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Biomedical subjects

P Roux

Publications and source records attributed to P Roux.

At least 19 recordsLinked to original sources

Candidemia in French hospitals: incidence rates and characteristics.

OBJECTIVE: To determine the incidence of candidemia in French hospitals. MATERIALS AND METHODS: A representative sample of 25 French hospitals [nine teaching hospitals (TH), ten general hospitals (GH) and six cancer referral centers (CRC)] was randomly selected. The incidence rates of candidemia per number of admissions and per patient-days of hospitalization were determined and extrapolated to the national level. RESULTS: From January 1, 1995 to December 31, 1995, the overall incidence rate per 1000 admissions was 0.29, ranging from 0.71/1000 in CRC, to 0.17/1000 in GH. The overall incidence for 1000 patient-days was 0.035 and the highest incidence was also observed in CRC (0.116/1000), followed by TH (0.052/1000). Candida albicans (53%) was the most common species isolated, a central venous catheter (26%) was the most common portal of entry and 50% of the candidaemic patients had a neoplasm. CONCLUSION: This study should enable us to optimize surveillance, prevention and treatment of these potentially life-threatening infections.

Candida↗

Absence of mutations associated with sulfa resistance in Pneumocystis carinii dihydropteroate synthase gene from non-human primates.

The dihydropteroate synthase (DHPS) gene from Pneumocystis carinii isolated from non-human primates was amplified using a polymerase chain reaction (PCR) and sequenced to analyse point mutations associated with sulfa resistance. P. carinii DHPS gene amplification was obtained from eight lung samples from five New World primate species and one Old World primate species. None of the animals had been exposed to sulfa drugs and only the wild-type P. carinii DHPS sequence at codons 55 and 57 was observed. These data support the hypothesis that high rates of DHPS mutants in P. carinii f. sp. hominis have arisen with increased use of sulfa drugs for P. carinii pneumonia prophylaxis.

Amino Acid Sequence↗

The proseal laryngeal mask: results of a descriptive trial with experience of 300 cases.

BACKGROUND: The ProSeal laryngeal mask airway (PLMA) is a new laryngeal mask device with a modified cuff and a drainage tube. METHODS: We assessed the PLMA in 300 anaesthetized adults either paralysed or breathing spontaneously. We assessed insertion characteristics, airway seal pressures, haemodynamic response to insertion, ease of gastric tube placement, gastric insufflation, and postoperative sore throat. RESULTS: Insertion was successful in 294 patients (98%) and graded as easy in 274 patients (91%). We found no difference in ease of insertion or success rate with either the introducer or the finger insertion method, or in paralysed or non-paralysed patients. Mean airway seal pressure was 29 cm H2O, and 59 patients (20%) had seal pressures greater than 40 cm H2O. No gastric insufflation was detected. Gastric tube placement was successful in 290 of 294 patients (98.6%). There was no cardiovascular response to insertion, with a small reduction in heart rate 5 min after insertion and significant decreases in mean arterial pressure at 1 and 5 min after insertion. Sore throat was noted in 23% patients after operation and in 16% of patients after 24 h, with 90% of the sore throats described as mild. CONCLUSIONS: The PLMA is a reliable airway management device that can give an effective glottic seal in paralysed and non-paralysed patients. The device allows the easy passage of a gastric tube, causes a minimal haemodynamic response to insertion, and an acceptable incidence of sore throat.

Adolescent↗

A role for cofilin and LIM kinase in Listeria-induced phagocytosis.

The pathogenic bacterium Listeria monocytogenes is able to invade nonphagocytic cells, an essential feature for its pathogenicity. This induced phagocytosis process requires tightly regulated steps of actin polymerization and depolymerization. Here, we investigated how interactions of the invasion protein InlB with mammalian cells control the cytoskeleton during Listeria internalization. By fluorescence microscopy and transfection experiments, we show that the actin-nucleating Arp2/3 complex, the GTPase Rac, LIM kinase (LIMK), and cofilin are key proteins in InlB-induced phagocytosis. Overexpression of LIMK1, which has been shown to phosphorylate and inactivate cofilin, induces accumulation of F-actin beneath entering particles and inhibits internalization. Conversely, inhibition of LIMK's activity by expressing a dominant negative construct, LIMK1(-), or expression of the constitutively active S3A cofilin mutant induces loss of actin filaments at the phagocytic cup and also inhibits phagocytosis. Interestingly, those constructs similarly affect other actin-based phenomenons, such as InlB-induced membrane ruffling or Listeria comet tail formations. Thus, our data provide evidence for a control of phagocytosis by both activation and deactivation of cofilin. We propose a model in which cofilin is involved in the formation and disruption of the phagocytic cup as a result of its local progressive enrichment.

Actin Depolymerizing Factors↗

Scattering of sound by a vorticity filament: an experimental and numerical investigation.

A vorticity filament is investigated experimentally using the transmission of an ultrasonic wave through the flow. The analysis of the wave-front distortion provides noninvasive measurements of the vortex circulation and size. The latter is estimated by analytical calculations of the scattering of a plane wave by a vorticity filament. The case of a cylindrical wave incident on a vortex leads to similar experimental results which are successfully compared to a parabolic equation simulation. Finally, a finite-difference code based on linear acoustics is presented, in order to investigate the structure of the scattered wave numerically.

Journal Article↗

Development of an RT-PCR on the heat shock protein 70 gene for viability detection of Pneumocystis carinii f. sp. hominis in patients with pneumocystosis and in air sample.

To test the viability of Pneumocystis carinii f. sp. hominis, an RT-PCR assay that employs specific primers from the Heat Shock Protein 70 gene was developed. Using this method, the viability of P.c. hominis in bronchoalveolar lavage fluids from patients developing PCP and in the environment of PCP patients was established.

AIDS-Related Opportunistic Infections↗

Multiple scattering in a reflecting cavity: application to fish counting in a tank.

Classical fisheries acoustics techniques are useless in the presence of multiple scattering or reflecting boundaries. A general technique is developed that provides the number and the scattering strength of scatterers in motion placed inside a highly reflecting cavity. This approach is based on multiple scattering theory. The idea is to measure the average effect of the scatterers on the acoustic echoes of the cavity interfaces. This leads to the measure of the scattering mean free path, a typical length that characterizes the scattering strength of the cloud of scatterers. Numerical results are shown to agree with a simple theoretical analysis. Experiments are performed with fish in a tank at two different scales: ultrasonic frequency (400 kHz) in a 1.4-l beaker with 1-cm-long fish as well as fisheries acoustics frequency (12.8 kHz) in a 30-m3 tank with 35-cm-long fish. These results have interesting applications to fish target strength measurement and fish counting in aquaculture.

Animals↗

Raf-MEK-Erk cascade in anoikis is controlled by Rac1 and Cdc42 via Akt.

Signals from the extracellular matrix are essential for the survival of many cell types. Dominant-negative mutants of two members of Rho family GTPases, Rac1 and Cdc42, mimic the loss of anchorage in primary mouse fibroblasts and are potent inducers of apoptosis. This pathway of cell death requires the activation of both the p53 tumor suppressor and the extracellular signal-regulated mitogen-activated protein kinases (Erks). Here we characterize the proapoptotic Erk signal and show that it differs from the classically observed survival-promoting one by the intensity of the kinase activation. The disappearance of the GTP-bound forms of Rac1 and Cdc42 gives rise to proapoptotic, moderate activation of the Raf-MEK-Erk cascade via a signaling pathway involving the kinases phosphatidlyinositol 3-kinase and Akt. Moreover, concomitant activation of p53 and inhibition of Akt are both necessary and sufficient to signal anoikis in primary fibroblasts. Our data demonstrate that the GTPases of the Rho family control three major components of cellular signal transduction, namely, p53, Akt, and Erks, which collaborate in the induction of apoptosis due to the loss of anchorage.

Animals↗

Orbital lymphangioma: clinical features and management.

PURPOSE: To report 5 cases of orbital lymphangioma. METHODS: All patients underwent ophthalmological, clinical and neuroradiological evaluation. RESULTS: At presentation all patients (4 children and one adult patient) had unilateral proptosis. Restricted eye movement was present in 3 patients, ptosis and amblyopia in 2. Compressive optic neuropathy with visual loss was noticed in one patient. Palatal localization was found in 2 patients, maxillofacial localization in one. Associated intracranial vascular anomaly was present in one patient. Three patients who underwent surgery, developed recurrences. No regression of lymphangioma was noticed nor with Interferon, nor with steroids. CONCLUSION: Lymphangioma has to be included in the differential diagnosis of childhood proptosis. Extraorbital localization, under which associated intracranial developmental venous vascular anomaly, has to be searched for. In most of the cases conservative treatment is mandatory.

Adolescent↗

Extinction of rac1 and Cdc42Hs signalling defines a novel p53-dependent apoptotic pathway.

Apoptosis is a normal physiological process which eliminates cells that do not receive adequate extracellular signals. One of the pathways signalling apoptosis is controlled by the small GTPases of the Rho family, also involved in cell proliferation, differentiation and motility. Another major apoptosis signalling pathway involves the p53 tumour suppressor which is activated by a variety of stress and mediates growth arrest or apoptosis in normal cells. We show here that upon detachment from the extracellular matrix, fibroblasts undergo rapid apoptosis that can be rescued by constitutive activation of Rac1 and Cdc42Hs GTPases. Conversely, inhibition of Rac1 and Cdc42Hs efficiently triggers apoptosis in adherent cells. Interestingly, apoptosis is not observed in p53-/- cells either cultured in suspension or inhibited for Rac1 and Cdc42Hs activity. Moreover, Rac1 and Cdc42Hs extinction in normal cells activates endogenous p53. Using specific inhibitors of MAPK pathways, we demonstrate that, in our experimental system, p38 signals survival, while ERK activity is required for apoptosis. Our data constitute the first demonstration that Rac1 and Cdc42Hs control pathways that require simultaneous signalling through MAPK ERK and p53 to induce apoptosis.

3T3 Cells↗

Differential effect of Rac and Cdc42 on p38 kinase activity and cell cycle progression of nonadherent primary mouse fibroblasts.

The Rho GTPases play an important role in transducing signals linking plasma membrane receptors to the organization of the cytoskeleton and also regulate gene transcription. Here, we show that expression of constitutively active Ras or Cdc42, but not RhoA, RhoG, and Rac1, is sufficient to cause anchorage-independent cell cycle progression of mouse embryonic fibroblasts. However, in anchorage free conditions, whereas activation of either Cdc42 or Ras results in cyclin A transcription and cell cycle progression, Cdc42 is not required for Ras-mediated cyclin A induction, and the two proteins act in a synergistic manner in this process. Surprisingly, the ability of Cdc42 to induce p38 MAPK activity in suspended mouse embryonic fibroblast was impaired. Moreover, inhibition of p38 activity allowed Rac1 to induce anchorage-independent cyclin A transcription, indicating that p38 MAPK has an inhibitory function on cell cycle progression of primary fibroblasts. Finally, a Rac mutant, which is unable to induce lamellipodia and focal complex formation, promoted cyclin A transcription in the presence of SB203580, suggesting that the organization of the cytoskeleton is not required for anchorage-independent proliferation. This demonstrates a novel function for Cdc42, distinct from that of Rac1, in the control of cell proliferation.

Animals↗

Purification of histidine-tagged mitochondrial ADP/ATP carrier: influence of the conformational states of the C-terminal region.

A functional recombinant mitochondrial ADP/ATP carrier from the yeast Saccharomyces cerevisiae that bears a six-histidine tag at the C-terminus, Anc2(His(6))p, has been engineered to allow its purification by immobilized metal-ion affinity chromatography (IMAC). The tagged carrier was expressed at a level similar to that of unmodified Anc2p as determined by immunodetection and titration of the specific atractyloside binding sites. Anc2(His(6))p, enriched by chromatography on hydroxyapatite of detergent extracts of mitochondria, was still contaminated by mitochondrial proteins and a large amount of ergosterol. It was highly purified after adsorption on Ni-NTA resin and elution by imidazole buffer, with a 90-95% overall yield. Anc2(His(6))p interacted differently with immobilized ions depending on whether it was unliganded or bound to carboxyatractyloside (CATR) or bongkrekic acid (BA), two specific inhibitors of the ADP/ATP transport, thus indicating that accessibility of the C-terminus is markedly influenced by the conformational state of the carrier. Fluorometric assays demonstrated that purified unliganded Anc2(His(6))p was in a functional state since it underwent CATR- and BA-sensitive and ADP (or ATP)-induced conformational changes. Large-scale purification of Anc2(His(6))p-CATR and Anc2(His(6))p-BA complexes by IMAC will be of major interest for structural analysis of the ADP/ATP carrier.

Anti-Bacterial Agents↗

A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE.

The Notch1 receptor is presented at the cell membrane as a heterodimer after constitutive processing by a furin-like convertase. Ligand binding induces the proteolytic release of Notch intracellular domain by a gamma-secretase-like activity. This domain translocates to the nucleus and interacts with the DNA-binding protein CSL, resulting in transcriptional activation of target genes. Here we show that an additional processing event occurs in the extracellular part of the receptor, preceding cleavage by the gamma-secretase-like activity. Purification of the activity accounting for this cleavage in vitro shows that it is due to TACE (TNFalpha-converting enzyme), a member of the ADAM (a disintegrin and metalloprotease domain) family of metalloproteases. Furthermore, experiments carried out on TACE-/- bone marrow-derived monocytic precursor cells suggest that this metalloprotease plays a prominent role in the activation of the Notch pathway.

ADAM Proteins↗

Vitamin A status in relation to electroretinographic and electrooculographic findings in HIV infection.

OBJECTIVES: To investigate the electrooculogram (EOG) and an expanded battery of electroretinograms (ERGs) in HIV-infected subjects without retinopathy at two different levels of immunosuppression. Consideration was given to the possible effects of serum levels of vitamin A. METHODS: Two groups of neurologically normal HIV-positive subjects with CD4+ cell counts of <200 (n=17) or >400 (n=19) were contrasted with 20 HIV-negative controls. Rod ERGs, oscillatory potentials and cone ERGs were obtained using ganzfeld stimulation. A sequence of dark- and light-adapted EOG recordings was analyzed to obtain light/dark ratios. The HIV-positive subjects underwent a comprehensive ophthalmologic examination. RESULTS: Intergroup comparisons failed to reveal any significant intergroup differences. Abnormal ERG findings, those exceeding the 98% confidence limits, occurred in 11% (4/36) of the HIV-positive subjects. One of these subjects was hyporetinemic and another had a subnormal retinol level. No subjects had abnormal EOGs. CONCLUSIONS: HIV infection influenced retinal function in 11% of a group of neurologically normal subjects without clinical signs of retinopathy. The profile of electrophysiological findings suggested predominant functional deficits involving middle or inner retinal layers. Vitamin A deficiency and possible vascular changes could account for the observed ERG abnormalities.

Adolescent↗

Critical activities of Rac1 and Cdc42Hs in skeletal myogenesis: antagonistic effects of JNK and p38 pathways.

The Rho family of GTP-binding proteins plays a critical role in a variety of cellular processes, including cytoskeletal reorganization and activation of kinases such as p38 and C-jun N-terminal kinase (JNK) MAPKs. We report here that dominant negative forms of Rac1 and Cdc42Hs inhibit the expression of the muscle-specific genes myogenin, troponin T, and myosin heavy chain in L6 and C2 myoblasts. Such inhibition correlates with decreased p38 activity. Active RhoA, RhoG, Rac1, and Cdc42Hs also prevent myoblast-to-myotube transition but affect distinct stages: RhoG, Rac1, and Cdc42Hs inhibit the expression of all muscle-specific genes analyzed, whereas active RhoA potentiates their expression but prevents the myoblast fusion process. We further show by two different approaches that the inhibitory effects of active Rac1 and Cdc42Hs are independent of their morphogenic activities. Rather, myogenesis inhibition is mediated by the JNK pathway, which also leads to a cytoplasmic redistribution of Myf5. We propose that although Rho proteins are required for the commitment of myogenesis, they differentially influence this process, positively for RhoA and Rac1/Cdc42Hs through the activation of the SRF and p38 pathways, respectively, and negatively for Rac1/Cdc42Hs through the activation of the JNK pathway.

Animals↗

Acoustical imaging through a multiple scattering medium using a time-reversal mirror.

Acoustical imaging is based on the ability to focus an acoustic beam inside the zone of interest. This remains an issue through a high-order multiple scattering medium because the electronic delay lines that enable one to focus through a multiple scattering medium are a priori unknown. Using time-reversal principles, we show that images can be obtained through a very disordered medium. Surprisingly, the images are better than those obtained in a homogeneous medium with a classical imaging device.

Acoustics↗