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Biomedical subjects

Olivier Martin

Publications and source records attributed to Olivier Martin.

9 recordsLinked to original sources
PubMed2006

Alpha-1-C-octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease.

The most common lysosomal storage disorder, Gaucher disease, is caused by inefficient folding and trafficking of certain variants of lysosomal beta-glucosidase (beta-Glu, also known as beta-glucocerebrosidase). Recently, Sawker et al. reported that the addition of subinhibitory concentrations (10 microM) of the pharmacological chaperone N-nonyl-1-deoxynojirimycin (NN-DNJ) (10) to Gaucher patient-derived cells leads to a 2-fold increase in activity of mutant (N370S) enzyme [Proc. Natl. Acad. Sci. U.S.A.2002, 99, 15428]. However, we found that the addition of NN-DNJ at 10 microM lowered the lysosomal alpha-glucosidase (alpha-Glu) activity by 50% throughout the assay period in spite of the excellent chaperoning activity in N370S fibroblasts. Hence, we prepared a series of DNJ derivatives with an alkyl chain at the C-1alpha position and evaluated their in vitro inhibitory activity and potential as pharmacological chaperones for Gaucher cell lines. Among them, alpha-1-C-octyl-DNJ (CO-DNJ) (15) showed 460-fold stronger in vitro inhibitory activity than DNJ toward beta-Glu, while NN-DNJ enhanced in vitro inhibitory activity by 360-fold. Treatment with CO-DNJ (20 microM) for 4 days maximally increased intracellular beta-Glu activity by 1.7-fold in Gaucher N370 cell line (GM0037) and by 2.0-fold in another N370 cell line (GM00852). The addition of 20 microM CO-DNJ to the N370S (GM00372) culture medium for 10 days led to 1.9-fold increase in the beta-Glu activity without affecting the intracellular alpha-Glu activity for 10 days. Only CO-DNJ showed a weak beta-Glu chaperoning activity in the L444P type 2 variant, with 1.2-fold increase at 5-20 microM, and furthermore maximally increased the alpha-Glu activity by 1.3-fold at 20 microM. These experimental results suggest that CO-DNJ is a significant pharmacological chaperone for N370S Gaucher variants, minimizing the potential for undesirable side effects such as alpha-Glu inhibition.

1-Deoxynojirimycin↗
PubMed2006

Different impact of staining procedures using visible stains and fluorescent dyes for large-scale investigation of proteomes by MALDI-TOF mass spectrometry.

Replicate 2-D gels were stained with four visible or fluorescent dyes using published procedures, and 48 co-detected spots were selected for contrasting values in abundance, M(r) and pI. Success rate of identification and sequence coverage were affected in a dye-dependent manner by the three parameters. Frequency of missed cleavages and recovery of sulfur-containing peptides also depended on the dye. Finally, the dataset was used to predict the number of proteins identifiable when integrating the differential contribution of each parameter. Sypro Ruby appeared to combine several favorable features: no dependence of the identification rate upon the physicochemical properties of proteins, no impact on frequency of missed cleavages, and a higher predicted identification rate.

Arabidopsis Proteins↗
PubMed2005

Coordination between posture and movement: interaction between postural and accuracy constraints.

We examined the interaction between the control of posture and an aiming movement. Balance control was varied by having subjects aim at a target from a seated or a standing position. The aiming difficulty was varied using a Fitts'-like paradigm (movement amplitude=30 cm; target widths=0.5, 1.0, 2.5 and 5 cm). For both postural conditions, all targets were within the reaching space in front of the subjects and kept at a fixed relative position with respect to the subjects' body. Hence, for a given target size, the aiming was differentiated only by the postural context (seated vs. upright standing). For both postural conditions, movement time (MT) followed the well-known Fitts' law, that is, it increased with a decreasing target size. For the smallest target width, however, the increased MT was greater when subjects were standing than when they were seated suggesting that the difficulty of the aiming task could not be determined solely by the target size. When standing, a coordination between the trunk and the arm was observed. Also, as the target size decreased, the center of pressure (CP) displacement increased without any increase in CP speed suggesting that the subjects were regulating their CP to provide a controlled referential to assist the hand movement. When seated, the CP kinematics was scaled with the hand movement kinematics. Increasing the index of difficulty led to a strong correlation between the hand speed and CP displacement and speed. The complex organization between posture and movement was revealed only by examining the specific interactions between speed-accuracy and postural constraints.

Adaptation, Physiological↗
PubMed2004

Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial.

CONTEXT: A recent trial showed that placing patients with acute lung injury in the prone position did not increase survival; however, whether those results hold true for patients with hypoxemic acute respiratory failure (ARF) is unclear. OBJECTIVE: To determine whether prone positioning improves mortality in ARF patients. DESIGN, SETTING, AND PATIENTS: Prospective, unblinded, multicenter controlled trial of 791 ARF patients in 21 general intensive care units in France using concealed randomization conducted from December 14, 1998, through December 31, 2002. To be included, patients had to be at least 18 years, hemodynamically stable, receiving mechanical ventilation, and intubated and had to have a partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FIO2) ratio of 300 or less and no contraindications to lying prone. INTERVENTIONS: Patients were randomly assigned to prone position placement (n = 413), applied as early as possible for at least 8 hours per day on standard beds, or to supine position placement (n = 378). MAIN OUTCOME MEASURES: The primary end point was 28-day mortality; secondary end points were 90-day mortality, duration of mechanical ventilation, incidence of ventilator-associated pneumonia (VAP), and oxygenation. RESULTS: The 2 groups were comparable at randomization. The 28-day mortality rate was 32.4% for the prone group and 31.5% for the supine group (relative risk [RR], 0.97; 95% confidence interval [CI], 0.79-1.19; P = .77). Ninety-day mortality for the prone group was 43.3% vs 42.2% for the supine group (RR, 0.98; 95% CI, 0.84-1.13; P = .74). The mean (SD) duration of mechanical ventilation was 13.7 (7.8) days for the prone group vs 14.1 (8.6) days for the supine group (P = .93) and the VAP incidence was 1.66 vs 2.14 episodes per 100-patients days of intubation, respectively (P = .045). The PaO2/FIO2 ratio was significantly higher in the prone group during the 28-day follow-up. However, pressure sores, selective intubation, and endotracheal tube obstruction incidences were higher in the prone group. CONCLUSIONS: This trial demonstrated no beneficial outcomes and some safety concerns associated with prone positioning. For patients with hypoxemic ARF, prone position placement may lower the incidence of VAP.

Acute Disease↗
PubMed2004

Pointing to a target from an upright standing position: anticipatory postural adjustments are modulated by the size of the target in humans.

To examine the influence of the target size onto postural EMG activity, eight subjects performed, from a standing position, rapid and accurate pointings to a target located within reach. The target size was varied across blocks of trials. Hand movement time increased when the target size was decreased. Interestingly, the magnitude of the integrated EMG activity of lower limb muscles (TAi, TFLc, RFi) decreased with a decreasing target size, while that of the erector spinae increased. The effects were observed as early as 200 ms before the hand movement onset. When standing, these early commands could influence the control of the hand during the acceleration phase. The target size was specified within the postural command before any hand movement took place suggesting the characteristics of the pointing task were integrated in a feedforward manner.

Adult↗
PubMed2004

Proteomic investigation of natural variation between Arabidopsis ecotypes.

Two-dimensional (2-D) gel electrophoresis and peptide mass fingerprinting were used to investigate the natural variation in the proteome among 8 Arabidopsis thaliana ecotypes, of which 3 were previously shown to display atypical responses to environmental stress. Comparison of 2-D maps demonstrated that only one-quarter of spots was shared by all accessions. On the other hand, only 15% of the 25 majors spots accounting for half the total protein amount could be classified as major spots in all ecotypes. Identification of these major spots demonstrated large differences between the major functions detected. Accordingly, the proteomes appeared to reveal important variations in terms of function between ecotypes. Hierarchical clustering of proteomes according to either the amount of all anonymous spots, that of the 25 major spots or the functions of these major spots identified the same classes of ecotypes, and grouped the three atypical ecotypes. It is proposed that proteome comparison has the capacity to evidence differences in the physiological status of ecotypes. Results are discussed with respect to the possibility to infer such differences from limited comparisons of major proteins. It is concluded that classical proteomics could constitute a powerful tool to mine the biodiversity between ecotypes of a single plant species.

Arabidopsis↗
PubMed2003

[Patients refused in admission to an intensive care unit. Prospective evaluation of the causes and outcome].

OBJECTIVES: To determine the reasons for refusing admission to an intensive care unit and the immediate outcome of the patients refused. METHOD: All patients triaged for admission to a medical intensive care unit ICU during a three-month period were studied prospectively. The frequency and reason for refused admission were studied. The immediate outcome of the refused patients, together with the time lapse before their subsequent management were determined. RESULTS: Out of 251 patients, 132 (53%) were refused admission. Primary reasons for refusal was lack of beds (92%). Nearly one patient out of 5 was not subsequently treated in an intensive care unit. CONCLUSION: Some refusals could have been avoided if the downstream networks (short-hospitalisation, re-habilitation centres.) had been able to accommodate the patients proposed. Moreover, by abandoning the strategy of wide admission to intensive care to the benefit of a selective triage of the patients proposed, a certain number of refusals would probably have been avoided. Nevertheless, there are obvious difficulties in the application of the latter method.

Aged↗
PubMed2003

On-line modification of saccadic eye movements by retinal signals.

A saccade is a rapid shift of the position of the eyes (< 100 ms). Saccades are generally considered too quick to be influenced by retinal signals. To address this idea, we displaced the visual target of a rightward horizontal saccade at eye movement onset (when there is suppression of conscious perception). To prevent adaptive and learning effects to occur, jump saccades were always followed by a random series of 10 no-jump saccades. Results indicated that the target jump influenced significantly the amplitude and the peak velocity of the ongoing saccade (opposite effects were found for rightward and leftward jumps). Changes in saccade kinematics occurred as early as 50 ms after the target jump. These results show that retinal information is processed quickly during eye movements, presumably through sub-cortical pathways.

Biomechanical Phenomena↗