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Biomedical subjects

S Vincent

Publications and source records attributed to S Vincent.

At least 73 records · Page 4Linked to original sources
PubMed1997

Systemic activation of the vascular endothelial growth factor receptor KDR/flk-1 selectively triggers endothelial cells with an angiogenic phenotype.

The hypothesis that tumor growth is angiogenesis dependent has been documented by a considerable body of direct and indirect experimental data. A prerequisite for the development of novel anti-angiogenic agents is the design of drugs that would be active only on those endothelial cells with an angiogenic phenotype. We took advantage of the anti-idiotypic strategy to obtain circulating agonists specific for the vascular endothelial growth factor receptor KDR/flk-1 (J-IgG). They induced in the absence of VEGF cell proliferation in vitro and angiogenesis in the corneal pocket assay either through local or systemic delivery. Intraperitoneal injections of J-IgG in nude mice grafted with a prostatic adenocarcinoma led to tumor enlargement associated with an increase in both tumor vascularization and proliferation. In contrast KDR/flk-1 overstimulation had no detectable effect on normal tissues. These data underline that KDR/flk-1 is a functional marker of the angiogenic phenotype of endothelial cells.

Adenocarcinoma↗
PubMed1996

Quantitative videobronchoscopy: a new technique to assess airway caliber.

Quantitative assessment of airway caliber is generally confined to indirect physiologic methods or to radiographic techniques. Fiberoptic bronchoscopy provides a direct view of airways, permitting quantification of airway caliber by image analysis. We investigated the characteristics of a bronchoscopic imaging system, determined its limitations in quantification and the corrections necessary for accurate assessment of image dimension, validated the methodology with airway models, and applied the technique to airways in vivo. The system comprised a bronchoscope, videocamera, videocassette recorder (VCR), computer with a frame grabber, and image-analysis program. Image quantification was affected by two sources of distortion: (1) Distance distortion: a loss of image resolution with increasing distance between the object and bronchoscope, requiring determination of the operational distance range. (2) Radial distortion: a progressive reduction in image size from the center to the periphery of the bronchoscopic field of view (FOV), requiring correction of airway dimension according to airway size and location in FOV. Validation of the methodology with different sized airway models indicated an underestimation of measured diameters, which normalized with distortion correction. We provide an example of quantitative videobronchoscopy with measurements of in vivo airway narrowing due to vagal stimulation in the anesthetized dog. Measurements of airway narrowing made with videobronchoscopy were also compared with those made with high-resolution computer-assisted tomography (HRCT) which suggested that the two technologies provide unique but complementary perspectives on airway dimensions. We conclude that videobronchoscopy and image analysis provide a novel and accurate method for the quantification of airway caliber.

Animals↗
PubMed1996

Glide directs glial fate commitment and cell fate switch between neurones and glia.

Glial cells constitute the second component of the nervous system and are important during neuronal development. In this paper we describe a gene, glial cell deficient, (glide), that is necessary for glial cell fate commitment in Drosophila melanogaster. Mutations at the glide locus prevent glial cell determination in the embryonic central and peripheral nervous system. Moreover, we show that the absence of glial cells is the consequence of a cell fate switch from glia to neurones. This suggests the existence of a multipotent precursor cells in the nervous system. glide mutants also display defects in axonal navigation, which confirms and extends previous results indicating a role for glial cells in these processes.

Animals↗
PubMed1996

[Modulation of the tumoral progression by anti-idiotypic antibodies of angiogenesis factors].

We took advantage of the anti-idiotypic strategy to design circulating probes mimicking the biological effects of VEGF (vascular endothelial growth factor) or FGF2 (fibroblast growth factor 2). The activation of the VEGF receptor KDR/flk-1 induced endothelial cell proliferation but not their migration, whereas that of the FGF receptor FGF-R1 gave opposite results. The long lasting delivery of KDR/flk-1 agonists, but not that of FGF-R1, in nude mice grafted with tumor fragments enhanced the tumor volume. Microscopic examination showed an increase in both the vascularization and the proliferation of cancer cells. In contrast, no difference in cell proliferation was observed within normal tissues.

Adenocarcinoma↗
PubMed1996

[Individual variability of pharmacokinetic parameters of amikacin in the elderly: retrospective studies].

UNLABELLED: In previous works, we have shown: i) good parameter predictive performances of the USC*PACK Clinical Programs for amikacin therapy in the elderly, ii) no significant difference generally detected between estimated parameter values at days 7 and 14 after the beginning of therapy, iii) assurance of neither accumulation nor toxicity during therapy up to 14 days or more, in our conditions. The objectives of this study were to explore which elements best explained differences found in the pharmacokinetic parameters (PK) of the elderly patients, who had received several courses of amikacin therapy. METHODS: patients' pharmacokinetic data and their medical records were retrospectively analyzed. Only patients who received amikacin therapy with at least a 2-month washout between their courses were studied. Two parameterizations of the 1-compartment PK model were used: one without covariates: Kel-Vol, where Kel = elimination rate constant and Vol = distribution volume, and another including covariates: Ks-Vs, with: Kel = Ks. CCr + Ki, where: Ks = renal fraction of Kel, Ki - non renal elimination, CCr = estimated creatinine clearance, and Vs = Vol/W, where Vs = distribution volume per kg and W = weight. RESULTS: 14 patients, 3 men and 11 women, fulfilled the criteria (4 of them satisfied the condition with 3 courses). They were 66 to 89 years old, their mean weight was 53.86 +/- 11.03 kg (46-71.5), their CCr averaged: 55.45 +/- 17.16 mL/min (14.84-96.27). CONCLUSION: Among patients exhibiting changes (67%) in PK parameters between different courses of therapy, 42% could have the variability related to covariate (W, CCr) changes; in the others 58% the residual variability could be explained by different factors: severity of infection, immune system deficiency and/or particularly parenteral nutrition. Based on these result, we suggest including septic choc and parenteral nutrition as covariates during amikacin adaptive control.

Age Factors↗
PubMed1995

Growth-regulated expression of FKBP-59 immunophilin in normal and transformed fibroblastic cells.

Expression of many primary response cellular genes is observed during the early stages of transition from a resting G0 state to DNA synthesis. To identify gene products implicated in long-term response to growth factors, we have isolated genes sequentially activated several hours after serum stimulation of fibroblastic CCL39 cells. We report here the characterization of one of them as encoding the immunophilin of 56-59 kDa (FKBP-59), a component of the steroid receptor complex. FKBP-59 is encoded in several mammalian species by a unique gene located within the transition protein 2 gene locus. FKBP-59 mRNA is ubiquitously expressed at various levels in human organs. FKBP-59 gene activation in CCL39 fibroblasts requires protein synthesis during the first 2 h of stimulation, a period of time during which proto-oncogenes such as c-fos or c-jun are expressed. FKBP-59 mRNA degrades upon serum withdrawal and accumulates in proportion to the mitogenic strength of various purified growth factors. Its expression is reduced in CCL39 mutant-transformed cells or cells able to grow in low serum-containing medium, suggesting that FKBP-59 might participate in the negative feedback control to cell proliferation.

Alternative Splicing↗
PubMed1995

[Specification of glial lineage in invertebrates].

Glial cells in invertebrates have been known for a long time, however, a systematic analysis of the development and the role of these cells has been missing. In the last few years, the development of new markers and the identification of genes specifically expressed in glial cells have shed some light on the mechanisms leading to gliogenesis in Drosophila melanogaster. The organisation of glial cells in the central and in the peripheral nervous system has been described and the origin of some of these cells has also been assessed. Lineage studies have shown that glial cells display different mechanisms of differentiation depending on their position in the nervous system. In some cases, glial differentiation seems intimately associated with neurogenesis, as has already been shown in the vertebrate peripheral nervous system. This suggests that similar developmental mechanisms have been conserved during evolution and that Drosophila can be used as a model system to study glial differentiation in vertebrates.

Animals↗
PubMed1994

Histamine H3 binding sites in rat brain: localization in the nucleus of the solitary tract.

The distribution of high-affinity binding sites for the histamine H3 agonist [3H]-N alpha-methylhistamine ([3H]NAMH, 4 nM) in the rat brain was examined by autoradiography. Binding in all brain regions was displaceable with the H3 antagonist thioperamide (2 microM). The pattern of H3 binding was heterogeneous: highest levels were in the striatum and substantia nigra, which receives sparse histaminergic innervations. Intermediate H3 binding was present in neocortex and diencephalon, while low binding was evident in the medial septum and dorsal hippocampus. Hitherto unreported H3 binding sites were noted in the dorsolateral tegmentum and in the nucleus of the solitary tract (NTS). Because the NTS receives a dense histaminergic innervation, [3H]NAMH binding in the NTS was further studied by Scatchard analysis. The presence of saturable binding (Bmax = 10 +/- 4 fmol/mg, Kd = 0.6 +/- 0.3 nM, n = 3) suggested that histamine may act via H3 receptors in the NTS.

Animals↗
PubMed1994

General practitioners' reasons for not attending a higher professional education course.

BACKGROUND: A proposal to run a higher professional education course attracted strong initial interest. However, only 12% of those 74 general practitioners expressing an interest subsequently enrolled on the course. AIM: A study was undertaken to examine the factors that demotivated the remaining 88% from attending. METHOD: A questionnaire was sent to the non-attenders, asking them to rank the impact of each of six factors on their decision not to attend. RESULTS: Major factors included time commitment, general practice workload and family pressures. Cost, attitudes of practice partners and structure of the course were much less important. CONCLUSION: It seems that the conditions imposed by the current demands of working as a general practitioner, rather than the attitudes of the general practitioners themselves, inhibit this form of continuing professional development.

Attitude of Health Personnel↗
PubMed1993

Serum-induced inhibition of myogenesis is differentially relieved by retinoic acid and triiodothyronine in C2 murine muscle cells.

We recently reported that triiodothyronine (T3) enhances MyoD gene expression and accelerates terminal differentiation in murine C2 myoblasts. In this paper, we are interested in the effects of other hormones acting through related nuclear receptors. Retinoic acid (RA), but not estradiol or dexamethasone, is also able to enhance MyoD gene expression (about threefold). However, the effects of RA and T3 on myogenesis are quite distinct, with a much more potent RA action. Indeed, although T3 and RA positively regulate myogenesis with similar efficiency in poorly mitogenic conditions, in presence of high serum concentrations T3 can no longer trigger terminal differentiation whereas RA still remains efficient. Thus, serum concentration is a crucial parameter in discriminating between the effects of T3 and RA on myogenesis. The differential effects between these two hormone are likely to be related to the ability of RA-activated endogenous retinoic acid receptors (RARs) to induce C2 myoblasts growth-arrest and to extinguish AP1 activity (thought to act as an inhibitor of myogenesis) whereas T3-activated endogenous thyroid hormones receptors (THRs) are relatively inefficient. We propose that the much higher level of RARs in C2 cells versus THRs could to some extent account for the differential ability of T3 and RA to antagonize serum-regulated mitogenic pathways in myogenic cells. This study provides clear evidence for an important role of RA on MyoD gene expression and myogenesis and suggests that T3 and RA could play overlapping, but distinct, roles on muscle development.

Animals↗
PubMed1993

Influence of external defibrillator electrode polarity on cardiac resuscitation.

Eight hundred forty-seven consecutive patients discovered in cardiac arrest by first responding firefighters received initial defibrillation attempts using automatic external defibrillators. The effect of electrode polarity on defibrillation and resuscitation was determined in the subset of 289 (34%) with ventricular fibrillation in a prospective, randomized trial. The ECG was recorded in 205 consecutive patients whose initial rhythm was ventricular fibrillation. Eighty-seven of 114 patients (76%) in whom the apex chest electrode was positive were defibrillated with the first 200-joule shock, compared to 70 of 91 patients (77%) in whom the apex electrode was negative. There was no difference in the type of rhythm established, e.g., organized versus brady-asystole following defibrillation with either electrode polarity. Resuscitation was possible in 56% of patients in whom the apex electrode was positive and 60% of those in whom the apex electrode was of negative polarity. Hospital survival rates (26% vs 27%) were also similar for both treatment groups. Unlike results during experimental external defibrillation of animals or those obtained using implantable defibrillators, this randomized trial of external defibrillation conducted during attempted out-of-hospital resuscitation showed no difference in outcomes related to electrode polarity.

Aged↗
PubMed1993

Teicoplanin-resistant Staphylococcus aureus expresses a novel membrane protein and increases expression of penicillin-binding protein 2 complex.

In the recent clinical trials of teicoplanin therapy of endocarditis caused by Staphylococcus aureus, at least one instance of the emergence of teicoplanin-resistant strains during therapy has been reported (G.W. Kaatz, S. M. Seo, N. J. Dorman, and S. A. Lerner, J. Infect. Dis 162:103-108, 1990). We have confirmed, using conventional electrophoresis of EcoRI-digested chromosomal DNA and pulsed-field gel electrophoresis of SmaI-digested chromosomal DNA, that the resistant strain (12873) (MIC, 16 micrograms/ml) is genetically very similar to the susceptible parent (12871) (MIC, 4 micrograms/ml). Kaatz et al. were able to select spontaneous teicoplanin-resistant mutants (10(-9)), suggesting that a single gene might be involved. We have shown that the mutation is highly stable during growth in the absence of teicoplanin. Using Tn551, we have selected insertion mutants of 12873 that become teicoplanin susceptible. We have examined a number of aspects of cell wall physiology in strains 12871 and 12873 and the teicoplanin-susceptible Tn551 mutants of 12873. 12873 was more susceptible to lysostaphin lysis than 12871 and the susceptible Tn551 derivatives of 12873. Autolysis in phosphate buffer (pH 7.5) and cell wall turnover rates were similar in 12871 and 12873. An analysis of membrane proteins revealed the expression of a ca. 35-kDa protein and increased expression of both polypeptides of penicillin-binding protein (PBP) 2 (PBP2) in 12873 relative to 12871 and the Tn551 mutants of 12873. This increased expression was not related to PBP2', since both strains were susceptible to oxacillin in 2% NaCl (MIC, < or = 0.25 microgram/ml) and cellular DNA from neither strain hybridized with a specific mec gene probe. Two independent Tn551 inserts have been mapped to a ca. 117-kb SmaI fragment of the chromosome. These data suggest the possibility that the mutation resulting in resistance to teicoplanin involves the regulation of expression of both polypeptides of PBP2 and a 35-kDa membrane protein.

Autolysis↗