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Biomedical subjects

M Laurent

Publications and source records attributed to M Laurent.

At least 55 records · Page 3Linked to original sources

Cephalometric estimation of vertical dimension of occlusion.

The literature does not establish a single proven method for determining lower facial height, which is called the Vertical Dimension of Occlusion (VDO), and the concept of a vertical comfort range is generally accepted. This study aimed to test the statistical significance of correlations of mandibular shape versus lower facial height in occlusion, using cephalometric measurements. Correlations for 505 consecutive healthy adults were calculated between angles that estimate the lower facial height and angles that estimate the mandibular shape. The mandibular angle (gonial) showed a higher coefficient of correlation (r = 0.691) than the inferior gonial angle. The dispersion remained large, i.e. r2 = 0.478. Cephalometric measurements, despite theirs imperfections, could help the practitioner to understand what the best course of treatment would be in order to obtain a lower facial height in occlusion showing a skeletal harmony with the mandibular shape.

Adult↗

fac-tricarbonyl

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Journal Article↗

The study of locomotor pointing in virtual reality: the validation of a test set-up.

The goal of this experiment was to validate an experimental set-up for studying locomotor pointing. The specific and also original element of this set-up was the interactive nature of virtual reality and movement production. This interaction was achieved through the coupling of a treadmill and a Silicon Graphics system. This latter system generated on a screen (3 x 2.3 m) an environmental array that moved according to the action produced by subjects on a treadmill. The task was to place either foot on a spatial target that appeared on the floor in front of the subject's displacement trajectory. We analyzed the step length patterns of subjects approaching these targets, along with the current target-subject relationship. The results are in agreement with a perception-action coupling type of control mechanism that operates continuously as the subject approaches the desired target. Apparently, these findings mirror observations of real-life locomotion, indicating that the present set-up provides a valid and useful tool for examining human locomotion.

Adult↗

[Pregnancy and anticoagulant therapy. Indications and strategies].

Anticoagulant therapy is sometimes required during pregnancy either for the prevention of thromboembolic disease, for patients already on long-term antithrombotic treatment (for valvular prostheses) or for the prevention of complications of risk factors such as hereditary or acquired thrombophilia. Pregnancy is in itself a hyper-coagulable condition and the risk of thromboembolic complications is raised. Anticoagulation is a risk to the mother and to the foetus, and the management (heparin or vitamin K antagonists, respective doses) must be adapted to the underlying pathology and the stage of pregnancy. Mechanical valve prostheses are the most difficult problem and different strategies are proposed. The use of low molecular weight heparin may improve the outcome of these patients, but further trials are necessary.

Anticoagulants↗

Elderly patients treated with tinzaparin (Innohep) administered once daily (175 anti-Xa IU/kg): anti-Xa and anti-IIa activities over 10 days.

Since low molecular weight heparins (LMWH) are partly eliminated by renal excretion, their pharmacodynamic profile may be modified in very elderly patients with age-related renal impairment. The aim of this prospective study was to determine whether tinzaparin (Innohep) 175 anti-Xa IU/kg administered subcutaneously once daily over 10 days does accumulate in hospital patients greater than 70 years of age. Plasma anti-Xa and anti-IIa amidolytic levels and APTT were determined prior to the first injection (day 0), and then, at peak level i.e. 5 h after the second injection (day 2) and subsequently on days 5, 7 and 10. Thirty consecutive inpatients (6 men, 24 women) requiring LMWHs at a curative dose for acute thromboembolic disease were included. Patients' characteristics (mean +/- SD) were: age 87.0+/-5.9 years (range 71-96), body weight 62.7+/-14.6 kg (range 38-90) and creatinine clearance 40.6+/-15.3 mL/min (range 20-72). The mean actual dose of tinzaparin delivered was 174.8 anti-Xa IU/kg. Since no patient had an anti-Xa activity above 1.5 IU/mL, the dose of tinzaparin remained fixed over 10 days. Anti-Xa and anti-IIa peak levels measured on day 2 were 0.66+/-0.20 IU/mL (range 0.26-1.04) and 0.33+/-0.10 IU/mL (range 0.18-0.55), respectively. Ex vivo anti-Xa/anti-IIa ratios were close to 2.1. APTT ratios (patient/control) were strongly correlated with anti-IIa activity (p <0.01). There was no progressive increase of the anti-Xa and anti-IIa activities after repeated administration of tinzaparin over the 10 day treatment period. No correlation was found between anti-Xa and anti-IIa activities and age, weight, or creatinine clearance. No major bleeding occurred during the study and only one minor haematoma at the injection site was reported. No thrombo-embolic complication or death occurred. Tinzaparin may thus be administered safely at a treatment dose (175 anti-Xa IU/kg) in older patients with age-related renal impairment. Neither dose adjustment, nor serial anti-Xa activity monitoring seems to be required in patients with creatinine clearance above 20 mL/min during the first ten day treatment.

Age Factors↗

[Influence of saggital inclination of the teeth and the orientation of the occlusal plane on mesial drift in the dental arch].

As a rule, the occlusal plane in man is not flat but curved in the three dimensions. This curved organization is related to a specific phenomena: the continuity of the dental arch without diastema. The Page's proposal of the tangent law explains the sagittal organization of the mandibular teeth by geometrical analyses. A cephalometric analysis of 485 subjects, in natural dentition, is the basis for the present statistical study of the mandibular teeth sagittal inclination, related to the direction of the tangent. Mandibular incisors follow the tangent law, but the long axis of the posterior mandibular teeth exhibits a postero-anterior and progressive differential angle with the direction of the tangent: 15 degrees, 20 degrees, 25 degrees, 28 degrees. The differential angle with the direction of vertical strength during closure movement generates an horizontal strength component, with a tendency to create a forward tooth movement. This horizontal component of force is tightening the proximal contacts, maintaining the continuity of the dental arch: it also originates the mesial "drift" and mandibular incisor crowding.

Adult↗

The regulation of externally paced human locomotion in virtual reality.

The goal of the present experiment was to study regulation of human locomotion under externally paced temporal constraints. On a screen placed in front of a treadmill a virtual hallway was projected (Silicon Graphics systems) in which a pair of doors were presented that continuously opened and closed at a rate of 1 Hz. Subjects were attached to a locometer and instructed to regulate walking pace such that the doors were passed correctly. Performance outcome, movement kinematics (stride duration, stride length and synchronization of stride and door cycles) and flow patterns (change in visual angle of door aperture) were used to examine the data. The analysis of the synchronization patterns indicates that stride cycles were not linked to the period of door oscillation. Moreover, results for stride duration reveal that subjects walked at their preferred speed up to the final phase of the approach. This observation is supported by the inspection of the flow patterns, revealing a final increase in variability as a result of regulation. In sum, regulation of locomotion under externally paced temporal constraints seems to generate a specific functional behavior. It appears that regulations are postponed until the final stage of the approach during which adaptations are made according to the requirements of the current situation.

Biomechanical Phenomena↗

The vascular endothelial-cadherin promoter directs endothelial-specific expression in transgenic mice.

Vascular endothelial-cadherin (VE-cadherin) is a calcium-dependent adhesive molecule, exclusively and constitutively expressed in endothelial cells. Analysis of the VE-cadherin promoter fused to a reporter gene in bovine aortic endothelial cells showed three major functional regions. The proximal region alone (-139, +24) promoted nonspecific transcription; the addition of the (-289, -140) and (-2226, -1190) domains abolished transcription in fibroblasts while expression in endothelial cells remained unchanged, suggesting that fragments (-2226, +24) and longer contain the full endogenous promoter activity. To study the transcriptional specificity of the promoter region in vivo, we generated transgenic mice carrying the chimeric construct containing the (-2486, +24) region. The promoter directed reporter expression in all examined organs of adult transgenic mice. During embryonic development, transgene expression was detected at the early steps of vasculogenesis. Later, the expression persisted during development of the vascular system and was restricted to the endothelial layer of the vessels. Together, these data provide evidence for specific regulatory regions within the VE-cadherin promoter. Furthermore, the identification of DNA sequences restricting gene expression to the endothelium has many potential applications for the development of animal models of cardiovascular or angiogenic diseases or for the delivery of therapeutic molecules.

5' Untranslated Regions↗

Movement reversals in ball catching.

This study aimed to determine whether the interception of a moving object is achieved by implementing a predictive or a prospective strategy. We examined the kinematics of catching movement in a situation in which the catching hand was constrained to move along a single dimension. In line with predictions based on a prospective strategy, the results obtained indicated that, for the same interception point and the same initial hand position, modification of the spatiotemporal characteristics of the ball's trajectory (via modification of the angle of approach of the ball) gave rise to systematic changes in the kinematics of catching movement. Moreover, the production of movement reversals when the hand was already positioned at the interception point, while in line with the predictions of the prospective strategy formalized by Bootsma et al. (1997), allowed for rejection of a predictive strategy.

Adult↗

Multistability: a major means of differentiation and evolution in biological systems.

Very simple biochemical systems regulated at the level of gene expression or protein function are capable of complex dynamic behaviour. Among the various patterns of regulation associated with non-linear kinetics, multistability, which corresponds to a true switch between alternate steady states, allows a graded signal to be turned into a discontinuous evolution of the system along several possible distinct pathways, which can be either reversible or irreversible. Multistability plays a significant role in some of the basic processes of life. It might account for maintenance of phenotypic differences in the absence of genetic or environmental differences, as has been demonstrated experimentally for the regulation of the lactose operon in Escherichia coli. Cell differentiation might also be explained as multistability.

Biological Evolution↗

[Comparison of apical and infundabular pacing in patients with primary dilated or ischemic cardiomyopathy].

Dual chamber pacing has been proposed as an alternative treatment to patients with cardiac failure refractory to optimal medical therapy. The influence of the site of ventricular pacing was studied in 15 patients with an average age of 68.7 +/- 8.7 years with dilated cardiomyopathies and an average left ventricular ejection fraction of 22.3 +/- 6.8%. Three temporary USCI electrodes were positioned in the right atrium, the right ventricular outflow tract (RVOT) and the right ventricular apex. The average duration of the QRS complexes and the haemodynamic parameters (PAP, PCP and cardiac index) were measured in sinus rhythm and during DDD apical, RVOT and simultaneous apical and RVOT pacing. The RVOT and simultaneous pacing significantly reduced the QRS duration (135 +/- 14 ms and 137 +/- 17 ms, p < 0.0001 respectively) compared with apical pacing (150 +/- 19 ms). The mean PAP and mean PCP remained unchanged in the different modes of pacing but the cardiac index increased significantly during RVOT pacing (2.99 +/- 0.67 l/min/m2) and simultaneous pacing (3 +/- 0.77 l/min/m2) compared with apical pacing (2.66 +/- 0.62 l/min/m2) (p < 0.001 and p < 0.01 respectively) and compared with sinus rhythm (2.62 +/- 0.7 l/min/m2) (p < 0.001 and p < 0.005 respectively). This study suggests that better results may be obtained with RVOT screw in lead than with the traditional right ventricular apical electrode.

Aged↗

Species barrier in prion diseases: a kinetic interpretation based on the conformational adaptation of the prion protein.

Prion diseases are thought to result from the conformational change of the normal cellular prion protein to a pathogenic protease-resistant isoform. However, brain extracts not containing the protease-resistant isoform of the prion protein can be infectious following interspecies transmission. The 'protein-only' hypothesis of pathogenesis is extended to provide possible explanations which could be interpreted in terms of a different infectious agent. It is proposed that normal cellular protein (PrPC) may be transformed into a form (PrP*) that is conformationally distinct from the host-specific abnormal isoform (PrPSc). In infection from a heterologous donor, the dimeric forms of heterologous PrPSc, which may catalyse the formation of host PrP* from PrPC, host PrP* and host PrPSc are all considered to be capable of catalysing, to some extent, the conversion of PrPC into PrPSc. However, depending on the species involved, PrP* may, or may not, be pathogenic, and may, or may not, be sensitive to proteolysis. It is shown, by numerical integration of the differential rate equations derived from this model, that a strain may be stabilized after two or three passages through a different species and that transmission might occur in the absence of detectable protease-resistant prion protein. The natural transmission of scrapie to cattle is discussed in relation to the model.

Animals↗

Production and oestrogen regulation of FGF1 in normal and cancer breast cells.

To investigate the relationship between the FGF1 oestrogen regulation and the normal/cancer status of breast cells, we have studied FGF1 17beta-oestradiol regulation in normal, transformed and cancerous cells. Normal (NMEC), transformed (HBL-100) and cancerous (MCF-7, MDA-MB-231) human mammary epithelial cells express different levels of FGF1 mRNAs. Western blot analysis allowed us to characterize FGF1 as an 18 kDa form of this polypeptide. Using a neutralizing anti-FGF1 antibody we demonstrated that FGF1 is secreted by all mammary cells studied and stimulates their proliferation in an autocrine manner. We have examined the regulation of FGF1 mRNAs in response to 17beta-oestradiol. FGF1 mRNAs were upregulated in hormone-dependent NMEC but was not upregulated either in hormone-sensitive HBL-100 cells or in the hormone-dependent cancerous cell line MCF-7. However, enzyme linked immunosorbent assay indicated an increase of FGF1 protein in NMEC, HBL-100 and MCF-7 cells. We have also examined the 17beta-oestradiol regulation of the four alternatively spliced FGF1 mRNAs: 1.A, 1.B, 1. C and 1.D. Only 1.B transcripts were downregulated by 17beta-oestradiol in normal cells. These results show that 17beta-oestradiol regulates FGF1 mRNAs in a cell-specific manner, and that this regulation may be transcriptional or translational depending on cell phenotype. The specificity of oestradiol effects was checked using its receptor antagonist tamoxifen.

Alternative Splicing↗

Bistability and the species barrier in prion diseases: stepping across the threshold or not.

The infectious agent of transmissible spongiform encephalopathies is thought to be a cellular protein, the prion protein, which undergoes, under some circumstances, a dramatic conformational change leading to pathogenesis. The conversion between the normal and pathogenic isoforms corresponds to a autocatalytic mechanism and the metabolism of the prion protein exhibits switches between a normal, stable steady state and a pathogenic one. When the disease can be transmitted between two species, a primary infection from a heterologous donor has to be followed by two passages in the same host species so that the incubation period is stabilized. Sometimes, no pathogenic isoform of the prion protein is detected after the first passage, although corresponding brain extracts remain infectious. The observation that three and only three passages are needed in order to stabilize the strain strongly suggests that, during the course of the primary infection by the heterologous donor, an intermediary conformational species is formed. Within this assumption, a common mechanism involving only conformational changes of the prion protein can give a unifying interpretation of the problem of species barrier, lag characteristics and apparent lack of detection of the pathogenic isoform after the first passage in experiments dealing with interspecies transmission of prion diseases.

Journal Article↗

Degradation versus aggregation of misfolded maltose-binding protein in the periplasm of Escherichia coli.

The periplasmic fates of misfolded MalE31, a defective folding mutant of the maltose-binding protein, were determined by manipulating two cellular activities affecting the protein folding pathway in host cells: (i) the malEp promoter activity, which is controlled by the transcriptional activator MalT, and (ii) the DegP and Protease III periplasmic proteolytic activity. At a low level of expression, the degradation of misfolded MalE31 was partially impaired in cells lacking DegP or Protease III. At a high level of expression, misfolded MalE31 rapidly formed periplasmic inclusion bodies and thus escaped degradation. However, the manipulated host cell activities did not enhance the production of periplasmic, soluble MalE31. A kinetic competition between folding, aggregation, and degradation is proposed as a general model for the biogenesis of periplasmic proteins.

ATP-Binding Cassette Transporters↗

How is body orientation controlled during somersaulting?

How body orientation is controlled during somersaulting was investigated in 2 experiments that analyzed the kinematics of 223 backward standing somersaults. In Experiment 1, open-loop, initial-condition (flight duration), and prospective (time to contact, or TC1) control strategies were tested as candidates for the regulation of body moment of inertia during the jump. Decreasing between-trials variability of body orientation over time as well as a negative correlation between body angular velocity and TC1 suggested that the moment of inertia was regulated prospectively. In Experiment 2, the visual basis for this regulation was examined by asking experts and novices to execute somersaults either with eyes closed or open. Results showed that the prospective regulation observed in the vision condition disappeared in the no-vision condition with the experts, arguing in favor of a visual control during the jump. Such a coupling was absent with the novices, thus illustrating the role played by the perception-action cycle in the learning process.

Humans↗

novH: differential expression in developing kidney and Wilm's tumors.

We previously established that the expression of the human nov gene (novH) was altered in Wilms' tumors and that levels of novH and WT1 mRNA were inversely correlated in individual Wilms' tumors. Insofar as novH has been shown to be a target for WT1 regulation, novH might play an important role during normal nephrogenesis and in the development of Wilms' tumors. We now show that during normal nephrogenesis novH protein is tightly associated with differentiation of glomerular podocytes. NovH expression is not restricted to renal differentiation but is also detected in endothelium and neural tissue of the kidney. Our results establish that alteration of novH expression in sporadic and heritable Wilms' tumors is associated with dysregulated expression of both novH mRNA and protein. In general, the highest novH expression was noted in the Wilms' tumor, genitourinary anomalies, aniridia, and mental retardation (WAGR)-associated Wilms' tumors. Expression in the Denys-Drash syndrome (DDS)-associated Wilms' tumors fell within the variable spectrum observed in sporadic Wilms' tumor cases. As in developing kidney podocytes, novH protein was also prominent in the abnormal hypoplastic podocytes from DDS cases and in kidney podocytes adjoining Wilms' tumors. In Wilms' tumors exhibiting heterotypic differentiation, novH protein was expressed at high levels in tumor-derived striated muscle and at lower levels in tumor-derived cartilage. These observations taken together indicate that novH may represent both a marker of podocytic differentiation in kidney and a marker of heterotypic mesenchymal differentiation in Wilms' tumors. In addition, absence or very low levels of WT1 are correlated with higher novH expression, and its variable expression in cases with mutant WT1 (sporadic and DDS) suggests that the potential activation and repression transcriptional functions possessed by WT1 are likely dependent on the specific mutation incurred.

Animals↗