Search PubMed⌕ Search

Biomedical subjects

E Escudier

Publications and source records attributed to E Escudier.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effect of increased pressure on tracheal ciliary beat frequency.

Effects of increased ambient pressure on mucociliary clearance have been poorly investigated. The effects of increasing pressures on ciliary beat frequency (CBF) of guinea-pig tracheal rings were studied in vitro. Increased pressures of 25 and 100 kPa induced a significant and equivalent enhancement of CBF from 30 min after the pressure increase. The increase in CBF observed after a pressure increase of 50 kPa (inspiratory oxygen fraction = 21%), was significantly greater than that observed with an equivalent oxygen tension at atmospheric pressure, i.e. with a gas mixture containing 30% oxygen. Addition of N(G)-nitro-L-arginine methylester (L-NAME) inhibited the enhancement in CBF observed after the 25 kPa pressure increase. Addition of L-arginine reversed the effect of L-NAME. These results demonstrate that a pressure increase applied to tracheal rings, in vitro, induces an enhancement of ciliary beat frequency and that generation of nitric oxide may be involved in this ciliary stimulation.

Animals↗
PubMed1999

Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a group of heterogeneous disorders of unknown origin, usually inherited as an autosomal recessive trait. Its phenotype is characterized by axonemal abnormalities of respiratory cilia and sperm tails leading to bronchiectasis and sinusitis, which are sometimes associated with situs inversus (Kartagener syndrome) and male sterility. The main ciliary defect in PCD is an absence of dynein arms. We have isolated the first gene involved in PCD, using a candidate-gene approach developed on the basis of documented abnormalities of immotile strains of Chlamydomonas reinhardtii, which carry axonemal ultrastructural defects reminiscent of PCD. Taking advantage of the evolutionary conservation of genes encoding axonemal proteins, we have isolated a human sequence (DNAI1) related to IC78, a C. reinhardtii gene encoding a dynein intermediate chain in which mutations are associated with the absence of outer dynein arms. DNAI1 is highly expressed in trachea and testis and is composed of 20 exons located at 9p13-p21. Two loss-of-function mutations of DNAI1 have been identified in a patient with PCD characterized by immotile respiratory cilia lacking outer dynein arms. In addition, we excluded linkage between this gene and similar PCD phenotypes in five other affected families, providing a clear demonstration of locus heterogeneity. These data reveal the critical role of DNAI1 in the development of human axonemal structures and open up new means for identification of additional genes involved in related developmental defects.

Amino Acid Sequence↗
PubMed1998

Mucin gene (MUC 2 and MUC 5AC) upregulation by Gram-positive and Gram-negative bacteria.

Bacterial infection of the lung is associated with mucin overproduction. In partial explanation of this phenomenon, we recently reported that supernatant from the Gram-negative organism Pseudomonas (P.) aeruginosa contained an activity that upregulated transcription of the MUC 2 mucin gene [J.-D. Li, A. Dohrman, M. Gallup, S. Miyata, J. Gum, Y. Kim, J. Nadel, A. Prince, C. Basbaum, Transcriptional activation of mucin by P. aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease, Proc. Natl. Acad. Sci. U.S.A., 94 (1997) 967-972]. The purpose of the present study was to determine whether mucin genes other than MUC 2 are so regulated and whether Gram-positive organisms also contain mucin stimulatory activity. Results from in situ hybridization and RNase protection assays showed that P. aeruginosa upregulates MUC 5AC as well as MUC 2 in both bronchial explants and cultured airway epithelial cells. The upregulation of both genes by P. aeruginosa can be mimicked by lipopolysaccharide (LPS) and can be blocked by the tyrosine kinase inhibitor genistein. In addition, both genes are upregulated by a variety of Gram-positive as well as Gram-negative organisms showing the same rank order of potency. These data indicate the existence of a general mechanism by which epithelial cells respond to the presence of bacteria by increasing mucin synthesis.

Bronchi↗
PubMed1998

Expression of the transforming growth factor beta isoforms in inflammatory cells of nasal polyps.

OBJECTIVE: To determine the expression and the potential role of transforming growth factor beta (TGF-beta) in nasal polyposis. DESIGN: Comparison of TGF-beta expression between normal and inflammatory nasal mucosa and polyps; in inflammatory nasal polyps, characterization of the TGF-beta isoforms expression and their potential location in macrophages and eosinophils. SETTING: Patients and samples were selected at the Hôpital Intercommunal, Créteil, France, and immunohistochemistry and immunoblots were performed at the Institut National de la Sante et de la Recherche Medicale U296 (Universite Paris XII, France). SUBJECTS: Nasal polyps and nasal mucosa were sampled in 21 patients during ethmoidectomy, and muscosa was sampled in 6 healthy patients during rhinoplasty. METHODS: Immunohistochemistry and Western blot analysis were performed using specific antibodies to TGF-beta1-3, TGF-beta1, TGF-beta2, and TGF-beta3 isoforms. Double labeling was also performed using anti-TGF-beta1 antibody together with macrophages or eosinophil-specific antibodies. RESULTS: The expression of TGF-beta(1-3) was significantly higher in inflammatory nasal polyps than in inflammatory nasal mucosa and higher in inflammatory nasal mucosa than in nasal mucosa from healthy patients. Transforming growth factor beta1 was the main isoform detected in inflammatory nasal polyps, and it was present in numerous macrophages and in some eosinophils. CONCLUSIONS: Transforming growth factor beta, mainly TGF-beta1, is strongly expressed in inflammatory nasal mucosa, where it could be produced by macrophages and eosinophils. Transforming growth factor beta could induce epithelium and connective tissue modifications and therefore be involved in the pathogenesis of nasal polyposis.

Adult↗
PubMed1998

Results of tympanoplasty in children with primary ciliary dyskinesia.

OBJECTIVE: To assess the results of tympanoplasty in children with primary ciliary dyskinesia complicated by tympanic perforation or cholesteatoma with hearing loss and/or recurrent otorrhea. DESIGN: Retrospective study. Postoperative follow-up of 26.3 months in the type 1 tympanoplasty group and 46 months in the child with cholesteatoma. SETTING: Hospitalized care, referral center. PATIENTS: Seven children with primary ciliary dyskinesia, complicated in 6 children by 9 tympanic perforations (3 bilateral perforations) and in 1 child by an attical cholesteatoma. RESULTS: After 9 type 1 tympanoplasties, the grafts were intact in 9 ears, with no recurrence of otorrhea, but serous otitis media was present in 6 of the 9 ears. Auditory improvement was significant, with an average gain of 17-dB hearing level in speech frequencies. After a canal wall-down tympanoplasty with mastoidectomy for attic cholesteatoma in 1 ear, the cavity that was operated on showed no signs of otorrhea or residual cholesteatoma after a follow-up of 46 months. CONCLUSION: In children with primary ciliary dyskinesia, tympanoplasty has a high probability of graft success and auditory improvement, despite the frequent recurrence of serous otitis media.

Adolescent↗
PubMed1998

Epithelial cell proliferation, apoptosis, and apoptosis inhibition in inverted papillomas.

Inverted papillomas (IPs) are rare benign tumors of nasal epithelium with high recurrence rates and malignant transformation potential. Their etiology is still uncertain, and the mechanism of their growth has not yet been fully described. The purpose of this study was to detect, quantify, and compare cell proliferation, apoptosis, and apoptosis inhibition in hyperplastic epithelium from IPs and in inflammatory nasal polyps (NPs). IP samples were obtained after surgical removal of tumor in 13 patients, and NPs were sampled during endoscopic ethmoidectomy in 10 patients with nasal polyposis. Cell proliferation and apoptosis inhibition, respectively, were assessed by immunohistochemical identification of the proliferating cell nuclear antigen (PCNA) and the oncoprotein Bcl-2. Apoptosis was evaluated by analyzing the DNA fragmentation. Cell proliferation and apoptosis were significantly higher in IPs than in NPs (P = .0002 and P = .043, respectively), while apoptosis inhibition was significantly lower in IPs than in NPs (P = .001). Concerning IPs, cell proliferation was significantly higher than apoptosis (P = .0029) and apoptosis inhibition (P = .0015). The increase in epithelial cell proliferation seemed to be greater in IPs with dysplasia than in IPs without dysplasia. Increased epithelial cell proliferation, but not apoptosis and apoptosis inhibition, seems to be involved in the development of IP.

Adult↗
PubMed1997

Isolation of several human axonemal dynein heavy chain genes: genomic structure of the catalytic site, phylogenetic analysis and chromosomal assignment.

Dynein heavy chains (DHCs) are the main components of multisubunit motor ATPase complexes called dyneins. Axonemal dyneins provide the driving force for ciliary and flagellar motility. Recent molecular studies demonstrated that multiple DHC isoforms are produced by separate genes. We describe the isolation of five human axonemal DHC genes. Analysis of the human genomic clones revealed the existence of intronic sequences that were used to demonstrate that human axonemal DHC genes are located on different chromosomes. The cloned human DHC sequences were integrated into an evolutionary approach based on phylogenetic analysis. Tissue expression studies showed that these human axonemal DHCs are expressed in testis and/or trachea, two tissues with axonemal structures that can be altered in primary ciliary dyskinesia, making DHC genes strong candidates in the genesis of these human diseases.

Amino Acid Sequence↗
PubMed1997

Myofibroblast accumulation induced by transforming growth factor-beta is involved in the pathogenesis of nasal polyps.

Myofibroblasts that express alpha-smooth muscle actin (alpha-SMA) are detected in many chronic inflammatory diseases. Transforming growth factor-beta (TGF-beta) is a potent inducer of myofibroblast accumulation in tissues. In this study, scattered myofibroblasts and TGF-beta were quantified and localized in nasal polyps (NPs) and normal nasal mucosa (NM). NPs were sampled in 16 patients during ethmoidectomy and NM was obtained from 10 control subjects during rhinoplasty. alpha-SMA and TGF-beta were detected using immunohistochemistry and the numbers of labeled cells were quantified (alpha-SMA and TGF-beta indices) and compared between NPs and NM. In eight NPs, in which the pedicle was preserved, alpha-SMA and TGF-beta were evaluated and compared in the pedicle, central, and tip areas. Finally, TGF-beta expression was compared between low (zone 1), moderate (zone 2), and high (zone 3) zones of alpha-SMA positivity. alpha-SMA and TGF-beta indices were significantly higher in NPs than in NM. In the eight selected NPs, alpha-SMA-positive cells were significantly more abundant in the pedicle than in the central and tip areas, whereas TGF-beta-positive cells were significantly more numerous in the pedicle than in the tip area. The number of TGF-beta-positive cells was significantly higher in zone 3 than in zone 1 of alpha-SMA positivity. Myofibroblasts, which are abundant in NPs but rare in NM, could be involved in the growth of NPs by inducing extracellular matrix accumulation. The local development of myofibroblasts in NPs could be controlled by TGF-beta, locally produced by inflammatory cells.

Actins↗
PubMed1997

Incidence of primary ciliary dyskinesia in children with recurrent respiratory diseases.

The goal of the study was to evaluate the incidence of primary ciliary dyskinesia (PCD) in children suffering from recurrent respiratory tract infections (RRIs) by means of noninvasive method. Respiratory ciliated cells were collected by nasal brushing in 118 children (4.6 +/- 2.5 years) with RRIs. The ciliary beat frequency (CBF) was measured with a stroboscopic method, and when the CBF was abnormal, the ciliary ultrastructure was analyzed by a quantitative method. The CBF could be measured in 106 patients (90%) and was abnormal in 15 patients. The ciliary ultrastructure was found to be abnormal in 11 of 15 patients: PCD was diagnosed in 6 cases, and acquired ciliary defects were observed in the remaining 5 patients. Our conclusion, that PCD is rare but net exceptional (5.6%) in children with RRIs, justifies the systematic investigation of ciliated cells in such patients. For this purpose, nasal brushing can be used to sample ciliated cells even in young children.

Algorithms↗
PubMed1996

Increased epithelial cell proliferation in nasal polyps.

OBJECTIVE: To detect, quantify, and compare respiratory epithelial cell proliferation in nasal mucosa and polyps from patients with nasal polyposis. DESIGN: Cohort study. SETTING: Patients and samples were selected at the Hôpital Intercommunal de Créteil (France). Flow cytofluorometry and immunohistochemistry were performed at Hôpitaux Tenon and Mondor (Université Paris [France] VI et XII). PATIENTS: Twenty-one patients undergoing endoscopic ethmoidectomy for treatment of nasal polyposis. METHODS: In 10 cases, epithelial cells were removed from frozen inferior turbinate mucosa and polyps by mechanical disaggregation and were then analyzed by flow cytofluorometry, providing the cell DNA content (propidium iodide labeling) and the percentage of S-phase cells. In 11 cases, inferior turbinate mucosa and polyps were fixed in formaldehyde and embedded in paraffin. Proliferating cell nuclear antigen expression in the epithelium was quantified by immunohistochemistry; a proliferating cell nuclear antigen index was calculated for each sample in the basal area, suprabasal area, and full height of the epithelium. RESULTS: All cell populations studied were diploid, and percentages of S-phrase cells were significantly higher in nasal polyps than in mucosa. Proliferating cell nuclear antigen indexes were significantly higher in nasal polyps than in the suprabasal area and full height of the mucosal epithelium. CONCLUSION: Cell proliferation is increased in epithelium from nasal polyps. Epithelial damage caused by inflammatory mediators could induce this increased cell proliferation via epithelial repair processes. Inflammatory cells could up-regulate epithelial cell proliferation by secreting growth factors.

Cell Division↗
PubMed1996

Secondary alveolar proteinosis in cancer patients.

Pulmonary alveolar proteinosis (AP) is a rare cause of progressive respiratory failure in the normal host. It was first described by Rosen and coworkers in 1958 on the morphological basis of the accumulation of a PAS-positive material in the alveolar space. A couple of years later, AP was found to be unexpectedly associated with malignant diseases, especially with acute or chronic myeloid leukemias. These forms were called secondary AP in opposition to the primary forms observed in normal hosts. Probably because of its morphological definition and late diagnosis by means of histology or autopsy material, secondary AP has been considered to be life-threatening for a long time. However, recent observations show that AP can be diagnosed early in the course of the disease, especially through bronchoalveolar lavage, as long as the pathologist is aware of this possibility. Another point is that secondary AP can be reversible, both clinically and morphologically. This article summarizes the clinical features, morphological findings, and the main malignant diseases associated with secondary AP. We also comment on the hypotheses proposed in the literature to explain the association of AP, malignant disease, and immunosuppression. Alveolar macrophage is likely a key factor in the occurrence of secondary AP.

Biopsy↗
PubMed1996

Epithelial cell proliferation in nasal polyps could be up-regulated by platelet-derived growth factor.

The modifications of epithelial differentiation and proliferation observed in nasal polyps (NP) could be related to local secretion of growth factors, among which platelet-derived growth factor (PDGF) could play a key role. We therefore prospectively studied, by immunohistochemistry, proliferating cell nuclear antigen (PCNA, an S-phase cell marker), PDGF, and CD-68 (activated macrophages marker) expression in NP and inferior turbinate mucosa (NM) in 11 patients. Our data show that PCNA and PDGF expression are increased in NP epithelium, while CD-68 expression is increased in NP epithelium and lamina propria when compared to NM. Increased local PDGF secretion by numerous activated macrophages could therefore be involved in epithelial cell proliferation up-regulation in NP. PDGF could also be involved in the pathogenesis of NP via its connective tissue remodeling actions.

Antigens, CD↗
PubMed1996

Bronchoalveolar lavage in adult sickle cell patients with acute chest syndrome: value for diagnostic assessment of fat embolism.

Fat embolism of necrotic bone marrow could be a frequent cause of acute chest syndrome (ACS) in sickle cell syndromes (SC), as suggested by postmortem findings. To check this hypothesis in living patients, we evaluated the presence of fatty macrophages recovered by bronchoalveolar lavage (BAL) in ACS. We investigated 20 consecutive cases of ACS by BAL, and identification of alveolar cells containing fat droplets was performed using oil red O (ORO), a specific neutral fat stain. The specificity of the method was determined on control groups, including eight SC patients without acute chest syndrome and 15 non-SC patients. A cut-off of > 5% of alveolar macrophages containing fat droplets was determined from the control groups to assess the diagnosis of fat embolism. In 12 ACS episodes, BAL exhibited > 5% of fatty macrophages, ranging from 10% to 100% (median value 46.5%). In 11 cases, fat embolism was associated with proven (n = 8) or probable (n = 3) bone marrow infraction, which mostly predated ACS. Eight ACS episodes were associated with a low percentage (< or = 5%) of fatty alveolar macrophages and could be related to a cause other than fat embolism in six episodes, such as sepsis, in-situ thrombosis, or rib infarcts generating hypoventilation. This study supports the diagnostic yield of BAL for fat embolism, which can be incriminated in 60% of cases of ACS in this adult population.

Adolescent↗
PubMed1996

Airway epithelial damage induced by sulfur mustard in guinea pigs, effects of glucocorticoids.

Sulfur mustard (SM) represents a potential chemical warfare agent. In order to characterize SM-induced airway epithelial damage, we studied the effects of an intratracheal injection of 0.3 mg/kg of SM in guinea pigs, 5 h, 24 h, 14 days and 35 days after exposure. During the acute period, lesions prevailed in tracheal epithelium exhibiting intra-epithelial blisters, inflammatory cell infiltration and columnar cell shedding with exposure of basal cells. Fourteen days after intoxication, tracheal epithelium appeared disorganized and showed a significant decrease in height and cell density. Tracheal epithelium recovery was still not complete even 35 days after SM-intoxication. At day 14, in SM-intoxicated guinea pigs treated with betamethasone from day 7 to day 14, epithelium height, cell density and cell proliferation (evaluated by immunohistochemistry) were significantly increased compared to untreated guinea pigs. In conclusion, the lesions observed in SM-intoxicated guinea pigs seem to be in accordance with clinical human observations and are relevant to the study of airway epithelial damage induced by SM. This animal model could be used to illustrate tracheal epithelium regeneration mainly derived from basal cells and to show glucocorticoid effects on airway epithelial recovery after chemical aggression.

Animals↗
PubMed1996

Modified epithelial cell distribution in chronic airways inflammation.

Although airway epithelium is known to be modified during chronic respiratory diseases, epithelial cells have rarely been precisely quantified. We therefore intended to evaluate epithelial cell distribution in inflammatory airways, using a cytological approach. Nasal airway cells in 12 patients with nonallergic chronic rhinitis were sampled by brushing, quantified after cytocentrifugation and compared to those from eight controls. Cell populations were quantified after May-Grünwald Giemsa staining and alpha-tubulin immunolabelling to demonstrate ciliary differentiation. When compared to controls, rhinitis patients exhibited lower percentages of ciliated cells (59 +/- 4 versus 32 +/- 2%, respectively), and higher percentages of goblet (24 +/- 3 versus 37 +/- 2%) and basal cells (9 +/- 1 versus 18 +/- 2%). After tubulin immunolabelling, positive staining was specifically detected in cells with cilia (LC+), and in the cytoplasm of some small round cells without obvious cilia (LC-). Fewer immunolabelled cells were detected in rhinitis patients than in controls (with significantly lower percentages of LC+ and higher percentages of LC-). Nasal brushing is an effective technique for quantification of airway epithelial cells. Tubulin immunolabelling is useful to detect ciliated cells and distinguishes another cell population, possibly preciliated cells. These cytological findings suggest the presence of modifications of epithelial differentiation and proliferation, possibly related to local chronic inflammation.

Adult↗
PubMed1996

Nasal polyposis pathogenesis: a flow cytometric and immunohistochemical study of epithelial cell proliferation.

In nasal polyps, constantly associated with chronic inflammation, frequent epithelial morphological changes (squamous metaplasia, secretory hyperplasia) suggest a dysregulation of epithelial cell proliferation. Cell proliferation in nasal respiratory epithelium was therefore evaluated in nasal polyposis. In 20 patients, we compared cell proliferation in mucosa from the inferior turbinate to these in nasal polyps using two methods: Flow cytometry analyzing first the ploidy and the percentage of S-phase cells (propidium iodide DNA labeling), secondly the percentage of Ki-67-labeled cells and the green fluorescent index (fluorescein-conjugated anti-human Ki-67 antigen labeling, and thirdly the percentage of Ki-67-labeled cells being in S-phase. Immunohistochemistry, quantifying the expression of Ki-67 antigen in the epithelium permitting to calculate a Ki-67 index. All cell-populations studied were diploid. Percentages of S-phase cells, Ki-67-labeled cells, Ki-67 labeled cells being in the S-phase and green fluorescence index was significantly higher in nasal polyps than in mucosa Ki-67 index were significantly higher in nasal polyps than in mucosa in the epithelium. Epithelial cell proliferation which is therefore increased in nasal polyp could play an important role in nasal polyposis pathogenesis and its relationships with inflammation can be suggested.

Cell Division↗
PubMed1996

Acquired ciliary abnormalities of nasal mucosa in marrow recipients.

Respiratory symptoms are frequent after bone marrow transplantation (BMT). Most studies focus on lesions of the lower respiratory tract. However, sinusitis is also common in this setting, especially after allogeneic BMT. The nasal respiratory epithelium is the first line of airway defense and is very similar to the bronchial epithelium, especially in terms of ciliary beat frequency and ultrastructural pattern of ciliated cells. We have prospectively studied the nasal respiratory epithelium of 20 marrow recipients (four autologous, 16 allogeneic) with or without sinusitis, by brushing and biopsy of the median turbinate between 2.5 and 148 months after transplant. Samples were studied for ciliary beat frequency, cytology, ultrastructural pattern and HLA-DR expression. We found that 17 of our 20 patients had abnormalities of their nasal epithelium, mainly consisting of either squamous metaplasia or heterogeneous axonemal defects of peripheral and central microtubules. No relationship between these findings and the presence of acute or chronic sinus infection, previous irradiation, graft-versus-host disease or immunosuppressive therapy could be demonstrated in this preliminary study. These abnormalities probably have multiple causes. Prospective studies are needed to determine the respective roles of treatments, infections and immune disorders associated with BMT in these abnormalities, and to know their natural evolution over time and their impact on the occurrence of upper or lower respiratory tract infections.

Acute Disease↗