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Biomedical subjects

C Leroy

Publications and source records attributed to C Leroy.

At least 19 recordsLinked to original sources
PubMed2006

Amplification of apoptosis through sequential caspase cleavage of the MET tyrosine kinase receptor.

Activation of the MET tyrosine kinase receptor by hepatocyte growth factor/scatter factor is classically associated with cell survival. Nonetheless, stress stimuli can lead to a caspase-dependent cleavage of MET within its juxtamembrane region, which generate a proapoptotic 40 kDa fragment (p40 MET). We report here that p40 MET is in fact generated through an additional caspase cleavage of MET within its extreme C-terminal region, which removes only few amino acids. We evidenced a hierarchical organization of these cleavages, with the C-terminal cleavage favoring the juxtamembrane one. As a functional consequence, the removal of the last amino acids of p40 MET increases its apoptotic capacity. Finally, cells expressing a MET receptor mutated at the C-terminal caspase site are unable to generate p40 MET and are resistant to apoptosis, indicating that generation of p40 MET amplifies apoptosis. These results revealed a two-step caspase cleavage of MET resulting in the reshaping of this survival receptor to a proapoptotic factor.

Amino Acid Sequence↗
PubMed2006

IntAct--open source resource for molecular interaction data.

IntAct is an open source database and software suite for modeling, storing and analyzing molecular interaction data. The data available in the database originates entirely from published literature and is manually annotated by expert biologists to a high level of detail, including experimental methods, conditions and interacting domains. The database features over 126,000 binary interactions extracted from over 2100 scientific publications and makes extensive use of controlled vocabularies. The web site provides tools allowing users to search, visualize and download data from the repository. IntAct supports and encourages local installations as well as direct data submission and curation collaborations. IntAct source code and data are freely available from http://www.ebi.ac.uk/intact.

DNA↗
PubMed2006

Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylation.

Sumoylation and ubiquitinylation reversibly regulate the activity of transcription factors through covalent attachment to lysine residues of target proteins. We examined whether the Ets-1 transcription factor is modified by sumoylation and/or ubiquitinylation. Among four potential SUMO motifs in Ets-1, we identified lysines 15 and 227 within the LK(15)YE and IK(227)QE motifs, as being the sumoylation acceptor sites. Using transfection of Ets-1 wildtype (WT) or its sumoylation deficient version (Ets-1 K15R/K227R), as well as WT or mutant proteins of the SUMO pathway, we further demonstrated that the E2 SUMO-conjugating enzyme Ubc9 and a E3 SUMO ligase, PIASy, can enhance Ets-1 sumoylation, while a SUMO protease, SENP1, can desumoylate Ets-1. We also found that Ets-1 is modified by K48-linked polyubiquitinylation independently of the sumoylation acceptor sites and is degraded through the 26S proteasome pathway, while sumoylation of Ets-1 does not affect its stability. Finally, sumoylation of Ets-1 leads to reduced transactivation and we demonstrated that previously identified critical lysine residues in Synergistic Control motifs are the sumoylation acceptor sites of Ets-1. These data show that Ets-1 can be modified by sumoylation and/or ubiquitinylation, with sumoylation repressing transcriptional activity of Ets-1 and having no clear antagonistic action on the ubiquitin-proteasome degradation pathway.

Animals↗
PubMed2006

Simulation of special bubble detectors for PICASSO.

The PICASSO project is a cold dark matter (CDM) search experiment relying on the superheated droplet technique. The detectors use superheated freon liquid droplets (active material) dispersed and trapped in a polymerised gel. This detection technique is based on the phase transition of superheated droplets at about room temperature and ambient pressure. The phase transition is induced by nuclear recoils when an atomic nucleus in the droplets interacts with incoming subatomic particles. This includes CDM particles candidate as the neutralino (a yet-to-discover particle predicted in extensions of the standard model of particle physics). Simulations performed to understand the detector response to neutrons and alpha particles are presented along with corresponding data obtained at the Montreal Laboratory.

Computer Simulation↗
PubMed2006

Impact of selective screening in the emergency department on meticillin-resistant Staphylococcus aureus control programmes.

Identification of the meticillin-resistant Staphylococcus aureus (MRSA) reservoir by active screening followed by the implementation of contact precautions is one of the major components of MRSA control programmes. The objective of this study was to evaluate the results of a programme of selective screening in an emergency department (ED) and the appropriateness of the contact precautions implemented. This was estimated by distinguishing necessary and unnecessary days of contact precautions. This estimation was performed for all days of contact precautions and, more specifically, for days of preventive contact precautions implemented before the availability of screening results. During a three-year period, screening of MRSA carriers was performed on 0.95% (N=605) of patients visiting the emergency ward. Among the 193 (31.9%) MRSA carriers identified, 159 were hospitalized in the short-length-hospitalization area (SLHA) of the ED and/or in other wards. Among the 140 patients admitted to the SLHA, 44 were hospitalized for at least 48 h, with a mean length of hospitalization of 5.9 days. The cumulative duration of hospitalization of carriers identified by screening was 1897 days. In total, 2370 days of contact precautions (including 924 days of preventive precautions) were implemented for patients screened in the ED. Considering the whole hospital, the appropriateness of this entire programme of contact precautions for patients screened in the ED was 80.0% (52.1% for the SLHA), whereas the specific appropriateness of preventive isolation days was 48.6% (43.6% for the SLHA). This study underscores the risk of MRSA cross-transmission in the SLHA, and the usefulness of implementing a control programme of screening carriers in the ED.

Emergency Service, Hospital↗
PubMed2006

Direct dark matter search using large-mass superheated droplet detectors in the PICASSO experiment.

The PICASSO experiment investigates the presence and nature of dark matter in the Universe. The experiment is based on the detection of acoustic signals generated in explosive phase transitions induced by dark matter particles. This technique is an alternative more traditional detection technique like scintillation and ionisation, which are largely employed for dark matter search. One of the main advantages of this technique, besides its sensitivity to very low nuclear recoil energies (few keV), is its excellent background suppression features. A pilot experiment consisting of six superheated droplet detectors (40 g of active mass) is presently taking data at the Sudbury Neutrino Observatory (SNO) at a depth of 2000 m. We discuss the operation, calibration and data acquisition of the experiment and also the ongoing work to increase the sensitivity and the active mass of the detectors.

Cosmic Radiation↗
PubMed2005

Increasing incidence of megabacteriosis in canaries (Serinus canarius domesticus).

A total of 312 post-mortem examinations of 178 canaries (Serinus canarius domesticus), 40 parakeets (Melopsittacus undulatus, Nymphicus hollandicus) and 94 parrots (Amazona aestiva, Psitaccus erithacus) were conducted at the Birds and Rabbits Service of the University of Liège, Belgium. After a detailed gross examination, tissue samples were collected for virological and/or bacteriological and/or parasitological examination to complete the diagnosis. In all cases, a microscopic examination of the proventricular mucus layer was undertaken for the detection of the anamorphic ascomycetous yeast Macrorhabdus ornithogaster, which causes the non-zoonotic but important disease in cage birds known as megabacteriosis. At the time of death, megabacteriosis was diagnosed respectively in 28% of canaries and 22.5% of budgerigars (P value for Fisher's exact test=0.5576), but was not diagnosed in parrots (P value for Fisher's exact test <0.0001). The incidence of megabacteriosis significantly increases along the years (P value for chi2 test <0.0001, Cramer's coefficient=0.3405). The most common gross lesions seen at necropsy of the 59 megabacteriosis cases was proventricular dilatation (86.1%). All the birds diagnosed as typical megabacteriosis cases were free of Salmonella spp. infections and of any parasitic infections. Four megabacteriosis cases (three canaries, one parakeet) were not included in statistical analysis as salmonellosis, pseudotuberculosis, coccidiosis and chlamydophilosis were diagnosed concomitantly in these birds. With the exception of megabacteriosis, the most frequent causes of death were protozoan (coccidiosis, lankesterellosis) infections (18.4%) and salmonellosis (17.1%) in canaries, and psittacosis (31.5%) and viral hepatitis (26.3%) in parakeets. In parrots, the most common causes of death were psittacosis (28.6%) and aspergillosis (28.5%).

Animals↗
PubMed2005

[Imaging in the management of urinary tract infections].

This review analyzes the role of imaging in the diagnosis, follow-up and management of urinary tract infections. Uncomplicated infection of the urinary tract is frequent and usually resolves rapidly with treatment; in such cases imaging is unnecessary except to exclude dilatation or the existence of an obstacle. Progression towards complex infection often occurs in patients with predisposing factors. Imaging helps in evaluating the extent of the disease; it has a role in the selection of therapy and interventional procedures.

Chronic Disease↗
PubMed2005

[Imaging of acute pancreatitis].

Acute pancreatitis usually is a benign disease. However it can sometimes be severe with a 5% mortality. CT is the imaging technique of choice and should be performed in all cases. When clinical symptoms and laboratory findings are typical, the role of CT is to detect complications. In those cases, CT is ideally performed 72 hours after the beginning of symptoms. In other cases, CT can be performed earlier. The main usefulness of CT is to detect complications: necrosis, fluid collections and vascular involvement. Non-invasive imaging techniques, including US, are poorly sensitive for diagnosis of biliary pancreatitis.

Acute Disease↗
PubMed2005

Spectrum of CFTR mutations on Réunion Island: impact on neonatal screening.

The large heterogeneity in the cystic fibrosis (CF) gene is the main difficulty for genotype characterization. Numerous studies have reported considerable variations in frequencies of CF transmembrane conductance regulator (CFTR) mutations in different populations, such as African, Asian, or European populations. To completely characterize the spectrum of mutations in the CFTR gene in the Réunion Island population, we screened 228 CF chromosomes using denaturing high-pressure liquid chromatography and denaturing gradient gel electrophoresis following by direct sequencing. We identified 27 mutations, accounting for 93% of CF chromosomes. They included three novel mutations (M1T, 3121-3C-->G, and L1324P), which are described in this paper. The detection of such a high proportion of Réunion Island CFTR mutations is important for improving neonatal screening of CF on Réunion Island.

Cystic Fibrosis↗
PubMed2004

[Severe blunt liver injury: reappraisal of criteria for nonoperative management decision. Experience with 88 cases].

AIM OF THE STUDY: To analyze the predictive value of computed tomography (CT) and initial physiologic and laboratory data findings in the immediate operative (OP) or non-operative (NOP) management of blunt liver injury (BL). METHODS: Eighty-eight BL, grade III (51), grade IV (28) and nine grade V (9), aged 26.2 years (16-75) were identified. Hemoperitoneum on CT, hemodynamic status, physiologic and laboratory data <24 hours or preoperative (transfusion, vascular filling) and follow-up >48 hours were analyzed. RESULTS: Data of 71/88 (80%) NOP and 17/88 (20%) OP patients were reviewed. A secondary laparotomy or laparoscopy was necessary in 11/71 TNO. Six OP (35%) and 1 NOP patients died. Blood units transfused were 1.33 (0-10) vs 5.9 (0-22) and vascular filling 1.45 (0.5-5.5) vs 3.6L (2-12) (P<10(-6), P<4.10(-3) respectively). NOP patients had less severe hemoperitoneum (31 vs 94%, P<10(-5)) and hemodynamic instability (8.5 vs 94%, P<10(-4)). But, there was an overlap of values of blood units transfused, amount of vascular filling and initial haemoglobin levels between NOP and OP patients and among CT grades of liver injury. No cut-off values could be determined: 33% NOP received >4 blood units and >3 L vascular filling; 30% had severe hemoperitoneum. In OP group 23.5% patients had lower values and no severe hemoperitoneum. CONCLUSION: In the management of BL, vascular filling and blood transfusion increased with the grade of CT liver injury and were globally more elevated in the operative group but did not individually correlate with hemodynamic stability and did not authorize, by themselves, to decide between operative versus non-operative management.

Adolescent↗
PubMed2004

[Merkel cell carcinoma].

Merkel cell carcinoma is a neuroendocrine tumor of the skin, originating from neuroendocrine cells. A case report of Merkel cell carcinoma, discovered in a 77-Year-old woman, was diagnosed and confirmed on a biopsy. Diagnostic and therapeutic orientations of this unusual but malignant tumor are described.

Aged↗
PubMed2004

[Imaging in urinary tract infections in adults].

Uncomplicated infection of the urinary tract is frequent and usually resolves rapidly with treatment and imaging is unnecessary. Progression to complex infection often occurs in patients with predisposing factors. Imaging assists in evaluating the extent of disease, plays a role in directing therapy and guides interventional procedures if necessary. This pictorial essay reviews the role of imaging and intervention in infections of the urinary tract.

Abscess↗
PubMed2004

Functional importance of Myc-associated zinc finger protein for the human parathyroid hormone (PTH)/PTH-related peptide receptor-1 P2 promoter constitutive activity.

The aim of the present study was to analyze the functional importance for the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTHR1) gene P2 promoter activity of the putative proximal Myc-associated zinc finger protein (MAZ) site localized at position bp -45 to -39 bp, taking advantage of a G/A mutation identified at position -40 in the human sequence. Wild-type 'full-length' (1285P2) and truncated (760P2) promoter sequences were inserted upstream to the luciferase basic (pLucB) and enhancer (pLucE) reporter gene expression vectors. Transient transfections in osteoblast-like SaOS-2 cells and renal cells (RC.SV3A2) showed that the -40 G/A mutation significantly impaired transcriptional activity of wild-type 1285P2-pLucB and 760P2-pLucE promoter constructs. Further truncation of the P2 sequence demonstrated that the sequence -109/-37 bp was essential for promoter activity. Co-transfection with a MAZ expression vector did not modify the wild-type 1285P2-pLucB construct reporter activity but significantly increased 2-fold the mutated construction activity (P<0.05). Electrophoretic mobility shift assays using SaOS-2 nuclear extracts and a double-stranded DNA fragment encompassing the -45 to -39 putative MAZ site (ds-MAZ-oligo) disclosed two specific DNA-protein complexes. Complex II (fast moving) had a lower affinity for the mutated MAZ motif than for the wild-type MAZ motif while complex I (slow moving) had the same affinity for both wild-type or mutated MAZ sequences. Competition studies with Sp1 consensus oligonucleotide (ds-Sp1-oligo) markedly reduced complex I intensity, with a concomitant increase in that of complex II. Finally, ribonuclease protection assays showed that P2-specific PTHR1 mRNA transcript expression was significantly decreased in SaOS-2 cells transfected with ds-MAZ-oligo as compared with that for control (P<0.001) and ds-Sp1-oligo (P<0.05). Taken together, our studies suggest that the putative -45 to -39 MAZ-binding site regulates the constitutive activity of human PTHR1 P2 promoter.

Cell Nucleus↗
PubMed2003

[Out-of hospital management of elderly patients].

OBJECTIVE: To evaluate prehospital management of elderly patients, agreement between prehospital and hospital diagnosis and to observe clinical course during hospitalization. TYPE OF STUDY: Retrospective study. PATIENTS AND METHOD: Out-of hospital patients of 65-year-old or more were included. Apart from demographic data, were collected: reasons for call, medicalization length, SAPS score, prehospital management, destination, prehospital and hospital diagnosis and patients evolution. Three groups were defined: G1 (65-74), G2 (75-84), G3 (> 84 year old). Statistical analysis was done by an Anova for quantitative data and by a Chi squared test for qualitative data. RESULTS: Two hundred and seventy-one patients were included (mean age 80 +/- 8 years, 43% of men). Eighty-two per cent of interventions were followed by a medicalized transport. Twelve per cent of patients died in the field. Forty-four per cent were hospitalised in intensive care unit, but patients of more than 84 year-old were significantly less often admitted in intensive care unit. There was no difference between the three groups in term of degree medicalization during transport. Eight per cent of patients required tracheal intubation in the field. Prehospital diagnoses were in agreement with reason for call in 61% of patients and with in-hospital diagnosis in 85% of patients. Fifty three per cent of patients came back home after hospitalisation. CONCLUSION: Analysis of elderly patient evolution after hospitalisation confirms the idea that the age should not influence the decision and the degree of prehospital medicalization.

Age Factors↗