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PubMed1987

Direct evidence that cancer cell locomotion contributes importantly to invasion.

This study was undertaken to clarify whether active locomotion of cancer cells is important for their ability to invade. The most rapidly moving cells were isolated from a cultured murine parent fibrosarcoma by successive cycles of migration through a micropore membrane. Cells were isolated by unstimulated locomotion and by haptotaxis to laminin, and the selected cells did indeed constitute rapidly locomoting subpopulations. These cells invaded biological tissues more efficiently than did the unselected parent cells. The cells selected by haptotaxis to laminin invaded most rapidly through amnion with basement membranes (containing laminin). Cancer cell haptotaxis to laminin in basement membranes thus promotes penetration of these tissue barriers. These results show in a direct manner that cancer cell locomotion is in fact important in invasion of biological tissues.

Amnion↗
PubMed1996

Role of the muscle belly and tendon of soleus, gastrocnemius, and plantaris in mechanical energy absorption and generation during cat locomotion.

The functional significance of tendons, and the differences in tendon properties among synergistic muscles, is not well established for normal locomotion. Previous studies have suggested that tendons may store mechanical energy during the early phase of support, and then release this energy during the late phase of support. The storage and release of mechanical energy by tendons may modify the velocity of shortening and elongation and the power produced by the muscle belly and the fibers, and may influence the metabolic cost of locomotion. The aims of this study were (1) to estimate the amount of negative and positive work done by the tendon and the muscle belly of the cat soleus (SO), gastrocnemius (GA), and plantaris (PL), and (2) to determine the relative contribution of the elastic energy stored in the tendons to the total mechanical work done by these three muscles during walking and trotting. Forces of SO, GA, and PL muscles were measured using standard force transducers in three cats walking and trotting at speeds of 0.4-1.8 ms-1 on a motor-driven treadmill. Video records and a geometrical model of the cat hindlimb were used for calculating length of the muscle-tendon complexes of SO, GA, and PL during locomotion. Instantaneous lengths of the tendons of SO, GA, and PL during a step cycle were estimated from the stress-strain properties, the effective lengths, the cross-sectional areas, and the instantaneous forces of the tendons. Stress-strain properties for the tendons were obtained experimentally from one animal. The length of the belly was defined as the difference between the muscle-tendon complex length and the tendon length. Mechanical power of the tendon and the muscle belly was calculated as the product of the measured muscle force and the calculated rates of change in tendon and muscle belly lengths, respectively. Mechanical power and work of the tendons and bellies of SO, GA, and PL were calculated for 144 step cycles. During a step cycle, peak negative and peak positive velocities as well as peak powers of the muscle-tendon complexes of SO, GA, and PL were typically higher than those of the muscle bellies. Positive work done by the muscle-tendon complexes exceeded the positive work done by the muscle bellies. GA and PL tendons stored more mechanical energy than the SO tendon. The contributions of the elastic energy stored in the tendons to the positive work done by the muscle-tendon complexes decreased with increasing speeds of locomotion for two of the three cats studied and did not change for the third one. These contributions equaled 50-21%, 30-14%, and 25-18% for the three cats, respectively. The results of this study suggest that energy absorption and release by the tendons of cat SO, GA, and PL make up a substantial part of the total energy absorbed and generated by the corresponding muscle-tendon complexes.

Absorption↗
PubMed1993

Lymphocyte locomotion in three-dimensional collagen gels. Comparison of three quantitative methods for analysing cell trajectories.

We evaluated three different quantitative evaluation methods for lymphocyte locomotion in three-dimensional collagen gels: (1) the length of the two-dimensional migration path (distance migrated) was compared to (2) the resulting average displacement from the starting to the end point and (3) the displacement of the furthest migrating population (cells with high displacement). Locomotion of immunomagnetically isolated human CD4+ and CD8+ peripheral blood lymphocytes suspended in type I collagen gels was recorded using time-lapse videomicroscopy. Paths of randomly selected locomoting cells were digitized, reconstructed and quantitatively analysed. For spontaneously locomoting CD4+ and CD8+ lymphocytes (90 min observation period) the mean total distance migrated was 10.0 +/- 3.7 microns/min (CD4+; n = 114 cells) and 5.6 +/- 3.3 microns/min (CD8+; n = 90 cells). The mean displacement from the individual starting point amounted to 1.3 +/- 0.7 micron/min for CD4+ and 1.1 +/- 0.7 micron/min for CD8+ cells, thus representing only 5-25% of the total migration path (index range displacement/distance migrated: 0.13-50%). Incubation with interleukin-8 and/or receptor blocking by monoclonal antibodies against VLA-2 (Gi9) or VLA-4 (HP2/1) integrins significantly altered the mean length of the migration paths for six out of ten different experimental conditions. Average displacement or displacement of the most active cells detected significant changes in two and three out of ten samples. Whereas the interleukin-8 induced locomotory changes were correctly represented by end point determination, relatively slight but significant modulation in lymphocyte behaviour by anti-integrin antibodies was revealed solely by analysis of the complete cell trajectory. In conclusion, the cell trajectory may represent a sensitive method for evaluating induced subtle changes in lymphocyte locomotory characteristics.

CD4-Positive T-Lymphocytes↗
PubMed1985

Locomotion and chemotaxis of mononuclear phagocytes.

The capacity for locomotion and for chemotaxis is probably very different in monocytes and macrophages from different sources. Numerous techniques have been established for studying the locomotion of these cells. Many of the factors are sparsely documented and the reports are scattered among various cell types. Heterogeneity of locomotion and chemotactic responsiveness is evident when established macrophage lines and mouse peritoneal macrophage are studied. The effects of mononuclear phagocytes and their released products on the locomotion of other cell types are reviewed.

Animals↗
PubMed2006

A comparison analysis of hindlimb kinematics during overground and treadmill locomotion in rats.

The convenience of the motor-driven treadmill makes it an attractive instrument for investigating rat locomotion. However, no data are available to indicate whether hindlimb treadmill kinematic findings may be compared or generalized to overground locomotion. In this investigation, we compared overground and treadmill locomotion for differences in the two-dimensional angular kinematics and temporal and spatial measurements for the hindlimb. Ten female rats were evaluated at the same speed for natural overground and treadmill walking. The walking velocity, swing duration and stride length were statistically indistinguishable between the two testing conditions. Significant differences were found between overground and treadmill locomotion for step cycle duration and stance phase duration parameters. During the stance phase of walking, the angular movement of the hip, knee and ankle joints were significantly different in the two conditions, with greater flexion occurring on the overground. Despite this, the sagittal joint movements of the hindlimb were similar between the two walking conditions, with only three parameters being significantly different in the swing. Hip height and angle-angle cyclograms were also only found to display subtle differences. This study suggests that reliable kinematic measurements can be obtained from the treadmill gait analysis in rats.

Animals↗
PubMed2004

Antidromic discharges in dorsal roots of decerebrate cats. II: studies during treadmill locomotion.

In a previous companion paper [Brain Res. 846 (1999) 87-105] we have shown that the dorsal root activity of a decerebrate cat is composed of both orthodromic and antidromic discharges as determined by spike triggered averaging (STA). Furthermore we have shown that, during fictive locomotion in decerebrate and paralyzed cats, antidromic discharges peak in different parts of locomotion cycle but mainly in the flexion phase. In the present study, we have recorded unit potentials from dorsal rootlets during treadmill locomotion in order to understand better the role of movement-related feedback in the generation of antidromic potentials. The unitary activity of 92 antidromically discharging units was recorded in proximal stumps of cut dorsal roots, and that of 20 such units was recorded in uncut roots using two bipolar Ag/AgCl electrodes in both cases. The activity of 80% (74/92) units in cut filaments and of 70% (14/20) units in uncut ones was phasewise related to stepping movements. The peaks of activity of different units occurred during different phases of the step cycle both in cut and uncut filaments. In most cases, the peak of activity was superimposed upon a background of sustained discharge. After blocking the orthodromic flow in a filament (local anesthesia or distal section), the antidromic discharges continued to peak during the same phase but the rate of the discharges increased. We conclude that movement-related afferent feedback significantly modulates the antidromic discharges in dorsal roots during treadmill locomotion. We suggest that these antidromic discharges have a role in controlling afferent feedback during movement.

Action Potentials↗
PubMed2006

"Fatigue" of medullary but not mesencephalic raphe serotonergic neurons during locomotion in cats.

Single unit activity of presumed serotonergic neurons in the medulla [n. raphe obscurus (NRO) and pallidus (NRP)] or the mesencephalon [n. raphe dorsalis (DRN)] was recorded in adult male cats during prolonged treadmill locomotion. Treadmill speed was set at a moderate level (0.4 m/s) in order to induce long-duration locomotion. The typical time to "fatigue" (failure to keep pace, falling behind and reluctance to continue) was approximately 40 min in both groups, at which point cats typically displayed marked panting and vocalization. The activity of DRN neurons was unchanged from baseline during the locomotion trial and during the recovery phase. By contrast, the activity of NRO/NRP neurons decreased steadily across the locomotion trial, reaching a mean decrease of approximately 50% (during the first min after the treadmill was turned off). Full recovery of single unit activity to a level approximating the baseline discharge rate required 30-45 min. Possible mechanisms underlying these changes are discussed as is the role of serotonin and fatigue in human pathology.

Animals↗
PubMed2004

Step width variability, but not step length variability or step time variability, discriminates gait of healthy young and older adults during treadmill locomotion.

The variability of spatial and temporal step kinematics have separately been shown to prospectively predict falls by older adults. However, the published literature has not addressed the relative importance of the information related to locomotion control contributed by variability of spatial variables, temporal variables, or both. We conducted a post hoc analysis to determine the extent to which the variability of spatial and temporal step kinematics are independent descriptors of locomotion control in healthy young and older adults. A second purpose of the analysis was to establish the extent to which treadmill walking mimics overground walking using a benchmark for step kinematics. Eighteen young adults and 12 older adults walked at a self-selected velocity on an instrumented treadmill from which step length variability, step width variability and step time variability were computed. Stepwise discriminant analysis correctly classified group membership of 70 percent of the 30 subjects (i.e., young or older adult) using only step width variability (p=0.037, Wilk's lamda=0.854). Step width variability was 70+/-57 percent larger than step length variability (p<0.001). This relationship was similar to that of the benchmark established for overground locomotion. The results suggest that for healthy younger and older adults step width variability is a more meaningful descriptor of locomotion control than step length variability and step time variability. Given the potential clinical impact, further systematic study and improvement of the methods and technology for acquiring step kinematic data are warranted.

Adult↗
PubMed2006

From bone to plausible bipedal locomotion using inverse kinematics.

The purpose of this study is to validate a method based on anatomical data and biomechanical locomotor hypotheses that could be applied in palaeontology to simulate locomotion in fossil hominids. The main problem is to ensure that purely mathematical simulation, based on anatomical descriptions, is enough to test hypotheses on human motion control. A 3D geometric model of the lower limb was therefore processed from anatomical descriptions. From this 3D model, we developed a method to retrieve natural lower-limb motion depending on chosen constraints. We assumed that the role of lower-limb motion is to make the feet move from one footprint to the next by following a trajectory that resembles that of living humans (primary task). This method based on inverse kinematics also allows biomechanical laws of bipedal locomotion to be taken into account (secondary tasks). The laws tested in this study relate to preserving joint limits, minimizing energy and minimizing the distance to a rest posture proposed by anthropologists and viewed as input to our system. A weighted sum of the resulting derivable cost functions enabled us to select a specific solution in the null space of the primary task. In order to validate this approach, we compared simulated and captured motion from ten subjects for whom anthropometrical data were recorded. We concluded that this "anatomically based bipedalism simulation" seems promising as a means of investigating natural locomotion behaviour and might also be used to retrieve natural locomotion in fossil hominids where only little knowledge is available.

Adult↗
PubMed2004

Brain activation patterns during imagined stance and locomotion in functional magnetic resonance imaging.

Posture and gait are sensorimotor actions that involve peripheral, spinal, and supraspinal structures. To investigate brain activity during stance and locomotion, 13 healthy subjects were asked to stand, walk, run, and lie down; subsequently, they were trained to imagine standing, walking, running, and lying [imagined lying as rest condition in functional magnetic resonance imaging (fMRI)]. Separate and distinct activation/deactivation patterns were found for the three imagined conditions: (1) standing imagery was associated with activation in the thalamus, basal ganglia, and cerebellar vermis; (2) walking imagery was associated with activation in the parahippocampal and fusiform gyri (areas involved in visuospatial navigation), occipital visual areas, and in the cerebellum; (3) running imagery caused a predominantly cerebellar activation in the vermis and adjacent hemispheres (six times larger than during imagination of walking or standing), but activations in the parahippocampal and fusiform gyri were smaller than during walking. Deactivations were found for walking and running, but not for standing imagery. They were located in the vestibular (posterior insula, superior temporal gyrus, supramarginal gyrus) and somatosensory (postcentral gyrus) cortex with right-hemispheric dominance. These findings support the concept of a hierarchical organization of posture and locomotion. Automated locomotion, for example, running, is based on spinal generators whose pace is driven by the cerebellar locomotor region. Deactivation in the vestibular and somatosensory cortex prevents adverse interactions with the optimized spinal pattern and sensory signals; this confirms earlier findings of a multisensory inhibition during unhindered locomotion. During slow walking, spatial navigation, mediated by the parahippocampal cortex, becomes more important. Postural control during standing involves a low intensity cerebellar activity and sensorimotor control via the thalamus and basal ganglia.

Adult↗
PubMed2003

Rewarding injections of the cholinergic agonist carbachol into the ventral tegmental area induce locomotion and c-Fos expression in the retrosplenial area and supramammillary nucleus.

Previously we found that intra-ventral tegmental injections of the cholinergic agonist carbachol induce reward; such injections induce conditioned place preference and rats learn quickly to self-administer carbachol directly into the ventral tegmental area (VTA). To determine what brain regions are activated by such rewarding injections we studied the expression of the transcription factor c-Fos in local and distant brain regions following ventral tegmental injections of carbachol in rats. We also measured locomotion induced by such injections. Carbachol injections into the VTA induced vigorous locomotion while carbachol injections into the regions 1 mm dorsal or 1 mm lateral to the VTA induced delayed attenuated locomotion. Ventral tegmental injections of carbachol induced c-Fos expression throughout the brain. Significant correlations between locomotion c-Fos positive nuclei were found in the retrosplenial area the posterior hypothalamus including the supramammillary nucleus. These results suggest that the retrosplenial area supramammillary nucleus may be parts of the circuitry for the reward triggered by ventral tegmental cholinergic stimulation.

Animals↗
PubMed1997

Locomotion and stereotypy induced by scopolamine: contributions of muscarinic receptors near the pedunculopontine tegmental nucleus.

In this study, we test whether blockade of muscarinic receptors near mesopontine cholinergic cell groups may contribute to locomotor activation induced by scopolamine. Unilateral or bilateral injections of scopolamine (10-150 micrograms) into the pedunculopontine tegmental nucleus (PPT) increased horizontal locomotion by 2-15 times in a dose-related way. Unilateral or bilateral injections of scopolamine into the PPT increased stereotypic behaviors (such as sniffing in one location or over large areas), self-biting and grooming. Carbachol (4 micrograms) injected into PPT reduced locomotion for 20 min, followed by 70 min of increased locomotion. When carbachol (4 micrograms) was injected into the PPT before scopolamine (3 mg/kg, i.p.), the activating effect of scopolamine was attenuated, but not when carbachol was injected after scopolamine. Therefore, carbachol appears to compete with scopolamine for muscarinic receptors near the PPT that mediate locomotor activating effects of systemic scopolamine. Haloperidol (0.1 mg/kg, i.p.) also attenuated the stereotypy and locomotion induced by scopolamine in the PPT. We hypothesize that scopolamine acts by blocking muscarinic receptors on mesopontine cholinergic neurons, thereby disinhibiting cholinergic neurons that can activate dopamine neurons.

Animals↗
PubMed2000

Studies of human locomotion: past, present and future.

The study of human locomotion and its applications are examined from a historical viewpoint. Several critical steps in the advancement of the discipline are considered in the context of addressing a particular need to answer fundamental questions regarding the process of human locomotion. In addition, changes in the methods of observation are discussed in terms of the advancement of the field. As an example, the application of a newly developed point cluster technique to reduce the artifact due to skin movement is described. The method was applied to a study of patients with anterior cruciate ligament (ACL) deficient knees. The results demonstrate that patients with ACL-deficient knees have significantly greater than normal anterior-posterior displacement of the femur relative to the tibia during walking. Many of the advancements in the tools for observation and interpretation have been driven by new demands on our fundamental knowledge. Future advancements in the study of human locomotion will likely be motivated by new treatment modalities that require an in depth understanding of the subtle complexities of human locomotion. Future directions are discussed in the context of new methods for reducing errors associated with skin movement combined with information obtained from other imaging methods, such as magnetic resonance imaging.

Animals↗
PubMed1997

Suppression of polarity, locomotion and F-actin levels of Walker carcinosarcoma cells by the inhibitor CI-959.

Locomotor activity of tumor cells is an important factor for the capacity for invasion and metastasis. Therefore, inhibitors interfering with cellular mechanisms regulating spontaneous cell locomotion are of particular interest for cancer therapy. CI-959, a new benzothiophene cell activation inhibitor, has the capacity to suppress spontaneous polarity and locomotion of Walker carcinosarcoma cells. Suppression of polarity and locomotion was closely associated with a reduction in the relative amount of F-actin. The mechanisms involved in suppression of motility are Ca2(+)-independent and not related to cell-substratum adhesion. Walker carcinosarcoma cells appear to be able to locomote at very low (nM) levels of free [Ca2+]i.

Actins↗
PubMed2005

Modulation of cutaneous reflexes in hindlimb muscles during locomotion in the freely walking rat: A model for studying cerebellar involvement in the adaptive control of reflexes during rhythmic movements.

This study aims to demonstrate stepphase-dependent modulation in the gain of cutaneously triggered reflexes in the freely locomoting rat. Electromyographic recordings of biceps femoris (mainly involved in knee flexion) and gastrocnemius (mainly involved in ankle extension) muscles were continuously monitored during locomotion and cutaneous reflexes were induced by subcutaneously placed stimulation electrodes in the lateral malleolal region. The results show that the reflex responses in both muscles during locomotion were generally reduced compared to reflexes induces in rest. For the biceps femoris reduction of reflex gain was highest during the stance phase whereas for the gastrocnemius the period of highest depression was found during the swing phase. We conclude that stepphase-dependent modulation of peripheral reflexes can be measured in freely locomoting rats and generally concur with previous studies in cat and man that this type of modulation may be functionally important for maintaining and adjusting gait. Moreover, although the mechanism of inducing and maintaining this modulation is not fully known, it is now open to experimental investigation in rodents.

Adaptation, Physiological↗
PubMed1991

Glutathione-induced enhancement of neutrophil locomotion.

Both reduced glutathione (GSH) and and its oxidized form, glutathione disulfide (GSSG), enhance neutrophil locomotion. The enhancement is mainly due to a chemokinetic effect, and partly due to a chemotactic effect. A number of other SH-group containing compounds were not effective in enhancing neutrophil migration. While random locomotion is not inhibited by the slowly-penetrating sulfhydryl agent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), the enhancement of migration due to GSH is completely inhibited. Pretreatment of neutrophils with pertussis toxin completely inhibited the GSH-induced stimulation of locomotion, suggesting that stimulation of migration by glutathione was mediated by a pertussis toxin sensitive G-protein. Chemotaxis towards GSH is inhibited by the same agents that inhibit fMet-Leu-Phe induced chemotaxis, except that colchicine was a more effective inhibitor of GSH-induced chemotaxis than of fMet-Leu-Phe directed chemotaxis. GSH enhances the intracellular concentration of cGMP, which might indicate that the effect on neutrophil locomotion is mediated by an effect on cGMP.

Animals↗
PubMed2002

Conditioned locomotion is not correlated with behavioral sensitization to cocaine: an intra-laboratory multi-sample analysis.

Pre-clinical and clinical studies have demonstrated the importance of associative factors in regulating craving for drugs of abuse. To model these conditioned effects, we have examine cue-induced conditioned locomotion in rodents. The present study involved analysis of several of our prior studies to evaluate the relationship between conditioned locomotion and behavioral sensitization using a within-subjects analysis. Both are animal models used to study addiction, so it is important to know if one is predictive of the other, and more generally, if drug effects are predictive of conditioned effects. In all of our studies, Paired subjects received cocaine during presentation of conditioned stimuli while Unpaired subjects received saline with the stimuli and cocaine at the home cages an hour later. Paired subjects typically displayed behavioral sensitization over the course of training. After the completion of training, all subjects were tested with the conditioned stimuli in the absence of drug and conditioned locomotion was measured. The response of Unpaired subjects on the last training day was positively correlated with their response on test day, as expected since both days were nearly identical (stimuli presented without cocaine). However, for Paired subjects, the magnitude of conditioned locomotion on the drug-free test day was not positively correlated with the magnitude of behavioral sensitization. These results underscore the importance of focusing research on drug-free conditioned behaviors when attempting to model conditioned responses to drug related cues in human addicts.

Animals↗
PubMed1998

Intra-stride belt-speed variation affects treadmill locomotion.

For overground and treadmill locomotion to be mechanically similar, it is required that the belt speed of the treadmill is constant and the same to that of overground locomotion. Variation of the belt speed during a stride causes exchange of energy between the subject and the treadmill. This might be the cause of different kinematic patterns between overground and treadmill locomotion, which have been reported in literature. The aim of this study was to investigate whether the intra-stride belt-speed is variable, and whether differences in kinematic patterns can be attributed to these variations. Nine subjects walked and ran overground and on two treadmills that were differently susceptible to subjects' braking and accelerating forces. It was found that the speed variations during treadmill locomotion affect the kinematic parameters significantly. The amount of intra-stride belt-speed variation was found to depend on the power of the treadmill and the mass of the subject. Copyright 1998 Elsevier Science B.V.

Journal Article↗