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Biomedical subjects

C Weill

Publications and source records attributed to C Weill.

12 recordsLinked to original sources
PubMed2002

[Staphylococcal toxic syndrome, atypical presentation of Kawasaki syndrome or staphylococcal skin syndrome?].

CASE REPORT: A three-year-old girl was admitted for persistent fever, erythermatous rash with subsequent desquamation, stomatitis, cheleitis and cervical lymphadenopathy following development of a buttock abscess secondary to an insect bite. A TSS-positive Staphylococcus aureus strain was isolated from the abscess. COMMENTS: Both clinical and bacteriological features led to discuss a "toxic shock syndrome without shock", an atypical form of Kawasaki syndrome without thrombocytosis and coronary arteritis or a staphylococcal skin syndrome. An early treatment with antibiotics could have limited the toxin production explaining both symptomatology and favourable course of the disease.

Abscess↗
PubMed1999

Functional characterization and potential applications for enhanced green fluorescent protein- and epitope-fused human M1 muscarinic receptors.

Four recombinant human M1 (hM1) muscarinic acetylcholine receptors (mAChRs) combining several modifications were designed and overexpressed in HEK293 cells. Three different fluorescent chimera were obtained through fusion of the receptor N terminus with enhanced green fluorescent protein (EGFP), potential glycosylation sites and a large part of the third intracellular (i3) loop were deleted, a hexahistidine tag sequence was introduced at the receptor C terminus, and, finally, a FLAG epitope was either fused at the receptor N terminus or inserted into its shortened i3 loop. High expression levels and ligand binding properties similar to those of the wild-type hM1 receptor together with confocal microscopy imaging demonstrated that the recombinant proteins were correctly folded and targeted to the plasma membrane, provided that a signal peptide was added to the N-terminal domain of the fusion proteins. Their functional properties were examined through McN-A-343-evoked Ca2+ release. Despite the numerous modifications introduced within the hM1 sequence, all receptors retained nearly normal abilities (EC50 values) to mediate the Ca2+ response, although reduced amplitudes (Emax values) were obtained for the i3-shortened constructs. Owing to the bright intrinsic fluorescence of the EGFP-fused receptors, their detection, quantitation, and visualization as well as the selection of cells with highest expression were straightforward. Moreover, the presence of the different epitopes was confirmed by immunocytochemistry. Altogether, this work demonstrates that these EGFP- and epitope-fused hM1 receptors are valuable tools for further functional, biochemical, and structural studies of muscarinic receptors.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1999

[Situation and role of local structures of hospital ethics: s survey of Hospital Public Care in Paris].

This article presents the main results of a survey carried out among the local structures for hospital ethics of the Public Assistance sector of the Hospitals of Paris. The results show that the situation of these structures has completely transformed itself since the law of 1988 on human research. Only four ethics committees subsist out of the 16 university-hospital committees that existed in 1991. Seven new structures have been created since 1994, which are open to all categories of personnel and within which doctors are a minority. The four ethics committees provide almost no decision making opinions anymore and are, like the new groups, fora for discussion, reflection, or even information on issues of hospital ethics. Almost none of these structures has an official mission. This situation presents the question of the role that a local ethics structure can hold within a hospital.

Data Collection↗
PubMed1997

Pharmacological and structural integrity of muscarinic M2 acetylcholine receptors produced in Sf9 insect cells.

Muscarinic acetylcholine receptors (human m2 subtype), expressed in Sf9 cells, using the baculovirus system, were purified and found to display the expected ligand binding properties, whether membrane-bound or affinity-purified. The purified recombinant receptors were specifically photolabelled with p-N,N-[3H]dimethylamino and p-N,N-[3H]dibutylamino benzene diazonium derivatives. Electrophoretic patterns for covalent radioactive incorporation of the probes were essentially similar to those for [3H]propylbenzilylcholine mustard-labelled receptor sites but were dependent on the infection time of Sf9 cells. Pharmacological properties of the recombinant receptors being unaltered did not reflect structural integrity of the protein as substantial proteolytic fragmentation was detected at a prolonged infection time, i.e., at the highest level of expression. Selection of overexpression conditions, as illustrated here for muscarinic receptors, thus requires not only pharmacological controls, but also analysis of the covalently labelled protein under strongly dissociating conditions.

Animals↗
PubMed1997

Covalent labeling of muscarinic acetylcholine receptors by tritiated aryldiazonium photoprobes.

p-dimethylamino (A) and p-dibutylamino (B) benzenediazonium salts, previously characterized as efficient labels of membrane-bound and solubilized muscarinic receptor sites, are endowed with overall interesting photochemical and alkylating properties that allow their use as structural probes of the muscarinic ligand binding domain to be considered. Under reversible binding conditions, these antagonists display no binding selectivity towards the 5 muscarinic acetylcholine receptor (mAChR) subtypes. They were used here, in a tritiated form, as photoaffinity labels of purified muscarinic receptors from porcine striatum, and their irreversible binding was assessed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. When irradiated under energy transfer conditions, [3H]A and [3H]B were both found to covalently label purified muscarinic receptor sites in a light-dependent and atropine-protectable manner. The electrophoretic migration properties of the alkylated sites were similar to those of [3H]propylbenzilylcholine mustard (PrBCM)-labeled mAChRs. Specific radioactive incorporation showed a clear dependency on probe concentration. Labeling efficiency was rather high, with up to 30% and even 60% of the receptor population being photolabeled by [3H]A and [3H]B, respectively. These two photoactivatable ligands have proven to be powerful tools for the structural analysis of other cholinergic targets (acetylcholinesterase and the nicotinic acetylcholine receptor) by allowing the characterization of a number of different residues belonging to their acetylcholine-binding domain. Altogether, these results reinforce the interest of our site-directed labeling approach because [3H]A- and [3H]B-alkylated mAChRs may now be considered as suitable materials to investigate the muscarinic receptor-binding pocket through peptide mapping, sequence analyses, and identification of radiolabeled amino acid residues.

Affinity Labels↗
PubMed1993

Minimally invasive therapy: the French case study.

The diffusion in France of the 10 selected technologies is quite different, depending on the technology. Some are 'ancient', widely diffused and stabilized techniques, such as arthroscopy for knee surgery and lithotripsy for bladder stones. Others are very new but quickly disseminating technologies, such as laparoscopic cholecystectomy, and others, especially those based on lasers, have only a restricted diffusion related in some cases to a lasting skepticism of most physicians. It is therefore not possible to draw a common sketch that would apply to 'minimally invasive surgery in France' as a whole. Nevertheless, it is possible to stress some common points which characterize the dissemination of innovation in the French health care system since the 1980s. These include the lack of methods available to health authorities to control medical innovation; the organizational and financial constraints on health care institutions, restricting their ability to adapt to changing circumstances; a limited judicial response in the face of potentially dangerous technologies; the high degree of freedom that medical practitioners have in adopting innovations; the weakness of French industry; and the important and sometimes destructive role the media play in diffusion of health care innovations.

Diffusion of Innovation↗
PubMed1987

The diffusion and use of diagnostic imaging equipment in France. The limits of regulation.

The paper presents a French national survey on diagnostic imaging equipment and activity showing that conventional x-ray radiology still dominates and that the rate of diffusion of technological innovations has been very different, being slower than in other industrialized countries for such technologies as CT scanners, nuclear medicine, and magnetic resonance imaging, but on the other hand, very quick for ultrasound and digital angiography. The variety of regulations for this equipment, although it plays an important role, is not sufficient to explain these differences in the rate of diffusion. The paper shows that other explanatory variables must be taken into account, at least in the French context: the situation of the domestic biomedical industry, the relations between private and public sectors of health care delivery, and even the "technical" culture and tradition of French radiologists.

Communication↗
PubMed1979

Thymidylate synthetase catalyzed exchange of tritiumfrom [5-3H]-2'-deoxyuridylate for protons of water.

Thymidylate synthetase catalyzes an exchange of tritium of [5-3H]dUMP for protons of water in the absence of CH2-H4folate. The turnover number for this reaction is some 45,000-fold lower than that of dTMP formation and Km is 1.2 X 10(-5) M, similar to the dissociation constant of the enzyme-dUMP complex determined by equilibrium dialysis. The presence of 4 mM folate has no effect on Vmax but results in a decrease in the Km of dUMP to a value close to that in the normal enzymic reaction. The exchange reaction provides definitive evidence that the enzymic reaction involves attack of a nucleophile of the enzyme on the 6 position of dUMP to provide a 5,6-dihydro-dUMP intermediate which is covalently bound to the enzyme. Stereochemical considerations of the exchange reaction require proposal of a partial reaction which is not completely sterospecific or a complex reaction in which protons of water are handled with complete stereospecificity in a fashion similar to the one carbon unit of the normal enzymic reaction.

Isotope Labeling↗
PubMedDate not supplied

Health care technology in France.

The French health care system combines freedom of medical practice with nation-wide social security. The system is centrally regulated with specific attention to technology. Prices and budgets are also regulated. Despite these controls, concerns about quality of care began to appear in France in the 1970s. At the same time, increasing costs became an issue. Health care technology assessment has been under discussion as part of the solution to these problems since the early 1980s, but little was done until 1989, when a national agency was established to develop and coordinate health care technology assessment in France. In 1991, a new law on hospitalization strengthened the role of the government in health care and required extensive evaluation activities. The law has made legal requirements for the health care system and the government at all levels, as well as establishing specific institutions and public grants to support evaluation and related activities. While further evolution of the health care system is inevitable, it seems clear that technology assessment is becoming one of the key tools for addressing problems of quality of care and rising costs.

Cost-Benefit Analysis↗
PubMedDate not supplied

Fluorescent muscarinic EGFP-hM1 chimeric receptors: design, ligand binding and functional properties.

We describe the construction, expression and characterization of recombinant proteins comprising the enhanced green fluorescent protein (EGFP) fused to the amino-terminal part of the muscarinic hM1 receptor together or not with an additional hexahistidine tag placed at the C-terminal end of the receptor. Expression of the fluorescent proteins reaches levels identical to those of the wt hM1 receptor, provided that fusion takes place at the very N-terminal end of the receptor. Also correct protein folding and targeting to plasma membrane is obtained upon addition of a signal peptide promoting amino-terminal domain translocation through the membrane. Ligand binding properties of--and activation of the calcium release response by--the fusion proteins are almost identical to those of the wild-type muscarinic receptor, indicating that such fluorescently-labelled receptors are valuable model systems for further functional, biochemical and structural studies.

Base Sequence↗