📇 Rhumatologue · PARIS CEDEX 20 · (75) · Hospitalier

MME ANNE FAJAC

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Plateau technique de référence
Assistance publique – Hôpitaux de Paris (APHP) — équipements et expertise pointus pour les cas complexes
Praticien-chercheur
18 articles scientifiques publiés — formation continue solide
Délais de RDV courts dans la région
336.2 rhumatos / 100 000 hab. — département bien doté

Rhumatologue

📍 PARIS CEDEX 20 (75)HospitalierRPPS 10000525559

📊 Reconnaissance scientifique : 20/100📝 84 articles publiés🇫🇷 Publications académiques françaises (8)

✨ Génération du profil synthétique IA en cours…

Activité de recherche & publications

Indicateurs publics agrégés sur 250 M+ d'œuvres scientifiques (OpenAlex, PubMed). Traduits ici en langage patient.

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Données ANS publiques (Licence Ouverte 2.0) · Enrichissements MonRhumato 100 % opt-in · Toute personne référencée peut demander la suppression ou la rectification.

Top publications · les plus citées

In vitro prediction of stop-codon suppression by intravenous gentamicin in patients with cystic fibrosis: a pilot study

BMC medicine · 2007

📚 129 citations🎯 RCR 3.11Top 15% NIH🩺 Clinique🔓 Open Access📄 PDF gratuit ↗

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Abstract Background Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which acts as a chloride channel activated by cyclic AMP (cAMP). The most frequent mutation found in 70% of CF patients is F508del, while premature stop mutations are found in about 10% of patients. In vitro aminoglycoside antibiotics (e.g. gentamicin) suppress nonsense mutations located in CFTR permitting translation to continue to the natural termination codon. Pharmacologic suppression of stop mutations within the CFTR may be of benefit to a significant number of patients. Our pilot study was conducted to determine whether intravenous gentamicin suppresses stop codons in CF patients and whether it has clinical benefits. Methods A dual gene reporter system was used to determine the gentamicin-induced readthrough level of the most frequent stop mutations within the CFTR in the French population. We investigated readthrough efficiency in response to 10 mg/kg once-daily intravenous gentamicin perfusions in patients with and without stop mutations. Respiratory function, sweat chloride concentration, nasal potential difference (NPD) and CFTR expression in nasal epithelial cells were measured at baseline and after 15 days of treatment. Results After in vitro gentamicin incubation, the readthrough efficiency for the Y122X mutation was at least five times higher than that for G542X, R1162X, and W1282X. In six of the nine patients with the Y122X mutation, CFTR immunodetection showed protein at the membrane of the nasal epithelial cells and the CFTR-dependent Cl- secretion in NPD measurements increased significantly. Respiratory status also improved in these patients, irrespective of the gentamicin sensitivity of the bacteria present in the sputum. Mean sweat chloride concentration decreased significantly and normalised in two patients. Clinical status, NPD and sweat Cl- values did not change in the Y122X patients with no protein expression, in patients with the other stop mutations investigated in vitro and those without stop mutations. Conclusion Suppression of stop mutations in the CFTR gene with parenteral gentamicin can be predicted in vitro and is associated with clinical benefit and significant modification of the CFTR-mediated Cl- transport in nasal and sweat gland epithelium.

Normal function of the cystic fibrosis conductance regulator protein can be associated with homozygous (Delta)F508 mutation

Pediatric research · 2002

📚 34 citations🔓 Open Access📄 PDF gratuit ↗

Chloride transport in nasal ciliated cells of cystic fibrosis heterozygotes

American journal of respiratory and critical care medicine · 2005

📚 32 citations

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Abstract Studying subjects heterozygous for mutations of the cystic fibrosis (CF) gene may help clarify the impact on disease onset of CF transmembrane conductance regulator protein (CFTR-)–dependent chloride secretion. CFTR-mediated chloride transport was evaluated in 52 heterozygous subjects, 32 healthy control subjects, and 77 patients with CF with class I or II mutations. We measured the change in nasal potential difference in response to chloride-free isoproterenol solution for each subject and used a video-imaging fluorescent dye assay to assess the percentage of nasal ciliated cells with cAMP-dependent anion conductance. Our findings did not confirm the standard assumption that heterozygosity implies 50% of normal CFTR function. Half the heterozygous subjects had CFTR-mediated chloride transport levels below 50% of the normal range, and one-third had levels similar to those of the patients with CF. This reduced CFTR function was not associated with an elevated prevalence of CF-like symptoms in heterozygous subjects but was highly related to respiratory status in the patients with CF. These data suggest that CFTR-dependent chloride conductance does not directly modulate disease severity but may be part of a more global defect in patients with CF involving other CFTR functions or currently unknown modulatory factors.

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MME ANNE FAJAC

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Publications académiques en France

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Publications scientifiques (18) — classées par pathologie

Transversal10

Génétique2

Pédiatrie2

Biomarqueurs / Auto-Ac1

Case report / série1

Corticothérapie1

Maladie à IgG41

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