PubMed Health⌕ Search

Biomedical subjects

M Bonnard

Publications and source records attributed to M Bonnard.

At least 19 recordsLinked to original sources
PubMed2003

Stride variability in human gait: the effect of stride frequency and stride length.

This study focused on spatial and temporal variability of the stride in human gait. We determined the role of stride frequency (F) and stride length (L) on those parameters. Eight healthy subjects walked on a treadmill using 25 different FL combinations (0.95<L<1.5 m, and 0.8<F<1.26 Hz). The results showed that spatial and temporal variabilities tend to increase in concert with respect to change in stride parameters. In addition, stride variability was found (1) to be minimal at F=1 Hz; and (2) to increase with smaller L. During additional trials, subjects walked freely at various speeds. Although it is generally hypothesized that freely chosen behaviors are optimal in terms of variability, our data show that this is not always the case in human gait.

Adult↗
PubMed2000

Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription.

Induction of NF-kappaB-dependent transcription requires phosphorylation and subsequent degradation of I-kappaB, an inhibitor of NF-kappaB, followed by nuclear translocation and DNA binding of NF-kappaB. Tumor necrosis factor receptor-associated factor 2 (TRAF2) plays a role in NF-kappaB activation in response to cytokines such as tumor necrosis factor alpha (TNFalpha). In this study, we purified and characterized a novel kinase (T2K, also known as TBK1 or NAK), which associates with TRAF2 and exhibits kinase activity towards I-kappaBalpha in vitro. The physiological function of T2K was investigated using T2K-deficient mice. Heterozygotes appear normal, but t2k(-/-) animals die at approximately E14.5 of massive liver degeneration and apoptosis. Never theless, hematopoietic progenitors from T2K-deficient fetal liver support normal lymphocyte development. Furthermore, t2k(-/-) embryonic fibroblasts and thymocytes do not display increased sensitivity to TNFalpha-induced apoptosis. In response to either TNFalpha or IL-1 induction, t2k(-/-) embryonic fibroblasts exhibit normal degradation of I-kappaB and kappaB-binding activity. However, NF-kappaB-directed transcription is dramatically reduced. These results demonstrate that, like I-kappaB kinase beta and the RelA subunit of NF-kappaB, T2K is critical in protecting embryonic liver from apoptosis. However, T2K has a unique role in the activation of NF-kappaB-directed transcription, apparently independent of I-kappaB degradation and NF-kappaB DNA binding.

Amino Acid Sequence↗
PubMed2000

Protein kinase B regulates T lymphocyte survival, nuclear factor kappaB activation, and Bcl-X(L) levels in vivo.

The serine/threonine kinase protein kinase B (PKB)/Akt mediates cell survival in a variety of systems. We have generated transgenic mice expressing a constitutively active form of PKB (gag-PKB) to examine the effects of PKB activity on T lymphocyte survival. Thymocytes and mature T cells overexpressing gag-PKB displayed increased active PKB, enhanced viability in culture, and resistance to a variety of apoptotic stimuli. PKB activity prolonged the survival of CD4(+)CD8(+) double positive (DP) thymocytes in fetal thymic organ culture, but was unable to prevent antigen-induced clonal deletion of thymocytes expressing the major histocompatibility complex class I-restricted P14 T cell receptor (TCR). In mature T lymphocytes, PKB can be activated in response to TCR stimulation, and peptide-antigen-specific proliferation is enhanced in T cells expressing the gag-PKB transgene. Both thymocytes and T cells overexpressing gag-PKB displayed elevated levels of the antiapoptotic molecule Bcl-X(L). In addition, the activation of peripheral T cells led to enhanced nuclear factor (NF)-kappaB activation via accelerated degradation of the NF-kappaB inhibitory protein IkappaBalpha. Our data highlight a physiological role for PKB in promoting survival of DP thymocytes and mature T cells, and provide evidence for the direct association of three major survival molecules (PKB, Bcl-X(L), and NF-kappaB) in vivo in T lymphocytes.

Animals↗
PubMed2000

Intentional on-line adaptation of stride length in human walking.

The intentional control of stride length is a fundamental basis for the adaptation of the stride to environmental constraints (obstacle avoidance, for example). Controlling the propulsive forces during the stance and/or controlling the pendular movement of the oscillating leg constitute the two potential and non-exclusive mechanisms underlying intentional stride length modulation. The present experiment was conducted in order to determine if these two mechanisms contribute to voluntary length modulation and, if so, how they cooperate according to whether the subject has to lengthen or shorten a stride and how these mechanisms are implemented at the neuromuscular level. Subjects had to produce a temporarily modulated stride of the same length, but originating from two different initial steady-states: one from shorter stride length and one from longer stride length. We found that the shortening was essentially realized by a swing-duration decrease (an increased activity in the hip extensor--biceps femoris--during the swing of the ipsilaterally shortened stride stopped the pendular leg movement earlier). The lengthening was realized by two mechanisms: (1) an increase in the propulsive forces (via an increased activity of the ankle extensor muscles--soleus--and the hip extensors--biceps femoris--from the stance of the ipsilaterally modulated stride, which was prolonged during the following stance of the contralateral leg), and (2) an increase in swing duration on the ipsilateral leg (an increased activity in hip and ankle flexors--rectus femoris and tibialis anterior--maintained the ipsilateral leg in flexion during the lengthened swing so that the foot landed later). In this experiment, the subjects were faced with a spatial constraint of the same magnitude in the direction of stride lengthening and stride shortening. However, under these conditions, subjects used a different balance between swing control (that directly modifies the foot trajectory without affecting the trajectory of the head-arm-trunk system) and/or the control of propulsive forces (that indirectly influences foot trajectory by modifying the trajectory of the head-arm-trunk system). In the first case, this concerns a voluntary control of gesture produced by the legs and usually implicated in the locomotor pointing; in the second case, this concerns a voluntary control of propulsive forces.

Acclimatization↗
PubMed2000

Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development.

Casper (c-FLIP) associates with FADD and caspase-8 in signaling complexes downstream of death receptors like Fas. We generated Casper-deficient mice and cells and noted a duality in the physiological functions of this molecule. casper-/- embryos do not survive past day 10.5 of embryogenesis and exhibit impaired heart development. This phenotype is reminiscent of that reported for FADD-/- and caspase-8-/- embryos. However, unlike FADD-/- and caspase-8-/- cells, casper-/- embryonic fibroblasts are highly sensitive to FasL- or TNF-induced apoptosis and show rapid induction of caspase activities. NF-kappaB and JNK/SAPK activation is intact in TNF-stimulated casper-/- cells. These results suggest that Casper has two distinct roles: to cooperate with FADD and caspase-8 during embryonic development and to mediate cytoprotection against death factor-induced apoptosis.

Animals↗
PubMed2000

Adaptation of neuromuscular synergies during intentional constraints of space-time relationships in human gait.

Tight frequency-to-amplitude relationships are observed in spontaneous human steady gait. They can be modified, if required; that flexibility forms a fundamental basis of the intentional adaptive capabilities of locomotion. In the present experiments, the processes underlying that flexibility were investigated at both the level of joint kinematics and the level of neuromuscular synergies. Subjects (N = 4) walked at the same speed either with a preferred or a nonpreferred frequency-to-amplitude relationship (i.e., constrained, short steps at a high frequency [COS condition] or constrained, long steps at a low frequency [COL condition]); their swing and stance phases were separately analyzed. In the COS condition, increases in EMG activity were specifically required during the swing phase. In the COL condition, several muscles required increases in EMG activity during the stance phase, but decreases of the hamstring muscles were needed during the swing phase. Whereas, in preferred walking, modification of the frequency affects the EMG patterns globally (the gain increasing with the frequency in both the stance and swing phases), the present results show that changing the frequency in a constrained manner either affects the swing phase specifically or affects both phases, but in the opposite direction. That finding indicates that a separate control is needed in both the swing and the stance phases.

Adult↗
PubMed1999

CD4-mediated inhibiton of IL-2 production in activated T cells.

The role of CD4 in T cell activation has been attributed to its capacity to increase the avidity of interaction with APC and to shuttle associated Lck to the TCR/CD3 activation complex. The results presented in this study demonstrate that ligation of CD4 inhibits ongoing responses of preactivated T cells. Specifically, delayed addition of CD4-specific mAb is shown to inhibit Ag- or mAb-induced responses of both primary T cells and T cell clonal variants. The Ag responses of the latter are independent of the adhesion provided by CD4; thus the observed inhibition is not due to blocking CD4-MHC interactions. Further, analysis of the clonal variants demonstrates that CD4-associated Lck is not essential for the inhibition observed, as anti-CD4 inhibits responses of clonal variants, expressing a form of CD4 unable to associate with Lck (double cysteine-mutated CD4). The inhibition is counteracted by the addition of exogenous IL-2, demonstrating that the block is not due to a lesion in IL-2 utilization, rather its production. It is demonstrated that the delayed addition of anti-CD4 results in a rapid reduction in steady-state levels of IL-2 mRNA in both primary T cells and clonal variants.

Animals↗
PubMed1999

Contribution of proprioceptive information to preferred versus constrained space-time behavior in rhythmical movements.

Rhythmical movements are well-known to exhibit spontaneous and well-defined relationships between frequency and amplitude (preferred behavior). However, if required, these relationships can be modified (constrained behavior). This flexibility constitutes a fundamental basis for adapting motor functions to the subject's intentions in a given environment. In order to assess the role of proprioceptive information in the stabilization of preferred versus constrained rhythmical movements, we compared both cases in a deafferented patient and in a control group. Initially, the subjects were given as much time as they needed to adopt different, steady rhythmical movements in the presence of external feedback. Afterwards, the feedback was suppressed and the subjects had to maintain the same oscillating regimes for one additional minute. In the absence of feedback, the deafferented patient was able to stabilize the timing of both the preferred and the constrained movements. The spatial properties remained stationary for the preferred movements; however, large effects were observed in the constrained movements. By contrast, the control subjects were able to keep both the preferred and the constrained behaviors stationary. Our results show that, when reaching preferred regimes, the behavior remains stationary even in the absence of proprioceptive information. By contrast, proprioceptive feedbacks were shown to be necessary in order to maintain non-preferred regimes. In this case, error-correction mechanisms based on proprioceptive information allows for compensation of the natural tendency of the system to return to its preferred behavior.

Adult↗
PubMed1999

Studies on the corticospinal control of human walking. I. Responses to focal transcranial magnetic stimulation of the motor cortex.

Experiments were done to determine the extent to which the corticospinal tract is linked with the segmental motor circuits controlling ankle flexors and extensors during human walking compared with voluntary motor tasks requiring attention to the level of motor activity. The motor cortex was activated transcranially using a focal magnetic stimulation coil. For each subject, the entire input-output (I-O) curve [i.e., the integral of the motor evoked-potential (MEP) versus stimulus strength] was measured during a prescribed tonic voluntary contraction of either the tibialis anterior (TA) or the soleus. Similarly, I-O curves were measured in the early part of the swing phase, or in the early part of the stance phase of walking. The I-O data points were fitted by the Boltzmann sigmoidal function, which accounted for >/=80% of total data variance. There was no statistically significant difference between the I-O curves of the TA measured during voluntary ankle dorsiflexion or during the swing phase of walking, at matched levels of background electromyographic (EMG) activity. Additionally, there was no significant difference in the relation between the coefficient of variation and the amplitude of the MEPs measured in each task, respectively. In comparison, during the stance phase of walking the soleus MEPs were reduced on average by 26% compared with their size during voluntary ankle plantarflexion. Furthermore, during stance the MEPs in the inactive TA were enhanced relative to their size during voluntary ankle plantarflexion and in four of six subjects the TA MEPs were larger than those of the soleus. Finally, stimulation of the motor cortex at various phases of the step cycle did not reset the cycle. The time of the next step occurred at the expected moment, as determined from the phase-resetting curve. One interpretation of this result is that the motor cortex may not be part of the central neural system involved in timing the motor bursts during the step cycle. We suggest that during walking the corticospinal tract is more closely linked with the segmental motor circuits controlling the flexor, TA, than it is with those controlling the extensor, soleus. However, during voluntary tasks requiring attention to the level of motor activity, it is equally linked with the segmental motor circuits of ankle flexors or extensors.

Adult↗
PubMed1997

Physical association of CD4 and CD45 in primary, resting CD4+ T cells.

CD45 is a family of transmembrane protein tyrosine phosphatases that are essential to T lymphocytes' responses to antigen-receptor stimulation. It is involved in the regulation of Src-family protein tyrosine kinases, Lck and Fyn. The object of this study was to determine how CD45 molecules are directed to such substrates at the antigen-receptor complex upon stimulation of resting T cells. We demonstrate that CD45 is physically associated with CD4 in resting, primary lymph node T cells. Further, CD4-dependent, antigen-mediated activation of primary CD4+ T cells results in disruption of CD4-CD45 complexes, suggesting a role for these complexes in the activation process. Moreover, CD45 coprecipitates with CD4 molecules which are associated with Lck, as well as with those which are not associated with Lck. Consistent with these observations and the role of CD45 in the regulation of Lck function, effects on CD4-associated membrane Lck are demonstrable. Since antigen presentation by MHC class II results in the coaggregation of CD4 with the antigen-receptor complex, the association described in this study provides a physical basis through which CD45 could be included.

Animals↗
PubMed1997

Intentional on-line control of propulsive forces in human gait.

In locomotion, the capability to control and modulate intentionally the propulsive forces is fundamental for the adaptation of the body's progression, both in speed and direction. The purpose of this experiment was to determine how human beings can achieve such control on-line. To answer this question, four subjects walking steadily were faced with a linear increase in resistance (impeding forward displacement), lasting 3 s, once per minute. At the end of the variation, the new resistance was maintained. There were two tasks; in both tasks, in the initial steady state, the subjects had to walk steadily at 1.3 m s-1. As the resistance increased, subjects were either required to maintain their walking speed (compensation task) or to let the walking speed and amplitude adapt freely (no-intervention task). This provided an estimate of the effects of the perturbation alone. Throughout the experiment, the stride frequency (114 step min-1) was fixed by a metronome. Subjects maintained their stride frequency on both tasks. In the no-intervention task, walking speed was 1.3 and 1 m s-1 under normal and high resistance respectively. In the compensation task, under high steady resistance, walking speed was maintained by an increase in the activation gain of the neuromuscular synergy: all recorded muscles increased their EMG activity, but without any change in the shape of their activation profile throughout the cycle. During the transitional phases, however, as the resistance began to increase, the walking speed decreased temporarily (-2%) before returning rapidly to its initial value. By contrast, at the end of the resistance increase, no such changes in speed were observed. During the transitional phases, the on-line compensation for the resistance increase induced modifications in the shape of the activation burst in the medial gastrocnemius such that the transitional cycles clearly differed from the steady state cycles. The results observed in the compensation task suggest that the subjects used two different modes of control during steady states and transitional phases. In stable dynamic conditions, there appears to be an "intermittent control" mode, where propulsive forces are globally managed for the entire stance phase. As a result, no compensation occurred at the beginning of the perturbation. During the resistance increase, subjects appeared to switch to an "on-line control" mode in order to continuously adapt the propulsive forces to the time course of the external force, resulting in an observable compensation at the end of the resistance change.

Adaptation, Physiological↗
PubMed1996

Autonomy versus forcing in the organization of human rhythmic forearm movements.

In biological systems, obviously dissipative, some injection of muscle force is required in order to sustain rhythmic movement. As the movement frequency increases, the way the muscle-force-to-movement relationship evolves (in timing and amplitude) can be used to characterize some fundamental control properties, including whether the observed system is autonomous or forced. In the case of a simple rhythmic, biological movement (single-joint horizontal forearm movement), this question can be addressed by assuming that the processed electromyographic activity (EMG) is related to the muscle torques. In this case, 2 interesting phenomena can be observed as the frequency increases. The first is that the phase lag between the force and movement remains constant (40 degrees), and the second is that the co-contraction of the agonist and antagonist muscle groups increases with the square of the frequency. These results showed that the contribution of muscle forces to movement organization cannot be regarded in terms of an escapement in an autonomous system, nor in terms of a forcing function in a forced system.

Adult↗
PubMed1995

Joint-dependent mechanisms to adapt to an imbalance between flexion and extension forces in human gait.

In human gait, alternating leg flexion/extension movements essentially require the production of extension muscle forces due to the large contribution of passive forces to leg flexion. In this experiment, we studied the adaptive capabilities of walking subjects constrained with elastic cords which further facilitated leg flexion and impeded leg extension. In order to walk, the subjects let the moments created by the elastic cords increase the ankle flexion during the whole cycle, which allowed them to reduce part of these moments. By contrast, at the knee level, they increased their extension muscle activity to compensate for the remaining constraint moments during the swing phase, which resulted in unchanged kinematics. Although neuromuscular locomotor synergy is often considered to control the lower limb as a unit, we showed here that different adaptive mechanisms can act at different joints of the same leg.

Adult↗
PubMed1995

Ca2+ and UVB radiation have no effect on E-cadherin-mediated melanocyte-keratinocyte adhesion.

Direct cell-cell contact between melanocytes and keratinocytes has been shown to play an important role in the regulation of human melanocyte function and skin pigmentation. An important role for the calcium-dependent epithelium-specific cell adhesion molecule, E-cadherin, in melanocyte-keratinocyte adhesion was suggested previously. To further clarify regulation of E-cadherin-mediated melanocyte-keratinocyte interactions, we investigated the effects of physiological (Ca2+) and environmental (ultraviolet B [UVB] radiation) stimuli on the expression and functional activity of E-cadherin in melanocyte-keratinocyte adhesion. Expression of E-cadherin mRNA was detected by Northern blot analysis in cultured normal human melanocytes at levels similar to those in keratinocytes. Flow cytometry analysis with anti-human and anti-mouse-E-cadherin antibodies (anti-uvomorulin and ECCD-2) showed that cultured normal human keratinocytes, melanocytes, and two metastatic melanoma cell lines express E-cadherin strongly on the cell surfaces. Melanocyte adhesion, particularly to differentiating keratinocytes (cultured in 1.2 mM calcium) but not to proliferating keratinocytes or to fibroblasts, was decreased by 41.7 +/- 4.5% in the absence of 1 mM Ca2+ during the binding assay. Addition of anti-mouse-E-cadherin antibody (ECCD-1) to the binding assay inhibited the adhesion of melanocytes to differentiating keratinocytes by 88.2 +/- 1.1%, while addition of anti-P-cadherin antibody (PCD-1) had no effect. The levels of E-cadherin expression in melanocytes were not changed by the presence of calcium (1 mM) in the medium or by UVB irradiation (20 mJ/cm2) for one day before flow cytometry analysis. Moreover, these treatments had no effect on melanocyte-keratinocyte adhesion. These results demonstrate that E-cadherin is strongly involved in melanocyte adhesion to keratinocytes and suggest the implication of E-cadherin in the overall regulation of the skin pigmentary system.

Adult↗
PubMed1994

Different strategies to compensate for the effects of fatigue revealed by neuromuscular adaptation processes in humans.

An initially submaximal hopping task was maintained with the same global power output until it became the maximal performance; since there was no decrease in performance, any change in behavior occurring with fatigue characterizes the strategies allowing to compensate for the effects of fatigue. In a prolonged hopping task, fatigue is likely to be most prominent in the ankle extensor muscles since they are the main contributors to vertical propulsion in the hop. With fatigue, all subjects landed with more flexed knees and with an increased activity in the biarticular rectus femoris muscle indicating some compensation between the knee and ankle joint. Furthermore, two different strategies appeared to further compensate for the important fatigue of the ankle extensor muscles: one was organized across joints and consisted in a heavier reliance of the knee extensor vastus lateralis, and the other was organized within the fatigued joint and consisted in an earlier preactivation of the gastrocnemius. As a consequence, two different adaptations of the ground reaction force profiles appeared at the end of the session; each being related to one of these two strategies.

Adaptation, Physiological↗
PubMed1993

Intentionality in human gait control: modifying the frequency-to-amplitude relationship.

Tight frequency-to-amplitude relationships are observed in spontaneous human steady gait. If required, however, they can be modified. The following experiments were aimed at the processes underlying this flexibility, which forms the fundamental basis of the intentional adaptive capabilities of locomotion. In Experiment 1, Ss had to intentionally modify the frequency-to-amplitude relationship (leading to preferred or nonpreferred steady states). In Experiment 2, they had to temporarily perturbate the stride-frequency-to-amplitude relationship to intentionally shorten or lengthen 1 stride. Within the important constraints exerted by the head-arm-trunk system on leg movement, the results pointed out 2 main strategies that allow the S to intentionally adapt stride organization on-line: adjustment of the tonic properties of the oscillating leg to achieve nonpreferred steady states and phasic action to ensure temporary movement away from a steady state.

Acceleration↗
PubMed1993

Reconstruction of epidermis on a chitosan cross-linked collagen-GAG lattice: effect of fibroblasts.

Reconstruction of epidermis on a fibroblast containing chitosan cross-linked collagen-GAG lattice at the air-liquid interface gives rise to a multilayered stratified epithelium, covered with a compact stratum corneum. Immunohistological studies reveal that the markers of epidermal differentiation are essentially distributed as in normal human skin and that the major proteins of the dermal-epidermal junction are present. Reconstruction of epidermis under identical culture conditions on a dermal equivalent that does not contain fibroblasts gives rise to an epithelium consisting of disorganized cell layers where the markers of differentiation are either displaced or not at all expressed, as in the case with filaggrin. In contrast, expression of the major constituents of the dermal-epidermal junction by the keratinocytes is completely independent of the presence of fibroblasts, even though it seems that the presence of fibroblasts is essential for the organization of the basement membrane proteins, creating a tight junction between dermal equivalent and the reconstructed epidermis.

Cells, Cultured↗