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1.
Front Physiol ; 11: 377, 2020.
Article in English | MEDLINE | ID: mdl-32390872

ABSTRACT

The way we can correct our ongoing movements to sudden and unforeseen perturbations is key to our ability to rapidly adjust our behavior to novel environmental demands. Referred to as sensorimotor flexibility, this ability can be assessed by the double-step paradigm in which participants must correct their ongoing arm movements to reach targets that unexpectedly change location (i.e., target jump). While this type of corrections has been demonstrated in normogravity in the extent of reasonable spatiotemporal constraints underpinning the target jumps, less is known about sensorimotor flexibility in altered gravitational force fields. We thus aimed to assess sensorimotor flexibility by comparing online arm pointing corrections observed during microgravity episodes of parabolic flights with normogravity standards. Seven participants were asked to point as fast and as accurately as possible toward one of two visual targets with their right index finger. The targets were aligned vertically in the mid-sagittal plane and were separated by 10 cm. In 20% of the trials, the initially illuminated lower target was switched off at movement onset while the upper target was concomitantly switched on prompting participants to change the trajectory of their ongoing movements. Results showed that, both in normogravity and microgravity, participants successfully performed the pointing task including when the target jumped unexpectedly (i.e., comparable success rate). Most importantly, no significant difference was found in target jump trials regarding arm kinematics between both gravitational environments, neither in terms of peak velocity, relative deceleration duration, peak acceleration or time to peak acceleration. Using inverse dynamics based on experimental and anthropometrical data, we demonstrated that the shoulder torques for accelerating and decelerating the vertical arm movements substantially differed between microgravity and normogravity. Our data therefore highlight the capacity of the central nervous system to perform very fast neuromuscular adjustments that are adapted to the gravitational constraints. We discuss our findings by considering the contribution of feedforward and feedback mechanisms in the online control of arm pointing movements.

2.
Neuroscience ; 300: 155-62, 2015 Aug 06.
Article in English | MEDLINE | ID: mdl-25987200

ABSTRACT

Updating the position of an earth-fixed target during whole-body rotation seems to rely on cognitive processes such as the utilization of external feedback. According to perceptual learning models, improvement in performance can also occur without external feedback. The aim of this study was to assess spatial updating improvement in the absence and in the presence of external feedback. While being rotated counterclockwise (CCW), participants had to predict when their body midline had crossed the position of a memorized target. Four experimental conditions were tested: (1) Pre-test: the target was presented 30° in the CCW direction from participant's midline. (2) Practice: the target was located 45° in the CCW direction from participant's midline. One group received external feedback about their spatial accuracy (Mackrous and Simoneau, 2014) while the other group did not. (3) Transfer T(30)CCW: the target was presented 30° in the CCW direction to evaluate whether improvement in performance, during practice, generalized to other target eccentricity. (4) Transfer T(30)CW: the target was presented 30° in the clockwise (CW) direction and participants were rotated CW. This transfer condition evaluated whether improvement in performance generalized to the untrained rotation direction. With practice, performance improved in the absence of external feedback (p=0.004). Nonetheless, larger improvement occurred when external feedback was provided (ps=0.002). During T(30)CCW, performance remained better for the feedback than the no-feedback group (p=0.005). However, no group difference was observed for the untrained direction (p=0.22). We demonstrated that spatial updating improved without external feedback but less than when external feedback was given. These observations are explained by a mixture of calibration processes and supervised vestibular learning.


Subject(s)
Feedback, Psychological , Space Perception , Adult , Humans , Learning , Memory , Proprioception , Psychophysics , Rotation , Young Adult
3.
Neuroscience ; 260: 12-22, 2014 Feb 28.
Article in English | MEDLINE | ID: mdl-24342565

ABSTRACT

To maintain perception of the world around us during body motion, the brain must update the spatial presentation of visual stimuli, known as space updating. Previous studies have demonstrated that vestibular signals contribute to space updating. Nonetheless, when being passively rotated in the dark, the ability to keep track of a memorized earth-fixed target (EFT) involves learning mechanism(s). We tested whether such learning generalizes across different EFT eccentricities. Furthermore, we ascertained whether learning transfers to similar target eccentricities but in the opposite direction. Participants were trained to predict the position of an EFT (located at 45° to their left) while being rotated counterclockwise (i.e., they press a push button when they perceived that their body midline have cross the position of the target). Overall, the results indicated that learning transferred to other target eccentricity (30° and 60°) for identical body rotation direction. In contrast, vestibular learning partly transferred to target location's matching body rotation but in the opposite rotation direction. Generalization of learning implies that participants do not adopt cognitive strategies to improve their performance during training. We argue that the brain learned to use vestibular signals for space updating. Generalization of learning while being rotated in the opposite direction implies that some parts of the neural networks involved in space updating is shared between trained and untrained direction.


Subject(s)
Generalization, Psychological , Learning , Motion Perception , Space Perception , Adult , Humans , Rotation , Young Adult
4.
Gait Posture ; 35(4): 616-20, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22243988

ABSTRACT

Anticipatory postural adjustments (APAs) prior to step execution are thought to be immutable once released. Here we challenge this assumption by testing whether APAs can be modified online if a body perturbation occurs during execution. Two directions of perturbation (resisting and assisting) relative to the body weight transfer were used during the execution of APAs. We found that APAs are modified online (increase in both ground pressure and muscle activity) to compensate for resisting perturbations. The outcomes of a biomechanical model confirmed that the early changes in the APAs resulted from an active control of the APAs and were not merely mechanical consequences of the perturbation. However, no modification of the initial feedforward command was observed for assisting perturbations. The motor command changes for the resisting perturbation may originate from the mismatch between passively originated forces and those actively specified by the central command when acting in the opposite direction. The absence of a mismatch in the assisting perturbation might explain why the central nervous system was not prompted to modify the APAs in this condition.


Subject(s)
Adaptation, Physiological , Movement/physiology , Posture/physiology , Psychomotor Performance/physiology , Analysis of Variance , Anticipation, Psychological , Biomechanical Phenomena , Computer Simulation , Electromyography/methods , Exercise Test/methods , Humans , Models, Biological , Muscle, Skeletal/physiology , Postural Balance/physiology , Reference Values , Reproducibility of Results , Sampling Studies , Young Adult
5.
Neuroscience ; 195: 45-53, 2011 Nov 10.
Article in English | MEDLINE | ID: mdl-21839149

ABSTRACT

Following body rotation, optimal updating of the position of a memorized target is attained when retinal error is perceived and corrective saccade is performed. Thus, it appears that these processes may enable the calibration of the vestibular system by facilitating the sharing of information between both reference frames. Here, it is assessed whether having sensory information regarding body rotation in the target reference frame could enhance an individual's learning rate to predict the position of an earth-fixed target. During rotation, participants had to respond when they felt their body midline had crossed the position of the target and received knowledge of result. During practice blocks, for two groups, visual cues were displayed in the same reference frame of the target, whereas a third group relied on vestibular information (vestibular-only group) to predict the location of the target. Participants, unaware of the role of the visual cues (visual cues group), learned to predict the location of the target and spatial error decreased from 16.2 to 2.0°, reflecting a learning rate of 34.08 trials (determined from fitting a falling exponential model). In contrast, the group aware of the role of the visual cues (explicit visual cues group) showed a faster learning rate (i.e. 2.66 trials) but similar final spatial error 2.9°. For the vestibular-only group, similar accuracy was achieved (final spatial error of 2.3°), but their learning rate was much slower (i.e. 43.29 trials). Transferring to the Post-test (no visual cues and no knowledge of result) increased the spatial error of the explicit visual cues group (9.5°), but it did not change the performance of the vestibular group (1.2°). Overall, these results imply that cognition assists the brain in processing the sensory information within the target reference frame.


Subject(s)
Brain/physiology , Learning/physiology , Psychomotor Performance/physiology , Space Perception/physiology , Adult , Cues , Humans , Rotation , Young Adult
6.
Int J Obes (Lond) ; 34(5): 936-42, 2010 May.
Article in English | MEDLINE | ID: mdl-20101249

ABSTRACT

OBJECTIVE: Overweight individuals sway more than normal weight individuals. Major weight loss improves their balance control despite a related decrease in muscle strength. Presumably, muscular strength is an important factor for balance control. This study investigated the effect that a change in body mass has on relative strength and balance control. METHODOLOGY: Force (isometric knee extension) and balance control (center of pressure speed and range) were studied in three groups; normal weight (BMI <25 kg m(-2)), obese (30 kg m(-2) 40 kg m(-2)) Caucasian male individuals. RESULTS: The excess obese individuals who underwent bariatric surgery as a weight loss strategy were studied before, 3 and 12 months after losing on average, 66.9 kg (+/-95% CI 55.8, 77.9 kg; on average, 45% of their weight). The obese individuals who underwent diet modifications were studied before dieting and when resistance to weight loss occurred after losing on average 11.7 kg (+/-95% CI 9.3, 14.2 kg; on average, 12% of their weight). The control group was studied twice, 50 weeks apart. In obese and excess obese individuals, losing weight reduced absolute knee muscular strength on average, by 8.2 kg (+/-95% CI 3.9, 12.5 kg; on average, 10% of their strength) and 23.9 kg (+/-95% CI 12.1, 35.8 kg; on average, 33% of their strength). However, it also increased balance control measured with speed of the center of foot pressure, on average, by 0.10 cm s(-1) (+/-95% CI 0.05, 0.14 cm s(-1); or increased of 12%) and 0.28 cm s(-1) (+/-95% CI 0.07, 0.47 cm s(-1); increased of 27%), respectively. Relative strength increased approximately by 22% for only the excess obese group 12 months post surgery. CONCLUSION: This suggests, in overweight individuals, weight loss is more efficient at improving balance control than increasing, or even maintaining muscle strength. In these individuals, training programs aimed at improving balance control should primarily target weight loss.


Subject(s)
Muscle Strength/physiology , Obesity/physiopathology , Postural Balance/physiology , Weight Loss/physiology , Adult , Analysis of Variance , Bariatric Surgery , Biomechanical Phenomena , Body Mass Index , Caloric Restriction , Humans , Male , Obesity/surgery
7.
Int J Obes (Lond) ; 31(1): 153-60, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16682978

ABSTRACT

OBJECTIVE: To investigate the effect of weight loss on balance control in obese and morbid obese men. METHODS: In a longitudinal and clinical intervention study, postural stability was measured with a force platform before and after weight loss in men. Weight loss was obtained in obese men (mean body mass index (BMI)=33.0 kg/m(2)) by hypocaloric diet until resistance and in morbid obese men (mean BMI=50.5 kg/m(2)) by bariatric surgery. Morbid obese men were tested before surgery, and 3 and 12 months after surgery when they had lost 20 and nearly 50% of initial body weight, respectively. Normal weight individuals (mean BMI=22.7 kg/m(2)) were tested twice within a 6- to 12-month period to serve as control. Body fatness and fat distribution measures, and posturographic parameters of the center of foot pressure (CP) along the antero-posterior and medio-lateral axes for conditions with and without vision were performed in all subjects. RESULTS: Weight loss averaged 12.3 kg after dieting and 71.3 kg after surgery. Body weight remained unchanged in the control group. After weight loss, nearly all measures of postural stability were improved with and without vision (i.e., CP speed and range in antero-posterior and medio-lateral axes). A strong linear relationship was observed between weight loss and improvement in balance control measured from CP speed (adjusted R (2)=0.65, P<0.001). CONCLUSION: Weight loss improves balance control in obese men and the extent of the improvement is directly related to the amount of weight loss. This should decrease the habitual greater risk of falling observed in obese individuals.


Subject(s)
Obesity/physiopathology , Postural Balance/physiology , Weight Loss/physiology , Adult , Bariatric Surgery/methods , Biomechanical Phenomena , Body Size/physiology , Caloric Restriction/methods , Humans , Longitudinal Studies , Male , Obesity/diet therapy , Obesity/surgery , Obesity, Morbid/physiopathology , Treatment Outcome , Vision, Ocular/physiology
8.
Int J Obes (Lond) ; 30(12): 1750-7, 2006 Dec.
Article in English | MEDLINE | ID: mdl-16619057

ABSTRACT

INTRODUCTION: Obesity yields a decreased postural stability. The potentially negative impact of obesity on the control of upper limb movements, however, has not been documented. This study sought to examine if obesity imposes an additional balance control constraint limiting the speed and accuracy with which an upper limb goal-directed movement performed from an upright standing position can be executed. METHOD: Eight healthy lean subjects (body mass index (BMI) between 20.9 and 25.0 kg/m(2)) and nine healthy obese subjects (BMI between 30.5 and 48.6 kg/m(2)) pointed to a target located in front of them from an upright standing posture. The task was to aim at the target as fast and as precisely as possible after an auditory signal. The difficulty of the task was varied by using different target sizes (0.5, 1.0, 2.5 and 5.0 cm width). Hand movement time (MT) and velocity profiles were measured to quantify the aiming. Centre of pressure and segmental kinematics were analysed to document postural stability. RESULTS: When aiming, the forward centre of pressure (CP) displacement was greater for the obese group than for the normal BMI group (4.6 and 1.9 cm, respectively). For the obese group, a decrease in the target size was associated with an increase in backward CP displacement and CP peak speed whereas for the normal BMI group backward CP displacements and CP peak speed were about the same across all target sizes. Obese participants aimed at the target moving their whole body forward whereas the normal BMI subjects predominantly made an elbow extension and shoulder flexion. For both groups, MT increased with a decreasing target size. Compare to the normal BMI group, this effect was exacerbated for the obese group. For the two smallest targets, movements were on average 115 and 145 ms slower for the obese than for the normal BMI group suggesting that obesity added a balance constraint and limited the speed with which an accurate movement could be done. SUMMARY: Obesity, because of its effects on the control of balance, also imposes constraints on goal-directed movements. From a clinical perspective, obese individuals might be less efficient and more at risk of injuries than normal weight individuals in a large number of work tasks and daily activities requiring upper limb movements performed from an upright standing position.


Subject(s)
Arm/physiopathology , Movement , Obesity/physiopathology , Adult , Anthropometry , Biomechanical Phenomena , Body Mass Index , Elbow Joint/physiopathology , Hip Joint/physiopathology , Humans , Knee Joint/physiopathology , Male , Middle Aged , Postural Balance , Posture , Shoulder Joint/physiopathology
9.
Exp Brain Res ; 148(3): 338-49, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12541145

ABSTRACT

While much is known about reflex and mechanical contributions to the control of head stability, little is known about predictive control. The goal of this experiment was to determine the contribution of predictive mechanisms to head stability in space, in the pitch plane, during forward trunk perturbations. Eleven standing healthy subjects had their trunk pulled forward by a load-pulley apparatus. The perturbation was either self-triggered or imposed (triggered by the experimenter). Subjects were exposed to two loads: 2% and 4% of their body weight. The contributions of torques acting on the head-neck system were inferred from head and trunk kinematics, neck muscle EMG, and the torques acting on the head, which were computed using inverse dynamics. The results showed that both the head and trunk moved less during the self-triggered than imposed condition during both loads for most of the participants. There was no evidence of predictive neck countertorque or increased neck muscle co-contraction during the self-triggered condition. These findings suggest that most of the subjects improved head stability in the self-triggered condition by reducing trunk motion and the associated interactive torque that perturbed the head.


Subject(s)
Head Movements/physiology , Neck/physiology , Vestibular Diseases/physiopathology , Adaptation, Physiological , Adult , Biomechanical Phenomena , Electromyography , Humans , Kinetics , Muscle Contraction , Posture/physiology , Reference Values , Reflex , Time Factors , Torque
10.
Gait Posture ; 14(3): 203-10, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11600323

ABSTRACT

The aim of this experiment was to examine if, with aging, the task of reintegrating sensory information perturbs balance and requires additional attentional demand. Young adults and the elderly were asked to maintain a stable upright posture while standing on a force platform. Visual and ankle proprioceptive information were removed or perturbed and suddenly reinserted. Subjects also had to respond vocally as quickly as possible to an unpredictable auditory stimulus presented before or following a sensory reintegration and in control conditions. Reaction times to the auditory stimuli were used as an index of the attentional demands necessary for calibrating the postural system. Reintegration of proprioception in absence of vision and under vision yielded a faster center of pressure velocity for both groups. This effect, however, was more important for the elderly than the young adults. An increased attentional demand was observed for both groups when proprioceptive information had to be reintegrated in absence of vision. Altogether, these results propose that, for the elderly persons, postural contexts requiring a reweighting of sensory inputs could lead to increased risk for loss of balance and falls if insufficient attentional resources are allocated to the postural task.


Subject(s)
Attention , Posture , Proprioception , Adult , Age Factors , Aged , Female , Humans , Male , Postural Balance/physiology , Proprioception/physiology , Reaction Time , Task Performance and Analysis
11.
IEEE Trans Neural Syst Rehabil Eng ; 9(2): 126-36, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11474965

ABSTRACT

Recent epidemiological studies report that obesity is positively related to fracture incidence. In the present experiment, a model of postural control was used to examine the impact of an abnormal distribution of body fat in the abdominal area upon postural stability. Obese and lightweight humanoids were destabilized by imposing a small initial angular speed from a neutral standing position. To avoid a loss of stability yielding a stepping reaction or a fall, an ankle torque is necessary to counteract the perturbation. Three torque parameters--ankle torque onset, time to peak torque, and muscular ankle torque--were entered in a program to simulate the intrinsic variability of the human postural control system. A loss of stability was detected when the center of pressure exceeded stability margins. The most striking observation is the nonlinear increase of torque needed to stabilize the humanoid when the motor response was characterized by delayed temporal parameters. The effect was more pronounced when an anterior position of the center of mass was included in the simulations. This suggests that, when submitted to daily postural stresses and perturbations, obese persons (particularly those with an abnormal distribution of body fat in the abdominal area) may be at higher risk of falling than lightweight individuals.


Subject(s)
Accidental Falls , Models, Theoretical , Obesity/complications , Posture , Abdomen , Adipose Tissue/anatomy & histology , Risk Assessment , Torque
12.
Recept Channels ; 7(1): 41-52, 2000.
Article in English | MEDLINE | ID: mdl-10800775

ABSTRACT

The inositol 1,4,5-trisphosphate (InsP3) receptor forms a tetrameric channel responsible for the release of Ca2+ from intracellular stores. In the present study we showed that the experimental approach used to separate bound and free ligands may discriminate between two populations of InsP3 binding sites in bovine adrenal cortex microsomes. A large population of low affinity sites and a small population of high affinity sites were detected with centrifugation and filtration approaches, respectively. Both populations were found in the supernatant and the cytoskeleton fractions of Triton X-100 solubilized microsomes. After treatment of microsomes with thimerosal, an alkylating reagent known to increase InsP3 receptor affinity, the filtration and the centrifugation approaches yielded identical results. With selective anti-InsP3 receptor antibodies, we showed that types 1, 2 and 3 InsP3 receptors are present in intact microsomes and in the cytoskeleton fraction. Binding studies on immunoprecipitated receptors revealed that anti-type 1 antibody recognizes a large population of low affinity sites whereas anti-type 2 antibody recognizes a small population of high affinity sites. Our results indicate that the three types of InsP3 receptors are expressed at different levels in the bovine adrenal cortex. The presence of different types of InsP3 receptors with different ligand binding affinities and their association with the cytoskeleton offer a convenient way for the cell to simultaneously regulate its intracellular Ca2+ concentration and reorganize the spatial distribution of its Ca2+ stores.


Subject(s)
Adrenal Cortex/metabolism , Calcium Channels/classification , Inositol 1,4,5-Trisphosphate/metabolism , Receptors, Cytoplasmic and Nuclear/classification , Amino Acid Sequence , Animals , Binding Sites , Blotting, Western , Calcium Channels/metabolism , Cattle , Cell Line , Humans , Inositol 1,4,5-Trisphosphate Receptors , Precipitin Tests , Rats , Receptors, Cytoplasmic and Nuclear/metabolism
13.
Neurosci Lett ; 281(1): 53-6, 2000 Mar 03.
Article in English | MEDLINE | ID: mdl-10686414

ABSTRACT

Human subjects performed, from a standing position, rapid hand pointings to visual targets located within or beyond the prehension space. To examine the interaction between posture and the goal-directed movement we introduced a visual double-step perturbation requiring a reprogramming of the hand movement. Trials directed towards the same spatial goal but differentiated only by the likeliness of a visual double-step were compared. The hand kinematics was not affected by the uncertainty of the visual perturbation; an increased trunk bending, however, was observed. This suggests that uncertainty constraints are integrated in a predictive manner for the optimal coordination of the hand and postural control systems.


Subject(s)
Posture/physiology , Proprioception/physiology , Adult , Electromyography , Fingers/innervation , Hand/innervation , Humans , Male , Photic Stimulation , Psychomotor Performance/physiology , Visual Perception/physiology
14.
Oncogene ; 19(54): 6317-23, 2000 Dec 14.
Article in English | MEDLINE | ID: mdl-11175346

ABSTRACT

In a previous study, loss of heterozygosity (LOH) of 28 chromosome 9 microsatellite markers was assessed on 139 Ta/T1 bladder tumors. LOH at one or more loci was detected in 67 tumors, 62 presenting subchromosomal deletions. One hundred and thirty-three of these patients have now been followed for up to 8 years. The purpose of the present study was to evaluate the potential biological significance of chromosome 9 deletions in superficial bladder tumors at initial diagnosis. High grade was associated with LOH (P=0.004). Large tumors carried more frequently 9p deletions (P=0.022). Female patients had more chromosome 9q LOH than male patients did (P=0.010). Chromosome 9 LOH at all loci was associated with an elevated risk of recurrence but four regions were associated with a particularly high risk of recurrence. Multivariate analysis taking into account grade, stage, size and number of tumors showed that tumors deleted in the regions 9ptr-p22, 9q22.3, 9q33, and 9q34 recurred significantly more rapidly than those without deletions (Recurrence rate ratio=2.32, 2.53, 2.52 and 2.43 respectively). Log-rank statistics comparing Kaplan-Meier survival curves for the same chromosomal regions confirmed the correlation (P=0.0002, 0.010, 0.002 and 0.009 respectively). Only four patients progressed to muscle-invasive disease. They all had extensive deletions on 9q but none had deletions at 9ptr-p22. This study suggests a link between chromosome 9 anomalies and recurrence of superficial bladder cancer.


Subject(s)
Chromosomes, Human, Pair 9 , Loss of Heterozygosity , Neoplasm Recurrence, Local/genetics , Urinary Bladder Neoplasms/genetics , Aged , Disease-Free Survival , Female , Follow-Up Studies , Genetic Markers , Humans , Male , Microsatellite Repeats , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Prognosis , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
15.
Carcinogenesis ; 21(1): 101-6, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10607740

ABSTRACT

Sequencing of p53 exons 5-8 was carried out on 51 initial superficial bladder tumors selected on the basis of high grade and/or p53 overexpression (immunohistochemistry without antigen retrieval). Fourteen point mutations in 13 tumors and one 21 bp deletion in another tumor were identified. In addition, a germ-line mutation corresponding to a previously described polymorphism was detected in exon 6, in two tumors. Mostly G-->A transitions (10) were found. Only three occurred at CpG sites, suggesting a major role for exogenous carcinogens in bladder tumorigenesis. Immunostaining for p53 and MDM2, using antigen retrieval, was carried out on the same tumors. A correlation was found between the percentage of p53-positive cells and the presence of p53 mutations (P = 0.005). No correlation was found between overexpression of p53 and MDM2 in this selected cohort of mostly high grade tumors. The presence of p53 mutations was also analyzed as a function of the smoking habits of the patients. A significant association was found between the presence of p53 point mutations and the number of years of smoking (P = 0.043). All patients with tumors carrying missense or nonsense p53 mutations had smoked for >/=30 years and if former smokers, had stopped for

Subject(s)
Genes, p53 , Nuclear Proteins , Point Mutation , Smoking/adverse effects , Urinary Bladder Neoplasms/genetics , Humans , Immunohistochemistry , Neoplasm Recurrence, Local/etiology , Proto-Oncogene Proteins/analysis , Proto-Oncogene Proteins c-mdm2 , Sequence Analysis, DNA , Smoking/genetics , Tumor Suppressor Protein p53/analysis , Urinary Bladder Neoplasms/etiology
16.
J Biol Chem ; 274(42): 29819-25, 1999 Oct 15.
Article in English | MEDLINE | ID: mdl-10514460

ABSTRACT

Integrins are important mediators of cell-laminin interactions. In the small intestinal epithelium, which consists of spatially separated proliferative and differentiated cell populations located, respectively, in the crypt and on the villus, laminins and laminin-binding integrins are differentially expressed along the crypt-villus axis. One exception to this is the integrin alpha(6)beta(4), which is thought to be ubiquitously expressed by intestinal cells. However, in this study, a re-evaluation of the beta(4) subunit expression with different antibodies revealed that two forms of beta(4) exist in the human intestinal epithelium. Furthermore, we show that differentiated enterocytes express a full-length 205-kDa beta(4)A subunit, whereas undifferentiated crypt cells express a novel beta(4)A subunit that does not contain the COOH-terminal segment of the cytoplasmic domain (beta(4)A(ctd-)). This new form was not found to arise from alternative beta(4) mRNA splicing. Moreover, we found that these two beta(4)A forms can associate into alpha(6)beta(4)A complexes; however, the beta(4)A(ctd-) integrin expressed by the undifferentiated crypt cells is not functional for adhesion to laminin-5. Hence, these studies identify a novel alpha(6)beta(4)A(ctd-) integrin expressed in undifferentiated intestinal crypt cells that is functionally distinct.


Subject(s)
Antigens, CD/metabolism , Cell Differentiation , Intestinal Mucosa/metabolism , Adult , Antigens, CD/chemistry , Base Sequence , DNA Primers , Humans , Integrin beta4 , Intestinal Mucosa/cytology , Tumor Cells, Cultured
17.
Exp Brain Res ; 128(1-2): 236-42, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10473766

ABSTRACT

The performances of a deafferented patient and five control subjects have been studied during a self-driven passing task in which one hand has to grasp an object transported by the other hand and in a unimanual reach-to-grasp task. The kinematics of the reach and grasp components and the scaling of the grip aperture recorded for the self-driven passing task were very similar in controls and the deafferented subject (GL). In contrast, for the unimanual task when vision was absent, GL's coordination between reaching and grasping was delayed in space and time compared with the control subjects. In addition, frequent reopening of the grip was observed in GL during the final closure phase of the unimanual prehension task. These results support the notion that afferent proprioceptive information resulting from the reaching movement - which seemed to be used to coordinate reaching and grasping commands in the unimanual task - is no longer necessary in the self-induced passing task. Finally, for the externally driven passing task, when the object was passively transported by the experimenter, the coordination was consistently modified in all subjects; grip aperture onset was delayed, thus asserting a specific contribution of the central command or feedforward mechanisms into the anticipation of the grasp onset observed in the self-driven passing task. The origin and nature of the information necessary for building up the feedforward mechanisms remains to be elucidated.


Subject(s)
Hand Strength/physiology , Proprioception/physiology , Psychomotor Performance/physiology , Adult , Afferent Pathways/physiology , Analysis of Variance , Case-Control Studies , Feedback , Humans , Middle Aged
18.
Urol Res ; 27(3): 180-4, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10422819

ABSTRACT

The involvement of human papillomavirus (HPV) in bladder cancer remains controversial. We previously reported detection of L1-HPV DNA in 39% of bladder cancers of mixed grade and stage. To clarify the possible etiologic role of HPV we studied, using the same technique, a more homogeneous group of initial low-stage tumors. We investigated a total of 187 newly diagnosed superficial papillary bladder tumors for the presence of L1-HPV DNA by the polymerase chain reaction method and hybridization with specific probes for HPV 6, 11, 16, 18, 33. HPV DNA was detected in 16 (8.5%) of the 187 specimens tested, although in a low copy number compared with SiHa cervical cancer cells used as control. HPV type 16 was observed in eight tumors while HPV type 6 and type 11 were each observed in three tumors. Two tumor specimens contained two types of HPV: one tumor hybridized with type 6 and 16 and the other with type 11 and 18. This low rate of HPV detection (8.5%) in initial tumors does not favor a prominent role for HPV in bladder carcinogenesis.


Subject(s)
Carcinoma, Transitional Cell/virology , Papillomaviridae/isolation & purification , Urinary Bladder Neoplasms/virology , Carcinoma, Transitional Cell/etiology , DNA Probes, HPV , DNA, Viral/genetics , DNA, Viral/isolation & purification , Humans , Papillomaviridae/genetics , Papillomaviridae/pathogenicity , Polymerase Chain Reaction , Urinary Bladder Neoplasms/etiology
19.
Oncogene ; 18(1): 157-63, 1999 Jan 07.
Article in English | MEDLINE | ID: mdl-9926930

ABSTRACT

The most common genetic alteration identified in transitional cell carcinoma (TCC) of the bladder is loss of heterozygosity (LOH) on chromosome 9. However, localization of tumor suppressor genes on 9q has been hampered by the low frequency of subchromosomal deletions. We have analysed 139 primary, initial low stage TCC of the bladder using a panel of 28 microsatellite markers spanning chromosome 9 at an average distance of 5 Mb, following a primer-extension preamplification (PEP) technique. Sixty-seven (48%) tumors showed LOH at one or more loci and partial deletions were detected in 62 (45%) tumors; apparent monosomy 9 was detected in only five (4%) tumors. Deletions were more frequent on 9q (44%) than on 9p (23%), the latter being mostly associated with 9q deletion, suggesting that alteration of genes on 9q may be an early event associated with superficial papillary tumors. Combined data from the cases with partial 9q deletions displayed four candidate regions for tumor suppressor loci, based on the frequency of deletion observed and tumors with unique deletions at these sites. In two tumors, the unique partial deletion comprised D9S12 at 9q22.3, a region encompassing loci for the Gorlin syndrome and multiple self-healing squamous epithelioma gene. In two other tumors, the single LOH was identified at the D9S172 locus at 9q31-32 where the dysautonia and Fukuyama-type congenital muscular dystrophy genes have been located. One tumor showed unique LOH at the GSN locus at 9q33, a region frequently deleted in other sporadic tumors while the fourth region of deletion was observed at 9q34 between ASS and ABL-1, in two tumors. This region is frequently deleted in tumors and encompasses the locus for the hereditary hemorrhagic telangiectasia gene. These findings suggest four target regions on 9q within which suppressor genes for TCC may reside.


Subject(s)
Chromosomes, Human, Pair 9 , Genes, Tumor Suppressor , Urinary Bladder Neoplasms/genetics , Humans , Loss of Heterozygosity
20.
J Am Geriatr Soc ; 47(2): 235-40, 1999 Feb.
Article in English | MEDLINE | ID: mdl-9988297

ABSTRACT

OBJECTIVE: To determine the effect of modifying the stable visual anchor on the postural stability of older individuals. The visual anchor was changed by opening doors similar to those found in an elevator cage. Lighting intensities inside and outside the cage were varied to create increasing or decreasing luminosity conditions. The effect of adding a cognitive load (counting backwards) was also tested. DESIGN: A controlled laboratory study. SETTING: Tests performed in a balance laboratory. MEASUREMENTS: Sensory and clinical measurements to insure the integrity of the central and peripheral nervous system. Measures of balance were derived from the recordings of the center of foot pressure. These measures included range and speed of the center of foot pressure. PARTICIPANTS: Eight older, community-dwelling subjects and nine young subjects participated. A sensorimotor evaluation was used to insure that all older individuals were free from any pathologies affecting postural stability. All participants had a low score (indicating high balance confidence) on the Falls Efficacy Scale and no history of falls. RESULTS: Older individuals were affected by modification of the stable visual anchor induced by the opening of doors similar to that of an elevator cage. They showed greater ranges of the center of foot pressure (COP) and speed of the COP after than before the opening of the doors. Furthermore, the increased ranges and speed were two to three times greater than that observed for the young subjects. A lighting intensity considered as comfortable for reading inside the elevator affected the overall postural stability of the older participants negatively. Counting backwards also decreased their overall stability. CONCLUSION: Changing the stable visual anchor, as when exiting an elevator cage, could be a significant risk factor for older persons. Moreover, when combined with a cognitive load or lower lighting intensity inside the elevator cage, the negative effects on the postural stability of older persons are exacerbated.


Subject(s)
Aging/psychology , Orientation , Postural Balance , Posture , Visual Perception , Accidental Falls/prevention & control , Adult , Aged , Attention , Elevators and Escalators , Female , Humans , Lighting , Male , Neurologic Examination
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