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Biomedical subjects

M Faucher

Publications and source records attributed to M Faucher.

16 recordsLinked to original sources

Motor determinants of gait in 100 ambulatory patients with multiple sclerosis.

A prospective analysis of gait and strength parameters was performed in 100 patients diagnosed with MS and pyramidal involvement admitted in a rehabilitation unit The patients were divided into two groups based on their ability to walk in daily life (nonassisted or cane-assisted gait) and into four clinical subgroups depending on associated involvements such as sensory loss or cerebellar ataxia. Twenty healthy subjects were studied as a control group. Gait parameters were evaluated with a Locometre and muscle strength with an isokinetic dynamometer. The results showed that the average velocity and strength of the hamstring and quadriceps were strongly correlated and reduced in the MS group in comparison with the control, and in the cane-assisted group compared with the nonassisted group. Gait velocity tended to be more correlated to hamstring strength in the nonassisted group with a determination coefficient (r2) reaching a value of 0.44 in the sensory subgroup. These findings provide evidence that a correlation between strength reduction and gait impairment is obvious whatever the clinical form in patients with MS. This correlation is higher with hamstrings but may change depending on the disability level and the clinical form. This could be taken into account in the individual assessment of further rehabilitation programmes.

Activities of Daily Living↗

[Evaluation of physiological properties of ankle braces based on a review of the literature].

INTRODUCTION: The objective of this work was to proceed to a review of the literature to assess the physiological basis of the ankle brace use. METHOD: An analysis of the international literature relating to the years 1980-2002 was carried out by questioning the Medline data bank. RESULTS: Three hundred and twenty-two articles were collected and 25 physiological studies were retained. Various changes can occur during brace use, first of all stability parameters and proprioceptive sense. Main changes affect position sense, stiffness, mobility and stability of ankle when standing. DISCUSSION: This review of the literature allows to specify the mechanisms involved by brace use in ankle stability. Some studies allow to compare the principal devices used to stabilize the ankle (taping, semi rigid braces) but, no physiological study was able to discriminate between different orthosis models. CONCLUSION: Many studies have been conducted in the field of the physiological evaluation of ankle orthosis. When these devices are widely used in current medical practice, physiological studies do not allow to characterize a better device with a specific test. These data point out the methodological difficulties in ankle brace evaluation.

Ankle Joint↗

Increased diaphragmatic strength and tolerance to fatigue after bilateral lung transplantation: an electromyographic study.

We evaluated the diaphragmatic function of seven patients with severe chronic respiratory failure before and after a bilateral lung transplantation (BLT), with follow-up at one year of pulmonary function tests, maximal inspiratory mouth pressure (MIP) and surface diaphragmatic electromyogram (Edi). The patients were asked to sustain target inspiratory pressures at -15, -30, and -50 cmH(2)O. We measured the endurance time (Tlim) to sustain inspiratory efforts and the power spectrum density function of Edi at each inspiratory maneuver. The Edi power spectra was analysed in terms of median frequency (MF), total power (TP) and energies in high-and low-frequency bands (EL and EH). Before BLT, a defect of the diaphragmatic function was evident: MIP was 62+/-7% of the predicted value and the Tlim measured at each inspiratory effort was very short ( 13+/-1 s, 10+/-1 s and 8+/-1 s at pressures of -15, -30, and -50 cmH(2)O, respectively). One month after BLT, the Tlim began to increase at all target inspiratory pressures and at 6 months MIP recovered to normal values. One month after BLT, there was a significant decrease in TP measured at the beginning of each inspiratory efforts and also an increase in the concomitant MF value. BLT markedly accentuated the maximal variations of TP, MF and low-frequency Edi energy. Some hypotheses are raised to explain this dramatic improvement in diaphragmatic function after BLT.

Adolescent↗

Electromyographic signs of neuromuscular fatigue are concomitant with further increase in ventilation during static handgrip.

We questioned if a non-linear increase in ventilation defining a ventilatory threshold (V(Th)) accompanied the electromyographic (EMG) signs of neuromuscular fatigue. Indeed, the intramuscular accumulation of metabolites may activate the afferent nervous pathways responsible for both the 'muscle wisdom' phenomenon and the respiratory centre activation. During inframaximal (50%) handgrip sustained until exhaustion, minute ventilation (V(E)), V(E)/V(O2) and V(E)/V(CO2) ratios were measured simultaneously with surface EMG of the 'flexor digitorum' muscle. V(Th) was defined as a non-linear V(E) increase and/or an abrupt V(E)/V(O2) increase without any concomitant increase in the V(E)/V(CO2) ratio. Handgrip was repeated during complete arterial blood flow interruption in order to suppress any venous return from the exercising forearm. In both control and blood flow interruption conditions, an abrupt increase in the V(E)/V(O2) ratio was measured in the majority of trials (13 of 15 and 14 of 15, respectively) and the EMG signs of neuromuscular fatigue (a decline in median frequency and/or a non-linear increase in low-frequency EMG energies, E(L)) were concomitant with the V(Th) determination. Thus, V(Th) occurs during sustained static contraction and is concomitant with EMG signs of neuromuscular fatigue. Neurogenic factors seem to be responsible for the two responses which persist despite the absence of any release of metabolites in the circulation.

Adult↗

[Botulinum toxin in headache].

Use of botulinum toxin in headache is a recent method. More and more studies are dedicated to this method. However, despite the large number of published studies, results are contradictory. It is actually difficult to conclude that this therapy is effective or not due to the disparity of clinical studies. Nevertheless, some results are encouraging and studies with a large number of patients have to be done. Here, we take stock about pathophysiological data on the effect of botulinum toxin on pain. Then, we'll report a review of clinical studies available on literature.

Anti-Dyskinesia Agents↗

Algo-functional assessment of knee osteoarthritis: comparison of the test-retest reliability and construct validity of the WOMAC and Lequesne indexes.

OBJECTIVE: To assess and compare the test-retest reliability and the construct validity of the Lequesne and the French-Canadian version of the WOMAC indexes. DESIGN: Patients with symptomatic knee osteoarthritis (OA) fulfilling the revised criteria of the American College of Rheumatology completed both the Lequesne and the French-Canadian version of the WOMAC indexes twice at a 3-h interval. Impairment outcome measures, patients' perceived discomfort in walking and handicap were recorded. For both questionnaires, an analysis was performed item by item. Repeatability was assessed using the intraclass correlation coefficient (ICC) and the Bland and Altman method. Construct validity was investigated using the Spearman rank correlation coefficient and a factor analysis was performed. RESULTS: 88 patients were included. Eight questions of the WOMAC section C and one question of the Lequesne index had insufficient psychometric properties. Although repeatability of questionnaires was fair to excellent (0.82, 0.68, 0.74, 0.95 for the WOMAC sections A, B, C and Lequesne index respectively), construct validity could not be demonstrated. Factor analysis of the WOMAC extracted five factors which differed from the a priori triple stratification. Factor analysis of the WOMAC section C extracted two factors explaining 71% of the variance which could not be clinically characterized. For the Lequesne index, expected convergent correlations were not always achieved. Three factors were extracted by factor analysis explaining 58% of the variance. CONCLUSION: Despite their good test-retest reliability, the two composite indexes evaluated are not valid to assess the concept of functional disability induced by knee OA in a French population.

Adult↗

Interindividual variability of surface EMG changes during cycling exercise in healthy humans.

We studied surface electromyogram (SEMG) changes during 1-h endurance cycling in 12 healthy subjects of whom five were involved in mountain bike training programme. The work load was set at 50% of the predicted maximal heart rate. The surface EMG and the compound evoked muscle action potential (M-wave) from the vastus lateralis muscle were recorded at rest, during the 1-h cycling period, and the 20-min recovery period. The root mean square (RMS) and the median frequency (MF) of SEMG power spectrum were computed. In all subjects, there was no shift in the median frequency throughout the cycling period and the increase in RMS remained stable. In subjects untrained to endurance cyclism, the M-wave duration increased at the end of the cycling period and these changes persisted for a consecutive 15-min period during recovery of exercise. By contrast, in trained mountain bikers the M-wave duration decreased after 2 min of exercise--the effect persisting for 2 min during recovery. These data suggest that the interpretation of M-wave changes during cycling must take into consideration the sport practices of the subjects and also that SEMG power spectrum and M-wave explore different electrophysiological events.

Adult↗

Carrier-mediated uptake and phloem systemy of a 350-Dalton chlorinated xenobiotic with an alpha-amino acid function.

In a previous paper we have shown that epsilon-(phenoxyalkanecarboxylyl)-L-Lys conjugates are potent inhibitors of amino acid transport systems and that it is possible to modulate the uptake inhibition by hydrophobic or hydrophilic additions in the 4-position of the aromatic ring (J.F. Chollet, C. Delétage, M. Faucher, L. Miginiac, J.L. Bonnemain [1997] Biochem Biophys Acta 1336: 331-341). In this report we demonstrate that epsilon-(2,4-dichlorophenoxyacetyl)-L-Lys (2,4D-Lys), one of the largest molecules of the series and one of the most potent inhibitors, is a highly permeant conjugate. Uptake of 2,4D-Lys by broad bean (Vicia faba) leaf discs is mediated by an active carrier system (Km1 = 0.2 mM; Vmax1 = 2.4 nmol x cm(-2) x h(-1) at pH 5.0) complemented by an important diffusive component. Among the compounds tested (neutral, basic, and acidic amino acids, auxin, glutathione, and sugars), only the aromatic amino acids clearly compete with 2,4D-Lys. The conjugate accumulates in the vein network, is exported toward the growing organs, and exhibits a distribution pattern different from that of the herbicide moiety. However, over time 2,4D-Lys progressively splits into 2,4D and lysine. Analyses by high-performance liquid chromatography and liquid scintillation spectrometry of the phloem sap collected from the castor bean system, used as a systemy test, indicate decreasing capacities of 2,4D, 2,4D-Lys, and glyphosate, respectively, to move from the epidermis cell wall to the sieve element. Our results show that it is possible to design synthesis of large-size xenobiotics (approximately 350 D) with a lipophilic pole, exhibiting high mobility within the vascular system.

4-Chloromercuribenzenesulfonate↗

Synthesis and structure-activity relationships of some pesticides with an alpha-amino acid function.

The synthesis of several derivatives of a xenobiotic (phenoxyalkanecarboxylic acid) and an alpha-amino acid (L-lysine) is described. Various substituents were introduced in the aromatic ring of the phenoxyalkanecarboxylic acid and the side-chain was modified. They were tested for their effect on the transport of a neutral (L-threonine), an acidic (L-glutamic acid) and a basic (L-lysine) amino acid, and a sugar (sucrose). All compounds markedly inhibited threonine uptake by leaf tissues of Vicia faba L.--and more specifically phloem loading--with two exceptions, when the aromatic ring was substituted in the 4-position by a primary amino group or when D-lysine was used instead of L-lysine. By contrast, the addition of a chlorine atom in the 4-position of the aromatic ring enhanced the inhibitory activity. Similar results were obtained for inhibition of glutamate uptake and, to a lesser extent, for lysine uptake. pH dependence of the inhibitory activity as well as electrophysiological data indicate that permeases mediating active transport of amino acids are the target of these conjugates. These, in addition to other data obtained with other xenobiotics, show that the amino acid carrier system is capable of recognizing a wide range of conjugates of various sizes, structures and octanol/water partition coefficients.

Amino Acids↗

Effects of single and repeated blood withdrawals on circulating mononuclear cells in BB rats. Failure to prevent diabetes despite acute changes in counts.

Repeated large-volume blood withdrawals started at a young age previously appeared to correct lymphopenia and prevent diabetes in Ottawa diabetes-prone BB (BBdp) rats. Therefore, we sought an early effect 24 h after withdrawal of 25% of estimated blood volume and then reexamined the long-term effects in BBdp rats. The reexamination was prompted by the occurrence of variable numbers of BBdp rats positive for RT6.1 (a T-lymphocyte differentiation alloantigen) whose presence appears to "protect" against diabetes development (identified as BBp rats). Four groups were studied: non-diabetes-prone (BBn), RT6.1- BBdp, RT6.1+ BBp, and acutely diabetic BB (BBd) rats. An acute increase in the number of peripheral blood mononuclear cells and many subsets occurred in BBd and BBp rats. Despite these acute effects, a long-term effect of repeated blood withdrawal was not found in circulating cell counts or prevention of diabetes in BBdp rats. Thus, the previous finding was probably attributable to the presence of BBp rats. The long-term study demonstrated that RT6.1 expression in BBn rats increased from low levels at 15 days, peaked at 50 days, and decreased thereafter, an important finding in interpreting RT6.1 status at different ages. Furthermore, in contrast with other subsets, MARK-1+ B lymphocytes and OX42+ monocytes/macrophages decreased markedly in number at 120 and 150 days in BBn and BBp rats, whereas counts were higher and sustained in BBdp rats. The latter finding could be related to BBdp rats successfully resisting the autoaggressive process beyond the peak age of diabetes onset.

Analysis of Variance↗

Regulation of the epidermal growth factor receptor phosphorylation state by sphingosine in A431 human epidermoid carcinoma cells.

The regulation of protein phosphorylation by sphingosine in A431 human epidermoid carcinoma cells was examined. Sphingosine is a competitive inhibitor of phorbol ester binding to protein kinase C (Ca2+/phospholipid-dependent enzyme) and potently inhibits phosphotransferase activity in vitro. Addition of sphingosine to intact A431 cells caused an inhibition of the phorbol ester-stimulated phosphorylation of two protein kinase C substrates, epidermal growth factor (EGF) receptor threonine 654 and transferrin receptor serine 24. We conclude that sphingosine inhibits the activity of protein kinase C in intact A431 cells. However, further experiments demonstrated that sphingosine-treatment of A431 cells resulted in the regulation of the EGF receptor by a mechanism that was independent of protein kinase C. First, sphingosine caused an increase in the threonine phosphorylation of the EGF receptor on a unique tryptic peptide. Second, sphingosine caused an increase in the affinity of the EGF receptor in A431 and in Chinese hamster ovary cells expressing wild-type (Thr654) and mutated (Ala654) EGF receptors. Sphingosine was also observed to cause an increase in the number of EGF-binding sites expressed at the surface of A431 cells. Examination of the time course of sphingosine action demonstrated that the effects on EGF binding were rapid (maximal at 2 mins) and were observed prior to the stimulation of receptor phosphorylation (maximal at 20 mins). We conclude that sphingosine is a potently bioactive molecule that modulates cellular functions by: 1) inhibiting protein kinase C; 2) stimulating a protein kinase C-independent pathway of protein phosphorylation; and 3) increasing the affinity and number of cell surface EGF receptors.

Carcinoma, Squamous Cell↗

Two alternative mechanisms control the interconversion of functional states of the epidermal growth factor receptor.

Epidermal growth factor (EGF) and transforming growth factor alpha bind to a common receptor at the cell surface. Both the affinity and the tyrosine protein kinase activity of the receptor are regulated by exogenous factors, such as platelet-derived growth factor. A protein kinase C-dependent (Ca2+/phospholipid-dependent enzyme) and independent regulatory mechanism have been described. The protein kinase C-dependent mechanism results in the inhibition of the affinity and tyrosine kinase activity of the EGF receptor. We describe in this report an alternative mechanism of regulation of the receptor that is mediated by sphingosine. Treatment of WI-38 human fetal lung fibroblasts with 5 microM sphingosine for 2 min at 37 degrees C caused a marked increase in the affinity of the EGF receptor. Similar results were obtained when isolated plasma membranes prepared from these cells were incubated with sphingosine. A stimulation of the EGF receptor tyrosine protein kinase activity was also observed after sphingosine-treatment of plasma membranes. Sphingosine caused a decrease in the Km for ATP and an increase in the Vmax for the tyrosine phosphorylation of a synthetic peptide substrate. Control experiments demonstrated that these actions of sphingosine were not secondary to the inhibition of protein kinase C. These data indicate that sphingosine causes the functional conversion of the EGF receptor into an activated state that expresses both a high affinity for EGF and an increased tyrosine kinase activity. We conclude that sphingosine is a bioactive molecule in human fibroblasts.

Animals↗

Insulin-like growth factor I and epidermal growth factor regulate the expression of transferrin receptors at the cell surface by distinct mechanisms.

The transferrin receptor cycles rapidly between cell surface and endosomal membrane compartments. Treatment of cultured cells with epidermal growth factor (EGF) or insulin-like growth factor I (IGF-I) at 37 degrees C causes a rapid redistribution of transferrin receptors from an intracellular compartment to the cell surface. The effects of EGF and IGF-I on the kinetics of the cycling of the transferrin receptor in A431 human epidermoid carcinoma cells were compared. The primary site of EGF action was found to be an increase in the rate of transferrin receptor exocytosis. The exocytotic rate constant was measured to be 0.11 min-1 in control cells and 0.33 min-1 in EGF-treated cells. In contrast, IGF-I was found to increase the cell surface expression of transferrin receptors by causing a small increase in the rate of exocytosis (from 0.11 to 0.17 min-1) and a decrease in the rate of endocytosis (from 0.33 to 0.24 min-1). It is concluded that the mechanisms for EGF and IGF-I action to increase the cell surface expression of the transferrin receptor are distinct. A kinetic model of the cycling of the transferrin receptor based on experimentally determined rate constants is presented. The model predicts that a consequence of IGF-I action on transferrin receptor cycling is to decrease the apparent Km for the uptake of diferric transferrin by cells. This prediction is confirmed by direct measurement of the accumulation of 59Fe-labeled diferric transferrin by A431 cells. These data demonstrate that the accumulation of iron by cultured cells is a complex function of the rate of cycling of the transferrin receptor and that this process is under acute regulation by growth factors.

Carcinoma, Squamous Cell↗

Cystolytic events and the possible role of germinal cells in metastasis in chronic alveolar hydatidosis.

Two and six week old alveolar cysts of Echinococcus multilocularis were isolated from C57BL/6J and Balb/cJ mice and used to study the cystolytic events mediated by resident inflammatory cells. Ultramicroscopic degenerative changes in these cysts were compared with the ultrastructure of in vitro grown cysts (free of inflammatory cells). Macrophages, eosinophils and neutrophils were found to bind to the laminated layer of plasma membrane of the germinal layer of cysts. Hydrolytic enzymes and eosinophil granules released extracellularly from inflammatory cells at the cyst surface appear to dissolve the laminated layer and produce gaps in the plasma membrane. Macrophages actively phagocytose the granular ground substance of the disintegrated laminated layer. Cystolysis results in the release of germinal cells which measure 6-17 microns, possess nuclei with prominent nucleoli, sparse endoplasmic reticulum, Golgi complexes and oval mitochondria. Based on histologic evidence we believe that germinal cells may be the progenitors of cysts. The possibility that germinal cells may give rise to distant metastatic foci of alveolar cysts, in immunocompromised hosts, is discussed.

Animals↗