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Biomedical subjects

M Boutet

Publications and source records attributed to M Boutet.

At least 19 recordsLinked to original sources
PubMed1995

Increased expression of intercellular adhesion molecule-1 (ICAM-1) in a murine model of pulmonary eosinophilia and high IgE level.

T lymphocytes and eosinophils are probably involved in the pathogenesis of allergic bronchopulmonary aspergillosis (ABPA), a disease characterized by pulmonary eosinophilia and high serum and lavage IgE levels. We recently developed a murine model of ABPA. To investigate the mechanisms of T lymphocyte and eosinophil recruitment to the lung in this disease, we examined the expression of ICAM-1 in the lung tissue of mouse challenged with Aspergillus fumigatus (Af) antigen. C57B1/6 mice were intranasally exposed to Af (Af group) or saline (control group) three times a week for 1, 2 or 3 weeks. On days 4, 7, 14 and 21, mice were killed and lung tissue was fixed in acetone and embedded in glycol methacrylate. Serial 2-microns sections were stained with chromotrope 2R and MoAbs against ICAM-1, CD11a/CD18 (LFA-1) and CD3. Af-challenged mice presented significant increases in eosinophil, T lymphocyte and LFA-1-positive cell count and up-regulated expression of ICAM-1 in the lung tissue at all the time points examined. ICAM-1 expression intensity correlated with the number of T lymphocytes (r = 0.59, P < 0.01), LFA-1-positive cells (r = 0.68, P < 0.001), but not of eosinophils (r = -0.24, P > 0.05). These findings suggest that up-regulation of ICAM-1 expression is involved in the inflammatory process of this murine model of ABPA, and that this up-regulation may be more relevant to the the T lymphocyte accumulation in the lung.

Animals↗
PubMed1995

Increased maximal airway response to methacholine during seasonal allergic rhinitis in nonasthmatic subjects: relationships with airway wall thickness and inflammation.

This study was carried out to determine whether the increase in airway responsiveness induced by natural antigenic exposure in nonasthmatic subjects is associated with an increase in maximal bronchoconstrictor response (MBR), and if these changes could be due to an increase in airway wall thickness from allergen-induced increase in airway inflammation. In 11 nonasthmatic subjects with seasonal allergic rhinitis, a methacholine challenge was obtained monthly, during and out of pollen exposure. Each subject had a high-resolution chest tomography in and out of the pollen season, to determine the relative thickness of the right intermediary bronchus over its total diameter (T/D), as well as inflammatory cell counts, apparent basement membrane thickness as an indication of subepithelial fibrosis and epithelial desquamation in bronchial biopsy specimens. In season, the mean provocative concentration of methacholine producing a 20% decrease in forced expiratory volume in one second (PC20) decreased from 51.5 to 25.8 mg.mL-1, and the maximal post-methacholine fall in forced expiratory volume in one second (delta FEV1,max) or forced vital capacity (delta FVC) and the slope of the dose response curve (DRS) increased compared with out of season: delta FEV1,max 44 +/- 5 vs 25 +/- 5%; delta FVC 34 +/- 5 vs 16 +/- 4%; and slope of DRS 14.1 +/- 2.8 vs 6.9 +/- 1.3%/mg.mL-1. No significant change was observed in T/D ratio. The seasonal change in delta FVC was positively correlated with the delta FEV1,max (rs = 0.891) and the change in DRS (rs = 0.909), but not with the change in PC20, nor with changes in bronchial biopsy inflammatory features or T/D ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Is reactive airways dysfunction syndrome a variant of occupational asthma?

BACKGROUND: Reactive airways dysfunction syndrome (RADS) or irritant-induced asthma is a syndrome that leaves subjects with asthma-like symptoms after one or more exposures to a high concentration of an irritant substance. The degree of reversibility of airway obstruction in subjects with RADS is nevertheless unknown, as is the degree of associated lesions at the airway level. METHODS: We compared the acute reversibility of forced expiratory volume in 1 second (FEV1) after inhalation of albuterol (200 micrograms) in 15 subjects with RADS (12 cases caused by chlorine inhalation) with that of 30 subjects with occupational asthma (OA) caused by various agents. They were paired according to baseline airway obstruction (61% and 63% of predicted value in the RADS and OA groups), requirement for medication (bronchodilator only--7 of 15 subjects with RADS and 14 of 30 subjects with OA--as compared with bronchodilator + inhaled steroids in 8 of 15 subjects with RADS and 16 of 30 subjects with OA, respectively), and interval since removal from exposure (means of 30 and 24 months in the RADS and OA groups). In addition, five nonsmokers with RADS who had not received inhaled steroids underwent bronchoscopy with lavage and bronchial biopsies less than 2 years after the exposure. RESULTS: The percentage increase in FEV1 over baseline after inhalation of albuterol was 10% +/- 9% in the RADS group and 19% +/- 16% in the OA group (p = 0.005). Only 2 of 15 subjects (13%) with RADS and 12 of 30 subjects (40%) with OA showed an improvement in FEV1 of 20% or greater after inhalation of albuterol. Bronchoalveolar lavage showed an increased number of cells with a predominance of lymphocytes, and biopsy specimens showed increased basement membrane thickness in the five subjects with RADS who underwent bronchoscopy. CONCLUSION: Subjects with RADS are generally left with less airway reversibility than those with OA. We suggest that this difference is secondary to distinct pathologic changes.

Adult↗
PubMed1994

Airway inflammation in nonasthmatic subjects with chronic cough.

The physiopathology of chronic cough remains obscure. We evaluated the possibility that chronic cough in nonasthmatic subjects is associated with airway inflammation, and if this is so, what the relationship between this inflammation and the possible etiology of cough might be, as well as its response to inhaled steroids. Nineteen nonsmoking, nonasthmatic subjects referred for a persistent cough (mean: 3.8 yr) were evaluated and compared with 10 normal subjects. The evaluation included a respiratory questionnaire, a physical examination, allergy skin-prick tests, chest and sinus radiographs, esophageal pH monitoring, measurements of expiratory flows, methacholine and citric acid challenges, and flexible bronchoscopy for bronchoalveolar lavage (BAL) and bronchial biopsies. Fourteen subjects further accepted participation in a randomized, double-blind crossover trial of inhaled beclomethasone (500 micrograms four times daily) and a placebo for 1 mo each. Four groups of subjects were identified according to the presence of postnasal discharge (n = 4), gastroesophageal reflux (n = 6), both conditions (n = 5), or neither (n = 4). Subjects with chronic cough had an increased number of inflammatory cells in their bronchoalveolar lavage fluid (BALF), but there was no significant difference between the four subgroups of coughers. As compared with control subjects, the bronchial biopsies of subjects with chronic cough showed increased epithelial desquamation (p = 0.004) and inflammatory cells (p = 0.005), particularly mononuclear cells (p < 0.01), in addition to submucosal fibrosis, squamous-cell metaplasia, and loss of cilia. These findings were not significantly different between the different etiologic groups. In subjects with chronic cough, basement-membrane thickness was normal and not different from that of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗
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↗