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1.
Regnier V; Meddeb M; Lecointre G; Richard F; Duverger A; Nguyen VC; Dutrillaux B; Bernheim A; Danglot G 《Human molecular genetics》1997,6(1):9-16
Type 1 neurofibromatosis (NF1) gene encodes for a member of the GTPase
activating protein family and is considered to be a tumor suppressor gene.
Its very high rate of de novo mutation in humans led us to study a specific
feature of this gene: the presence of numerous NF1-related sequences.
According to our results, the human genome contains at least 11 NF1-related
sequences, nine of which are scattered near centromeric sequences of seven
different chromosomes. These NF1-related sequences, whose extent is quite
varied according to loci, are unprocessed copies of the NF1 gene, and bear
numerous mutations. A phylogenetic analysis of the six largest sequences
indicates that they are all derived from a common ancestor, which would
have appeared 22-33 million years ago, and was subsequently duplicated
several times during hominoid evolution. The most recent duplication and
interchromosomal transposition occurred in the last million years
suggesting that the process could still be ongoing. Intriguing similarities
between the evolution of alpha- satellite DNA and NF1-related sequences
suggest the involvement of a common genetic mechanism for the generation
and pericentric spreading of these NF1 partial copies.
相似文献
2.
Clear cell carcinoma has been described in numerous anatomic sites. Renal location is the most frequent. The occurrence in the gallbladder is exceptional. We report the case of a 71-Year-old woman who presented with sub-acute angiocrolitis. Computer tomographic scan revealed a polypoid mass close to the neck of the gallbladder; there was no renal lesion. Histological analysis of the gallbladder showed a primitive clear cell carcinoma with a papillary pattern associated with carcinoma in situ. Immunohistochemical study confirmed the primitive character of the tumor, characterized by an expression of KL-1, EMA and ACE and an absence of vimentin, CD 10 and CD15. Clear cell carcinomas of the gallbladder are uncommon neoplasms which could only be diagnosed on clinical, histological and immunohistochemical arguments. 相似文献
3.
Contribution of BK Ca2+-activated K+ channels to auditory neurotransmission in the Guinea pig cochlea 总被引:3,自引:0,他引:3
Skinner LJ Enée V Beurg M Jung HH Ryan AF Hafidi A Aran JM Dulon D 《Journal of neurophysiology》2003,90(1):320-332
Large-conductance calcium-activated potassium (BK) channels are known to play a prominent role in the hair cell function of lower vertebrates where these channels determine electrical tuning and regulation of neurotransmitter release. Very little is known, by contrast, about the role of BK channels in the mammalian cochlea. In the current study, we perfused specific toxins in the guinea pig cochlea to characterize the role of BK channels in cochlear neurotransmission. Intracochlear perfusion of charybdotoxin (ChTX) or iberiotoxin (IbTX) reversibly reduced the compound action potential (CAP) of the auditory nerve within minutes. The cochlear microphonics (CM at f1 = 8 kHz and f2 = 9.68 kHz) and their distortion product (DPCM at 2f1-f2) were essentially not affected, suggesting that the BK specific toxins do not alter the active cochlear amplification at the outer hair cells (OHCs). We also tested the effects of these toxins on the whole cell voltage-dependent membrane current of isolated guinea pig inner hair cells (IHCs). ChTX and IbTX reversibly reduced a fast outward current (activating above -40 mV, peaking at 0 mV with a mean activation time constant tau ranging between 0.5 and 1 ms). A similar block of a fast outward current was also observed with the extracellular application of barium ions, which we believe permeate through Ca2+ channels and block BK channels. In situ hybridization of Slo antisense riboprobes and immunocytochemistry demonstrated a strong expression of BK channels in IHCs and spiral ganglion and to a lesser extent in OHCs. Overall, our results clearly revealed the importance of BK channels in mammalian cochlear neurotransmission and demonstrated that at the presynaptic level, fast BK channels are a significant component of the repolarizing current of IHCs. 相似文献
4.
Jocelyne Enouf Maryline Lebret Raymonde Bredoux Sylviane Levy-Toledano Jacques P. Caen 《British journal of haematology》1987,65(4):437-440
Calcium uptake into isolated membrane vesicles from two patients with a grey platelet syndrome has been investigated. An increase in calcium transport appears in both patients when compared to controls. Determination of the kinetic parameters of the calcium transport system gave similar apparent affinity for calcium and an increase in the calcium uptake velocity. This increase in calcium transport is correlated with the increase of the associated Ca2+ activated ATPase activity. The results would suggest a new relationship between the ultrastructural and functional abnormalities of the grey platelet syndrome. 相似文献
5.
Maryline Beurg Lisa A. Schimmenti Alaa Koleilat Sami S. Amr Andrea Oza Amanda J. Barlow Angela Ballesteros Robert Fettiplace 《The Journal of neuroscience》2021,41(20):4378
Transmembrane channel-like protein isoform 1 (TMC1) is a major component of the mechano-electrical transducer (MET) channel in cochlear hair cells and is subject to numerous mutations causing deafness. We report a new dominant human deafness mutation, TMC1 p.T422K, and have characterized the homologous mouse mutant, Tmc1 p.T416K, which caused deafness and outer hair cell (OHC) loss by the fourth postnatal week. MET channels showed decreased Ca2+ permeability and resting open probability, but no change in single-channel conductance or expression. Three adjacent deafness mutations are TMC1 p.L416R, p.G417R, and p.M418K, the last homologous to the mouse Beethoven that exhibits similar channel effects. All substitute a positive for a neutral residue, which could produce charge screening in the channel pore or influence binding of an accessory subunit. Channel properties were compared in mice of both sexes between dominant (Tmc1 p.T416K, Tmc1 p.D569N) and recessive (Tmc1 p.W554L, Tmc1 p.D528N) mutations of residues near the putative pore of the channel. Tmc1 p.W554L and p.D569N exhibit reduced maximum current with no effect on single-channel conductance, implying a smaller number of channels transported to the stereociliary tips; this may stem from impaired TMC1 binding to LHFPL5. Tmc1 p.D528N, located in the pore''s narrowest region, uniquely caused large reductions in MET channel conductance and block by dihydrostreptomycin (DHS). For Tmc1 p.T416K and Tmc1 p.D528N, transduction loss occurred between P15 and P20. We propose two mechanisms linking channel mutations and deafness: decreased Ca2+ permeability, common to all mutants, and decreased resting open probability in low Ca2+, confined to dominant mutations.SIGNIFICANCE STATEMENT Transmembrane channel-like protein isoform 1 (TMC1) is thought to be a major component of the mechanotransducer channel in auditory hair cells, but the protein organization and channel structure are still uncertain. We made four mouse lines harboring Tmc1 point mutations that alter channel properties, causing hair cell degeneration and deafness. These include a mouse homolog of a new human deafness mutation pT416K that decreased channel Ca2+ permeability by introducing a positively-charged amino acid in the putative pore. All mutations are consistent with the channel structure predicted from modeling, but only one, p.D528N near the external face of the pore, substantially reduced channel conductance and Ca2+ permeability and virtually abolished block by dihydrostreptomycin (DHS), strongly endorsing its siting within the pore. 相似文献
6.
Maryline Drouet Feng Chai Christine Barthélémy Gilles Lebuffe Bertrand Debaene Bertrand Décaudin Pascal Odou 《Antimicrobial agents and chemotherapy》2015,59(2):930-934
Peripheral intravenous therapy is frequently used in routine hospital practice and, due to various factors, its most common side effect is phlebitis. The infusion of vancomycin is particularly associated with phlebitis despite its widespread use. French guidelines recommend central intravenous infusion for high concentrations of vancomycin, but peripheral intravenous therapy is often preferred in intensive care units. Methods of vancomycin infusion are either intermittent infusion or continuous infusion. A comparison of these methods under in vitro conditions simulating clinical use could result in better infusion efficacy. Human umbilical vein endothelial cells (HUVECs) were therefore challenged with clinical doses of vancomycin over a 24- to 72-h period using these infusion methods. Cell death was measured with the alamarBlue test. Concentration-dependent and time-dependent vancomycin toxicity on HUVECs was noted with a 50% lethal dose at 5 mg/ml after 24 h, reaching 2.5 mg/ml after 72 h of infusion, simulating long-term infusion. This toxicity does not seem to be induced by acidic pH. In comparing infusion methods, we observed that continuous infusion induced greater cell toxicity than intermittent infusion at doses higher than 1 g/day. The increasing use of vancomycin means that new guidelines are required to avoid phlebitis. If peripheral intravenous therapy is used to reduce infusion time, along with intermittent infusion, vein irritation and localized phlebitis may be reduced. Further studies have to be carried out to explore the causes of vancomycin endothelial toxicity. 相似文献
7.
Maryline Fresquet Thomas A. Jowitt Jennet Gummadova Richard Collins Ronan O’Cualain Edward A. McKenzie Rachel Lennon Paul E. Brenchley 《Journal of the American Society of Nephrology : JASN》2015,26(2):302-313
Phospholipase A2 receptor 1 (PLA2R) is a target autoantigen in 70% of patients with idiopathic membranous nephropathy. We describe the location of a major epitope in the N-terminal cysteine-rich ricin domain of PLA2R that is recognized by 90% of human anti-PLA2R autoantibodies. The epitope was sensitive to reduction and SDS denaturation in the isolated ricin domain and the larger fragment containing the ricin, fibronectin type II, first and second C-type lectin domains (CTLD). However, in nondenaturing conditions the epitope was protected against reduction in larger fragments, including the full-length extracellular region of PLA2R. To determine the composition of the epitope, we isolated immunoreactive tryptic fragments by Western blotting and analyzed them by mass spectrometry. The identified peptides were tested as inhibitors of autoantibody binding to PLA2R by surface plasmon resonance. Two peptides from the ricin domain showed strong inhibition, with a longer sequence covering both peptides (31-mer) producing 85% inhibition of autoantibody binding to PLA2R. Anti-PLA2R antibody directly bound this 31-mer peptide under nondenaturing conditions and binding was sensitive to reduction. Analysis of PLA2R and the PLA2R-anti-PLA2R complex using electron microscopy and homology-based representations allowed us to generate a structural model of this major epitope and its antibody binding site, which is independent of pH-induced conformational change in PLA2R. Identification of this major PLA2R epitope will enable further therapeutic advances for patients with idiopathic membranous nephropathy, including antibody inhibition therapy and immunoadsorption of circulating autoantibodies. 相似文献
8.
Anne‐Lise Alloin Vincent Barlogis Pascal Auquier Audrey Contet Maryline Poiree François Demeocq Iris Herrmann Virginie Villes Yves Bertrand Dominique Plantaz Justyna Kanold Pascal Chastagner Hervé Chambost Nicolas Sirvent Gérard Michel 《British journal of haematology》2014,164(1):94-100
Corticosteroid and central nervous system (CNS) irradiation can induce cataract in childhood lymphoblastic leukaemia survivors. Few prospective studies with systematic ophthalmological evaluation have been published. Cataract was prospectively assessed by serial slip lamp tests in 517 patients. All had acute lymphoblastic leukaemia, all had been treated by chemotherapy with or without CNS irradiation, and none had received haematopoietic stem cell transplantation. Median ages at last evaluation and follow‐up duration from leukaemia diagnosis were 16·8 and 10·9 years, respectively. Cataract was observed in 21/517 patients (4·1%). Cumulative incidence was 4·5 ± 1·2% at 15 years and reached 26 ± 8·1% at 25 years. CNS irradiation was the only risk factor: prevalence was 11·1% in patients who had received irradiation and 2·8% in those who did not. We did not detect any steroid dose effect: cumulative dose was 5133 and 5190 mg/m2 in patients with and without cataract, respectively. Cataract occurrence did not significantly impact quality of life. We conclude that, in the range of steroid dose reported here, the cataract risk proves very low 15 years after treatment without CNS irradiation but an even more prolonged follow‐up is required because of potential very late occurrence. 相似文献
9.