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Biomedical subjects

I Fajac

Publications and source records attributed to I Fajac.

33 records · Page 2Linked to original sources
PubMed1996

Exhaled nitric oxide during acute changes of airways calibre in asthma.

It has been shown that endogenous nitric oxide (NO), measured in exhaled air, is increased in asthmatic subjects and after allergen challenge in sensitized animals. NO is also a paracrine molecule with some, though weak, bronchodilator effects. However, whether the amount of endogenous NO that originates in the lungs can reflect the degree of bronchial tone and airways calibre in asthmatic subjects has not yet been investigated. The aim of this study was, therefore, to determine whether NO production could be modified by acute changes of airways calibre in mild, nonatopic, asthmatic subjects. NO output was measured in the exhaled air of 14 steroid-free asthmatics, 8 steroid-treated asthmatics and 21 control subjects. In seven steroid-free asthmatics, exhaled NO was measured after methacholine challenge, and then after salbutamol-induced bronchial dilatation. Exhaled tidal breathing was collected for 30 s and NO in the exhaled air was measured with a chemiluminescence analyser. Both NO concentration and its output were significantly higher in the steroid-free asthmatic patients (15.6 +/- 1.5 parts per billion (ppb) and 6.3 +/- 0.7 nmol.min-1, respectively) as compared with the control subjects (8.9 +/- 1.0 ppb and 3.5 +/- 0.3 nmol.min-1, respectively; p < 0.001 for both) and with the steroid-treated asthmatic patients (11.3 +/- 3.3 ppb and 3.7 +/- 0.9 nmol.min-1, respectively; p < 0.05 for both). Neither methacholine-induced bronchial obstruction nor salbutamol-induced bronchial dilatation caused a significant change in exhaled NO. We conclude that NO production is higher in steroid-free than in steroid-treated asthmatics and in control subjects. Furthermore, NO production is not affected by acute pharmacologically-induced changes of airways calibre in asthmatic subjects. Our results suggest that NO production is a marker of airways inflammation rather than an endogenous modulator of bronchial tone in asthma.

Adult↗
PubMed1996

Genotype-phenotype relationships in a cohort of adult cystic fibrosis patients.

In cystic fibrosis (CF), relationships between genotype and phenotype have been shown for pancreatic status but not for pulmonary disease. One hundred and ten adult CF patients were classified according to the expected effect of their mutations on cystic fibrosis transmembrane conductance regulator (CFTR) protein: Group 1 (n=48) included deltaF508 homozygotes; Group 2 (n=26), patients with two "severe" mutations and no expected CFTR production; Group 3 (n=17), patients with expected partly functional CFTR corresponding to at least one "mild" mutation; Group 4 (n=19), patients with no mutation identified or only one identified "severe" mutation. As compared to Groups 1 and 2: patients from Groups 3 and 4 had higher arterial oxygen tension (Pa,O2) (9.5+/-1.9 and 9.9+/-1.5 vs 8.8+/-1.5 and 8.3+/-1.7 kPa, respectively p<0.02); and a slower decline in their pulmonary function, estimated by the mean annual loss in forced vital capacity (FVC) (1.2+/-1.0 and 1.5+/-1.1 vs 2.0+/-0.9 and 2.2+/-1.0%, respectively; p<0.01) and in forced expiratory volume in one second (FEV1) (1.7+/-1.1 and 1.9+/-1.3 vs 2.6+/-1.0 and 2.8+/-1.0%, respectively; p<0.005). They had fewer episodes of colonization of the airways by Pseudomonas aeruginosa, and colonization occurred at a more advanced age (median age 25 and 19 vs 15 and 17 yrs, respectively; p<0.01) and required fewer intravenous antibiotic courses (p<0.01). Pancreatic insufficiency was less frequent in Groups 3 (23%) and 4 (63%) than in Groups 1 (100%) and 2 (96%). This study suggests that the phenotype of adult cystic fibrosis patients, including the severity of the lung disease, is related to the severity of the cystic fibrosis transmembrane conductance regulator mutations.

Adolescent↗
PubMed1995

Selective recruitment of eosinophils by substance P after repeated allergen exposure in allergic rhinitis.

We have investigated the nasal response to substance P after pollen exposure in seasonal allergic rhinitic patients. Seven patients with strictly seasonal allergic rhinitis were studied during the pollen season, 24 h after nasal challenge with pollen. They received increasing doses of nebulized substance P (0 to 80 nmol) in each nostril. Responses were assessed by measurement of nasal airway resistance by posterior rhinomanometry and quantification of albumin, histamine, and inflammatory cells in the nasal lavage fluid. Nasal airway resistance increased in a dose-dependent manner after substance P challenge. Protein and albumin in nasal lavage fluids increased after administration of substance P: from 2.6 +/- 0.3 to 6.8 +/- 1.1 mg for protein (P < 0.01) and from 0.2 +/- 0.1 to 3.1 +/- 0.6 mg for albumin (P < 0.02). Expressed as a percentage of total protein, albumin increased from 10.5 +/- 3.6% to 39.9 +/- 3.5% (P < 0.02), suggesting occurrence of plasma leakage. No histamine release was observed after challenge with substance P. Total cell counts significantly increased from 11.4 +/- 2.4 to 41.8 +/- 17.3 x 10(3) cells/ml after substance P (P < 0.05). Eosinophils were already numerous before substance P challenge (2.1 +/- 0.7 x 10(3) cells/ml), and the number of eosinophils markedly increased in all patients after substance P (for the whole group, 25.8 +/- 13.3 cells/ml, P < 0.05). In contrast, the number of neutrophils only slightly increased in five patients, and changes did not reach significance for the group as a whole. Our results show that substance P induces nasal obstruction and albumin extrusion in allergic rhinitic patients after repeated pollen exposure. These vascular phenomena are associated with recruitment of eosinophils. Since substance P is known to be released after nasal allergen challenge, our data suggest a role for substance P in the chronic eosinophilic inflammation of the nasal mucosa observed in symptomatic allergic rhinitis.

Administration, Intranasal↗
PubMed1995

[Airway neuropeptides--what is their role in physiopathology?].

Research work over the last ten years has identified a nonadrenergic, non cholinergic innervation in the upper and lower airways, in man and other animals. This innervation has two components: An excitatory bronchoconstrictor component, of which the neurotransmitters are peptides, substance P, neurokinin A, CGRP and gastrin-releasing peptide. A bronchodilating component known as inhibitor, of which the neurotransmitters are the vasoactive intestinal peptide and nitric oxide. Those neurotransmitters effect all the systems that are involved in allergic respiratory diseases, asthma and allergic rhinitis. They may therefore have a role to play in the physiopathology of these diseases.

Adrenergic Fibers↗
PubMed1994

[Neuropeptides of the nasal innervation and allergic rhinitis].

In the last decade, several neuropeptides have been localized in sensory, sympathetic and parasympathetic neurons of the upper and lower airways in animals and man. Tachykinins are sensory neuropeptides: after nasal allergen challenge in patients with allergic rhinitis, substance P is locally released and induces nasal obstruction. Like neurokinin A, another tachykinin of sensory C fibers, substance P induces an increase in vascular permeability and a recruitment of inflammatory cells. Thus, tachykinins partially mimic nasal response to antigen. Calcitonin gene-related peptide (CGRP) is another sensory neuropeptide and vasoactive intestinal peptide (VIP) is a neuropeptide localized to parasympathetic fibers. The distributions of CGRP and VIP fibers and of their binding sites, as well as their physiological effects described in other tissues, are consistent with a vasodilator effect. On the other hand, neuropeptide Y (NPY), a sympathetic neuropeptide, would seem to be a potent vasoconstrictor. Thus, nasal neuropeptides, and above all sensory neuropeptides, could play a role in the pathophysiology of allergic rhinitis.

Allergens↗
PubMed1994

[Bronchial hyperreactivity: neurogenic factors].

Over the last fifty years, the role of neurogenic factors in asthma and bronchial hyperreactivity has been intensively investigated. The roles of the cholinergic and adrenergic nervous systems have been clarified and several sub-types of muscarinic receptors identified. The localisation and functions of both muscarinic and adrenergic receptors have been further specified. It has also been shown that afferent nerve fibers as well as sympathetic and parasympathetic nerve fibers secrete various neuropeptides. The physiological role of these peptides is not yet known but it appears that they have a powerful effect on bronchial smooth muscle tone, microvascular permeability, mucus secretion and secretion of mediators by inflammatory cells. The results of numerous studies suggest that there are several abnormalities in the adrenergic and cholinergic nervous systems of asthmatic patients, but that these abnormalities are not themselves the cause of bronchial hyperreactivity. They may however contribute to enhance it. The role of the various newly identified neuropeptides in the genesis and maintenance of bronchial hyperreactivity remains to be determined.

Adrenergic Fibers↗
PubMed1992

Inhibition of histamine-induced nasal obstruction by cetirizine in allergic rhinitis.

This double-blind randomized crossover placebo-controlled study was designed to assess objectively the nasal antihistamine effect of cetirizine in patients with allergic rhinitis and control subjects. Nasal challenge was performed by nebulization of increasing doubling doses of histamine (0; 0.04 to 1.28 mg/nostril) in six patients with allergic rhinitis and six control subjects on cetirizine (2 x 10 mg daily for 3 days) or placebo. Sneezings were counted and nasal obstruction was assessed by subjective scoring and by objective measurement of nasal airway resistance by posterior rhinomanometry. Histamine induced sneezing and a dose-dependent increase in nasal airway resistance and in perceived sensation of obstruction. Responses were greater in patients with allergic rhinitis compared with controls, although of borderline significance for nasal obstruction. Cetirizine totally abolished sneezing and significantly reduced increase in nasal airway resistance and perceived sensation of nasal obstruction both in normal and rhinitic subjects. Our results demonstrate by an objective measurement the nasal antihistamine effect of cetirizine. We propose this simple provocation test to assess the time-course of the effect of antihistamines and to compare the relative potency of related compounds.

Adult↗
PubMed1992

Lymphocytes infiltrating normal human lung and lung carcinomas rarely express gamma delta T cell antigen receptors.

It has been suggested that T lymphocytes expressing gamma delta T cell receptors (TCR) could play an important role in the defence of epithelia against infection and neoplastic transformation, but the potential for gamma delta T lymphocytes to serve these functions in human respiratory epithelium has received little attention. In this study, we used immunohistochemical techniques and specific monoclonal antibodies to characterize the number and distribution of T lymphocytes expressing alpha beta and gamma delta TCR in normal human lung and in lung carcinomas. T lymphocytes present in normal bronchi and alveolar parenchyma were predominantly of the alpha beta TCR phenotype, whereas gamma delta T lymphocytes represented only 1.1 +/- 0.7% and 1.3 +/- 0.5% of total CD3+ lymphocytes respectively. An important lymphocytic infiltration was noted in the stroma of all primary lung carcinomas examined, and some T lymphocytes were also present infiltrating between tumour cells. These T lymphocytes were almost entirely alpha beta T cells and only rare gamma delta T cells were found, regardless of the histologic type of carcinoma (0.8 +/- 0.1% of CD3+ T cells). This study demonstrates that T cells present in normal bronchi and lung parenchyma and those infiltrating primary lung carcinomas express predominantly alpha beta TCR. These findings do not support the conclusion that gamma delta T lymphocytes play an important role either in the defence of human lung epithelia or in immune responses directed against primary lung carcinomas.

Adenocarcinoma↗
PubMed1992

Pulmonary Hodgkin's disease in HIV-infected patient. Diagnosis by bronchoalveolar lavage.

We report herein the pulmonary recurrence of Hodgkin's disease coincidental with a marked decrease in the peripheral blood CD4 lymphocyte count in an HIV-seropositive patient with alveolar consolidation on chest roentgenogram. The diagnosis of lung parenchyma involvement was made by bronchoalveolar lavage cell analysis and illustrates the reliability of Reed-Sternberg cell identification in bronchoalveolar lavage for the diagnosis of pulmonary localization of Hodgkin's disease.

Adult↗
PubMed1991

Clinical and inflammatory responses to exogenous tachykinins in allergic rhinitis.

Our purpose was to characterize the tachykinin receptor type involved in nasal obstruction to exogenous substance P in rhinitic patients. We also attempted to assess biochemical and cellular events associated with this response. Nasal challenges were performed in seven patients with allergic rhinitis. They received increasing doses (10 to 80 nmol) of substance P, of neurokinin A, of the N-terminal fragment of substance P, substance P(1-9), and of saline on 4 different days separated by 14 days. Nasal airway resistance (NAR) increased in a dose-dependent manner on substance P. Maximal increase reached 4.5-fold basal NAR. Response to neurokinin A was significantly lower (less than 2-fold basal NAR). No effect was observed on substance P(1-9) and saline. This order of activity [substance P much greater than neurokinin A greater than substance P(1-9) = saline] indicates an NK1 receptor-mediated mechanism inducing local vasodilation. No histamine release was found after any of the four challenges. Proteins significantly increased in nasal lavage fluid on both substance P and neurokinin A, whereas substance P(1-9) and saline had no effect. The percentage of albumin increased in nasal lavage fluid from 30 to 50% of total proteins on substance P and neurokinin A, indicating microvascular leakage. Polymorphonuclear cells significantly increased from 9 to 36% on substance P, from 13 to 49% on neurokinin A, and from 13 to 55% on substance P(1-9). Eosinophils increased in five patients on substance P (from 0.1 to 5% for the group), in three patients after neurokinin A, and in two after substance P(1-9).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Gamma/delta T-lymphocytes are not increased in number in granulomatous lesions of patients with tuberculosis or sarcoidosis.

gamma delta T-lymphocytes have been suggested to play a role in granuloma formation and to participate in the immune responses observed in tuberculosis and sarcoidosis. To further evaluate the role of gamma delta T-lymphocytes in these disorders, we used immunohistochemical techniques and specific monoclonal antibodies to characterize the number of distribution of T-lymphocytes expressing alpha beta and gamma delta T-cell receptors in granulomatous lesions from patients with sarcoidosis (n = 8) or tuberculosis (n = 4). The vast majority of T-lymphocytes present in lymph nodes from patients with tuberculosis or sarcoidosis expressed alpha beta TCR, whereas only rare gamma delta T-lymphocytes were observed inside or at the periphery of the granulomas. Recently formed granulomas induced by positive Kveim test reactions in patients with sarcoidosis also contained only small numbers of gamma delta T-lymphocytes, including those present in biopsies from two patients with increased numbers of circulating gamma delta T-lymphocytes. These observations demonstrate that T-cells involved in immune granulomatous reactions in sarcoidosis and tuberculosis express predominantly alpha beta TCR, and they do not support the conclusion that gamma delta T-lymphocytes necessarily play an important role in granuloma formation.

Adult↗
PubMedDate not supplied

Histidylated polylysine as a synthetic vector for gene transfer into immortalized cystic fibrosis airway surface and airway gland serous cells.

BACKGROUND: We recently designed a cationic polymer called histidylated polylysine made of polylysine partially substituted with histidyl residues which become protonated at slightly acidic pH. This polymer is thought to induce the leakage of acidic vesicles containing plasmid/histidylated polylysine complexes. METHODS: and results Here, we have analyzed the ability of histidylated polylysine to transfer reporter or CFTR genes into immortalized cystic fibrosis airway surface epithelial cells (sigmaCFTE29o- cells) and airway gland serous cells (CF-KM4 cells) which are both important targets for cystic fibrosis gene therapy. The luciferase reporter gene expression measured after gene transfer with histidylated polylysine into both cell lines was quite high and similar to that obtained with commercially available vectors. In addition, the level of expression was not dependent on the presence of a membrane disrupting agent such as chloroquine. Histidylated complexes were present in slightly acidic non-lysosomal cellular compartments as shown by a cytological approach using biotinylated plasmid, lysosome-specific antibodies and confocal microscopy. Histidylated complexes appeared to be of small size when prepared at low ionic strength and formed aggregates upon increasing the ionic strength. However, aggregate formation was prevented by the addition of 10% fetal bovine serum. Gene transfer efficiency varied with the size of the complexes and decreased when small particles were used. CONCLUSIONS: These results suggest that histidylated polylysine may be an efficient non-viral vector for gene transfer into cystic fibrosis airway surface epithelial cells and airway gland serous cells.

Animals↗
PubMedDate not supplied

Increased nitric oxide in exhaled air in patients with systemic sclerosis.

OBJECTIVE: To assess the lung production of nitric oxide (NO) in patients with systemic sclerosis. METHODS: The NO concentration and its rate of production by the lungs were measured in the exhaled air in 14 patients with systemic sclerosis and in 12 healthy control subjects using the chemiluminescent method. RESULTS: The NO concentration and its rate of production were significantly increased in scleroderma patients (mean +/- SEM, 18.7 +/- 1.7 ppb and 5.8 +/- 0.5 nmol/min, respectively), as compared with control subjects (11.2 +/- 0.8 ppb and 4.3 +/- 0.4 nmol/min, p < 0.01 and p < 0.05, respectively). CONCLUSION: The pulmonary production of NO is increased in scleroderma patients, which might reflect and contribute to the inflammatory processes of the lungs in systemic sclerosis.

Adult↗