. l-1) was isolated. The clinical status rapidly improved with erythromycine (3 gr/d) to which the strain was susceptible. "Bacteriological" Resistance to penicillin is demonstrated (10 percent in our sample, 17 percent in France during 1991). However amoxicillin to a sufficient dosage is still enough ("Clinical" Resistance < 1 percent in our sample) for the treatment of respiratory infections except when the MIC is at a high level.

Adult

In vitro effects of recombinant human interferon gamma on human mesothelioma cell lines.

Malignant mesothelioma is a tumor arising from serous surfaces and often related to asbestos exposure. Malignant mesothelioma is resistant to various forms of therapy. Radiotherapy, surgery or chemotherapy only slightly improve prognosis. IFN-gamma produces complete or partial responses in stage-I patients with malignant mesothelioma. The in vitro biological effect of IFN-gamma on malignant mesothelioma cells remains poorly elucidated. In the present study, 32 well-characterized human mesothelioma cell lines (HMCL) were treated with r-hu IFN-gamma at 4 doses and cell growth was determined by a colorimetric method (MTT assay). Among the 32 HMCLs tested, II exhibited significant cell-growth inhibition; 16 were insensitive to r-hu IFN-gamma, and 5 were slightly inhibited. The sensitive cell lines were strongly inhibited by r-hu IFN-gamma. Our results show that HMCL exhibit a large range of responses to r-hu IFN-gamma, some of which can be compared with those obtained in vivo in humans.

Aged

Pleural thickening: a comparison of oblique chest radiographs and high-resolution computed tomography in subjects exposed to low levels of asbestos pollution.

The present study was conducted to investigate the value of oblique chest radiographs, compared with high-resolution computed tomography (HRCT), in the assessment of pleural asbestosis in a group of subjects exposed to low levels of asbestos pollution. The study population consisted of 23 people derived from a previously reported cohort of subjects working in university buildings insulated with asbestos-containing material. Subjects were selected on a voluntary basis from among patients whose initial oblique chest X-rays showed pleural thickening. Sixteen patients were maintenance workers occupationally exposed to asbestos; the remaining seven were environmentally exposed to asbestos. For each subject, two standard chest radiographs [posteroanterior (PA) and right anterior oblique (RAO) views] were taken and HRCT was performed. Films were interpreted after agreement by three chest physicians and a radiologist. Pleural thickening was considered present in all 23 patients on RAO films and in six patients on PA films. HRCT revealed unequivocal pleural plaques in three maintenance workers and doubtful pleural abnormalities in three other maintenance workers. Considering HRCT as the "gold standard," the positive predictive value of RAO film was only 13%-26%. Most of the 17 false-positive diagnoses of pleural fibrosis were due to significant subpleural fat. These results suggest that the routine use of oblique radiographs as a screening test in cohorts of subjects exposed to low levels of pollution by asbestos should be reevaluated.

Air Pollutants, Occupational

Do nasal ciliary changes reflect bronchial changes? An ultrastructural study.

Ciliary dyskinesia is characterized by recurrent respiratory tract infections secondary to abnormal ciliary structure and function. The diagnosis of ciliary dyskinesia is based on the detection of axonemal ultrastructural abnormalities (AUA) is respiratory mucosa samples. In most cases, the diagnosis of AUA is made on samples obtained from nasal ciliated cells with little discomfort to the patient. However, no studies have been performed in the same patient to confirm whether nasal samples reflect bronchial ciliary changes. To answer this question and to determine whether it is necessary to sample bronchial cells for the diagnosis of ciliary dyskinesia, we investigated 12 patients (between the age of 5 and 63 yr) with chronic sputum production. The presence of situs inversus, bronchiectasis, chronic sinusitis, and sterility was investigated to determine an inherited disorder. Two groups were established: Group 1 = six patients with an inherited disorder and Group 2 = six patients without evidence of an inherited disorder. Samples were obtained by brushing or biopsy of nasal and bronchial mucosa and were processed for transmission electron microscopy. In Group 1, the mean AUA was 65.2 +/- 11.4%. The following predominant axonemal defects were found: absence of dynein arms (DA) (four patients), central complex abnormalities (CC) (one patient), and various AUA (one patient). Nasal and bronchial samples correlated significantly for total AUA (r' = 1, p < 0.01) and for outer DA defects (r' = 0.96, p < 0.05). A good but not significant correlation was found for inner DA (r' = 0.83) and peripheral microtubule (PM) defects (r' = 0.71). In Group 2, the mean AUA was 9.6 +/- 2.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent