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Biomedical subjects

M Boutet

Publications and source records attributed to M Boutet.

At least 37 records · Page 2Linked to original sources
PubMed1994

Airway inflammation after removal from the causal agent in occupational asthma due to high and low molecular weight agents.

In order to determine 1) the features of airway inflammation after removal from exposure to high (HMW) and low (LMW) molecular weight agents 2) if there are any differences in the pattern of inflammation induced by these two types of agents, we studied 18 subjects with a recently confirmed diagnosis of occupational asthma (OA) due to HMW (n = 11) and LMW (n = 7) agents. The duration of asthma symptoms varied from 2 to 108 months (mean 33 months), and withdrawal from exposure to the sensitizing agent from 3 to 24 weeks (mean 10 weeks). All subjects underwent measurements of expiratory flow rates, methacholine inhalation tests, and a flexible bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsies. Endoscopic findings were compared with a group of 10 normal subjects. At the time of the bronchoscopy, asthma symptoms were minimal in most subjects. Although 15/18 subjects had normal forced expiratory volume in one second (FEV1 > 80% pred), all subjects had increased airway responsiveness to methacholine (provocation concentration producing a 20% fall in FEV1 = 0.2-10.0 mg.ml-1). BAL analysis showed similar median percentages of the total number of cells and differentials in control subjects and those exposed to HMW and LMW agents. Bronchial biopsies showed that mean inflammatory cell count, both epithelial and sub-epithelial, was similarly raised in OA subjects exposed to either HMW or LMW agents, compared to controls, except for epithelial lymphocyte count. In contrast to the controls, bronchial biopsy of both groups with OA also showed other changes such as extensive epithelial desquamation, ciliary abnormalities of the epithelial cells, smooth muscle hyperplasia and subepithelial fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

An innovative technical approach for repetitive intratracheal instillation without anesthesia in small animals.

Intratracheal instillation in small laboratory animals often involves repeated anesthesia and upper airway intubation. To facilitate this approach, we developed an indwelling system for repeated intratracheal administrations that was assembled from widely available simple components. Its installation can be considered a minor surgical procedure and is done under sterile surgical conditions. This system allows repeated intratracheal administration of substances in the lungs in unanesthetized animals, with the possibility to increase the frequency of instillations and lower the dose. Thoracic radiography was performed to document the reliability of this permanent instillation system. Furthermore, a potent toxic nitrosamine (NNK; N-nitrosamine 4-[nitrosomethylamino]-1-[3-pyridil]-1-butanone) was used to demonstrate appreciable pulmonary toxicity at low dosage but with repetitive administration. This simple technique brings a significant simplification and improvement to small animal studies that require repeated bronchoalveolar administration of substances.

Anesthesia↗
PubMed1993

Influence of natural antigenic exposure on expiratory flows, methacholine responsiveness, and airway inflammation in mild allergic asthma.

BACKGROUND: This study looked at respiratory symptoms, peak expiratory flow rates (PEFRs), airway responsiveness to methacholine and inflammatory changes on bronchial biopsies, bronchial lavage (BL), and bronchoalveolar lavage (BAL) during natural antigenic exposure in nine subjects with pollen-sensitized seasonal asthma. METHODS: The subjects recorded daily symptoms of asthma, cough and rhinitis, and morning and evening PEFRs between January and September, during and out of the pollen exposure. Baseline forced expiratory volume in 1 second, forced vital capacity, and methacholine responsiveness were measured every 3 to 4 weeks. BAL, BL, and bronchial biopsies were performed in the pollen season at the initial increase of asthma symptoms and out of pollen exposure. RESULTS: At the time of bronchoscopy during the pollen season compared with out of season, asthmatic subjects had an increase in asthma symptom score (1.18 +/- 0.24/0.44 +/- 0.18, p < 0.05), a reduction of PEFR (407 +/- 23/442 +/- 20 L/min, p = 0.02), and a decrease in PC20 (1.15/1.48 mg/ml, p = 0.05). In asthmatic subjects, median BAL and BL cell counts and cell differentials during or out of antigenic exposure were similar, but BAL and BL eosinophils and metachromatic cells counts were always higher than in healthy subjects. In comparison with controls, biopsies obtained in asthmatic subjects showed airway lesions such as epithelial desquamation, squamous cell metaplasia, thickening of basal membrane, inflammatory cells (p < 0.05 for neutrophils), edema, and ciliary abnormalities. During pollen exposure, inflammatory signs increased, but this change was only significant for the extent of epithelial desquamation and neutrophil counts. No significant correlation was found between the intensity of airway inflammation and changes in airway responsiveness. CONCLUSIONS: In subjects with mild allergic asthma and pollen-induced asthma, seasonal antigenic exposure was associated with an increase in epithelial shedding and in the number of neutrophils on bronchial biopsies, suggesting a mild increase in baseline airway inflammation. However, these changes were not correlated with increases in airway responsiveness.

Adult↗
PubMed1989

Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by hamster respiratory tissues cultured with ellagic acid.

Previous studies have shown that the nicotine-derived N-nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces tracheal papillomas and lung carcinomas in Syrian golden hamsters. In this study, we showed that hamster tracheal and lung explants metabolize NNK by alpha-carbon hydroxylation, pyridine N-oxidation and carbonyl reduction. alpha-Methylene hydroxylation and methyl hydroxylation yield methylating and pyridyloxobutylating intermediates, respectively. Levels of binding of the pyridyloxobutyl moiety to explant proteins was 200 times lower than the total amount of metabolites formed by alpha-carbon hydroxylation and released in the culture medium. Viable and heat-treated lung explants were cultured with [CH3-3H]NNK or [5-3H]NNK. In viable explants, the rate of binding of the methyl group was 2-fold higher than the rate of binding of the pyridyloxobutyl moiety of NNK. Heat treatment reduced 54-fold the binding of [CH3-3H] NNK but only 5-fold the binding [5-3H]NNK. Tracheal explants were cultured with [5-3H]NNK (5.6 microM) and ellagic acid (EA, 10 microM), a naturally-occurring plant phenol. EA did not inhibit any of the three metabolic pathways nor the binding of the pyridyloxobutyl moiety to explant proteins. Lung explants were cultured with NNK (3.7 microM) and with or without EA (100 microM). EA inhibits alpha-carbon hydroxylation by 19% and the overall metabolism of NNK by 6%. Formation of 7-methylguanine and O6-methylguanine was observed in lung explants and the levels of both adducts were reduced by EA (100 microM). These results suggest that high concentrations of EA modulate the metabolism of NNK and that NNK does not necessarily require enzymatic activation to bind to protein.

Alkylation↗
PubMed1987

Cellular changes induced by the tobacco-specific carcinogen 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone in the respiratory tract of Syrian golden hamsters.

The N-nitrosamine 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) is abundant in cigarette smoke and is a potent pulmonary carcinogen in Syrian golden hamsters. After intratracheal instillation of NNK to Syrian golden hamsters, we observed focal cell death in the trachea and bronchi followed by cellular regeneration. Regenerating cells were not ciliated and led to mucous-cell hyperplasia followed by squamous-cell metaplasia. Lung alterations consisted of bronchiolar hyperplasia with severe dysplastic changes in association with interstitial pneumonitis. NNK induces preneoplastic cellular changes similar to those observed in the pulmonary epithelium of smokers.

Animals↗
PubMed1986

[Congestive cardiomyopathies in children. Natural history and studies].

Congestive cardiomyopathies represent a group of diseases having in common an intrinsic abnormality of the myocardial contraction, of which the cause often remains unknown. In children, there is a more marked incidence during the first year of life. At the Cardiology Institute of Quebec, 25 patients have been diagnosed with a congestive cardiomyopathy since January 1967. The mortality remains high at 48 per cent, and the morbidity at 28 per cent. Thus, the chance of total survival at 16 years was 33 percent. The evaluation and the treatment of the cardiac function as well as the search for a specific etiology must be carried out because the etiological treatment is sometimes possible. Biopsy of the skeletal muscle as the study of fatty acids metabolism have become very important since the identification of a carnitine deficiency. On the other hand, biopsy of the endomyocardium remains the only means to make a pathological diagnosis. Since the treatment of persisting myocarditis is feasible, the histological diagnosis is a pre-requisite in children. So, in four patients with congestive cardiomyopathy, biopsy of the endocardium has enabled to demonstrate a chronic inflammation of the myocardium in one patient. In three other cases, two had non specific lesions on histological examination an one had an extensive fibro-elastosis. As the symptomatic treatment is often deceiving, an in-depth investigation is mandatory in a child suffering from a congestive cardiomyopathy in order to identify an etiology. Such an approach will enable to apply a specific treatment, to achieve a better understanding and perhaps modify its natural history.

Adolescent↗
PubMed1983

Endothelial cell coat modifications in rat thoracic aorta. Effect of ovariectomy and cigarette smoke.

The effects of acute cigarette smoking and bilateral ovariectomy on the thickness of rat aortic cell coat (Con A) were investigated. Ovariectomized rats showed a significant increase in the thickness of the cell coat. When cigarette smoking was combined with ovariectomy the thickness of the reaction product was similar to controls. Cigarette smoke without ovariectomy resulted in a decreased thickness, but these changes were not significant.

Animals↗
PubMed1983

Reperfusion injury. A possible link between catecholamine-induced and ischemic myocardial alterations.

In this study we have compared myocardial lesions induced by catecholamines and coronary occlusion and reperfusion injuries in rats. Although microcirculatory factors were found to play an important role in catecholamine-induced cardiac muscle cell injury, alterations in sarcolemmal membrane permeability suggest a direct cardiotoxic effect. Cardiac muscle cells damaged irreversibly by ischemia reveal sarcomeres in extreme relaxation and mitochondria with floccular densities; cardiac muscle cells that die following reperfusion exhibit contraction band formation and mitochondria with calcium phosphate deposits. The ultrastructural appearance of reperfused ischemic cardiac muscle cells was similar to that observed following administration of catecholamines. These morphological similarities suggest a common causal pathway for stress-induced and ischemic heart diseases.

Animals↗
PubMed1981

[Cardiovascular effects of cigarette smoke in the rat. Aortic endothelial and myocardial capillary permeability in the rat].

The permeability of aortic endothelium and myocardial capillaries was examined in 72 Sprague-Dawley rats (approximately 350 g) using the diffusion tracer peroxidase. Animals were subjected to cigarette smoke for periods of 1 day (acute effects), 2 weeks (sub-acute effects) and 15 weeks (chronic effects) and were sacrificed 5 minutes or 8 hours after smoking. Peroxidase was not generally present at the sub-endothelial level in the aortic endothelium of control animals and sham-smokers. However, in smokers, the increase in peroxidase permeability is proportional to the smoking period. Moreover, in these smokers we observed junctional and subendothelial vacuolar dilatations which correspond to degenerative morphologic changes. Cigarette smoke has a different effect on the right ventricle. Endothelial permeability of the myocardial capillaries increases in animals subjected to cigarette smoke for 1 day and those who smoked for 2 weeks sacrificed 5 minutes after smoking. This increase in permeability is not related to the significant morphologic changes observed in the myocardium and endothelial capillaries. However, the myocardial endothelial capillaries, the sub-endothelial space and the adjacent interstitial space were generally free of peroxidase in animals subjected to cigarette smoke for 15 weeks and in those smoking for 2 weeks sacrificed 8 hours later. An adaptive phenomenon to the effects of cigarette smoke appear to exist in the myocardial endothelium capillaries contrary to that which is observed in the thoracic aorta.

Animals↗
PubMed1980

Effects of cigarette smoke on rat thoracic aorta.

Using the fine structural macromolecular tracer horseradish peroxidase (HRP) the permeability of thoracic aorta was studied in 72 male Sprague-Dawley rats. Rats smoked for 1 day (acute effect), 14 days (subacute effect) and 15 weeks (chronic effect). Thoracic aorta sections from control rats and sham smokers were free of HRP reaction product. In smokers' thoracic aortas, permeability to peroxidase increased proportionately to the increase in length of the smoking period. Furthermore, smokers' thoracic aortas exhibited focal vacuolar dilatations (subendothelial blebs) and an increased number of subendothelial macrophages.

Animals↗
PubMed1976

Permeability alteration of sarcolemmal membrane in catecholamine-induced cardiac muscle cell injury. In vivo studies with fine structural diffusion tracer horse radish peroxidase.

Cardiac muscle cell injury was produced in male Sprague-Dawley rats weighing 300 to 450 gm. with catecholamines, norepinephrine, and isoproterenol; sarcolemmal membrane alteration was tested in vivo using the extracellular macromolecular tracer, horseradish peroxidase. Norepinephrine was administered in continuous intravenous infusion in a dose of 4 to 6 mug. per 100 gm. of body weight per minute, whereas isoproterenol was given as a single subcutaneous injection in a dose of 8.5 mg. per 100 gm. of body weight. Horseradish peroxidase was injected intravenously and localized in the right ventricular myocardium following 6 and 30 minutes of circulation time by light and electron microscopy. As early as 10 minutes after norepinephrine infusion, horseradish peroxidase appeared within cardiac muscle cells possessing normal fine structure. Selective deposition of the tracer on normal and altered myofilaments was noted. Similar observations were made in the isoproterenol model at 60 to 90 minutes. The results indicate that sarcolemmal membrane permeability alteration is an early event in catecholamine-induced cardiac muscle injury. The possible functional significance of the findings is discussed.

Animals↗
PubMed1976

Chronic inhalation of marijuana and tobacco in dogs: pulmonary pathology.

The pulmonary effects of chronic marijuana (M) and tobacco (T) smoke inhalation were studied in adult female dogs. The smoke was inhaled through a tracheostomy tube: four cigarettes containing either tobacco (3.2 g/dog) or marijuana (3.0 g/dog) were used per day over 900 days. At autopsy, the pulmonary volume and alveolar surface of the T group had decreased, compared to controls (C) and the M group. The tracheostomy (Tr) produced itself result in chiolitis; in order of severity the M group greater than T greater than Tr greater than C. The incidence of squamous metaplasia also followed this order but the T group showed more abnormalities affecting the mucosal membrane. Our findings reported that chronic inhalation of marijuana and tobacco produced the bronchiolitis with the macrophage infiltration in the wall of the terminal air-passages. This may thereafter induce the pulmonary emphysema.

Animals↗
PubMed1975

Membrane permeability alterations as manifestation of early cardiac muscle cell injury.

Studies with extracellular fine structural diffusion protein tracers, horseradish peroxidase and ferritin, were carried out on catecholamine-induced cardiac muscle cell injury. Epinephrine, norepinephrine, and isoproterenol were administered in a dose of 4- 6 mug/100g body weight by continuous intravenous infusion. For follow-up studies, isoproterenol was also given subcutaneously in a dose of 8.5 mg/100 g body weight as a single injection. In contrast to saline-infused controls and following epinephrine infusion, where these tracers always remained extracellular, norepinephrine- and isoproterenol-infused animals exhibited alteration of sarcoplasmic membrane permeability to macromolecules in the early stage of evolution preceding fine structural changes of cardiac muscle cells. This was reflected by the intrasarcoplasmic presence of peroxidase in some cardiac muscle cells which otherwise showed no ultrastructural alteration. Deposition upon and selective binding of the extracellular protein tracer, peroxidase, to intact myofilament was also a characteristic early change that may affect the contraction-relaxation mechanism of the myofilaments and may contribute to the evolution of necrobiotic alteration. In structurally altered cells, peroxidase showed similar affinity to contraction bands and fragmented myofilaments. Furthermore, these studies disclosed different sensitivities of various membrane components of the cardiac muscle cell. While in the early pahse of cell damage no peroxidase could be detected in various intrasarcoplasmic compartments, with increasing severity of the lesion the external and internal mitochondrial membranes as well as the sarcoplasmic reticulum were also affected. When the large molecular tracer, ferritin, was used, the sequence of events in altered cardiac muscle cells followed that outlined for peroxidase. However, free ferritin molecules could not be demonstrated in the sarcoplasm of cardiac muscle cells which exhibited normal ultrastructure.

Animals↗