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Biomedical subjects

D Aubert

Publications and source records attributed to D Aubert.

At least 37 records · Page 2Linked to original sources
PubMed2002

GLOB-1: a prospective randomised clinical phase III trial comparing vinorelbine-cisplatin with vinorelbine-ifosfamide-cisplatin in metastatic non-small-cell lung cancer patients.

BACKGROUND: The standard doublet, vinorelbine-cisplatin, was compared with a triplet of vinorelbine-ifosfamide-cisplatin, in terms of survival, in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: From February 1998 to June 1999, 259 chemonaïve patients entered the study and were randomised to receive either vinorelbine-cisplatin (NP; vinorelbine 30 mg/m(2) on days 1, 8 and 15 with cisplatin 80 mg/m(2) on day 1) or vinorelbine-ifosfamide-cisplatin (NIP; vinorelbine 25 mg/m(2) on days 1 and 8, ifosfamide 3 g/m(2) on day 1 and cisplatin 75 mg/m(2) on day 1), with both regimens being repeated every 3 weeks. All patients had stage IV or relapsed disease and a performance score of 0 or 1. RESULTS: The overall response rate was 34.6% for NP and 35.7% for NIP. Median and 1-year survival rates were 10.0 months and 38.4% for NP, and 8.2 months and 33.7% for NIP, respectively. A median of four cycles was administered in each arm. The major World Health Organization grade 3-4 toxicities for NP and NIP, respectively, were: neutropenia (20.3% compared with 9% of cycles), anaemia (4.1% compared with 5% of cycles), nausea and vomiting (22.2% compared with 19.4% of patients) and alopecia (5.6% compared with 29.8% of patients). Four toxic deaths occurred in the NP arm and eight in the NIP arm. CONCLUSIONS: The different schedules of vinorelbine in the two arms led to a greater survival in the NP arm without impairing the tolerance profile, although this is not statistically significant. This confirms that the two-drug combination NP is a reference treatment for metastatic NSCLC. The role of three-drug combinations remains questionable in this subset of patients.

Adolescent↗
PubMed2002

Preconception seroconversion and maternal seronegativity at delivery do not rule out the risk of congenital toxoplasmosis.

We describe two unusual cases of congenital toxoplasmosis, one occurring after preconception maternal infection with cervical adenopathies and the other occurring after maternal infection at the very end of pregnancy with maternal seronegativity at delivery. These documented cases of congenital toxoplasmosis demonstrate the value of extending the serologic monitoring period during pregnancy, according to the individual clinical context.

Adult↗
PubMed2001

Efficient retroviral gene transfer to the liver in vivo using nonpolypeptidic mitogens.

Recombinant retroviral vectors are attractive tools for achieving sustained expression of a therapeutic gene in the liver. However, cell division is required for efficient transduction with these vectors. Here we report that two widely used liver mitogens, triiodothyronin (T3) and cyproterone acetate (CPA), enable hepatocyte transduction with recombinant retroviral vectors delivered in vivo into the bloodstream. Treatment with T3 as well as CPA, alone or in combination, resulted in an increase in hepatocyte replication predominantly around the portal tract. The mitogenic activity made it possible to transduce hepatocytes in the same location. Moreover, when administered together, the two drugs synergized and the transduction level reached 5% of hepatocytes. This transduction level is compatible with clinical applications for a number of inherited liver diseases. Since these two compounds have a long history of safe clinical use, we propose that these liver mitogens may have potential for clinical application in liver-directed gene therapy.

Animals↗
PubMed2001

Multicenter study of a commercial, automated polymerase chain reaction system for the rapid detection of Mycobacterium tuberculosis in respiratory specimens in routine clinical practice.

A cooperative study was conducted among six laboratories to compare the performance of the Cobas Amplicor (CA) polymerase chain reaction (PCR) system (Roche Molecular Systems, USA) for the detection of Mycobacterium tuberculosis with that of microscopy and culture in routine clinical laboratory diagnosis. A total of 5,221 decontaminated respiratory specimens were tested. The use of an internal control allowed detection of PCR inhibition in 144 (2.8%) specimens. Only two culture-positive samples were CA PCR inhibitory and therefore could not be detected by PCR testing. Of the 333 culture-positive specimens, 278 (83.5%) were positive by the CA PCR. Of the 4,744 culture-negative specimens, 52 (1.1%) were positive by the CA PCR. After analysis of discrepancies, 40 of the 52 culture-negative, CA PCR-positive specimens were classified as true positive. Thus, the overall sensitivities of culture, CA PCR and microscopy were 89.3%, 85.2% and 55.5%, respectively. The overall specificity of the CA PCR was 99.7%. Five of the six centers found similar performances for the CA PCR, with sensitivities ranging from 85.7 to 90.9%. The CA PCR was more sensitive for smear-positive samples, exhibiting overall sensitivities of 96.1% and 71.7% for smear-positive and smear-negative specimens, respectively. These results indicate that the Cobas Amplicor system enables microbiology laboratories with reasonable previous experience in molecular biology testing to perform PCR and to detect Mycobacterium tuberculosis in more than 70% of specimens obtained from infected patients.

Automation↗
PubMed2001

Membrane potential changes after infection of monocytes by Toxoplasma gondii.

Membrane potential changes in host cell plasma membrane were analyzed and the parasitophorous vacuole membrane (PVM) potential was characterized after infection by Toxoplasma gondii. Human monocytes infested by T. gondii were stained with two membrane potential sensitive dyes, DiOC(6)(3) carbocyanine and DiSBAC(2)(3) bis-oxonol, before fluorescence emission analysis by confocal laser scanning microscopy. After 24 and 48 h of infection, 34 and 39%, respectively, of monocytes showed several parasites (from two to six) per cell. At these infection times, significant decreases in cytoplasmic emissions were observed for both DiOC(6)(3) and DiSBAC(2)(3). Thus, hyperpolarisation of the host plasma membrane would occur consecutively to infection. Inside the parasitophorous vacuole, the fluorescence intensity of DiOC(6)(3) and DiSBAC(2)(3) increased significantly from 6 to 24 h after infection and the PVM became less polarised. Involvement of different ATPases in the membrane potential of infected monocytes was evaluated with ouabain, DCCD, omeprazole and sodium orthovanadate, ATPase inhibitors. All inhibitors induced a depolarisation of the plasma membrane. In the parasitophorous vacuole compartment, DCCD, omeprazole and sodium orthovanadate but not ouabain caused a significant depolarisation of the PVM, suggesting that H(+), H(+)/K(+) and P-type ATPases were at the origin of the PVM potential. This is the first report showing the presence of ion transporters in the T. gondii PVM and the existence of at least two members of the P-type family of ion pumps: an electrogenic H(+)ATPase and an electroneutral H(+)/K(+) ATPase.

Adenosine Triphosphatases↗
PubMed2001

OXA-35 is an OXA-10-related beta-lactamase from Pseudomonas aeruginosa.

Pseudomonas aeruginosa clinical isolate PA35 is resistant to amino- and ureido-penicillins, has intermediate susceptibility to cefsulodin, cefepime and aztreonam, and is susceptible to imipenem and ceftazidime. Cloning and sequencing revealed a new beta-lactamase variant, OXA-35, sharing 96% amino acid identity with OXA-10. OXA-35 displays a restricted-substrate hydrolysis profile with improved hydrolysis of amoxicillin and cloxacillin compared with OXA-10. OXA-35 differs from derivatives OXA-19 and OXA-28 by one amino acid substitution and may be a progenitor of these OXA-13-like extended-spectrum beta-lactamases.

Aged↗
PubMed2001

EMF1, a novel protein involved in the control of shoot architecture and flowering in Arabidopsis.

Shoot architecture and flowering time in angiosperms depend on the balanced expression of a large number of flowering time and flower meristem identity genes. Loss-of-function mutations in the Arabidopsis EMBRYONIC FLOWER (EMF) genes cause Arabidopsis to eliminate rosette shoot growth and transform the apical meristem from indeterminate to determinate growth by producing a single terminal flower on all nodes. We have identified the EMF1 gene by positional cloning. The deduced polypeptide has no homology with any protein of known function except a putative protein in the rice genome with which EMF1 shares common motifs that include nuclear localization signals, P-loop, and LXXLL elements. Alteration of EMF1 expression in transgenic plants caused progressive changes in flowering time, shoot determinacy, and inflorescence architecture. EMF1 and its related sequence may belong to a new class of proteins that function as transcriptional regulators of phase transition during shoot development.

Amino Acid Sequence↗
PubMed2001

Oxacillinase-mediated resistance to cefepime and susceptibility to ceftazidime in Pseudomonas aeruginosa.

Pseudomonas aeruginosa clinical isolate SOF-1 was resistant to cefepime and susceptible to ceftazidime. This resistance phenotype was explained by the expression of OXA-31, which shared 98% amino acid identity with a class D beta-lactamase, OXA-1. The oxa-31 gene was located on a ca. 300-kb nonconjugative plasmid and on a class 1 integron. No additional efflux mechanism for cefepime was detected in P. aeruginosa SOF-1. Resistance to cefepime and susceptibility to ceftazidime in P. aeruginosa were conferred by OXA-1 as well.

Cefepime↗
PubMed2001

Efficient transmission of two different sheep scrapie isolates in transgenic mice expressing the ovine PrP gene.

We produced transgenic mice expressing the sheep prion protein to obtain a sensitive model for sheep spongiform encephalopathies (scrapie). The complete open reading frame, with alanine, arginine, and glutamine at susceptibility codons 136, 154, and 171, respectively, was inserted downstream from the neuron-specific enolase promoter. A mouse line, Tg(OvPrP4), devoid of the murine PrP gene, was obtained by crossing with PrP knockout mice. Tg(OvPrP4) mice were shown to selectively express sheep PrP in their brains, as demonstrated in mRNA and protein analysis. We showed that these mice were susceptible to infection by sheep scrapie following intracerebral inoculation with two natural sheep scrapie isolates, as demonstrated not only by the occurrence of neurological signs but also by the presence of the spongiform changes and abnormal prion protein accumulation in their brains. Mean times to death of 238 and 290 days were observed with these isolates, but the clinical course of the disease was strikingly different in the two cases. One isolate led to a very early onset of neurological signs which could last for prolonged periods before death. Independently of the incubation periods, some of the mice inoculated with this isolate showed low or undetectable levels of PrPsc, as detected by both Western blotting and immunohistochemistry. The development of experimental scrapie in these mice following inoculation of the scrapie infectious agent further confirms that neuronal expression of the PrP open reading frame alone is sufficient to mediate susceptibility to spongiform encephalopathies. More importantly, these mice provide a new and promising tool for studying the infectious agents in sheep spongiform encephalopathies.

ATP-Binding Cassette Transporters↗
PubMed2001

[Uretero-vesical implantation after failure of endoscopic treatment of reflux: anatomical and histological study of 61 resection specimens from 40 children].

OBJECTIVE: To evaluate the anatomy and histology of the ureterovesical junction resected during secondary surgical reimplantation for persistent reflux after failure of initial endoscopic treatment by polytetrafluoroethylene (Teflon) in 27 cases and polydimethylsiloxane (Macroplastique) in 13 cases. MATERIAL AND METHOD: 61 ureterovesical junctions from 40 children were studied histologically. The mean age of the patients at the time of the operation was 4.1 years (range: 1 to 15 years). The mean interval between endoscopic injection and surgical reimplantation was 15.3 months (range: 2 to 54 months). RESULTS: Persistent reflux was not correlated with the anatomical situation of the implant, which was found to be in a satisfactory position in 52.4% of cases. Both of the substances used induced a giant-cell macrophage reaction which colonized the implant and triggered new vessel formation. Macroplastique appeared to be associated with a more intense inflammatory reaction than Teflon. Despite the difference in particle size, the two substances induced a macrophage phenomenon characterized by microfragmentation into 6 micron particles. No conclusions can be drawn concerning distant migration, but this study showed rarefaction of particles which were replaced by fibrosis, the density of which was correlated with the age of the implant. CONCLUSION: Extinction of the local reaction induced by the products used in this study appears to be long and the end of this process is unknown, which justifies prolonged surveillance of children treated for reflux by endoscopic submeatal injection.

Adolescent↗
PubMed2000

[Streptococcus intermedius Lemierre syndrome: an unusual association].

BACKGROUND: Lemierre's syndrome is a potentially severe though uncommon entity consisting in septic emboli from an internal jugular vein thrombus after oropharyngeal infection. CASE REPORT: A 21-year-old man initially treated for acute pharnygeal infection developed fever and lower chest pain related to multiple pulmonary abscesses. The diagnosis of Lemierre's syndrome was retained due to the association of extensive thrombus formation in the internal jugular vein and Streptococcus intermedius septicemia. DISCUSSION: Lemierre's syndrome is a classical entity whose frequency is probably underestimated. The causal agent is not always an anaerobic germ. Use of anticoagulants is controversial.

Adult↗
PubMed2000

Effects of T3R alpha 1 and T3R alpha 2 gene deletion on T and B lymphocyte development.

Thyroid hormones bind to several nuclear receptors encoded by T3R alpha and T3R beta genes. There is now accumulating evidence that thyroid hormones act on the immune system. Indeed, mice deficient for thyroid hormones show a reduction in lymphocyte production. However, the mechanisms involved and, in particular, the role of the different thyroid hormone receptors in lymphocyte development have not been investigated. To address that question, we have studied lymphocyte development in mice deficient for the T3R alpha 1 and T3R alpha 2 gene products. A strong decrease in spleen cell numbers was found compared with wild-type littermates, B lymphocytes being more severely affected than T lymphocytes. A significant decrease in splenic macrophage and granulocyte numbers was also found. In bone marrow, a reduction in CD45+/IgM- pro/pre-B cell numbers was found in these mice compared with wild-type littermates. This decrease seems to result from a proliferation defect, as CD45+/IgM- cells incorporate less 5-bromo-2'-deoxyuridine in vivo. To define the origin of the bone marrow development defect, chimeric animals between T3R alpha-/- and Rag1-/- mice were generated. Results indicate that for B cells the control of the population size by T3R alpha 1 and T3R alpha 2 is intrinsic. Altogether, these results show that T3R alpha 1 or T3R alpha 2 gene products are implicated in the control of the B cell pool size.

Animals↗
PubMed2000

Involvement of tumor necrosis factor-alpha during infection of human monocytic cells by Toxoplasma gondii.

Although the involvement of tumor necrosis factor-alpha (TNF-alpha) during Toxoplasma gondii infection has largely been described in mouse models, only a few studies in human models have been reported. We demonstrated the role of TNF-alpha during the process of invasion by T. gondii in human monocytic cells. Cotreatment of cells with interferon-gamma (IFN-gamma) and lipolysaccharide (LPS) during T. gondii infection induced TNF-alpha production and decreased the number of parasitized cells (invasion index). Neutralization of the production of TNF-alpha using a specific monoclonal antibody or pentoxifylline enhanced the invasion index. The relationship between TNF-alpha production and protection of monocytic cells against T. gondii invasion was confirmed by treatment of infected cultures with exogenous TNF-alpha. Thus, in contrast to the results obtained in murine models but in accordance with those observed in other human models, the present study shows for the first time in human monocytic cells that T. gondii does not induce any TNF-alpha secretion and inhibits TNF-alpha production induced by IFN-gamma/LPS.

Animals↗
PubMed2000

SPAC: identification of polypeptides using their amino-acid composition.

We describe here new software able to retrieve from protein or nucleic acid databases, the sequence corresponding to a protein or peptide whose only amino acid composition and molecular weight are known. This algorithm is particularly devoted to the retrieval of partial sequences, a task that other available software performs poorly. Its accuracy for the attribution of a protein fragment to a sequence could represent an easy and economical first tool upstream the use of more sophisticated and expensive methods in proteomic research. SPAC (Sequence Protein Alignment with Composition) is a shareware available software on web site http://www.univ-tln.fr/ approximately grillas/SPAC/. This web site also presents help and a detailed description of the algorithm and interface.

Algorithms↗