Biomedical subjects

E Escudier

Publications and source records attributed to E Escudier.

At least 19 recordsLinked to original sources

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

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↗

PubMed1995

Alveolar hemorrhage. Diagnostic criteria and results in 194 immunocompromised hosts.

To establish the diagnosis of alveolar hemorrhage (AH) in cells recovered by bronchoalveolar lavage (BAL), Golde and colleagues created a score based on the hemosiderin content of alveolar macrophages stained with Prussian blue. We used an easier method, calculating the percentage of siderophages among the total alveolar macrophages recovered by BAL. We have retrospectively studied this method in 240 BALs performed in 194 immunocompromised patients. Prussian blue staining was performed on each BAL sample, and the Golde score was calculated for 47 samples chosen at random. The methods were compared for diagnosing AH. The percentage of siderophages correlated well with the Golde score. AH was defined by at least 20% siderophages. This definition was validated by comparison with the method of Kahn and coworkers. AH was present in 87 (36%) of the samples and was significantly associated with four parameters: thrombocytopenia (< 50,000/mm3), other abnormal coagulation parameters, renal failure (creatinine > or = 2.5 mg/dl), and a history of heavy smoking. The diagnosis of AH did not correlate with either the cause or the outcome of pneumonia. AH was seen more frequently in cardiac transplant patients (75%). In our experience, (1) a percentage of siderophages > or = 20% is sufficient and is an easier determinant of the diagnosis of AH than the Golde score; and (2) AH is rarely the sole cause of lung injury and is usually associated with other causes of pneumonia. AH may be considered more as a sign than as a distinct disease in this population.

Adolescent↗

PubMed1995

Ciliary abnormalities in bronchial epithelium of smokers, ex-smokers, and nonsmokers.

Although respiratory changes induced by tobacco smoke have been extensively described, no study has focused on ciliary abnormalities associated with chronic smoking. Ciliary ultrastructure was studied in 37 adults with chronic sputum production (CSP) consisting of 13 current smokers (Group 1), 5 ex-smokers (Group 2), and 19 nonsmokers (Group 3). Five healthy nonsmokers constituted the control group (Group 4). Clinical and radiologic data and respiratory function tests were recorded. Acute respiratory infection was diagnosed by culture of tracheobronchial secretions obtained during bronchoscopy. Bronchial ciliated cells were obtained and processed for transmission electron microscopy. Within each group, the percentages of abnormal cilia were similar in patients with either chronic bronchitis or bronchiectasis and in patients with or without acute infection. The percentage of axonemal ultrastructural abnormalities (AUA) was higher in smokers (16.5% +/- 2.7%) and ex-smokers (17.5% +/- 7%) than in nonsmokers (5.2% +/- 1%) or control subjects (0.7% +/- 0.2%) (p < 0.0002). The AUA were polymorphic, characteristic of acquired ultrastructural changes. These results suggest that chronic smoking may induce an increased number of abnormal cilia which could participate in impairment of tracheobronchial clearance and which appears to be independent of the etiology of CSP.

Adult↗

PubMed1994

Secondary alveolar proteinosis is a reversible cause of respiratory failure in leukemic patients.

We report here our experience of secondary pulmonary alveolar proteinosis (PAP) in patients with hematologic malignancies. The diagnosis of PAP was made by bronchoalveolar lavage (BAL) and based on the identification of periodic acid-Schiff-positive proteinaceous material with the characteristic ultrastructural pattern. Ten patients with leukemia and secondary PAP are described. Three patients had received bone marrow transplants. Data obtained from sequential BAL have shown that at least four of them--all of them achieving complete remission or recovery from neutropenia after bone marrow transplantation--had reversible PAP, and we emphasize this potential reversibility. Furthermore, in order to estimate the frequency of PAP in hematologic patients, we retrospectively studied 113 episodes of pneumonia occurring in our department over a 2-yr period. The incidence of secondary PAP in patients with pulmonary symptoms was so estimated at 5.3% among all the hematologic population, and to 10% in patients with myeloid disorders. This report (1) confirms that BAL is an accurate way to diagnose PAP in immunocompromised hosts, (2) emphasizes that PAP is not an unusual cause of respiratory failure in this population and that it is strongly associated with myeloid disorders, and (3) shows that secondary PAP is potentially reversible, especially if complete remission of the underlying disease is achieved.

Adolescent↗

PubMed1994

Bronchoalveolar lavage during neutropenic episodes: diagnostic yield and cellular pattern.

Few data are available concerning the relationship between alveolar and blood cell populations during neutropenia. We wanted to compare the value of pulmonary endoscopic procedures with lavage in neutropenic (polymorphonuclear (PMN) count < or = 1,000.mm-3) and non-neutropenic settings. We therefore, retrospectively, reviewed the results of 118 investigations for pneumonia in patients with malignant haematological diseases. All had bronchoalveolar lavage (BAL), and some had additional studies with protected bacteriological samples. Each BAL specimen was studied after cytocentrifugation by cytological examination for opportunistic infections, haemorrhage, virus, legionellae, and bacteriological cultures. The diagnostic yield of all endoscopic procedures (BAL, telescoping plugged catheter and protected specimen brush) was 53% in neutropenic (Group 1) and 61% in non-neutropenic (Group 2) patients. The aetiological pattern of pneumonia was nearly the same in the two groups, except for more alveolar proteinosis in Group 1 and more cytomegalovirus (CMV) in Group 2. The absolute number of alveolar cells recovered through BAL (total number, macrophages, lymphocytes and PMNs) was significantly lower in neutropenic patients. We conclude that: 1) neutropenic patients with pneumonia require the same investigative approach as non-neutropenic patients; 2) profound neutropenia may be concomitant with a decreased cellularity of alveoli, which may reflect the consequences of marrow aplasia on the pulmonary cell population and/or direct effect of chemotherapy on the lung.

Adolescent↗