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Biomedical subjects

J Bignon

Publications and source records attributed to J Bignon.

At least 55 records · Page 3Linked to original sources

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 In contrast, HIV-1 replication occurs when AM are withdrawn from their local environment, enhanced by GM-CSF and TNF-alpha stimulation.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↗

Cytogenetic study of five cases of lung adenosquamous carcinomas.

The cytogenetic study of five cases of untreated adenosquamous carcinoma of the lung allows us to propose a number of characteristic anomalies. All tumor cells were hyperdiploid, with a mean chromosome number ranging from 59 to 83, and had many clonal chromosome rearrangements. The chromosomes the most frequently affected by these rearrangements were, by decreasing order, 1, 3, and 15; 7 and 8; and 17. No recurrent breakpoints were observed in euchromatic regions, most breaks (45/66) involving juxtacentromeric heterochromatin or immediately adjacent regions. Although chromosome 3 was frequently rearranged, no recurrent deletions of its short arm were observed.

Adenocarcinoma↗

Nonfibrous mineral particles in bronchoalveolar lavage fluid and lung parenchyma from the general population.

It is recognized that bronchoalveolar lavage (BAL) gives access to particulate matter present at the surface of the peripheral airspace. The objective of the present study was to evaluate the ability of BAL fluid analysis to predict the lung parenchymal particulate content. A BAL fluid sample, the parenchyma sample having undergone BAL, and an adjacent parenchyma sample that had not undergone BAL were obtained at autopsy on 10 individuals without any known recent occupational exposure to mineral particles. The particles (larger than 0.1 micron) were analyzed using a transmission electron microscope equipped with a microanalysis system. Nineteen types of particles were distinguished. The distribution of particle types in the three samples was compared. No significant difference between the relative concentrations was found, except for two particle types: fly ash (excess in BAL fluid compared with lavaged lung) and kaolinite (excess in lavaged lung compared with adjacent area). Such differences may be due to limitations in methodology. Although no correlation could be found between the absolute concentrations of particles in BAL fluid and in lung tissue, analysis of particles in BAL fluid may provide information on the types of particles present in the lung parenchyma.

Adult↗

Decreased sialidase activity in alveolar macrophages of guinea pigs exposed to coal mine dust.

The origin of immune dysfunctions that are observed in pneumoconiotic miners still remains unknown. There is evidence that the carbohydrate moiety of membrane glycoconjugates is of primary importance in many functions of immunocompetent cells. The glycosylation, and especially the sialylation level of membrane components of various lymphocyte and macrophage subsets, vary depending on the state of cellular differentiation and activation. Sialidases, which may regulate the amount of sialic acids exposed on the cell membrane, can thus be considered as immunoregulatory enzymes. In this report, the sialidase activity has been measured in alveolar macrophages (AM) and in cell-free bronchoalveolar lavage fluid (BALF) from guinea pigs exposed for 4 months to coal mine dust at a concentration of 300 mg/m3. The samples were collected by bronchoalveolar lavage 2 months after cessation of exposure. The sialidase activity in the cell-free fluid and in the purified alveolar macrophages showed a 10-fold decrease (p less than 0.001). Kinetic parameters of the enzyme such as Km and optimum pH did not change. This changed activity was specific for sialidase, as two other lysosomal glycosidases, beta-galactosidase and N-acetylglucosaminidase, showed unchanged activities. These results suggest the possibility that, by inducing a decreased sialidase activity, exposure to coal mine dust may lead to a modified expression of AM membrane-associated sialic acids giving rise to altered immune functions (i. e., phagocytosis, antigen processing, response to cytokines, etc.).

Animals↗

Bronchoalveolar lavage in immunocompromised patients. Clinical and functional consequences.

Fiberoptic bronchoscopy and bronchoalveolar lavage are major tools in the diagnosis of acute pneumonia in immunocompromised patients. We conducted a prospective study to assess the morbidity associated with this procedure in 14 patients with AIDS and 16 patients with drug-induced immunosuppression. No patient had a PaO2 lower than 70 mm Hg with additional oxygen. Clinical data, chest roentgenogram, pulmonary function test, forced vital capacity, forced expiratory volume in one second, and arterial blood gases were recorded before and after bronchoscopy. Arterial oxygen saturation was monitored during the procedure, and initial, lowest, and final saturation values were noted. The patients were separated into three groups on the basis of chest roentgenographic findings. No procedure-induced pneumonia or need for tracheal intubation occurred. Minor clinical symptoms induced by the lavage in seven patients resolved spontaneously. By contrast, mean SaO2 decreased markedly during the procedure from 94 +/- 3 to 87 +/- 5 percent (p less than 0.0001) and returned to only 89 +/- 5 percent at the end of the procedure. Lowest SaO2 during the procedure and final SaO2 correlated poorly with initial SaO2 but correlated well with initial FVC and FEV1 (p less than 0.01). The PFT values were lower following bronchoscopy. O2 desaturation was more pronounced in patients with severe roentgenographic abnormalities. No significant differences were found between the three groups of patients, or between the AIDS and DII patients in terms of changes in PFT values. We conclude that in immunocompromised patients, bronchoscopy with BAL induces severe arterial oxygen desaturation which is correlated with initial PFT and chest roentgenographic findings, and most of these abnormalities are transient and do not lead to major complications.

Acquired Immunodeficiency Syndrome↗

[Sequential administration of a reduced dose of almitrine to patients with chronic obstructive bronchopneumopathies. A controlled multicenter study].

Recent multi-centre studies have shown that high doses of Almitrine (100-200 mg per day), lead to a significant improvement in the hypoxaemia of patients presenting with chronic airflow obstruction, but that a high blood level (greater than 500 ng/ml) is often seen after 1 year, sometimes associated with signs of peripheral neuropathy. In order to maintain Almitrine blood levels in the range 200-300 ng/ml we have used an intermittent regime (with a "window" of 1 month every 3 months) and a dose limited to 100 mg per day. 102 hypoxic patients with chronic airflow obstruction, who were in a stable state were included. 65 patients were in the Almitrine group (A) and 37 patients in the placebo group (P). The treatment lasted for 1 year. In addition there was a 3 monthly follow up with arterial blood gases and spirometry, a clinical neurological examination and also electrophysiology, initially and after 6 and 12 months. 43% of patients in group A and 32% of patients in group P, left the study, most often due to poor cooperation, but sometimes as a result of side effects. After 12 months the PaO2 rose significantly in group A from 59.1 +/- 0.7 to 65.8 +/- 1.6 mmHg (p less than 0.001) whilst it was not changed in group P. The PaCO2 did not change in either group. On the other hand there was a significant fall in the subgroup of patients with hypercapnia in group A (p less than 0.001). The outcome of the neurological and electrophysiological assessments did not show any significant difference between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Methods for clinical assessment of expectorants: a critical review.

The purpose of the paper is to discuss some aspects of the methods that are most appropriate for the clinical assessment of new expectorants. Expectorants are drugs devised to help in the removal of bronchial secretions. The evaluation of these drugs is aimed at demonstrating, in controlled trials, their efficacy, safety and, if possible, mechanism of action. Unfortunately, there is no universally accepted assessment technique available. Evaluation of symptoms with the use of self-reported measures is imprecise. Studies of quality of life can assist as a means of assessing the usefulness of this class of drug for patients. Lung function tests evaluate only the possible indirect effects of expectorants; the changes observed are often minor and they do not correlate with other methods of evaluation. Mucociliary clearance studies evaluate bronchial drainage by mucociliary transport and cough. They are a useful pharmacological approach but they cannot replace therapeutic trials. In vitro and ex vivo studies of bronchial secretion, while improving knowledge of the mechanisms of bronchial secretion, fail to predict the modifications of bronchial drainage produced in vivo by cough or mucociliary transport. To be considered efficient, expectorants should not only ease the removal of bronchial secretions, but also improve the patient's condition for the duration of treatment.

Animals↗