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Biomedical subjects

J Bignon

Publications and source records attributed to J Bignon.

At least 91 records · Page 5Linked to original sources
PubMed1989

Peroxidase activities in the hamster bronchoalveolar lining fluid: modifications induced by exposure to silica dust.

The modifications of peroxidase (Po) activity have been studied in bronchoalveolar lavage fluid (BALF) from hamsters exposed to silica dust. In silica-treated animals, the mean total BALF-Po activity was significantly increased compared to control animals. This increased activity was accompanied by an influx of polymorphonuclear neutrophils in airways. HPLC gel filtration of BALF from control animals separated 5 peaks with Po activity. They had an apparent molecular weight of 140, 110, 80, 57, and 42 kDa. In BALF from silica-exposed animals, with the exception of the 57-kDa fraction, the same peaks were found. Additional fractions with an apparent molecular weight of greater than 200, 180, 92, 65, and 20 kDa were detected. All the fractions but those at 57 and 92 kDa were detectable in a whole-blood homogenate. Exposing hamsters to silica induced both quantitative modifications and a different pattern of BALF proteins having Po activity in the alveolar lining fluid.

Animals↗
PubMed1989

Translocation of subcutaneously injected chrysotile fibres: potential cocarcinogenic effect on lung cancer induced in rats by inhalation of radon and its daughters.

Exposure to radon 222 and its daughters has been shown to induce lung cancer in rats. The cocarcinogenic effect of intrapleurally injected mineral fibres in rats which have previously inhaled radon has also been established. The aim of this work was to establish whether a similar process could be induced at a distance from the lungs by subcutaneous injection of chrysotile fibres. Three groups of animals were used: (1) 109 rats which inhaled radon only (dose: 1600 working-level months (WLM]; (2) 109 rats given a subcutaneous injection in the sacrococcygeal region of 20 mg of chrysotile fibres after inhalation of the same dose of radon; and (3) 105 rats injected with fibres only. No mesotheliomas occurred in any of the 3 groups. The incidence of lung cancer was 55% in group 2, 49% in group 1 and 1% in group 3. Statistical analysis using Pike's model showed that the carcinogenic insult was slightly higher in group 2 than in group 1. Electron microscopy analysis of fibre translocation from the injection site showed that less than 1% of injected fibres migrated to the regional lymph-nodes and only about 0.01% to the lungs. After injection, the mean length of the fibres recovered in lung parenchyma increased with time, suggesting that short fibres are cleared by pulmonary macrophages whereas long fibres are trapped in the alveolar walls. Although the high tumour incidence observed in group 1 might have masked the cocarcinogenic effect induced by the fibres, it is possible that this effect can occur only at short distances.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1989

Toxicity of an attapulgite sample studied in vivo and in vitro.

Conflicting data are found in the literature concerning the carcinogenic potency of attapulgite. We tested the carcinogenic potency of French attapulgite in rats, and compared it with 2 chrysotile samples: Rhodesian UICC (Ch A) and short Canadian fibres (Ch C). The mean length of the fibres was 0.77 micron (attapulgite), 3.21 microns (Ch A) and 1.25 microns (Ch C). The mean diameter was 0.06 micron in the 3 samples. The particles (20 mg) in saline were inoculated into the pleural cavity of Sprague-Dawley rats allowed to survive for their full lifespan. The incidence rates of mesothelioma were: 0% (saline controls), 0% (attapulgite), 19% (ChC) and 48% (Ch A). In vitro studies were carried out using cultures of rat pleural mesothelial cells (RPMC). Attapulgite and Ch C did not modify cell growth except at high doses of 10 micrograms/cm2. Unscheduled DNA synthesis (UDS) was detected using [3H]thymidine incorporation in confluent RPMC (GoG1 arrested) and a scintillation method. UDS was stimulated with either Ch A or Ch C at doses ranging from 2 to 10 micrograms/cm2. In contrast, attapulgite did not significantly enhance [3H]thymidine incorporation at doses ranging from 2 to 20 micrograms/cm2. The results show that the attapulgite tested here had no carcinogenic potency. The in vivo and in vitro reactivity of the fibres used in this experiment might perhaps be related to the fibre size; however, other parameters may also be important.

Animals↗
PubMed1988

[Chronic bronchitis. Value of RU 41740].

Chronic bronchitis is responsible for 20,000 deaths per annum in France, i.e. 5 per cent of the overall mortality rate. Infection of the bronchi and lung tissue is a frequent cause of death in these patients. Acute on chronic bronchitis ranks fifth among the causes of disablement and admission to hospital. Pneumococci and Haemophilus influenza are the organisms most frequently isolated. the incidence and potential severity of acute episodes of infection account for the repeated use of antibiotics which carries a risk of promotion bacterial resistance. RU 41740 is a non-specific immunomodulator agent which reinforces the non-specific means of the respiratory tract against infections. Three double-blind, drug versus placebo and therefore reliable therapeutic trials have shown that the drug is effective in preventing airway infection. In patients with moderately advanced chronic bronchitis, RU 41740 reduces the number and duration of acute infectious episodes as well as antibiotic consumption. This positive effect persists in patients with chronic respiratory failure, including those who present with extensive bronchial dystrophy. RU 41740 is particularly effective in patients with numerous previous episodes of infection, but it also acts at all stages of chronic bronchitis.

Adjuvants, Immunologic↗
PubMed1988

Quantitation of elastin in human urine and rat pleural mesothelial cell matrix by a sensitive avidin-biotin ELISA for desmosine.

A specific enzyme-linked immunosorbent assay (ELISA) was developed for the determination of desmosine, a cross-linked amino acid specific to fibrous elastin. Competition between solid phase-bound desmosine-protein conjugate and free desmosine for binding to monospecific anti-desmosine antiserum constituted the underlying principle of the assay. The conjugation of desmosine to different protein carriers was carried out with the 1-ethyl-3-(dimethylamino-propyl)carbodiimide (ECDI); rabbits were immunized with desmosine-bovine serum albumin and micro-titer plates were coated with desmosine-egg albumin. An avidin-biotin peroxidase system was used to reveal anti-desmosine antibodies bound to the desmosine-protein conjugate. As both conjugates revealed new non-specific common epitopes on the carrier proteins, prior absorption of the anti-desmosine antiserum on rabbit albumin polymerized with ECDI was required to remove the antibodies directed against these neo-antigens. The absorption procedure resulted in an increased specificity and sensitivity. Values ranging from 0.07 to 4 ng of desmosine/well could be detected and this sensitivity was greater than that obtained in previous immunoassays for desmosine. In order to assess the specificity of the test, samples containing aminoacids and urine hydrolysates were included in an assay. Some cross-reactivity was observed with the desmosine precursor lysinonorleucine and the desmosine isomer isodesmosine but, in contrast the very low cross-reactivity observed with collagen hydrolysate was similar to that exhibited by albumin hydrolysate. Analysis of urine samples from 118 normal male volunteers showed, firstly, that urinary creatinine measurement was a good indicator of the amount of urine which could be safely introduced in the assay without risk of non-specific interference by other organic compounds and, secondly, that the desmosine/creatinine ratio was a reliable index for an in vivo assessment of degraded elastin excretion. The assay also allowed quantitation of elastin fiber biosynthesis in the connective tissue matrix of cultured rat pleural mesothelial cells. This ELISA for demosine is a simple technique which should be useful for further in vivo or in vitro investigations of fibrous elastin tissue metabolism.

Amino Acids↗
PubMed1988

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.

Animals↗
PubMed1988

Growth of normal and neoplastic rat pleural mesothelial cells in the presence of conditioned medium from neoplastic mesothelial cells.

Several transformed cells have been demonstrated to secrete growth factors. We studied the effect of conditioned medium from neoplastic rat pleural mesothelial cells on normal and neoplastic mesothelial cell growth. The results showed that the concentrated conditioned medium stimulated neoplastic mesothelial cell growth but inhibited reversibly normal mesothelial cell growth.

Animals↗
PubMed1988

Stimulation of arachidonic acid metabolism by adherence of alveolar macrophages to a plastic substrate. Modulation by fetal bovine serum.

In previous studies on arachidonic acid (AA) metabolism by pulmonary macrophages in vitro, we observed that the presence of serum in the culture medium influenced the profile of AA metabolites released. To further characterize this phenomenon, rat alveolar macrophages were placed in plastic tissue culture dishes and allowed to adhere in the presence or absence of 7.5% fetal bovine serum (FBS) for 1 h. Adherent cells were then maintained in medium (equilibration) with or without FBS for 3.5 h before stimulation with the calcium ionophore A23187. The release of thromboxane B2 (TXB2) (the stable metabolite of TXA2) and leukotriene B4 (LTB4) during culture was measured by radioimmunoassay and reverse-phase high pressure liquid chromatography, respectively, at the end of each culture step. Cell adhesion to the plastic substrate in FBS-free medium induced an intense stimulation of AA metabolism, with the release of both TXB2 and LTB4. Adhesion and the accompanying TXB2 release appear to be mediated by trypsin-sensitive components since trypsin-pretreated macrophages showed a dramatic reduction in both adherence and TXB2 synthesis. The presence of FBS during the attachment phase of culture reduced both adhesion and release of TXB2 and LTB4 by more than 50%. On the other hand, addition of FBS to cells that had completed adhesion in serum-free medium stimulated release of both metabolites. When challenged with calcium ionophore after 4.5 h of culture, macrophages that had adhered in FBS-free medium released a much smaller amount of TXB2 than did macrophages that had been cultured in the presence of FBS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Asbestos bodies in bronchoalveolar lavage fluid and in lung parenchyma.

Numerical concentrations of asbestos bodies (AB) were measured by light microscopy both in samples of bronchoalveolar lavage (BAL) fluid and in samples of lung parenchyma from 69 patients with suspected asbestos-related diseases who had had lavages and later open lung biopsies or autopsies. Objectives were to study the recovery of pulmonary AB by BAL and the ability of BAL concentrations to predict parenchymal concentrations. BAL and parenchymal concentrations were both spread over 6 orders of magnitude and were positively correlated (r = 0.74 between logarithmic values). It is believed that, by a process of progressive elution, AB firmly adherent to the alveolar wall become suspended in BAL fluid; such suspended bodies represent roughly 2% of all the bodies stored in the portion of lung lavaged. Recovery is associated with great interindividual variations. When a measured BAL concentration exceeds 1 AB/ml, it can be quite confidently predicted, however, that the parenchymal concentration is in excess of 1,000 AB/g and that the patient has experienced a nontrivial asbestos exposure.

Asbestos↗
PubMed1988

The effects of urapidil therapy on hemodynamics and gas exchange in exercising patients with chronic obstructive pulmonary disease and pulmonary hypertension.

To examine the hemodynamic changes induced by vasodilator therapy with urapidil during exercise in patients with chronic obstructive pulmonary disease (COPD) and their potential impact on symptom-limited maximal oxygen consumption, we studied 12 clinically stable patients using a randomized, crossover design. Placebo or urapidil (60 mg orally thrice a day) was given during 48 h preceding each incremental maximal exercise testing. Urapidil compared to placebo consistently lowered the pulmonary artery pressure either at rest from 29 +/- 2.5 to 24 +/- 1.5 mm Hg (p less than 0.001) or during exercise from 55 +/- 3 to 46 +/- 2 mm Hg (p less than 0.01). At rest, the systemic arterial pressure was reduced from 97.5 +/- 4 to 88.5 +/- 3 mm Hg (p less than 0.001) with no significant difference in heart rate or cardiac index. During exercise, systemic arterial pressure decreased from 135 +/- 4 to 119 +/- 3 mm Hg (p less than 0.001). As compared to placebo, urapidil tended to increase the cardiac index from 6.1 +/- 0.4 to 6.6 +/- 0.4 L/min.m2 (NS) and to decrease heart rate, from 122 to 116 beats/min (NS); the resulting stroke volume index increased with urapidil from 49 +/- 3 to 57 +/- 4 ml/m2 (p less than 0.01); at rest, urapidil did not induce alteration in gas exchange, while during exercise, C(a-v)O2 decreased from 8.6 +/- 0.5 to 7.7 +/- 0.4 vol% (p less than 0.01), SVO2 increased from 39.5 +/- 2 to 44.5 +/- 1.5% (p less than 0.01), and SaO2 from 82 +/- 2 to 85 +/- 2% (p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

[Collagenase and diffuse interstitial pneumopathy].

Chronic elastolytic activity in the lung is currently believed to be a major factor in pathogenesis of emphysema. Collagenase may have similar role in disorganizing lung collagen network, leading to fibrotic lung diseases (FLD). The possible involvement of collagenase in FLD is suggested by: 1) an increase collagenolitic activity in bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis or adult respiratory distress syndrome; 2) the accumulation and the activation of cells able to produce collagenases in FLD: fibroblasts, macrophages, neutrophils and eosinophils. However the exact role of collagenase in FLD is still unknown: it could inhibit neocollagen deposition, limiting fibrotic process or lead to further destruction of collagen network. Recent data suggest that genomic macrophage activation (such the proto oncogene c-SIS) may lead to several cellular events: 1) increase number and activation of fibroblasts with collagen synthesis; 2) increase collagenase production resulting of accumulation and activation of fibroblasts, macrophages, neutrophils. So we conclude that such a genomic macrophage activation may be the major factor contributing to the collagen network damage leading to lung tissue fibrosis.

Animals↗
PubMed1988

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.

Aerosol Propellants↗
PubMed1988

Sialidase activity and antibodies to sialidase-treated autologous erythrocytes in bronchoalveolar lavages from patients with idiopathic pulmonary fibrosis or sarcoidosis.

Sialidases catalyse the hydrolysis of terminal sialic acid of the carbohydrate moiety of glycoconjugates. Sialic acids play a key role in the expression or masking of antigenic sites and in cell-cell interactions. As an example, removal of sialic acid from the human erythrocyte membrane unmasks underlying molecules such as the specific carbohydrates (Gal-GalNac) of the so-called T or Thomsen-Friedenreich cryptic antigen. A consequence of this, is the recognition of that antigen by natural serum antibodies. Since the T antigen has been shown to be present in the lung, we have investigated the possible presence of sialidase and of specific antibodies to sialidase-treated cells in bronchoalveolar lavage fluids (BALF) from patients with pulmonary sarcoidosis or idiopathic pulmonary fibrosis (IPF). By using a fluorogenic substrate (4-methyl umbelliferyl-alpha-D-N-acetyl sodium neuraminate), we were able to detect a sialidase activity in BALF from eight out of nine patients with IPF and from ten out of thirty-five patients with sarcoidosis. BALF from normal volunteers and serum from both patients and normal volunteers were devoid of activity. BALF sialidase has an optimum pH activity of 5.4, it is not inhibited by EDTA and has a molecular weight close to 21 kD. BALF anti-T antibodies (galactose specific) were detectable in minute amounts in only one out of the nine normal volunteers. By contrast, they were frequently present in BALF from sarcoidosis (77%) or IPF (66%) patients and sarcoidosis patients had a higher mean activity. No correlation was observed between the enzymatic and antibody activities.

Adult↗
PubMed1987

Lysosomal and cytosolic sialidases in rabbit alveolar macrophages: demonstration of increased lysosomal activity after in vivo activation with bacillus Calmette-Guerin.

Sialidase activity was assayed in homogenized rabbit alveolar macrophages using a fluorogenic substrate: sodium 4-methylumbelliferyl-alpha-D-neuraminate. After differential centrifugation one acid-active enzyme (optimum pH 4.2) was detected in the 16,000 X g pellet that contained lysosomes, mitochondria and peroxisomes. A second activity, with an optimum pH of 5.4, was found in the cytosolic fraction. The acid-active sialidase accounted for more than 95% of the total sialidase activity in crude homogenate. When alveolar macrophages were collected from rabbits stimulated with bacillus Calmette-Guerin (BCG), the acid-active sialidase specific activity was increased 2.5-fold whereas other lysosomal enzymes such as N-acetylglucosaminidase and beta-galactosidase were stable. The cytosolic sialidase activity did not change.

Animals↗
PubMed1987

Effect of low-level NO2 chronic exposure on elastase-induced emphysema.

The effect of chronic exposure to 2 ppm nitrogen dioxide (NO2) for 8 hr a day, 5 days a week, for 8 weeks was assessed in normal and emphysematous hamsters by measuring (1) lung morphometry (mean linear intercept [Lm] and internal surface area [ISA]), (2) lung mechanics (lung volume, compliance and coefficient of static deflation, pressure-volume curve fitted to an exponential equation), and (3) serum elastolytic activity and protease inhibitor capacity. Emphysema was induced by a single intratracheal injection of 6 IU porcine pancreatic elastase. Four groups of animals were used; Control, NO2-exposed, elastase-treated, and NO2-exposed postelastase. Our results show that NO2 exposure alone induced mild emphysematous lesions whose degree of severity estimated by morphometry increase in Lm and decrease in ISA. P less than 0.01) was of the same order as that of the lesions induced by 6 IU elastase. Exposure to 2 ppm NO2 enhanced elastase-induced emphysema (further increased Lm and further reduced ISA. P less than 0.01). By contrast, study of lung mechanics revealed no difference between the control and NO2-exposed groups or between the elastase-treated animals exposed to NO2 and those not so exposed. This apparent discrepancy between results of morphometry and lung mechanics may be due to the lower sensitivity of lung mechanics parameters and their consequent inability to reflect changes in the emphysematous lesions induced by elastase injection or 2 ppm NO2 inhalation. In vivo, serum elastolytic activity and protease inhibitor capacity were not modified in any group, indicating that either serum does not reflect the degree of protease inhibitor capacity in the alveolar spaces or chronic inhalation of low concentrations of NO2 is not sufficient to cause elastase/antielastase imbalance. Lastly, our results suggest that chronic exposure to 2 ppm NO2 may cause individuals with inherited or acquired emphysematous lesions to develop more severe emphysema.

Animals↗