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Biomedical subjects

A Didier

Publications and source records attributed to A Didier.

At least 19 recordsLinked to original sources

The lipid transfer proteins (LTP) essentially concentrate in the skin of Rosaceae fruits as cell surface exposed allergens.

The localization and distribution of non-specific lipid transfer proteins (nsLTP) allergens in the skin and pulp of Rosaceae fruits (apple, peach, apricot, plum) has been investigated. nsLTP essentially concentrate in the pericarp of the fruits whereas the pulp contains lower amounts of allergens. Immunolocalization showed they are primarily located in the cytosol but are subsequently excreted and finally accumulate at the plasmalemma-cell wall interface and in the cell wall. However, high discrepancies were observed in the content of allergens among, e.g. different cultivars of apple. As a consequence, the consumption of peeled-off fruits is recommended to reduce the risk of severe allergic reactions (anaphylactic shock) in individuals sensitized to Rosaceae fruits.

Allergens↗

Long-term fate and distribution of newborn cells in the adult mouse olfactory bulb: Influences of olfactory deprivation.

The adult subventricular zone produces neuroblasts that migrate to the main olfactory bulb, where they differentiate into interneurons in the glomerular and granular layers. Using bromodeoxyuridine labeling, the survival of newborn cells was assessed in these two layers of the MOB in control mice and in mice unilaterally deprived from sensory input by naris occlusion. In control main olfactory bulbs, bromodeoxyuridine-positive cell density decreased about 70% between 15 and 180 days post-bromodeoxyuridine administration but earlier in the glomerular layer than in the granular layer. At all time points examined, newborn cell density was higher in the deep granular layer than in the superficial granular layer. Occlusion started at the age of 2 months and lasted for 15, 30, 45, 60 or 180 days. The newborn cell survival was similarly reduced in both layers by occlusion, during a critical period 15 and 45 days post-occlusion. Interestingly, olfactory deprivation decreased bromodeoxyuridine-positive cell density in the deep granular layer only, indicating a greater dependence of cell fate on sensory input in this sub-layer. Neuronal differentiation was assessed in the granular layer and glomerular layer by multiple double-labeling 45 days post-bromodeoxyuridine-injections, the time point at which the proportion of bromodeoxyuridine-positive cells expressing a neuronal marker reached approximately 85% in the granular layer and approximately 50% in the glomerular layer. Naris occlusion did not significantly affect these proportions. Taken together, our results reveal that the survival of newborn cells has a different time course in the glomerular layer and in the granular layer, but is similarly decreased in each layer by olfactory deprivation. In addition, our data suggest a functional heterogeneity of neurogenesis within the granular layer.

Analysis of Variance↗

Prion protein expression in bovine podocytes and extraglomerular mesangial cells.

The cellular form of the prion protein (PrP(c)) is thought to be a substrate for an abnormal isoform of the prion protein (PrP(sc)). One emerging hypothesis is that the proposed conversion phenomenon takes place at the site at which the infectious agent meets PrP(c). PrP(c) is abundant in the central nervous system, but little is known about the cell-type-specific distribution of PrP(c) in non-neuronal tissues of cattle. We have studied whether PrP(c), a protein found predominantly in neurons, also exists in bovine podocytes, since neurons and podocytes share a large number of similarities. We have therefore examined the expression of PrP(c) by immunohistochemistry, reverse transcription/polymerase chain reaction and enzyme-linked immunosorbent analysis. Immunostained serial sections and specific antibodies against PrP(c) have revealed that PrP(c) is selectively localized in podocytes and is particularly strongly expressed in extraglomerular mesangial cells but not in endothelial or intraglomerular mesangial cells. The selective expression of PrP(c) in podocytes is of special importance, as it suggests that these cells represent possible targets for peripheral infection with prions and demonstrates that PrP(c) can be added to the list of neuronal factors expressed in mammalian podocytes.

Animals↗

[Exacerbations of COPD: An audit of emergency department practice in France].

INTRODUCTION: Exacerbations of COPD are potentially serious events, the recognition and treatment of which appear to be poorly understood by both patients and doctors. The aim of this study is to describe, on the basis of two case histories, the management of exacerbations of COPD in emergency departments, to compare it with the current guidelines and to evaluate the extent of use of non-invasive ventilation in decompensated COPD. METHODS: The study took place between February and June 2004. Two case histories describing one moderate and one severe exacerbation with respiratory failure were written by the authors of the study and submitted to an emergency physician in a university hospital and a district hospital in each region. RESULTS: 110 questionnaires were returned from 20 university hospitals and 25 district hospitals. Only 38% of the episodes were identified correctly. 20% of doctors did not regard dyspnoea as a clinical sign of an exacerbation. 22% of doctors never prescribed bronchodilators, even in severe cases. Finally, non-invasive ventilation (NIPV) was used for only 9% of the moderate and 56% of the severe exacerbations. DISCUSSION: This study, although limited by certain factors, illustrates a number of points in need of improvement in the recognition and treatment of exacerbations of COPD in emergency departments, the use of NIPV, and the collaboration between emergency physicians, intensivists and respiratory physicians.

Emergency Service, Hospital↗

[Characteristics of mild asthma: clinical signs and medication use. Position statement of the Mild Asthma Working Group (174)].

OBJECTIVE: To update on the state of knowledge in mild asthma (intermittent and persistent mild asthma, according to the GINA classification) review the literature, and the position statement of the French Mild Asthma Working Group. METHODS: The French Mild Asthma Working Group (11 lung specialists, 4 paediatricians, 1 pharmacologist, and 1 general practitioner) selected, analysed, and summarised the literature on the descriptive epidemiology, physiopathology, clinical signs, and management of mild asthma. The position of the working group on the descriptive epidemiology (causal factors excluded) and the nature of the bronchial inflammation has been presented in a previous article. The present article focuses on the clinical features of mild asthma and the use of medication for it. RESULTS: Mild asthma was more frequent, more symptomatic, and less well controlled in children than in adults. Its generally benign evolution may in some (<10%) cases be complicated by severe episodes. Patients with mild persistent asthma require controller medication every day: permanent low-dose inhaled corticosteroid monotherapy is the reference foundation treatment for persistent mild asthma. CONCLUSIONS: The present findings should help clinicians and guide them in their approach to managing this condition.

Administration, Inhalation↗

Future developments in sublingual immunotherapy.

The increasing prevalence of allergic rhinitis and its progression to asthma has severe implications for patients and health care systems in many countries. An ideal therapy is one that is effective not only against symptoms but also towards the natural progression of the allergic disease. Immunotherapy is recognized to achieve both these aims. Administration of allergens by the sublingual route, a modality with a very low rate of systemic reactions, is widely considered a treatment of choice. However, if it is to be universally accepted, more developments are required. Although, it is effective against grass and other seasonal pollens, further controlled trials are needed to confirm its efficacy against perennial allergens. Additional studies, particularly in paediatric populations, are needed to confirm its long-term effects on disease progression. New vaccine developments, which take into account the increasing understanding of the underlying immune mechanisms and that exploit molecular engineering techniques will create allergens that are effective, stable, risk free and easy to administer.

Administration, Sublingual↗

[Characteristics of mild asthma: descriptive epidemiology and nature of bronchial inflammation. Position of the Mild Asthma Working Group].

INTRODUCTION: Update on the state of knowledge in the mild asthma (intermittent and persistent mild asthma, according to the GINA classification) literature, and position of a French Mild Asthma Working Group. STATE OF THE ART: The French Mild Asthma Working Group (11 lung specialists, 4 paediatricians, 1 pharmacologist, and 1 general practitioner) selected, analysed, and summarised the literature on the epidemiology, physiopathology, clinical signs, and management of mild asthma. The present article shows the position of the working group on mild asthma descriptive epidemiology (causal factors excluded) and the nature of the bronchial inflammation. Clinical signs and medicinal treatments will be presented in a second article. PERSPECTIVES: Between 50% and 75% of asthma patients, depending on the study, present mild asthma. Childhood-to-adulthood cohort monitoring found severity to be unchanged over developmental time. Its generally benign evolution may in some (<10%) cases be complicated by severe episodes. Inflammation and airway-wall remodelling were always found, although of variable intensity, and non-specific (except for absence of infiltration by polymorphonuclear neutrophils). Corticosteroid therapy by inhalation reduces bronchial inflammation, but with little impact on airway-wall remodelling. CONCLUSION: The present findings should help clinicians in identifying and understanding mild asthma.

Adrenal Cortex Hormones↗

Detection of oncogenic virus genomes and gene products in lung carcinoma.

We investigated a series of 122 cases of small cell lung carcinomas and non-small cell lung carcinomas for the presence of several viruses that are known to be oncogenic in humans. Thus, viral genomes (DNA) and/or RNA transcripts and/or proteins of human papillomaviruses (HPV) 16, 18, 31, 33, 51, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), human cytomegalovirus (HCMV) and simian virus 40 (SV40) were investigated on tissue sections (prepared in tissue microarrays) with different techniques of immunohistochemistry and in situ hybridisation. None of the cases displayed a single positive tumour cell for all the viruses tested whatever the technique applied. Of note, in five cases of tumours with lymphoid infiltrates, we detected scattered EBV (EBER)-positive bystander lymphocytes. In three cases, a faint nuclear staining was found with the anti-latent nuclear antigen/LANA1 (HHV-8) antibody. These cases were checked by PCR with two sets of primers (orf 26 and orf 75) and remained negative for this latter virus. Taken together, our data strongly suggest that the conventional human oncogenic viruses (HPV, EBV, HCMV, HHV-8 and SV40) are unlikely to play some role in the development of lung carcinomas..

Adenocarcinoma↗

Diagnostic value of bronchoscopy, CT and transbronchial biopsies in diffuse pulmonary lymphangiomatosis: case report and review of the literature.

The authors present the case of a 48-year-old man with diffuse pulmonary lymphangiomatosis. This rare lymphatic disorder is characterized by proliferation of anastomosing lymphatic vessels varying in size. Clinical presentation and imaging findings are highly suggestive. Bronchoscopic examination of this patient showed, for the first time to our knowledge, vesicles disseminated throughout the bronchial tree. Histopathological examinations are necessary to differentiate lymphangiomatosis from lymphangiectasis. The diagnosis can be made by transbronchial biopsy without performing open lung biopsy which was, until now, considered necessary for diagnosis.

Biopsy, Needle↗

Nasal nitric oxide, the guardian of paranasal sinuses, is paradoxically increased by high doses of intravenous glucocorticoids.

BACKGROUND: High concentrations of nitric oxide (NO) originating from a type-2 nitric oxide synthase (NOS2) located within the paranasal sinuses are measured in nasal air in man. NO is believed to play a central role in nonspecific defense of paranasal sinuses. Glucocorticoids (GCs), a therapeutic often used for a wide range of diseases, is known to strongly downregulate NOS2. AIMS OF THE STUDY: To investigate the effect of very high intravenous doses of GCs on nasal NO in man. METHODS: Nasal NO was measured in 15 patients without any history of allergy or chronic airway disorder who were treated for 3 days with a daily dose of 1000 mg methylprednisolone for an exacerbation of multiple sclerosis. Nasal NO was also measured in 30 matched control subjects. RESULTS: In control subjects, the maximal value of nasal NO [mean (SE)] was 233 (8) part per billion (ppb), and did not differ from patients with multiple sclerosis [maximum value: 219 (13) ppb; left nostril: 214 (12) ppb; right nostril: 215 (12) ppb]. After GCs treatment, nasal NO increased in patients [maximum value: 250 (13) ppb (P < 0.0001); left nostril: 249 (12) ppb (P < 0.0001); right nostril: 244 (13) ppb (P < 0.0001)]. CONCLUSIONS: We conclude that GCs do not decrease but even increase nasal NO.

Adult↗

Characterisation of steroid receptor expression in the human prostate carcinoma cell line 22RV1 and quantification of androgen effects on mRNA regulation of prostate-specific genes.

In this study, the effect of natural androgens on the expression of androgen-regulated genes in the human prostate carcinoma cell line 22RV1 was characterised. To clarify the usefulness of the cells for in vitro studies concerning activation of androgen responsive genes by various steroidal compounds steroid receptor expression patterns had to be characterised intensively. Expression of androgen receptor (AR), estrogen receptor alpha (ERalpha) and beta (ERbeta), progestin receptor (PR) and glucocorticoid receptor alpha and beta was investigated by the means of RT-PCR, immunocytochemistry, ligand binding or Western blot. 22RV1 cells were proved to express androgen receptor and less glucocorticoid receptor beta on mRNA level. The confirmed mutation of the androgen receptor at codon H874 slightly apart from the steroid binding pocket seemed not to cause alteration of natural steroid hormone binding. mRNA expression of all progestin and estrogen receptor isoforms as well as glucocorticoid receptor alpha could not be detected. To study functional relevance of above-mentioned findings nine androgen-regulated genes were chosen to characterise the cell line and to determine androgenic effects using highly sensitive real-time RT-PCR. Addition of the three natural steroids dihydrotestosterone (DHT), testosterone, and 19-nortestosterone significantly influenced mRNA expression profiles. All compounds under study showed clear time-dependent and androgen-specific effects on transcriptional level. The results demonstrate that the cultivated human prostate carcinoma epithelial cells have a hormonal sensitivity correlated with the presence of specific receptors and can, therefore, serve as a selective model to study hormone action.

Androgens↗

How should nasal symptoms be investigated in asthma? A comparison of radiologic and endoscopic findings.

BACKGROUND: To improve asthma control, the management of rhinosinusitis often leads the physician to perform sinonasal imaging and/or nasal endoscopy, but their respective contributions are still insufficiently understood. OBJECTIVE: To evaluate the potential contribution of a symptoms questionnaire, sinus radiography (SR) and computed tomography (CT) scan to the diagnosis of nasal diseases in asthmatic patients when compared with ENT examination. METHODS: A total of 124 patients completed a questionnaire on nasal symptoms administered by the chest physician. Then, they underwent ENT examination. On the same day, SR and CT scans were performed independently. RESULTS: Patients (80.3%) had nasal symptoms during the month preceding the consultation. The ENT examination was normal in 8.1% (n = 10) and revealed rhinitis in 57.3% (n = 71), rhinosinusitis in 14.5% (n = 18) and nasal polyposis in 20.2% (n = 25). For rhinitis, the negative predictive value of bilateral nasal obstruction was 87.8%. Both SR and CT had low sensitivity and specificity. For rhinosinusitis, the negative predictive value of nasal symptoms varied from 85.4 to 95.2%. Sinus CT was at least as accurate as SR for the diagnosis of rhinosinusitis. In a multivariate analysis, only the CT scan (score > or =12) appeared to be significantly associated with the diagnosis of nasal polyposis. CONCLUSION: In asthmatic patients, physicians need to enquire systematically about the existence of nasal symptoms by using this simple questionnaire which is sensitive for rhinitis, and has good negative predictive value for excluding rhinosinusitis and nasal polyposis.

Adult↗

Deprivation of sensory inputs to the olfactory bulb up-regulates cell death and proliferation in the subventricular zone of adult mice.

The main olfactory bulb (MOB) is the first relay on the olfactory sensory pathway and the target of the neural progenitor cells generated in the subventricular zone (SVZ) lining the lateral ventricles and which migrate along the rostral extension of the SVZ, also called the rostral migratory stream (RMS). Within the MOB, the neuroblasts differentiate into granular and periglomerular interneurons. A reduction in the number of granule cells during sensory deprivation suggests that neurogenesis may be influenced by afferent activity. Here, we show that unilateral sensory deafferentation of the MOB by axotomy of the olfactory receptor neurons increases apoptotic cell death in the SVZ and along the rostro-caudal extent of the RMS. The vast majority of dying cells in the RMS are migrating neuroblasts as indicated by double Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling/PSA-NCAM labeling. Counting bromodeoxyuridine-labeled cells in animals killed immediately or 4 days after tracer administration showed a bilateral increase in proliferation in the SVZ and RMS which was balanced by cell death on the operated side. These data suggest that olfactory inputs are required for the survival of newborn neural progenitors. The greatest enhancement in proliferation occurred in the extension of the RMS located in the MOB, revealing a population of local precursors mitotically stimulated following axotomy. Together, these findings indicate that olfactory inputs may strongly modulate the balance between neurogenesis and apoptosis in the SVZ and RMS and provide a model for further investigation of the underlying molecular mechanisms of this activity-dependent neuronal plasticity.

Animals↗

Characterisation of gene expression patterns in 22RV1 cells for determination of environmental androgenic/antiandrogenic compounds.

Alteration of androgen receptor function due to hormonally active compounds in the environment, may be responsible for impaired reproductive function in aquatic wildlife. Based on human prostate carcinoma 22RV1 cells, a cell culture expression system was established to test effects of putative androgenic/antiandrogenic compounds on endogenous gene expression. 22RV1 cells were shown to express human androgen receptor, but not human progestin (hPR) or human oestrogen receptor (hER) alpha and beta. Six androgen-regulated genes (ARGs) were chosen to determine androgenic/antiandrogenic action using highly sensitive real-time RT-PCR. Results showed that gene expression is altered in a time-dependent manner. After stimulation of cells by DHT (10nM), synthetic androgen R1881 (1 nM), or organic pesticides (difenoconazole, fentinacetate, tetramethrin) TMPRSS2 mRNA expression was down-regulated by the factor 0.6 after 24h of DHT treatment. Similar results were obtained when cells were assayed for mRNA expression of PSA after fentinacetate and R1881 stimulation. In contrast, TMPRSS2 expression was up-regulated by the factor 0.9 when cells were stimulated by tetramethrin. Final goal of the work is a sensitive determination of differential gene expression by different compounds under study, achievement of substance-specific expression patterns and function related analysis of potential androgens/antiandrogens.

Androgen Antagonists↗

[Nodular bronchioloalveolar carcinoma at early stage].

INTRODUCTION: The aim of our study was to describe the main characteristics of bronchioloalveolar carcinoma (BAC) in the light of the latest WHO classification. The clinical, pathological and radiological features of 16 consecutive resected cases of early BAC (stage IA) were reviewed. METHODS: Retrospective pathology of 249 adenocarcinomas over a 32 months period. RESULTS: Computerised tomography (CT) features which supported a diagnosis of BAC included a peripheral location, irregular margins forming a star pattern, pleural tagging, ground-glass attenuation and an air bronchogram. Immunochemistry was positive in all cases for cytokeratins 7 and 19, EMA and TTF-1, but was only variably positive for ACE, P53 and MIB-1. For 14 out of 16 patients clinical outcome was favourable with no evidence to date of recurrence since surgery. Of the others, one developed extra-thoracic metastases and the other a local recurrence requiring further surgery. CONCLUSION: Recognising these characteristics of BAC is important as early diagnosis and treatment of this condition can be associated with an excellent prognosis.

Adenocarcinoma, Bronchiolo-Alveolar↗

[Complementary tests in respiratory allergy].

Several complementary tests are currently available for the diagnosis and evaluation of allergic respiratory disease. Besides the classic skin prick tests which have been standardized, a number of assay methods have been developed for specific IgEs and different mediators as well as multiple tests for allergy screening. In the near future, several techniques for measuring allergens in the environment should become available for physicians and patients. The purpose of this review is to present the different complementary tests useful in respiratory allergy defining the contribution of each test in the management of patients with allergic disease.

Allergens↗

[Sport and atopy].

INTRODUCTION: The atopic diseases, asthma, allergic rhinitis and atopic dermatitis, are common in children, adolescents and young adults. They may have important consequences on physical exercise, especially asthma. STATE OF ART: Elite athletes have been observed to have a high prevalence of asthma (and perhaps also rhinitis). The reasons for this observation are still debated, but different mechanisms linked to the intensity of physical activity in athletes are probably involved. Exercise-induced symptoms should be confirmed not only from the clinical history but also by objective measurements of lung function. In elite athletes confirmation of exercise-induced asthma might be difficult and may require special diagnostic tests such as bronchial provocation by eucapnic voluntary hyperventilation. Several drugs are effective in exercise-induced prevention of nasal and bronchial symptoms. Therapeutic approaches for atopic diseases in international guidelines (GINA and ARIA) are generally compatible with anti-doping laws but require compliance with specific prescription rules. PERSPECTIVES: A better understanding of mechanisms and risk factors involved in the increase of asthma prevalence in elite athletes may permit prevention by modifying training conditions during exercise. CONCLUSIONS: Atopic diseases are common in athletes. They require special therapeutic considerations. The increasing prevalence of respiratory asthma-like symptoms in elite athlete is opening new paths for research into airway physiology in extreme conditions.

Adolescent↗