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  • 101
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 124 (1999), S. 422-428 
    ISSN: 1432-1106
    Keywords: Key words Lifting forces ; Size-weight illusion ; Microgravity ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Individuals usually report for two objects of equal mass but different volume that the larger object feels lighter. This so-called size-weight illusion has been investigated for more than a century. The illusion is accompanied by increased forces, used to lift the larger object, resulting in a higher initial lifting speed and acceleration. The illusion holds when subjects know that the mass of the two objects is equal and it is likely that this also counts for the enlarged initial effort in lifting a larger box. Why should this happen? Under microgravity, subjects might be able to eliminate largely the weight-related component of the lifting force. Then, if persistent upward scaling of the weight-related force component had been the main cause of the elevated initial lifting force under normal gravity, this elevated force might disappear under microgravity. On the other hand, the elevated initial lifting effort in the large box would be preserved if it had been caused mainly by a persistent upward scaling of the force component, necessary to accelerate the object. To test whether the elevated initial lifting effort either persists or disappears under microgravity, a lifting experiment was carried out during brief periods of microgravity in parabolic flights. Subjects performed whole-body lifting movements with their feet strapped to the floor of the aircraft, using two 8-kg boxes of different volume. The subjects were aware of the equality of the box masses. The peak lifting forces declined almost instantaneously with approx. a factor 9 in the first lifting movements under microgravity compared with normal gravity, suggesting a rapid adaptation to the loss of weight. Though the overall speed of the lifting movement decreased under microgravity, the mean initial acceleration of the box over the first 200 ms of the lifting movement remained higher (P=0.030) in the large box (1.87±0.127 m/s2) compared with the small box (1.47±0.122 m/s2). Under normal gravity these accelerations were 3.30±0.159 m/s2 and 2.67±0.159 m/s2, respectively (P=0.008). A comparable trend was found in the initial lifting forces, being significant in the pooled gravity conditions (P=0.036) but not in separate tests on the normal gravity (P=0.109) and microgravity (P=0.169) condition. It is concluded that the elevated initial lifting effort with larger objects holds during short-term exposure to microgravity. This suggests that upward scaling of the force component, required to accelerate the larger box, is an important factor in the elevated initial lifting effort (and the associated size-weight illusion) under normal gravity.
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  • 102
    ISSN: 1432-1106
    Keywords: Key words Microneurography ; Peripheral nerve ; Pacinian afferent ; Cutaneous mechanoreceptor ; Vibrotactile stimuli ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To further study the functional organisation of human peripheral nerves, the intrafascicular arrangement of afferent fibres supplying Pacinian corpuscles (PCs) was explored by percutaneous microneurography using thin-calibre, concentric needle electrodes. In normal adults, 20 PC afferents were identified in 13 recording sites. Low-amplitude (less than 30 µm) vibratory stimuli to the skin were applied with tuning forks oscillating at 128 Hz or 256 Hz and response patterns of individual PC units were studied. In many recording sites, two, sometimes even three, PC afferents with adjacent or overlapping receptive fields in the hand were clustered in the nerve. The observed incidence in the records containing a certain number of PC units was compared with the expected probability calculated according to the hypothesis that all nerve fibres are randomly organised in peripheral nerves. The results suggested that PC afferents are partially segregated in the nerve. In addition, PC afferents were neighbouring on slowly adapting type II (SAII) units and skin sympathetic activity in individual fascicles. SAII units often innervated the same skin area as PC units, but did not respond to vibration. The data provided additional information regarding the functional organisation of the human peripheral nerve and the mechanisms underlying the sense of vibration in man with special regard to population behaviour of neighbouring PC mechanoreceptors.
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  • 103
    ISSN: 1432-1106
    Keywords: Key words Motor development ; Reaching ; Anticipatory postural control ; EMG ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study focused on the developmental changes of postural adjustments accompanying reaching movements in healthy infants. We made a longitudinal study of ten infants between 6 and 18 months of age. During each session multiple surface electromyograms of arm, neck, trunk and leg muscles at the right side of the body were recorded during right-handed reaching movements in two positions (”upright sitting” in an infant chair and ”long-leg” sitting without support). Simultaneously the whole session was recorded on video. Comparable data were present from the same infants at 3–5 months. Additionally, 18 infants (8–15 months) were assessed once during similar reaching tasks, but in these infants electromyographic activity of the trunk and neck muscles at both sides of the body were recorded. Our data revealed two transitions in the development of postural adjustments. The first transition was present around 6 months of age. At this age the postural muscles were infrequently activated during reaching movements. At 8 months ample postural activity reappeared and the infants developed the ability to adapt the postural adjustments to task-specific constraints such as arm movement velocity or the sitting position at the onset of the reaching movement. The second transition occurred between 12 and 15 months. Before 15 months the infants did not show consistent anticipatory postural activity, but from 15 months onwards they did, particularly in the neck muscles.
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  • 104
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    Experimental brain research 126 (1999), S. 536-544 
    ISSN: 1432-1106
    Keywords: Key words Magnetic brain stimulation ; Afferent input ; Motor cortex ; Plasticity ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previously, we had described a technique for investigating probable GABAergic cortical inhibitory circuits in conscious man using transcranial magnetic stimulation. This type of inhibition has been termed intracortical inhibition. During voluntary contraction, activity in the circuits responsible for this inhibition is reduced. The mechanism by which this reduction in activity is brought about is unknown. However, evidence exists to suggest that afferent input may be, at least in part, responsible for the reduction in inhibition. The experiments described here were designed to investigate this possibility further. The results of these experiments showed that afferent input, produced by electrical peri- pheral-nerve stimulation, reduced the level of intracortical inhibition. Also, motor imagery, which activates similar brain regions as overt movement, but does not result in afferent input, failed to produce significant changes in intracortical inhibition. We conclude from these results that afferent input is capable of altering activity in cortical inhibitory circuits. The relevance of these findings to the mechanisms involved in cortical reorganisation is discussed.
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  • 105
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    Experimental brain research 126 (1999), S. 556-562 
    ISSN: 1432-1106
    Keywords: Key words Acceleration ; Ocular microtremor ; Eye movements ; Partial coherence ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A novel technique for the study of human eye movements was used to investigate the frequency components of ocular drift and microtremor in both eyes simultaneously. The tangential components of horizontal eye accelerations were recorded in seven healthy subjects using light-weight accelerometers mounted on scleral contact lenses during smooth pursuit movements, vestibulo-ocular reflexes and eccentric gaze with and without fixation. Spectral peaks were observed at low (up to 25 Hz) and high (60–90 Hz) frequencies. A multivariate analysis based on partial coherence analysis was used to correct for head movement. After correction, the signals were found to be coherent between the eyes over both low- and high-frequency ranges, irrespective of task, convergence or fixation. It is concluded that the frequency content of ocular drift and microtremor reflects the patterning of low-level drives to the extra-ocular muscle motor units.
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  • 106
    ISSN: 1432-1106
    Keywords: Key words Suprathreshold heat pain ; Adapting temperature ; Temporal parameters ; Spinal dorsal horn neuron ; Descending control ; Rat ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The influence of stimulus temperature rise rate (2.5ºC/s, 5.0ºC/s, and 10.0ºC/s), adapting (baseline) temperature (25ºC, 30ºC, and 35ºC), and duration of peak stimulus temperature (1.0 s, 2.5 s, 5.0 s, and 10.0 s) on responses evoked by noxious heat stimuli of suprathreshold intensity was studied in wide dynamic range (WDR) neurons of the rat spinal dorsal horn. The spinal neuronal responses were compared with human psychophysical data obtained using the same stimuli. Noxious heat stimuli with a peak temperature of 54ºC were applied with a contact thermostimulator to the glabrous skin of the hindfoot in rats or to the palmar skin in humans. With the highest ramp rate and the highest adapting temperature, the sensory and spinal neuronal response latencies were decreased more than expected on the basis of the change in physical parameters of the stimulus. The magnitudes of sensory and spinal neuronal response were independent of the stimulus ramp rate, whereas pain magnitude estimates and spinal neuronal impulse counts evoked by the same peak stimulus temperature were increased with an increase in the adapting stimulus temperature. The onset latencies of pain reactions and spinal neuronal responses were independent of the peak stimulus duration, whereas the latency of the maximum discharge in spinal neurons increased with prolongation of the peak stimulus. The sensory magnitude estimate of pain and the neuronal impulse count were increased with increase in stimulus duration. Following spinalization, the spinal neuronal responses were stronger and the stimulus duration-dependent increase in the impulse count developed faster. Moreover, the peak frequency of spinal neuronal response increased significantly with prolongation of the heat stimuli after spinalization, but not in animals with an intact spinal cord. The results indicate that stimulus rise rate, stimulus duration, and the adapting temperature are important factors in determining the sensory and spinal neuronal responses to high-intensity heat stimuli. The changes in the total impulse counts evoked by varying supraliminal heat stimuli in spinal dorsal horn WDR neurons corresponded well with the changes in pain magnitude estimates in humans. Also, the changes in spinal neuronal response onset latencies were accompanied by corresponding changes in onset latencies of human pain reactions but not with pain magnitude estimates. The effect of spinalization indicated that descending pathways control not only the response magnitude in the spinal dorsal horn WDR neurons but also the temporal characteristics of the spinal neuronal response.
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  • 107
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    Experimental brain research 125 (1999), S. 521-524 
    ISSN: 1432-1106
    Keywords: Key words Light touch ; Sway ; Centre of pressure ; Hand force ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It has previously been shown that light contact with the finger tip on a fixed surface reduces centre of pressure (CoP) fluctuations in the frontal plane when standing in an unstable posture with the feet in line (tandem Romberg stance). Positive cross-correlations between horizontal finger forces and CoP fluctuations with finger forces exhibiting a phase lead suggest the hand provides sensory input for postural stability. The present study investigates whether this is the case for normal posture. We report reduced CoP fluctuations in the sagittal plane when light touch is permitted during normal bipedal stance. Moreover, we find positive crosscorrelations between finger tip forces and CoP fluctuations which are of similar magnitude and phase lag to those observed in tandem Romberg stance. This shows the utility of hand touch input for regulation of normal upright posture as well as inherently unstable postures such as tandem Romberg.
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  • 108
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    European journal of clinical pharmacology 55 (1999), S. 349-352 
    ISSN: 1432-1041
    Keywords: Key words Ischaemic stroke ; Vinpocetine ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: To determine whether vinpocetine decreases short- and long-term case fatality and proportion of dependent survivors if administered within 2 weeks of stroke onset. Methods: All published and unpublished trials were attempted to be identified using the standard search strategy of the Cochrane Collaboration Stroke Review Group, using MEDLINE searches performed with all known manufacturer code names and trade names of vinpocetine and by contacting manufacturers of vinpocetine to give information of all randomised controlled trials on vinpocetine in stroke. Researchers who participated in trials on vinpocetine in Hungary were asked for further information. Only truly randomised, unconfounded clinical trials that compared the effect of vinpocetine to either placebo or another reference treatment for acute stroke where treatment started no later than 14 days after stroke onset were eligible for inclusion. Data synthesis and analysis was performed using the Cochrane Review Manager software (RevMan version 3.0). Results: Among the identified studies on vinpocetine in stroke, only one fulfilled the selection criteria for inclusion in the review. No death occurred in the study groups and no statistically significant difference was found in dependency between the treatment and the placebo groups. No adverse effects were reported. Conclusions: Based on only one small randomised controlled unconfounded study, presently there is not enough evidence to decide whether the administration of vinpocetine does or does not decrease case fatality and dependency in acute stroke.
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  • 109
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    Experimental brain research 128 (1999), S. 353-368 
    ISSN: 1432-1106
    Keywords: Key words Multijoint arm ; Simulations ; Muscle torques ; Kinetics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Adults are able to reach for an object for the first time with appropriate direction, speed, and accuracy. The rules by which the nervous system is able to set muscle activities to accomplish these outcomes are still debated and, indeed, the sensitivity of kinematics to variations in muscle torques is unknown for complex arm movements. As a result, this study used computer simulations to characterize the effects of change in muscle torque on initial hand path. The same change was applied to movements towards 12 directions in the horizontal plane, and changes were systematically manipulated such that: (1) torque amplitude was changed at one joint, (2) timing of torque was changed at one joint, and (3) amplitude and/or timing was changed at two joints. Results showed that simultaneous changes in torque amplitude at shoulder and elbow joints affected initial speed uniformly across direction. These results add to conclusions from previous experimental and modeling work that the simplest rule to produce a desired change in speed for any direction is to scale torque amplitude at both joints. In contrast, all simulations showed nonuniform effects on initial path direction. For some regions of the workspace, initial path direction was little affected by either a ±30% change in amplitude or a ±100-ms change in timing, whereas for other regions the same changes produced large effects on initial path direction. These findings suggest that the range of possible torque solutions to achieve a particular initial path direction varies within the workspace and, consequently, the requirements for an accurate initial path will vary within the workspace.
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  • 110
    ISSN: 1432-1106
    Keywords: Key words Aiming movements ; Target size ; Inertial load ; Strategies ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two experiments are reported that investigated the effects of target size and inertial load on the control of rapid aiming movements. Based on kinematic profiles, movements were partitioned into their preprogrammed initial impulse- and feedback-based error correction phases. Electromyographic (EMG) rise rates were examined to investigate whether participants used a speed-sensitive or speed-insensitive control strategy. The results from both experiments showed that initial impulse velocity and EMG rise rates varied as a function of target size, i.e., a speed-sensitive strategy. This was the case whether participants were allowed to make error corrections to their movements (experiment 1) or were instructed to produce initial impulses that hit the target (experiment 2). Both experiments also showed that initial impulse velocity and endpoint variability were inversely related to inertial load. The results from experiment 2 indicated that, while the manipulation of inertial load had no effect on EMG rise rates for movements to a large target, EMG slopes were modulated between inertial load conditions when the target was small.
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  • 111
    ISSN: 1432-1106
    Keywords: Key words Vibration-induced kinesthetic illusions ; Antagonist vibratory response ; Motor units ; Wrist extensor muscles ; Human ; Microelectromyography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In humans, vibration applied to muscle tendons evokes illusory sensations of movement that are usually associated with an excitatory tonic response in muscles antagonistic to those vibrated (antagonist vibratory response or AVR). The aim of the present study was to investigate the neurophysiological mechanisms underlying such a motor response. For that purpose, we analyzed the relationships between the parameters of the tendon vibration (anatomical site and frequency) and those of the illusory movement perceived (direction and velocity), as well as the temporal, spatial, and quantitative characteristics of the corresponding AVRs (i.e., surface EMG, motor unit firing rates and activation latencies). Analogies were supposed between the characteristics of AVRs and voluntary contractions. The parameters of the AVR were thus compared with those of a voluntary contraction with similar temporal and mechanical characteristics, involving the same muscle groups as those activated by vibration. Wrist flexor muscles were vibrated either separately or simultaneously with wrist extensor muscles at frequencies between 30 and 80 Hz. The illusory movement sensations were quantified through contralateral hand-tracking movements. Electromyographic activity from the extensor carpi radialis muscles was recorded with surface and intramuscular microelectrodes. The results showed that vibration of the wrist flexor muscle group induced both a kinesthetic illusion of wrist extension and a motor response in the extensor carpi radialis muscles. Combined vibration of the two antagonistic muscle groups at the same frequency evoked neither kinesthetic illusion nor motor activity. In addition, vibrating the same two antagonistic muscle groups at different frequencies induced both a kinesthetic illusion and a motor response in the muscle vibrated at the lowest frequency. The surface EMG amplitude of the extensor carpi radialis as well as the motor unit activation latency and discharge frequency were clearly correlated to the parameters of the illusory movement evoked by the vibration. Indeed, the faster the illusory sensation of movement, the greater the surface EMG in these muscles during the AVRs and the sooner and the more intense the activation of the motor units of the wrist extensor muscles. Moreover, comparison of the AVR with voluntary contraction showed that all parameters were highly similar. Mainly slow motor units were recruited during the AVR and during its voluntary reproduction. That the AVR is observed only when a kinesthetic illusion is evoked, together with the similarities between voluntary contractions and AVRs, suggests that this vibration-induced motor response may result from a perceptual-to-motor transformation of proprioceptive information, rather than from spinal reflex mechanisms.
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  • 112
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    Experimental brain research 124 (1999), S. 351-362 
    ISSN: 1432-1106
    Keywords: Key words Saccadic adaptation ; Gaze ; Short term adaptation ; Transfer to hand movements ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We investigated whether and how adaptive changes in saccadic amplitudes (short-term saccadic adaptation) modify hand movements when subjects are involved in a pointing task to visual targets without vision of the hand. An experiment consisted of the pre-adaptation test of hand pointing (placing the finger tip on a LED position), a period of adaptation, and a post-adaptation test of hand pointing. In a basic task (transfer paradigm A), the pre- and post-adaptation trials were performed without accompanying eye and head movements: in the double-step gaze adaptation task, subjects had to fixate a single, suddenly displaced visual target by moving eyes and head in a natural way. Two experimental sessions were run with the visual target jumping during the saccades, either backwards (from 30 to 20°, gaze saccade shortening) or onwards (30 to 40°, gaze saccade lengthening). Following gaze-shortening adaptation (level of adaptation 79±10%, mean and s.d.), we found a statistically significant shift (t-test, error level P〈0.05) in the final hand-movement points, possibly due to adaptation transfer, representing 15.2% of the respective gaze adaptation. After gaze-lengthening adaptation (level of adaptation 92±17%), a non-significant shift occurred in the opposite direction to that expected from adaptation transfer. The applied computations were also performed on some data of an earlier transfer paradigm (B, three target displacements at a time) with gain shortening. They revealed a significant transfer relative to the amount of adaptation of 18.5±17.5% (P〈0.05). In the coupling paradigm (C), we studied the influence of gaze saccade adaptation of hand-pointing movements with concomitant orienting gaze shifts. The adaptation levels achieved were 59±20% (shortening) and 61±27% (lengthening). Shifts in the final fingertip positions were congruent with internal coupling between gaze and hand, representing 53% of the respective gaze-amplitude changes in the shortening session and 6% in the lengthening session. With an adaptation transfer of less than 20% (paradigm A and B), we concluded that saccadic adaptation does not ”automatically” produce a functionally meaningful change in the skeleto-motor system controlling hand-pointing movements. In tasks with concomitant gaze saccades (coupling paradigm C), the modification of hand pointing by the adapted gaze comes out more clearly, but only in the shortening session.
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  • 113
    ISSN: 1432-1106
    Keywords: Key words Transcranial magnetic stimulation ; Silent period ; Voluntary motor drive ; Motor threshold ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To evaluate changes in the motor system during the silent period (SP) induced by transcranial magnetic stimulation (TMS) of the motor cortex, we investigated motor thresholds as parameters of the excitability of the cortico-muscular pathway after a suprathreshold conditioning stimulus in the abductor digiti minimi muscle (ADM) of normal humans. Since the unconditioned motor threshold was lower during voluntary tonic contraction than at rest (31.9±5.4% vs. 45.6±7.5%), it is suggested that the difference between active and resting motor threshold indicates the magnitude of the voluntary drive on the cortico-muscular pathway. Therefore, we compared conditioned resting and active motor threshold (cRMT and cAMT) during the SP. cRMT showed an intensity-dependent period of elevation of more than 200 ms in duration and approximately 17% of the maximum stimulator output above the unconditioned threshold, due to decreased excitability of the cortico-muscular pathway after the conditioning stimulus. Some 30–40 ms after the conditioning stimulus, cAMT approximated cRMT, indicating complete suppression of the voluntary motor drive. This suppression did not start directly after the conditioning stimulus since cAMT was still significantly lower than the cRMT within the first 30–40 ms. Threshold elevation was significantly longer than the SP (220±41 vs. 151±28 ms). Recovery of the voluntary motor drive started late in the SP and was nearly complete at the end of the SP, although thresholds were still significantly elevated. We conclude that the SP is largely due to a suppression of voluntary motor drive, while the threshold elevation is a different inhibitory phenomenon that is of less importance for the generation of the SP, at least in its late part. It is argued that the pathway of fast cortico-spinal fibers activated by TMS is partially different from the pathway involved in the maintenance of tonic voluntary muscle activation.
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  • 114
    ISSN: 1432-1106
    Keywords: Key words Motor control ; Multijoint movement ; Movement synergy ; Stroke ; Laterality ; Redundancy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous studies have shown that in neurologically normal subjects the addition of trunk motion during a reaching task does not affect the trajectory of the arm endpoint. Typically, the trunk begins to move before the onset and continues to move after the offset of the arm endpoint displacement. This observation shows that the potential contribution of the trunk to the motion of the arm endpoint toward a target is neutralized by appropriate compensatory movements of the shoulder and elbow. We tested the hypothesis that cortical and subcortical brain lesions may disrupt the timing of trunk and arm endpoint motion in hemiparetic subjects. Eight hemiparetic and six age-matched healthy subjects were seated on a stool with the right (dominant) arm in front of them on a table. The tip of the index finger (the arm endpoint) was initially at a distance of 20 cm from the midline of the chest. Wrist, elbow, and upper body positions as well as the coordinates of the arm endpoint were recorded with a three-dimensional motion analysis system (Optotrak) by infrared light-emitting diodes placed on the tip of the finger, the styloid process of the ulna, the lateral epicondyle of the humerus, the acromion processes bilaterally, and the sternal notch. In response to a preparatory signal, subjects lifted their arm 1–2 cm above the table and in response to a ”go” signal moved their endpoint as fast as possible from a near to a far target located at a distance of 35 cm and at a 45° angle to the right or left of the sagittal midline of the trunk. After a pause (200– 500 ms) they moved the endpoint back to the near target. Pointing movements were made without trunk motion (control trials) or with a sagittal motion of the trunk produced by means of a hip flexion or extension (test trials). In one set of test trials, subjects were required to move the trunk forward while moving the arm to the target (”in-phase movements”). In the other set, subjects were required to move the trunk backward when the arm moved to the far target (”out-of-phase movements”). Compared with healthy subjects, movements in hemiparetic subjects were segmented, slower, and characterized by a greater variability and by deflection of the trajectory from a straight line. In addition, there was a moderate increase in the errors in movement direction and extent. These deficits were similar in magnitude whether or not the trunk was involved. Although hemiparetic subjects were able to compensate the influence of the trunk motion on the movement of the arm endpoint, they accomplished this by making more segmented movements than healthy subjects. In addition, they were unable to stabilize the sequence of trunk and arm endpoint movements in a set of trials. It is concluded that recruitment and sequencing of different degrees of freedom may be impaired in this population of patients. This inability may partly be responsible for other deficits observed in hemiparetic subjects, including an increase in movement segmentation and duration. The lack of stereotypic movement sequencing may imply that these subjects had deficits in learning associated with short-term memory.
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  • 115
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    Experimental brain research 126 (1999), S. 134-138 
    ISSN: 1432-1106
    Keywords: Key words Upper limb ; Posture ; Geometric constraints ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Significant debate exists regarding the neural strategies underlying the positioning and orienting of the hand during voluntary reaching movements of the human upper extremity. Some authors have suggested that positioning and orienting are controlled independently, while others have argued that a strong interdependence exists. In an effort to address this uncertainty, our study employed computer simulations to examine the impact of physiological limitations of joint rotation on the proposed independence of hand position and orientation. Specifically, we analyzed the effects of geometric constraints on final arm postures using a 7 degree-of-freedom model of the human arm. For 20 different hand configurations within the attainable workspace, we computed sets of achievable joint angles by applying inverse kinematics. From each set, we then calculated the locus of possible elbow positions for the particular final hand posture. When the joints were allowed 360° of rotation, the loci formed complete circles; however, when joint ranges were limited to physiological values, the extent of the loci decreased to an average arc angle of 54.6° (±27.9°). Imposition of joint limits also led to practically linear relationships between joint angles within a solution set. These theoretical results suggest a requirement for coordinated interaction between control of the joints associated with hand position and those involved with hand orientation in order to ensure attainable joint trajectories. Furthermore, it is conceivable that some of the correlations observed between joint angles in the course of natural reaching movements result from geometric constraints.
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  • 116
    ISSN: 1432-1106
    Keywords: Key words Paired-pulse transcranial magnetic stimulation ; Threshold hunting ; Intracortical inhibition ; Intracortical I-wave facilitation ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Short-interval, paired-pulse transcranial magnetic stimulation (TMS) is usually used to demonstrate intracortical inhibition. It was shown recently that with short-interval, paired-pulse TMS a facilitation – called intracortical I-wave facilitation – can also be demonstrated. It was the aim of this study to investigate which stimulus conditions lead to intracortical inhibition and what conditions yield an intracortical I-wave facilitation in a hand muscle of normal subjects. Paired-pulse TMS responses with an interstimulus interval of 1.2 ms were obtained from the abductor digiti minimi muscle of four normal subjects. A threshold-hunting paradigm with hunting through first or second stimulus variation was used to obtain a curve of threshold-pair strengths. All subjects showed two branches of stimulus interaction on this diagram. If the first stimulus of a threshold pair was below approximately 65% of resting motor threshold it modified the response primarily due to the second stimulus through intracortical inhibition. However, if the first stimulus of a threshold pair exceeded approximately 65% of resting motor threshold it became responsible for the spinal action-potential initiation. The subsequent second stimulus served as a ”booster” for the ongoing intracortical I-wave activity, making it impossible to observe the intracortical inhibition evoked by the first stimulus.
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  • 117
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    Experimental brain research 127 (1999), S. 355-370 
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Motion ; Functional imaging ; Human ; Flicker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Functional magnetic resonance imaging was used to map motion responsive regions of the human brain by contrasting passive viewing of moving and stationary randomly textured patterns. Regions were retained as motion responsive if they reached significance either in the group analysis or in the majority of hemispheres in single-subject analysis. They include well-known regions, such as V1, hMT/V5+, and hV3A, but also several occipito-temporal, occipito-parietal, parietal, and frontal regions. The time course of the activation was similar in most of these regions. Motion responses were nearly identical for binocular and monocular presentations. Flicker-induced-activation introduced a dichotomy amongst these motion responsive regions. Early occipital and occipito-temporal regions responded well to flicker, while flicker responses gradually vanished as one moved to occipito-parietal and then parietal regions. Finally, over a more than four-fold range, stimulus diameter had little effect on the motion activations, except in V1.
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  • 118
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    Experimental brain research 128 (1999), S. 200-204 
    ISSN: 1432-1106
    Keywords: Key words Eye-hand coordination ; Human ; Saccade ; Vision ; Bimanual coordination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two different drawer tasks were investigated with the aim of assessing the role of eye movements in well-coordinated hand movements. In an unimanual step-tracking task, which had a predictive and an unpredictive movement, a two-way repeated-measures ANOVA showed a significant effect of prediction on the onset of grip-force (GF) rate (300±39 ms for the predictive condition versus 394±53 ms for the non-predictive condition, P〈0.0001). Correlation coefficients, computed from the eye and the hand movements were low for the right and the left hand. The saccade was more coupled with the visual step change than with the action of the hand per se. In a second bimanual pull-and-pick task, the instruction was to pull a drawer with the left hand from a closed position to a LED-cued open position and then to grasp and reinsert a small peg in the drawer with the right hand. Correlation coefficients, computed from the latencies of saccades and of the leading left hand or of the right hand, were significant in four of five subjects. Intermanual correlations were significant in all five subjects. In conclusion, we found that the initial saccade in the unimanual task was best related with the visual step change, but was poorly correlated with the pulling/pushing hand. In the bimanual task, a moderate, but significant temporal coupling between the eyes and hand events was observed. This coupling was, however, less tight than that between both hands.
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  • 119
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    Experimental brain research 129 (1999), S. 241-246 
    ISSN: 1432-1106
    Keywords: Key words Selective attention ; Visual attention ; Putamen ; Orienting ; Positron emission tomography ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We used positron emission tomography (PET) in ten subjects to study the brain regions involved in voluntary shifts of attention. For six scans, subjects performed a visual target detection task in which the location of the target was indicated in advance on some proportion of trials by the appearance of an arrow cue at fixation. The informative cues were successful in speeding reaction time to the target. Blood flow in the left putamen was correlated with the proportion of informative cues provided within a scan. We discuss this finding in terms of three possible interpretations: attentional shifts, response inhibition, and motor preparation related to the use of the right hand to respond. Blood flow in cortical regions commonly associated with attention was not related to cue ratio, a finding that may reflect automatization of the processes involved in interpreting and using the cues.
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  • 120
    ISSN: 1432-1106
    Keywords: Key words Frontal eye field ; Saccade ; Efference copy ; Spatial short-term memory ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Physiological studies in monkeys have shown that the frontal eye field (FEF) is involved in the preparation and triggering of purposive saccades. However, several questions of FEF function remain unclear: the role of the FEF in visual short-term memory, its ability to update its spatial map and its role in reflexive saccade inhibition. We have addressed these issues in a patient with a small acute ischemic lesion whose location corresponded very accurately to the region of the left FEF according to the most recent cerebral blood flow studies. An initial study was conducted on days 7 and 8 after the stroke, i.e., before substantial recovery. A first group of paradigms (smooth pursuit, simple saccade tasks) was performed to assess FEF dysfunction. In a second group of paradigms, (1) visual short-term memory was tested by means of memory-guided saccade paradigms with short and long delays (1 and 7 s), (2) spatial updating abilities were tested by a double-step saccade task and two memory-guided saccade tasks in which the central fixation point was displaced during the memorization delay, and (3) reflexive saccade inhibition was tested by the antisaccade task. Results show that the FEF is involved in short-term memorization of the parameters of the forthcoming memory-guided saccade encoded in oculocentric coordinates. Normal results in the antisaccade task suggest that the FEF is not involved in reflexive saccade inhibition.
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  • 121
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    Experimental brain research 129 (1999), S. 378-390 
    ISSN: 1432-1106
    Keywords: Key words Manual tracking ; Microgravity ; Visuomotor transformation ; Adaptation ; Human ; Spaceflight
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A series of step-tracking experiments was conducted before, during, and after a 3-week space mission to assess the effects of prolonged microgravity on a non-postural motor-control task. In- and post-flight accuracy was affected only marginally. However, kinematic analyses revealed a considerable change in the underlying movement dynamics: too-small force and, thus, too-low velocity in the first part of the movements was mainly compensated by lengthening the deceleration phase of the primary movement, so that accuracy was regained at its end. The observed in-flight decrements in peak velocity and peak acceleration point to an underestimation of mass, in agreement with the re-interpretation hypothesis of Bock et. al. Post-flight no reversals of the in-flight changes (negative aftereffects) were found. Instead, there was a general slowing down, which could be due to post-flight physical exhaustion.
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  • 122
    ISSN: 1432-1106
    Keywords: Key words Elbow movement ; Motor learning ; Reaction time ; Kinematics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Learning of a motor task, such as making accurate goal-directed movements, is associated with a number of changes in limb kinematics and in the EMG activity that produces the movement. Some of these changes include increases in movement velocity, improvements in end-point accuracy, and the development of a biphasic/triphasic EMG pattern for fast movements. One question that has remained unanswered is whether the time course of the learning-related changes in movement parameters is similar for all parameters. The present paper focuses on this question and presents evidence that different parameters evolve with a specific temporal order. Neurologically normal subjects were trained to make horizontal, planar movements of the elbow that were both fast and accurate. The performance of the subjects was monitored over the course of 400 movements made during experiments lasting approximately 1.5 h. We measured time-related parameters (duration of acceleration, duration of deceleration, and movement duration) and amplitude-related parameters (peak acceleration, peak deceleration, peak velocity), as well as movement distance. In addition, each subject’s reaction time and EMG activity was monitored. We found that reaction time was the parameter that changed the fastest and that reached a steady baseline earliest. Time-related parameters decreased at a somewhat slower rate and plateaued next. Amplitude-related parameters were slowest in reaching steady-state values. In subjects making the fastest movements, a triphasic EMG patterns was observed to develop. Our findings reveal that movement parameters change with different time courses during the process of motor learning. The results are discussed in terms of the neural substrates that may be responsible for the differences in this aspect of motor learning and skill acquisition.
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  • 123
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    Experimental brain research 125 (1999), S. 50-60 
    ISSN: 1432-1106
    Keywords: Key words Pointing errors ; Remembered target Navigation ; Active self-movements ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied pointing movements to remembered visual targets in a completely darkened room with and without self-made step movements in order to investigate in which coordinate system and to what extent target representations relative to the body are updated for self-induced egomotion. A small red-light-emitting diode on the fingertip provided visual feedback about fingertip position at all times. We asked subjects to make pointing movements that started 2 s after disappearance of a visual target. In this interval of 2 s the subject did or did not make a step. The pointing errors without a step showed that subjects undershot faraway targets in a systematic way, whereas they sometimes overshot nearby targets. We found that the step causes larger pointing errors both in amplitude and direction with a bias in the direction of the step. We explored three different versions of a descriptive model in which polar coordinates were used to describe the pointing movement, and in which either Cartesian or polar coordinates were used to update target position relative to the shoulder for the step. The results suggest that incorporation of the step displacement in the new target position relative to the subject is done in a Cartesian frame of reference. Moreover, the amplitude of the step displacement tends to be underestimated by subjects.
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  • 124
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    Experimental brain research 125 (1999), S. 109-114 
    ISSN: 1432-1106
    Keywords: Key words Motor control ; Visual pathways ; Illusions ; Prehension ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Visual size illusions have been shown to affect perceived object size but not the aperture of the hand when reaching to those same objects. Thus, vision for perception is said to be dissociated from vision for action. The present study examines the effect of visual-position and visual-shape illusions on both the visually perceived center of an object and the position of a grasp on that object when a balanced lift is required. The results for both experiments show that although the illusions influence both the perceived and the grasped estimates of the center position, the grasp position is more veridical. This partial dissociation is discussed in terms of its implications for streams of visual processing.
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  • 125
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    Experimental brain research 125 (1999), S. 302-312 
    ISSN: 1432-1106
    Keywords: Key words Overarm throwing ; Finger opening ; Proprioceptive feedback ; Perturbations ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Accuracy in an overarm throw requires great precision in the timing of finger opening. We tested the hypothesis that finger opening in an overarm throw is triggered by proprioceptive feedback from elbow extension or wrist flexion. The hypothesis was tested in two ways: first, by unexpectedly perturbing elbow extension or slowing wrist flexion and determining whether changes occurred in finger opening, and second, by measuring the latency from the start of these joint rotations to the start of finger opening. Subjects threw balls fast and accurately from a sitting or standing position while joint rotations were recorded with the search-coil technique. Elbow extension was unexpectedly blocked near the start of forward motion of the hand by a rope attached to the wrist that passed through a catch mechanism located behind the subject. In spite of a slowing or complete block of elbow extension, and in some cases a replacement of elbow extension by elbow flexion, finger opening always occurred and at the same latency as for normal throws. Wrist flexion was slowed in seven of eight subjects when subjects changed from throwing with a light ball (14 g, 70 mm diam.) to a heavy ball (210 g, 65 mm diam.). For the first throw with the heavy ball, this slowing was neither fully anticipated by the subject nor compensated for by the changed proprioceptive feedback associated with the slowing. Consequently, the timing of finger opening was unchanged and (to the surprise of the thrower) the ball went high. Furthermore, in unperturbed throws with tennis balls, the latency from onset of wrist flexion or elbow extension to onset of finger opening was too short for either to have triggered finger opening (across subjects means were 4 ms for wrist flexion and 21 ms for elbow extension). In additional analysis, no relation was found between the time of onset of earlier occurring rotations at the shoulder and the time of onset of finger opening. We concluded that, although a role for all proprioceptive feedback in triggering finger opening cannot be disproved by these experiments, it can be ruled out for feedback arising from elbow extension and wrist flexion, and it seems unlikely for feedback arising from events occurring very early in the throw. The more likely possibility is that finger opening in an overarm throw is triggered by a central command based on an internal model of hand trajectory.
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  • 126
    ISSN: 1432-1106
    Keywords: Key words Corticospinal tract ; Handedness ; Spinal premotoneurones ; Voluntary movement ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The possibility was investigated that human handedness is associated with an asymmetrical cortical and/or peripheral control of the cervical premotoneurones (PreMNs) that have been shown to mediate part of the descending command to motoneurones of forearm muscles . Heteronymous facilitation evoked in the ongoing voluntary extensor carpi radialis (ECR) electromyographic activity (EMG) by weak (0.8 times motor threshold) stimulation of the musculo-cutaneous (MC) nerve was assessed during tonic co-contraction of biceps and ECR. Suppression evoked by stimulation of a cutaneous nerve (superficial radial, SR) at 4 times perception threshold in both the voluntary EMG and in the motor evoked potential (MEP) elicited in ECR by transcranial magnetic stimulation (TMS) was investigated during isolated ECR contraction. Measurements were performed within time windows or at interstimulus intervals where peripheral and cortical inputs may interact at the level of PreMNs. Results obtained on both sides were compared in consistent right- and left-handers. MC-induced facilitation of the voluntary ECR EMG was significantly larger on the preferred side, whereas there was no asymmetry in the SR-evoked depression of the ongoing ECR EMG. In addition, the suppression of the ECR MEP by the same SR stimulation was more pronounced on the dominant side during unilateral, but not during bilateral, ECR contraction. It is argued that (1) asymmetry in MC-induced facilitation of the voluntary EMG reflects a greater efficiency of the peripheral heteronymous volley in facilitating PreMNs on the dominant side; (2) asymmetry in SR-induced suppression of the MEP during unilateral ECR contraction, which is not paralleled by a similar asymmetry of voluntary EMG suppression, reflects a higher excitability of cortical neurones controlling inhibitory spinal pathways to cervical PreMNs on the preferred side.
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  • 127
    ISSN: 1432-0851
    Keywords: Key words In vitro immunisation ; MUC1 ; Human ; antibodies ; Phage display ; Carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have recently described an efficient method to study the human humoral immune response in vitro and to generate isotype-switched, antigen-specific human B cells, which has allowed us to produce high-affinity IgG antibodies against different peptides. In an attempt to study the in vitro immune response against self-antigens, such as tumour-associated antigens, this protocol was used to immunise resting human peripheral blood B cells with a peptide epitope from the human-adenocarcinoma-associated antigen, MUC1. After the two-step in vitro immunisation, the secondary immunised cultures were tested for MUC-1-specific antibodies by enzyme-linked immunosorbent assay (ELISA). Phage molecular libraries were subsequently constructed, using the variable parts of Ig genes derived from cells taken from ELISA-positive wells. The libraries were selected on the MUC1 core peptide. Antigen-specific Fab fragments, specific for the self antigen MUC1, were found in the library of secondary immunised IgG+ B cells and these antibodies were evaluated by BIAcore analysis. The specific Fab fragments exhibited an unusually rapid dissociation rate constant and the overall response frequency was lower, as compared to other antibodies generated by this protocol, which might be explained by the repetitive nature of the core peptide used for immunisation.
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  • 128
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    Archives of toxicology 73 (1999), S. 7-14 
    ISSN: 1432-0738
    Keywords: Key words Organophosphates ; Acetylcholinesterase ; Oximes ; Human ; Reactivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human poisoning by organophosphates bearing two methoxy groups, e.g. by malathion, paraoxon-methyl, dimethoate and oxydemeton-methyl, is generally considered to be rather resistant to oxime therapy. Since the oxime effectiveness is influenced not only by its reactivating potential but also by inhibition, aging and spontaneous reactivation kinetics, experiments were performed with human acetyl- (AChE) and butyrylcholinesterase (BChE) to determine the respective kinetic constants. The efficacy of obidoxime in reactivating dimethylphosphoryl-AChE was 40, 9 and 3 times higher than of HI 6, pralidoxime and HLö 7, respectively. Aging (t 1/2 3.7 h) and spontaneous reactivation (t 1/2 0.7 h) occurred concomitantly, with the portion of the aged enzyme being dependent on the presence of excess inhibitor. Calculation of steady-state AChE activity in the presence of inhibitor and oxime revealed that obidoxime was superior to pralidoxime. In addition, organophosphate concentrations up to 10−6 M (paraoxon-methyl) and 10−4 M (oxydemeton-methyl) could be counteracted at clinically relevant oxime concentrations (10 μM). These data indicate that oximes may effectively reactivate human dimethylphosphoryl-AChE. Failure of oximes may be attributed to megadose intoxications and to prolonged time intervals between poison uptake and oxime administration. The potency of the oximes to reactivate dimethylphosphoryl-BChE was much lower and the spontaneous reactivation slower (t 1/2 9 h), while aging proceeded at a comparable rate. Thus, BChE activity determination for diagnosis and therapeutic monitoring may give no reliable information on AChE status.
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  • 129
    ISSN: 1432-2072
    Keywords: Key words Cannabinoids ; THC ; Dronabinol ; Binocular depth inversion ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Binocular depth inversion represents an illusion of visual perception that is sensitive to various behavioural and psychiatric conditions. It is affected by cannabinoids, reflecting associated changes in perception. The present study investigated the differences in binocular depth inversion of different classes of natural and artificial objects and the effect of synthetic Δ9-tetrahydrocannabinol (Dronabinol) on these illusionary perceptions. Using this model, the effects of orally administered Dronabinol on binocular depth inversion were investigated in 17 healthy male volunteers. Pictures from natural and artificial objects were presented stereoscopically and the depth perception of the volunteers was scored in an operationalized way. The time-course of the effects of Dronabinol on binocular depth inversion was analyzed with regard to the stimulus classes (natural and synthetic objects). Significant differences in binocular depth inversion of the different groups of stimuli were revealed. Objects with a higher degree of everyday familiarity were generally seen as more illusionary than those with a lower degree of everyday familiarity. A strong impairment of binocular depth inversion due to Dronabinol was found in most classes of objects. Analysis of different stimulus classes provides further information on the underlying perceptual processing of binocular depth inversion. An impairment of top-down processing of visual sensory data by Dronabinol is suggested. The anandamidergic system seems to be involved in areas of visual information processing.
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  • 130
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    Psychopharmacology 143 (1999), S. 339-346 
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Smoking ; Naltrexone ; Opiates ; Mechanism ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: The role of endogenous opiate systems in cigarette smoking remains unclear. In laboratory animals, opiate antagonists block many of the effects of nicotine, but in humans they do not consistently alter smoking behavior. Objective: This study explored the effects of naltrexone, alone and in combination with nicotine, on smoking behavior. Methods: In a double-blind, double-dummy, within-subjects design, 19 regular smokers received four treatments of 1 week duration: naltrexone tablet (50 mg) plus placebo skin patch, placebo tablet plus nicotine skin patch (21 mg/24 h), naltrexone tablet plus nicotine skin patch, and placebo tablet plus placebo skin patch. During each treatment, subjects rated their responses to nicotine-containing and denicotinized cigarettes in the laboratory, and to their own brand of cigarette smoked ad libitum outside the laboratory. Results: Pretreatment with the nicotine patch attenuated smoking-induced decreases in craving, negative affect, and rates of ad lib smoking, and potentiated the aversiveness of a cigarette. Naltrexone reversed these effects of the nicotine patch, and produced negative effects on mood. Conclusions: The blockade of nicotine’s effects by naltrexone supports a role for opioid mechanisms in cigarette smoking.
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  • 131
    ISSN: 1432-2072
    Keywords: Key words Alternative reinforcers ; Heroin ; Human ; Intranasal ; Intravenous ; Opioids ; Performance ; Progressive ratio ; Reinforcing effect ; Self-administration ; Subjective effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Eight heroin-dependent individuals, maintained on divided daily doses of oral morphine, participated in a 2.5-week inpatient study comparing the effects of intranasal (IN) (placebo, 12.5, 25, 50, 100 mg) and intravenous (IV) (placebo, 6.25, 12.5, 25, 50 mg) heroin. Each morning, participants received $20 and a sample dose of heroin, and each afternoon they had the opportunity to self-administer all or part of the morning heroin dose or money amount. Participants responded under a modified progressive-ratio schedule (PR 50, 100, 200, 400, 800, 1200, 1600, 2000, 2400, 2800) during a ten-trial self-administration task. During each trial, participants could respond for 1/10th of the heroin dose or 1/10th of the money amount. The total amount of heroin and/or money chosen during the self-administration task was given at the end of the task. Thus, participants received drug and/or money twice each day: once during the morning sample session and once during the afternoon self-administration session. Participants received IV solution and IN powder simultaneously during each dosing; only one route contained active drug. Heroin produced dose-related increases in break point values by both routes of administration. Although IV heroin was approximately four-fold more potent than IN heroin, the maximal break point values for both routes were not significantly different. A similar difference in potency between the IV and IN routes was found for several ratings of subjective effects (e.g., “I feel a good drug effect,”“I feel high”), but maximal subjective ratings were lower for IN compared to IV heroin. These results suggest that the reinforcing efficacy of heroin is similar by the two routes of administration, but that IN heroin is less potent than IV heroin. The results also underscore the importance of evaluating drug self-administration in the evaluation of the abuse liability of drugs.
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  • 132
    ISSN: 1432-2072
    Keywords: Key words MDMA (3 ; 4-methylenedioxymethamphetamine) ; Serotonin ; Psychopathology ; Human ; Rat ; Prepulse inhibition ; Habituation ; Schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: Prepulse inhibition of acoustic startle refers to the reduction in the startle response when the startling stimulus is preceded by a weak prepulse stimulus. This phenomenon provides an operational measure of sensorimotor gating that has been found to be reduced in patients with schizophrenia and rats treated with serotonin agonists or serotonin releasers. Objective: In this study, we compared the effects of a serotonin releaser, MDMA, on prepulse inhibition in laboratory rats and healthy human volunteers. In particular, we investigated whether MDMA disrupts PPI in humans as observed in animal studies. Methods: Rats were tested after placebo and MDMA in a counterbalanced order at an interval of 1 week, with separate groups of rats being used for each dose of MDMA (1.7, 5.4 and 17.0 mg/kg). On each test day, rats were first tested after no injections and retested 2 h later, 10 min after a subcutaneous injection of placebo or MDMA. For the human study, a placebo-controlled within-subject design and double-blind procedures were used. Subjects were examined twice at a 2 to 4 week interval after either placebo or drug administration (order being counterbalanced). On each test day, subjects underwent baseline testing including psychological and PPI measures. Ninety minutes later, subjects received placebo or MDMA (1.7 mg/kg PO) and were retested after 75 min during the peak of behavioral effects of MDMA. Results: As expected, MDMA decreased prepulse inhibition in a dose-related fashion in rats. In contrast, a typical recreational dose of MDMA (1.7 mg/kg, orally) increased prepulse inhibition in subjects experiencing robust psychological effects. Conclusions: This surprising disparity between the effects of the drug in rats and humans may reflect a species-specific difference in the mechanism of action of MDMA or in the behavioral expression of a similar pharmacological effect, or both.
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  • 133
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    Knee surgery, sports traumatology, arthroscopy 7 (1999), S. 177-183 
    ISSN: 1433-7347
    Keywords: Key words Knee joint ; Human ; Anterior knee pain ; Innervation ; Substance-P fibers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Sports Science
    Notes: Abstract The etiology of pain in anterior knee pain syndrome is a matter of controversy. The normal, articular cartilage is aneural, so defects in the surface are not thought to produce pain. Some authors have sought the origin of the pain in soft tissue structures around the knee. Knowledge of the distribution of nociceptive nerve fibers around the knee would provide insight for treating anterior knee pain syndrome. Twenty consecutive patients (28 knees), all women, with anterior knee pain syndrome (group I) participated in the study. For comparison we used two groups of patients: 20 patients with an osteoarthritic knee (group II) and 20 patients with anterior cruciate ligament rupture or meniscal lesion with no history of pain in the anterior compartment (group III). Immunohistochemical techniques using a monoclonal antibody to substance-P (SP) were employed to identify nociceptive fibers. For statistical analyses we used the one-way ANOVA test, which was corrected with the LSD test, at the level of significance P 〈 0.05. Results of the study demonstrate that SP-immunoreactive nerve fibers are widespread within the soft tissues around the knee. These tissues include the retinaculum, synovium, fat pad and, in some circumstances, bone. In cases of anterior knee pain, the presence of neuropeptide-containing fibers was statistically significant in the medial retinaculum (P 〈 0.005) and in the fat pad (P 〈 0.001) compared to group III, and compared to group II (P 〈 0.05 and P 〈 0.007, respectively). For lateral retinaculum this relationship was not so statistically strong (P 〈 0.02) and was equal in comparison between anterior knee pain patients (group I) and group II or group III. There were no statistically significant differences in the distribution of substance-P nerve fibers in the fat pad, lateral and medial retinaculum or synovium between groups II and III. The results of this study provide immunohistochemical evidence suggesting that pain may originate in the fat pad and medial retinaculum of many patients with anterior knee pain syndrome.
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  • 134
    ISSN: 1573-4943
    Keywords: Human ; aldehyde dehydrogenase ; 4-trans-(N,N-dimethylamino)cinnamaldehyde ; binding ; incorporation ; stoichiometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract 4-trans-(N,N-Dimethylamino)cinnamaldehyde (DACA) is a chromophoric substrate of aldehyde dehydrogenase (EC 1.2.1.3) whose fate can be followed during catalysis. During this investigation we found that DACA also fluoresces and that this fluorescence is enhanced and blue-shifted upon binding to aldehyde dehydrogenase. Binding of DACA to aldehyde dehydrogenase also occurs in the absence of coenzyme. Benzaldehyde (a substrate), acetophenone (a substrate-competitive inhibitor), and the substrate-competitive affinity reagent bromoaceto-phenone interfere with DACA binding. Thus, DACA binds to the active site and can be employed for titration of active aldehyde dehydrogenase. Both E1 and E2 isozymes, which are homotetramers, bind DACA with dissociation constants of 1–4 μM with a stoichiometry of 2 mol DACA/mol enzyme. The stoichiometry of enzyme–acyl intermediate was also found to be 2 mol DACA/mol enzyme for both E1 and E2 isozymes. Thus, both enzymes appear to have only two substrate-binding sites which participate in catalysis. The level of enzyme–acyl intermediate remained constant at different pH values, showing that enhancement of velocity with pH was not due to altered DACA–enzyme levels. When the reaction velocity was increased even further by using 150 μM Mg2+ the intermediate level was decreased, suggesting that both increased pH and Mg2+ promote decomposition of the DACA–enzyme intermediate. Titration with DACA permits study of aldehyde substrate catalysis before central complex interconversion.
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  • 135
    ISSN: 1432-2072
    Keywords: Key words Buprenorphine ; Naloxone ; Dose ratio ; Opiate dependence ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sublingual buprenorphine is a promising new treatment for opiate dependence, but its opioid agonist effects pose a risk for parenteral abuse. A formulation combining buprenorphine with the opiate antagonist naloxone could discourage such abuse. The effects of three intravenous (IV) buprenorphine and naloxone combinations on agonist effects and withdrawal signs and symptoms were examined in 12 opiate-dependent subjects. Following stabilization on a daily dose of 60 mg morphine intramuscularly, subjects were challenged with IV doses of buprenorphine alone (2 mg) or in combination with naloxone in ratios of 2:1, 4:1, and 8:1 (1, 0.5, or 0.25 mg naloxone), morphine alone (15 mg) or placebo. Buprenorphine alone did not precipitate withdrawal and had agonist effects similar to morphine. A naloxone dose-dependent increase in opiate withdrawal signs and symptoms and a decrease in opioid agonist effects occurred after all drug combinations. Buprenorphine with naloxone in ratios of 2:1 and 4:1 produced moderate to high increases in global opiate withdrawal, bad drug effect, and sickness. These dose ratios also decreased the pleasurable effects and estimated street value of buprenorphine, thereby suggesting a low abuse liability. The dose ratio of 8:1 produced only mild withdrawal symptoms. Dose combinations at 2:1 and 4:1 ratios may be useful in treating opiate dependence.
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  • 136
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Craving ; Cytidine ; CDP-choline ; Human ; Medication ; Drug dependent ; Citicoline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The administration of cytidine-5′-diphosphate choline (CDP-choline, citicoline) to animals increases the rate of membrane phospholipid synthesis and elevates brain dopamine levels. Because cocaine dependence has been associated with increases in brain phospholipid precursors, as well as depletion of dopamine within the central nervous system, the present outpatient study was conducted to assess the safety of citicoline (500 mg bid) and to determine if short-term treatment alters mood states and cocaine craving in subjects with a history of cocaine dependence. In addition, measures of drug craving and mood states after presentation of cocaine-related cues were collected on two occasions: before and after 14 days of double-blind treatment with either citicoline or placebo. Subjects did not experience any side effects and citicoline treatment was associated with decreases in self-reported mood states associated with cocaine craving. These preliminary data are encouraging and suggest that citicoline warrants further study as a promising potential treatment for cocaine abuse and dependence that is devoid of side effects.
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  • 137
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    Psychopharmacology 142 (1999), S. 149-157 
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Craving ; Smoking ; Rapid smoking ; Cigarette ; Self-report ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Craving is thought to play an important role in maintaining regular smoking patterns in current smokers, and in leading to relapse in smokers attempting to quit. Within the scientific community however, the concept is surrounded by controversy. In an effort to 1) identify interventions that can reliably influence cigarette cravings, and 2) assess the relationship between cigarette craving and smoking behavior, effects of aversive rapid smoking (up to nine cigarettes with puffs taken every 6 s) on self-reported craving and subsequent smoking behavior were compared to effects of self-paced smoking or no smoking. Subjects (n = 14) engaged in a rapid, self-paced or no smoking procedure at the start of three separate sessions. Craving levels, measured repeatedly during the next 3 h of no smoking, were significantly lower after rapid smoking than after either self-paced or no smoking. Measures of subsequent smoking behavior (latency to first cigarette, number of cigarettes, number of puffs) did not differ systematically across conditions. Thus, craving was reliably suppressed by aversive rapid smoking, but craving scores did not predict actual smoking behavior.
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  • 138
    ISSN: 1432-2072
    Keywords: Key words Acoustic startle response ; Alprazolam ; Placebo ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study, we assessed the effects of the potent benzodiazepine alprazolam on the human acoustic startle response in healthy volunteers. Eight undergraduate students received single oral doses of placebo and alprazolam 2 mg on 2 separate days, according to a double-blind balanced crossover design. Electromyographic activity of the orbicularis oculi muscle was recorded 5, 7 and 11 h after drug administration. At each recording time, subjects received 21 acoustic stimuli (1 KHz, 116 dB, 50 ms duration) separated by variable intervals (8–30 s, mean 16.5 s). Consistent with previous results obtained for diazepam in humans, alprazolam significantly reduced the amplitude of the startle reflex. A patent increase in onset latency was also observed, this being a novel effect not previously described for benzodiazepines in human studies. Both effects were maximum at 5 h after dosing, the startle response experiencing a recovery as the drug disappeared from systemic circulation. These results indicate a potent inhibitory effect of alprazolam on baseline startle at the dose used, with a robust time-dependent recovery of initial values effectively counteracting between-session habituation.
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  • 139
    ISSN: 1432-0878
    Keywords: Key words Apoptosis ; p53 ; Ischemia ; Enterocytes ; Proliferation ; Differentiation ; ISEL ; Glomeruli ; Mouse (Balb/c) ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Morphological changes associated with apoptosis are closely correlated with the expression of specific proteins. However, the cause-effect relationships between the expression of these proteins and DNA degradation are barely known. For studying expression of apoptosis-related proteins in relation to different degrees of DNA fragmentation, the small intestine with its spatially organized continuum of proliferation, differentiation and death is a very useful preparation. Enterocytes towards the apex of the villi become increasingly susceptible to apoptosis. Here, this ”apoptotic gradient” is used to demonstrate the presence of BAX and BCL-2 proteins in the cytoplasm of cells at the onset of apoptosis. In semithin serial sections of the small intestine, BAX, BCL-2 and DNA fragmentation were demonstrated. BAX and BCL-2 are always colocalized and only in cells with fragmented DNA. The gradient of BAX or BCL-2 staining is similar to the gradient of DNA fragmentation. Immunoreactivity for BCL-2 or BAX is most intense in cells that are prone to become apoptotic next in the course of cellular turnover but not in cells in an advanced apoptotic state, showing strongly condensed chromatin. When using the same technique on semithin sections of kidney biopsies, containing epithelia with low cellular turnover, we found DNA fragmentation mainly in the epithelial cells of the distal tubules. Similar to the situation in the enterocytes, BAX staining was confined to the cytoplasm of epithelial cells with a moderate degree of DNA fragmentation and reduced in epithelial cells with a high degree of DNA fragmentation. In contrast to the situation in the small intestine, very low levels of BCL-2 were found. The results suggest that expression of BCL-2 and BAX is related to cell damage as indicated by DNA fragmentation but not to advanced stages of cellular death, as indicated by chromatin condensation and cellular shrinkage.
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  • 140
    ISSN: 1432-0878
    Keywords: Key words Vesicle protein ; Physin ; Secretory carrier-associated membrane protein ; Vesicle-associated membrane protein ; Synaptobrevin ; Expression ; Liver ; Bovine ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The cell-type restricted expression of cytoplasmic microvesicle membrane protein isoforms may be a consequence of the functional adaptation of these vesicles to the execution of specialized processes in cells of different specialization. To characterize the expression of the vesicle protein pantophysin, an isoform of the synaptic vesicle proteins synaptophysin and synaptoporin, we have prepared and characterized antibodies useful for the immunological detection of pantophysin in vitro and in situ. Using these reagents, we show by immunoblot analyses that pantophysin expression is not homogeneous but differs significantly between various bovine tissues. Furthermore, these differences are not exactly paralleled by the expression of other vesicle proteins of the SCAMP (secretory carrier-associated membrane protein) and VAMP (vesicle-associated membrane protein) types that have previously been localized to pantophysin vesicles in cultured cells. By immunofluorescence microscopy, pantophysin expression is seen predominantly in non-neuroendocrine cells with pronounced membrane traffic. Pantophysin staining codistributes with SCAMP and VAMP immunoreactivities in most instances but differs in some. Remarkably, pantophysin staining in liver is restricted to cells surrounding sinusoids and is not detectable in hepatocytes, similar to that of the SCAMP and VAMP isoforms as detected by our reagents in tissue sections.
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  • 141
    ISSN: 1432-0878
    Keywords: Key words Mammary gland ; Differentiation ; Neoplasia ; Homeodomain ; Cancer ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  In the mouse mammary gland, homeobox gene expression patterns suggest roles in development and neoplasia. In the human breast, we now identify a family of Iroquois-class (IRX) homeobox genes. One gene, IRX-2, is expressed in discrete epithelial cell lineages being found in ductal and lobular epithelium, but not in myoepithelium. Expression is absent from associated mesenchymal adipose stroma. During gland development, expression is concentrated in terminal end buds and terminal lobules and is reduced in a subset of epithelial cells during lactation. In contrast to observations for many homeobox genes in the mouse mammary gland in which homeobox gene expression is lost on neoplastic progression, IRX-2 expression is maintained in human mammary neoplasias. Data suggest IRX-2 functions in epithelial cell differentiation and demonstrate regulated expression during ductal and lobular proliferation as well as lactation.
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  • 142
    ISSN: 1432-0878
    Keywords: Key words Cytokine ; ELISA ; FACScan ; Lipids ; Macrophage ; Monocyte ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Diabetes (type I and type II) affects approximately 13 million people in the United States. Delayed and incomplete healing of wounds can be a major problem for diabetic patients. Macrophages are an important cell in the complex process of wound repair representing the major source of cytokines throughout the wound-healing process. Cytokines mediate many of the cellular responses critical to timely wound repair. It has been suggested that diabetes impairs wound healing through disruption of local cytokine production. Our previous in vivo studies in rats demonstrated that diabetes-induced and diet-induced hyperlipidemia cause changes in macrophage phenotype and function (Iacopino 1995; Doxey et al. 1998), suggesting that alterations in macrophage cytokine profiles represent the cellular/molecular mechanism responsible for delayed wound healing. The purpose of this study was to investigate how monocyte maturation/differentiation and cytokine production were altered by serum lipids in an in vitro system using human cells. Commercially prepared purified human monocytes were cultured and exposed to serum lipids. Phenotypic analysis of differentiated macrophages was then performed by flow cytometry and fluorescent microscopy using surface antigens specific for various macrophage subsets. Selected cytokines in conditioned medium were assayed using commercial human enzyme-linked immunosorbent assay (ELISA) kits. We demonstrate that serum lipids cause an increase in monocytic differentiation leading to an inflammatory macrophage phenotype rather than a reparative/proliferative phenotype. We also show that serum lipids cause a generalized decrease in macrophage cytokine production using interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), platelet-derived growth factor (PDGF), and transforming growth factor beta 1 (TGF-β1) as marker cytokines. Our present in vitro results using human cells confirm our previous in vivo studies in the rat and support the hypothesis that diabetes-induced hyperlipidemia alters the monocyte differentiation process resulting in changes of macrophage subsets and cytokine release at the wound site, ultimately impairing the wound-healing process.
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  • 143
    ISSN: 1432-0878
    Keywords: Key words Cultured epidermis ; Keratinocyte ; Epithelialization ; Wound healing ; Human ; Mouse (NMRI)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Sheets of cultured allogeneic human keratinocytes have been used for the treatment of burns and chronic leg ulcers but there has been no animal assay for the therapeutic action of these cultures. In order to analyze the effects of frozen cultures of human keratinocytes on wound healing, we have developed such an assay based on the rate of repair of full-thickness skin wounds in immunocompetent NMR1 mice. Reepithelialization of the control wounds, originating from the murine epithelium at the edge of the wound, occurred at a constant rate of advance of 150 µm/day. When frozen cultured human epidermal sheets were thawed at room temperature for 5–10 min and applied to the surface of the wound, the murine epithelium advanced at 267 µm/day. Most wounds treated with frozen cultures completely healed after 10 days, whereas most control wounds required 16 days. The accelerated reepithelialization did not depend on the presence of proliferative human keratinocytes in the frozen cultures. The cultures also promoted early formation of granulation tissue and laminin deposition over the surface of the wound bed. This simple assay should permit quantitative analysis of the effects on healing exerted not only by cultured cells, but also by proteins and small molecules.
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  • 144
    ISSN: 1432-0878
    Keywords: Key words Interleukin-18 ; Hyperosmotic conditions ; Epithelial cells ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Interleukin-18 is a novel multifunctional cytokine, which enhances natural killer cell activity and promotes the induction of cytokine production, including that of interferon-γ by T cells and antitumor effects. Interleukin-18 is produced by cells of several different tissues (e.g., macrophages, keratinocytes, osteoblasts, and intestinal epithelium); however, it is unclear what physiological conditions or stimuli induce interleukin-18 production. To determine physiological conditions for the production of interleukin-18, we have examined the effect of mannitol-induced hyperosmotic conditions on normal human umbilical vein endothelial cells (HUVEC) and eight established human epithelial-like cell lines (Intestine 407, Caco-2, A253, HeLa, SCC25, HT1197, ACHN, A549). Hyperosmotic conditions induced interleukin-18 immunoreactivity in all the human cell lines tested, as detected by immunocytochemistry. The enhanced interleukin-18 production was also observed when mannitol was replaced with NaCl as the inducer of hyperosmotic stress. Enzyme-linked immunosorbent assays revealed that interleukin-18 concentrations in cell extracts were significantly increased by hyperosmotic conditions. Reporter gene assays also revealed that hyperosmotic conditions stimulated transcriptional activity of the interleukin-18 promoter. These results show for the first time that hyperosmotic stress is a stimulator of interleukin-18 production in epithelial-like cells.
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  • 145
    ISSN: 1432-0878
    Keywords: Key words α1-Microglobulin ; Bikunin ; Inter-α-trypsin inhibitor ; Mast cells ; Trypstatin ; Urinary trypsin inhibitor ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  We recently reported that the rat mast cell proteinase inhibitor trypstatin is genetically identical with the second half of inter-α-trypsin inhibitor light chain (ITI-LC), also known as bikunin or urinary trypsin inhibitor (UTI). In this study, therefore, immunoreactivities of mast cells of various human tissues were examined with three antibodies, anti-human ITI-LC, anti-ITI, which recognizes mainly heavy chains or the sugar moiety of ITI, and anti-α 1-microglobulin (α1mG). ITI-LC immunoreactivity was strongly found in mast cells in the connective tissues of various organs except for those of the propria mucosae of small intestine. Neither anti-ITI antibody nor anti-α1mG antibody reacted with mast cells in various tissues. By reverse transcription-polymerase chain reaction (RT-PCR) analysis, α1mG/ITI-LC mRNA was not detected in the skin and tongue, and only weakly in small intestine, although ITI-LC immunoreactivity was strongly detected in these tissues. Furthermore, the mRNA was not expressed in cultured human mast cells. These results suggest that ITI-LC protein is stored in the granules of human connective tissue mast cells, though is not produced by them.
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  • 146
    ISSN: 1432-0878
    Keywords: Key words Osteoblasts ; Extracellular matrix ; Transforming growth factor-β1 ; Basic fibroblast growth factor ; Apert’s syndrome ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The phenotype of Apert osteoblasts differs from that of normal osteoblasts in the accumulation of macromolecules in the extracellular matrix. Apert osteoblasts increase type I collagen, fibronectin and glycosaminoglycans secretion compared with normal osteoblasts. Because the extracellular matrix macromolecule accumulation is greatly modulated by transforming growth factor-β1, we examined the ability of normal and Apert osteoblasts to secrete transforming growth factor-β1 by CCL-64 assay and to produce transforming growth factor-β1 by analysis of the mRNA expression of transforming growth factor-β1. Northern blot analysis revealed an increased amount of transforming growth factor-β1 mRNA expression in Apert osteoblasts compared with normal ones. Moreover, the level of the active transforming growth factor-β1 isoform was higher in Apert than in normal media. In pathologic cells, the increase in transforming growth factor-β1 gene expression was associated with a parallel increase in the factor secreted into the medium. The level of transforming growth factor-β1 was decreased by the addition of basic fibroblast growth factor. Transforming growth factor-β1 is controlled temporally and spatially during skeletal tissue development and produces complex stimulatory and inhibitory changes in osteoblast functions. We hypothesise that in vitro differences between normal and Apert osteoblasts may be correlated to different transforming growth factor-β1 cascade patterns, probably due to an altered balance between transforming growth factor-β1 and basic fibroblast growth factor.
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  • 147
    ISSN: 1432-0878
    Keywords: Key words Endothelin ; Endothelin receptors ; Endothelin-converting enzyme ; Ovary ; In situ hybridization ; Human ; Cynomolgus monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The endothelin system is composed of three endothelin isoforms (ET-1, ET-2, and ET-3), the endothelin receptors ETA and ETB, and the endothelin-converting enzyme (ECE). Besides having a major vasoactive role, endothelins have roles in different cell types at a local level. We investigated the presence of the different components of the endothelin system in primate ovaries. Human ovaries and gonadotropin-stimulated monkey ovaries were studied using immunohistochemistry for endothelin, and in situ hybridization with probes for ET-1, ET-2, ET-3, ETA and ETB receptors, and ECE. ET-1 and ETA receptors were detected in endothelial cells and vascular smooth muscle cells, respectively, in stromal vessels adjacent to follicles and corpora lutea. ETB receptors and ET-1 were found in the endothelial cells of capillaries of corpora lutea. ECE was present in internal theca cells of secondary, de Graaf, atretic follicles, and in luteinized granulosa cells of the corpora lutea. The endothelin system components are present in or around the follicles of human and monkey ovaries. Although the components are not expressed in the same cell types, they are synthesized, mainly in follicles, by cells that are in close proximity. Thus, the endothelin system could act in a paracrine manner. ECE expression in steroid-producing cells changes its compartmentalization during follicle maturation.
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  • 148
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    Cell & tissue research 295 (1999), S. 297-305 
    ISSN: 1432-0878
    Keywords: Key words Trophoblast ; Macrophages ; Placenta ; Cell culture ; Paracrine regulation ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In view of the accumulating evidence for paracrine mechanisms regulating trophoblast function, we tested the hypothesis that placental macrophages affect trophoblast activity in a paracrine fashion. Trophoblast was isolated from 17 term placentas (–IP). One aliquot of cells was further immunopurified (+IP) using an HLA class I antibody. This increased the proportion of trophoblast (+IP 〉97%; –IP ∼70%) as identified by rigorous immunocytochemistry. Most (∼70%) non-trophoblast cells in –IP were macrophages. The cells were cultured for 5 days with a daily medium change. In addition, +IP cells from seven placentas were cultured with lipopolysaccharide (LPS)-stimulated or -unstimulated macrophage-conditioned media. The concentrations of lactate, trophoblast-specific hormones, human chorionic gonadotropin-β (hCG-β) and human placental lactogen (hPL), of several prostanoids and of endothelin-1 and angiotensin II were determined in the culture media. The accumulated amounts of substances released into the culture media, corrected for the greater proportion of trophoblast in +IP cultures, were on average two- to threefold higher (hCG-β: 18-fold) in +IP than in –IP, with the exception of endothelin-1,2 (no change), angiotensin II (–70%) and 6-keto-prostaglandin-F1α (–40%). [3H]leucine incorporation into the trichloroacetic acid (TCA)-precipitable pool measured on day 5 was twofold higher in +IP than in –IP. Addition of conditioned media reverted these changes. The data demonstrate that placental macrophages in culture affect trophoblast biosynthetic activity in a paracrine fashion. We conclude that macrophages are important regulators of trophoblast activity.
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  • 149
    ISSN: 1432-0878
    Keywords: Key words Cerebrovascular development and injury ; Hemangioma ; Angiogenesis ; Immunocytochemistry ; Adhesion molecules ; Conventional transmission and high-voltage electron microscopy ; Mouse (C57BL ; SJL/J) ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Blood vessels from the vasculature of mouse brains during postnatal development and from human brain tumors (hemangiomas) removed at biopsy were examined immunocytochemically by transmission electron microscopy (TEM) or high-voltage transmission electron microscopy (HVEM) to determine the expression of intercellular adhesion molecule-1 (ICAM-1). In the mouse brains, ICAM-1 was shown to be initially expressed on the luminal and abluminal endothelial cell (EC) surfaces on day 3 after birth. ICAM-1 intensity increased on the luminal EC surfaces and labeled vesiculotubular profiles (VTS, defined in the present report) between days 5 and 7. After 2 weeks and at 6 months after birth, ICAM-1 labeling was weak or absent on the luminal EC surfaces. The hemangiomas presented a strong ICAM-1 reaction product on the luminal EC surfaces of small and large blood vessels associated with the VTS, with a weaker labeling of the abluminal or adventitial aspects of larger blood vessels. TEM of vesiculovacuolar structures (VVOs) within ECs from arteries and veins also demonstrated reaction product for ICAM-1 labeling. Three-dimensional stereo-pair images in the HVEM enhanced the visualization of gold particles that were attached to the inner-delimiting membrane surfaces of EC VTS, and VVOs, respectively. These observations raise the possibility that the neonatal leukocytes and tumor cells may utilize these endothelial structures as a route across the developing and injured blood-brain barrier (BBB).
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  • 150
    ISSN: 1432-0878
    Keywords: Key words Atherosclerosis ; Culture model ; Endothelial cell ; Endothelin-1 ; Oxidized LDL ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We investigated the structural and functional properties of human umbilical vein endothelial cells (HUVECs) cultured on a two-chamber culture model system using an amnion membrane. Compared to HUVECs cultured on a plastic dish, HUVECs cultured on the model system exhibited several features similar to those of in vivo vessels, including formation of the intercellular junctional devices and expression of tight junction-associated protein ZO-1 and adherence junction-associated protein α-catenin. Furthermore, we found that HUVECs had a property of polar secretion of endothelin-1 (ET-1). About 90% of the total amount of synthesized ET-1 was found in the lower well, designated as the basal side. When HUVECs were incubated with either native low-density lipoproteins (nLDLs) or oxidized LDLs (oxLDLs) at a concentration of 100 μg/ml, ET-1 secretion was significantly increased, dependent on the cell side (apical vs basal) on which the nLDLs or oxLDLs were loaded. When the LDLs were loaded on the apical side, the secretion of ET-1 from HUVECs on the apical side was increased by 48% (nLDL) and 61% (oxLDL), whereas it was accompanied by a concomitant decrease of ET-1 on the basal side (45% by nLDLs and 38% by oxLDLs). When loaded on the basal side, however, ET-1 was increased by 23% (nLDLs) and 53% (oxLDLs) on the basal side, with a 26% simultaneous decrease of ET-1 on the opposite side for both nLDLs and oxLDLs. On the contrary, high-density lipoproteins (HDLs) inhibited ET-1 secretion from HUVECs on the opposite side of the well on which HDLs were loaded; there was a 57% decrease on the basal side when HDLs were loaded on the apical side, and a 46% decrease on the apical side when loaded on the basal side. These results indicate that modulation of ET-1 secretion from ECs by lipoproteins is virtually dependent on the place (apical vs basal) where these proteins are present. The finding that nLDLs and oxLDLs enhance ET-1 secretion by ECs in a polarized pattern suggests that ET-1 may be involved in pathophysiological processes such as atherogenesis.
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  • 151
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    Cell & tissue research 295 (1999), S. 151-158 
    ISSN: 1432-0878
    Keywords: Key words Class II MHC-positive cells ; Human leukocyte antigen-DR ; Dental pulp ; Dendritic cells ; Macrophages ; Ultrastructure ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The distribution and ultrastructure of class II major histocompatibility complex (MHC)-positive cells were investigated in human dental pulp, employing immunohistochemistry using an anti-human leukocyte antigen (HLA)-DR-monoclonal antibody. HLA-DR-immunopositive cells, appearing spindle-like or dendritic in profile, were densely distributed throughout the dental pulp. Under the electron microscope, these cells exhibited various sizes of vesicles containing clear or opaque contents, multivesicular bodies and characteristic fine tubulovesicular structures in their cytoplasm. Some reactive cells possessed coated pits and vesicles including electron-dense materials, indicating an active endocytosis. At the periphery of the pulp tissue, the HLA-DR-immunopositive cells were predominantly situated in the subodontoblastic layer, with some located in the odontoblast layer and/or predentin and extending their cytoplasmic processes into the dentinal tubules. Cell processes of these cells occasionally made contact with several odontoblast processes in the same way as the nerve fibers in the predentin. These cells never contained the typical phagosomes frequently observed in the HLA-DR-immunoreactive macrophages in the subodontoblastic layer and the pulp core. The results suggest that the HLA-DR-immunopositive cells in the odontoblast layer and/or predentin have some regulatory function on the odontoblasts under physiological conditions, in addition to their involvement in the initial defense reaction after tooth injury.
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  • 152
    ISSN: 1615-6102
    Keywords: Cumulus oophorus ; Ovarian follicle ; Fertilization ; Ultrastructure ; Immunocytochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The fine structure of the human cumulus oophorus has been reviewed on the basis of scanning and transmission electron microscopic observations as well as of immunofluorescence data. Tissues sampled from preovulatory ovarian follicles and cumulus-enclosed oocytes and fertilized eggs (collected from the oviduct or obtained during in vitro fertilization procedures) have been evaluated from a microtopographic and morphodynamic point of view in order to better clarify the possible role of this population of cells. In particular, the following aspects have been studied and discussed: the presence of multiple close contacts (modulated by the interposition of the zona pellucida) between the oocyte surface and the long microvillous evaginations projecting from the inner aspect of corona cells surface (through these structures the intraovarian cumulus oophorus may control oocyte growth and metabolism up until the time of ovulation); the occurrence of different subpopulations of cells (steroid-synthetic cells, cells producing adhesive proteins, leukocytes, macrophages) in the postovulatory, extraovarian cumulus oophorus surrounding oocytes, zygotes and early developing embryos. All these elements found in the cumulus mass may positively act, through their paracrine activities, on the chemical composition of the microenvironment in which fertilization occurs.
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  • 153
    ISSN: 1615-2573
    Keywords: Smooth muscle cell ; Heterogeneity ; Coronary artery ; Human ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The arterial media is composed of a heterogeneous population of smooth muscle cells (SMCs). Recently, the properties of SMCs were observed to be heterogeneous not only among individual cells but also among arteries of the same vascular bed. To test the hypothesis that a site-specific heterogeneity exists in the SMCs of human coronary arteries, we examined the expression of desmin, vimentin, calponin, and high-molecular-weight (h-) caldesmon in arteries of various sizes. Specimens of arteries were obtained at autopsy from 12 patients: 6 adults (67 ± 4 years old); 3 younger adults (26 ± 2 years old); and 3 neonates. The size of the arteries was estimated by the number of SMC layers of the media. The expression was compared in SMCs of large arteries (〉10 layers in adults, 〉5 layers in neonates), medium-sized arteries (5–10 layers in adults, 3–5 SMC layers in neonates), and small arteries (〈3 layers). In adults, the percentage of arteries positive for desmin was lower in the small (17% ± 3%) and medium-sized arteries (44% ± 12%) than in the large arteries (94% ± 6%) (P 〈 0.01). The percentage of arteries positive for calponin was also lower in the small (18% ± 2%) and medium-sized arteries (66% ± 5%) than in the large arteries (100%) (P 〈 0.01). The percentage for vimentin and h-caldesmon did not differ among large, medium-sized, and small arteries. These observations in adults were similar to those in younger adults or neonates. The phenotypes of medial SMCs are vessel sizedependent in human coronary arteries. This finding should be important for understanding the site-specific characteristics of vascular function in the regulation of myocardial perfusion or those of vascular responses to environmental changes.
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  • 154
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    European journal of applied physiology 80 (1999), S. 386-393 
    ISSN: 1439-6327
    Keywords: Key words Skeletal Muscle ; Human ; Force/velocity ; Fatigue ; Isokinetic testing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the study was to obtain force/velocity relationships for electrically stimulated (80 Hz) human adductor pollicis muscle (n = 6) and to quantify the effects of fatigue. There are two major problems of studying human muscle in situ; the first is the contribution of the series elastic component, and the second is a loss of force consequent upon the extent of loaded shortening. These problems were tackled in two ways. Records obtained from isokinetic releases from maximal isometric tetani showed a late linear phase of force decline, and this was extrapolated back to the time of release to obtain measures of instantaneous force. This method gave usable data up to velocities of shortening equivalent to approximately one-third of maximal velocity. An alternative procedure (short activation, SA) allowed the muscle to begin shortening when isometric force reached a value that could be sustained during shortening (essentially an isotonic protocol). At low velocities both protocols gave very similar data (r 2 = 0.96), but for high velocities only the SA procedure could be used. Results obtained using the SA protocol in fresh muscle were compared to those for muscle that had been fatigued by 25 s of ischaemic isometric contractions, induced by electrical stimulation at the ulnar nerve. Fatigue resulted in a decrease of isometric force [to 69 (3)%], an increase in half-relaxation time [to 431 (10)%], and decreases in maximal shortening velocity [to 77 (8)%] and power [to 42 (5)%]. These are the first data for human skeletal muscle to show convincingly that during acute fatigue, power is reduced as a consequence of both the loss of force and slowing of the contractile speed.
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  • 155
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    European journal of applied physiology 79 (1999), S. 347-352 
    ISSN: 1439-6327
    Keywords: Key words Citrate synthase activity ; Human ; Myoglobin concentration ; Protocols ; Resistance training ; Vastus lateralis muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to determine the effects of 8 weeks of resistance training (RT) on the myoglobin concentration ([Mb]) in human skeletal muscle, and to compare the change in the [Mb] in two different RT protocols. The two types of protocol used were interval RT (IRT) of moderate to low intensity with a high number of repetitions and a short recovery time, and repetition RT (RRT) of high intensity with a low number of repetitions and a long recovery time. A group of 11 healthy male adults voluntarily participated in this study and were divided into IRT (n = 6) and RRT (n = 5) groups. Both training protocols were carried out twice a week for 8 weeks. At the completion of the training period, the one-repetition maximal force values and isometric force were increased significantly in all the subjects, by about 38.8% and 26.0%, respectively (P 〈 0.01). The muscle fibre composition was unchanged by the 8 weeks of training. The muscle fibre cross-sectional areas were increased significantly by both types of training in all fibre types (I, IIa and IIb, mean +16.1%, P 〈 0.05). The [Mb] showed no significant changes at the completion of the training [IRT from 4.63 (SD 0.63) to 4.48 (SD 0.72), RRT from 4.47 (SD 0.75) to 4.24 (SD 0.80) mg · g−1 wet tissue] despite a significant decrease in citrate synthase activity [IRT from 5.27 (SD 1.45) to 4.49 (SD 1.48), RRT from 5.33 (SD 2.09) to 4.85 (SD 1.87) μmol · min−1 · g−1 wet tissue; P 〈 0.05] observed after both protocols. These results suggested that myoglobin and mitochondria enzymes were regulated by different mechanisms in response to either type of RT. Moreover, the maintained [Mb] in hypertrophied muscle should preserve oxygen transport from capillaries to mitochondria even when diffusion distance is increased.
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  • 156
    ISSN: 1439-6327
    Keywords: Key words Fatigue ; Movement ; Position ; Muscle ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have tested the hypothesis that agonist and antagonist muscle fatigue could affect the final position of rapid, discrete movements. Six subjects performed consecutive elbow flexion and extension movements between two targets, with their eyes closed prior to, and after fatiguing the elbow extensor muscles. The results demonstrate that elbow extension movements performed in the post-test period systematically undershot the final position as compared to pre-test movements. However, attainment of the aimed final position in elbow flexion movements was unaffected by fatiguing of the extensor muscles. Undershoot of the final position obtained in extension movements was associated with agonist muscle fatigue, a result that was expected from the point of view of current motor control theories, and that could be explained by a reduced ability of the shortening muscle to exert force. On the other hand, the absence of the expected overshoot of the final position when the antagonist is fatigued, indicates the involvement of various reflex and/or central mechanisms operating around the stretched muscle that could contribute to returning the limb to the standard final position after a brief prominent overshoot.
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  • 157
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    European archives of oto-rhino-laryngology and head & neck 256 (1999), S. 370-372 
    ISSN: 1434-4726
    Keywords: Key words Gastroesophageal reflux disease ; Human ; papilloma virus ; Laryngeal papillomatosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hallmark of gastroesophageal reflux disease (GERD) is an increased exposure of esophageal and laryngeal mucosa to gastric juice. This exposure can cause complications such as chronic laryngitis or chronic respiratory diseases. We report our experience in managing three pediatric patients with severe recurrent juvenile laryngeal papillomatosis (JLP) associated with GERD. All patients showed a high rate of recurrence requiring multiple laser surgeries. Systemic αinterferon therapy over a period of more than 1 year and photodynamic therapy with dihematoporphyrin produced no improvement. However, after therapy for GERD, the rate of recurrence of JLP decreased significantly. Although the course of respiratory papillomatosis is known to fluctuate, our findings suggest that gastroesophageal reflux may have a role in aggravating papillomatosis.
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  • 158
    ISSN: 1573-6792
    Keywords: EEG ; Alpha activity ; Spatial segmentation techniques ; Wakefulness ; Sleep onset ; REM sleep ; Dream imagery ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Spontaneous alpha activity clearly present in relaxed wakefulness with closed eyes, drowsiness period at sleep onset, and REM sleep was studied with spatial segmentation methods in order to determine if the brain activation state would be modulating the alpha spatial microstates composition and duration. These methods of spatial segmentation show some advantages: i) they extract topographic descriptors independent of the chosen reference (reference-free methods), and ii) they achieve spatial data reduction that are more data-driven than dipole source analysis. The results obtained with this study revealed that alpha activity presented a different spatio-temporal pattern of brain electric fields in each arousal state used in this study. These differences were reflected in a) the mean duration of alpha microstates (longer in relaxed wakefulness than in drowsy period and REM sleep), b) the number of brain microstates contained in one second (drowsiness showed more different microstates than did relaxed wakefulness and REM state), and c) the number of different classes (more abundant in drowsiness than in the rest of brain states). If we assume that longer segments of stable brain activity imply a lesser amount of different information to process (as reflected by a higher stability of the brain generator), whereas shorter segments imply a higher number of brain microstates caused by more different steps of information processing, it is possible that the alpha activity appearing in the sleep onset period could be indexing the hypnagogic imagery self-generated by the sleeping brain, and a phasic event in the case of REM sleep. Probably, REM-alpha bursts are associated with a brain microstate change (such as sleep spindles), as demonstrated by its phasic intrusion in a desynchronized background of brain activity. On the other hand, alpha rhythm could be the “baseline” of brain activity when the sensory inputs are minimum and the state is relaxed wakefulness.
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  • 159
    ISSN: 1573-6792
    Keywords: Magnetoencephalography ; Human ; Words ; Tones ; Cerebral dominance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The magnetic flux normal to the scalp surface was measured with a whole-head neuromagnetometer while right-handed subjects (N = 15) were engaged in either an auditory word- or a tone-recognition task. Sources of the recorded magnetic fields were modeled as equivalent current dipoles at 4 ms intervals and the number of sources in the later portion of the magnetic response was used as an index of the degree of brain activation. Significantly more sources were found in the left as compared to the right hemisphere in the word but not the tone task on a group basis. On an individual basis, 13/15 subjects had more sources in the left as compared to the right hemisphere during the word task, while in the tone task 3/10 subjects showed this pattern. Sources of activity were found in the left superior and middle temporal gyri in all subjects with available MRI scans. Sources were also found in the supramarginal gyrus and in medial temporal areas, including the hippocampus, in the majority of cases. MEG appears to be a promising tool for detecting activity in cerebral areas specialized for language and memory function.
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  • 160
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    Plant foods for human nutrition 53 (1999), S. 359-365 
    ISSN: 1573-9104
    Keywords: Consumed ; Different levels ; Fenugreek seeds (Trigonella foenum graecum) ; Germinated ; HDL ; Human ; Hypocholesterolemia ; LDL ; Triglycerides ; VLDL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The effect of consumption of germinated fenugreek seed powder at two different levels, i.e., 12.5 g and 18.0 g on the blood lipid profiles of twenty hypocholesterolemic adults of both sexes in the age range of 50–65 years was studied. The subjects were divided into two groups, i.e., Group I and Group II who were asked to incorporate the powder into any dish of their choice at the rates of one packet per day containing 12.5 g and 18.0 g of the germinated powder, respectively, for a period of one month. Fasting blood was drawn intravenously one day before and at the end of 30 days feeding trials. The findings revealed that germination had brought distinct changes in soluble fiber content of the seeds. Consumption of the seed at both the levels resulted in a hypocholesterolemic effect. Between the two levels, higher levels of consumption, i.e., 18.0 g of the germinated seed resulted in a significant reduction in total cholesterol and LDL levels. No significant changes were found in HDL, VLDL and triglyceride levels in all the subjects.
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  • 161
    ISSN: 1530-0358
    Keywords: Mechanical bowel preparation ; Bacterial translocation ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Prospective, randomized studies have shown that bowel preparation may adversely affect infectious complications following colonic resections. However, very little is known about the effects of bacterial translocation on these infectious complications. The aim of this prospective, randomized study was to assess the effects of bowel preparation on bacterial translocation. METHODS: A total of 82 consecutive patients undergoing elective abdominal operations were randomly assigned to four groups: control (I; n=20), mechanical (II; n=21), mechanical plus oral metronidazole (III; n=20), and polyethylene glycol preparation (IV; n=21). Patients with intra-abdominal infection, those receiving preoperative antibiotics for any reason, and those having lower gastrointestinal tract disease were excluded from the study. Peritoneal swab, ileocecal and pericolic mesenteric lymph nodes, liver wedge biopsy, portal venous blood, and peripheral blood samples were taken for culture. Patients were followed up for postoperative infectious complications. Groups were matched according to age, gender, body surface area, and Acute Physiology and Chronic Health Evaluation II scores. RESULTS: Bacterial translocation was identified by a positive culture in one patient in Group I, two in Group II, one in Group III, and three in Group IV, respectively. Differences in number of positive cultures among the groups were not statistically significant. Nine patients had major infectious complications. Only two had bacterial translocation, and the same micro-organisms grew in both patients, in one at the wound site and in the other at the cyst abscess. CONCLUSION: This study demonstrated that mechanical bowel preparation does not enhance the spontaneous occurrence of bacterial translocation in patients without any clinical signs of lower gastrointestinal tract disease.
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  • 162
    ISSN: 1530-0358
    Keywords: Colonic neoplasms/surgery ; Human ; Laparoscopy ; Prospective study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Laparoscopic colorectal surgery for cancer is currently under discussion. Results of large, randomized studies will not be available for a number of years yet. This study analyses the results of such resections in consecutive patients operated on by unselected surgeons. METHODS: A prospective, observational, multicenter study was initiated on August 1, 1995, in the German-speaking countries of Europe. One year after initiation of the study, findings are presented with respect to the quality of oncologic resections. RESULTS: Of 500 operations, 231 (46 percent) were performed for cancer, 167 (33 percent) with a curative intent. The most common curative resections were as follows: 63 anterior rectum resections (38 percent), 51 sigmoid resections (30 percent), and 27 abdominoperineal resections (16 percent). Segmental resections were performed in 20 patients (12 percent). Intraoperative tumor spillage was reported in 2 percent. Mean number of lymph nodes harvested was 13 (confidence interval, 5–95 percent; range, 11.5–14.6) and positive lymph nodes harvested was 2.2 (confidence interval, 5–95 percent; range, 0.9–3.4). Significant differences were noted between participating centers in terms of number of lymph nodes resected (P〈0.0001). Distal and proximal resection margins were tumorfree in every case. Lateral margins were tumor-free when examined. In the case of 63 curative anterior resections, the mean distal resection margin was 39 (confidence interval, 5–95 percent; range, 33–45) mm, and in 8 of these resections, it was less than 20 mm. Mean blood loss was 344 (confidence interval, 5–95 percent; 292–396) ml, and 21 percent of patients received blood transfusions. CONCLUSIONS: These data document that the average quality of laparoscopic colorectal procedures for cancer is satisfactory but differs among surgeons.
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  • 163
    ISSN: 1435-9456
    Keywords: Key words Attention ; Categorization ; Primate ; Baboon ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We examined attention shifting in baboons and humans during the learning of visual categories. Within a conditional matching-to-sample task, participants of the two species sequentially learned two two-feature categories which shared a common feature. Results showed that humans encoded both features of the initially learned category, but predominantly only the distinctive feature of the subsequently learned category. Although baboons initially encoded both features of the first category, they ultimately retained only the distinctive features of each category. Empirical data from the two species were analyzed with the 1996 ADIT connectionist model of Kruschke. ADIT fits the baboon data when the attentional shift rate is zero, and the human data when the attentional shift rate is not zero. These empirical and modeling results suggest species differences in learned attention to visual features.
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  • 164
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    Surgical and radiologic anatomy 20 (1998), S. 185-189 
    ISSN: 1279-8517
    Keywords: Lateral pterygoid muscle ; Masticatory muscles ; Innervation ; Human ; Anatomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The one- or two-headed arrangement of the lateral pterygoid m. (LPM) was analysed by studying the motor nerve distribution within the muscular tissue. In all subjects, the main innervation of the lateral pterygoid m. came from the anterior trunk of the mandibular n. by one to three nerves. These nerves divided into five or six vertical branches which ramified into parallel horizontal tiny fibers. Consequently, the lateral pterygoid m. appeared to be divided into oblique sagittal planes and horizontal layers by the nerve branches, reflecting the multipennate organisation of the muscle. These layers can be selectively recruited during mandibular movements, ensuing a fine medial-lateral control. According to its nerve supply, the LPM has to be considered as a single unit made of independent functional musulo-aponeurotic layers even though its morphologic conformation is in one, two or three heads.
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  • 165
    ISSN: 1279-8517
    Keywords: Human ; “Hamstrings” ; Nerve and vascular supply ; Fecal incontinence ; Muscle transposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anal neosphincter formation with electrically stimulated gracilis muscle is used increasingly for the surgical treatment of fecal incontinence. An alternative to gracilis might be of interest if this muscle is not available. 30 semitendinosus muscles and 15 long heads of biceps femoris were investigated on human cadavers. In particular, the nerve and vascular supply of these muscles was studied, both representing basic factors for muscle transposition. The long head of biceps femoris m. was found to receive its dominant vascular supply from the first and second perforating artery and its nerve supply from one motor branch out of the sciatic nerve, both as described in literature. The examination of semitendinosus m., however, revealed new anatomical aspects in its vascular supply. In all cases semitendinosus m. was found to receive dominant vascular pedicles from the medial circumflex femoral artery close to the ischial tuberosity and the second perforating artery. The nerve supply consisted of two motor branches out of the sciatic nerve. Both muscles fulfilled several basic criterias for transposition to the anus. However, regarding these requirements, semitendinosus offered distinct advantages in comparison with the long head of biceps femoris. Due to its vascular and nerve topography, semitendinosus seems suitable to serve as an alternative to gracilis.
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  • 166
    ISSN: 1432-1440
    Keywords: Key words Heart failure ; Human ; RNase protection assay ; Myocardial biopsies ; Gene expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  End-stage human heart failure is associated with changes in expression of steady-state messenger RNA (mRNA) levels. These changes correspond to alterations in protein levels and myocardial function and may have clinical implications regarding etiology, clinical state, or prognosis. However, analysis of mRNA levels in endomyocardial biopsies can be accomplished only by the quantitative polymerase chain reaction, which is difficult to standardize. The aim of the study was to evaluate whether the RNase protection assay is applicable to measure mRNAs of multiple genes simultaneously in small amounts of ventricular myocardium comparable to myocardial biopsies. Total RNA was prepared from left ventricular myocardium from terminally failing hearts with idiopathic (n=9) or ischemic cardiomyopathy (n=7) and from nonfailing control hearts (n=10). mRNA was measured by an optimized RNase protection assay for the β1-adrenoceptor, the stimulatory G protein α-subunit (Gsα), phospholamban, the calcium ATPase of the sarcoplasmic reticulum (SERCA), β-myosin heavy chain (β-MHC), and the atrial natriuretic peptide (ANP). We extracted 10.7±2.1 μg total RNA from three myocardial biopsies taken in vitro. All of the six genes were measurable in duplicate in a total of 7 μg RNA. mRNAs of β1-adrenoceptor, phospholamban, and SERCA were lower in failing than in nonfailing myocardium by 50%, 33%, and 42% respectively, whereas β-MHC and Gsα mRNAs were unchanged. mRNA of ANP was expressed at high levels only in the failing myocardium, providing a highly specific and sensitive marker for discriminating nonfailing and failing hearts. A direct comparison with ANP and Gsα levels obtained by Northern blot analysis with 7.5 μg total RNA showed a good correlation between the two methods. The RNase protection assay is thus a suitable method for simultaneous measurements of multiple mRNA levels in human myocardial biopsies. Changes in mRNA levels closely reflected those identified by other methods using larger amounts of RNA. Increased myocardial ANP mRNA levels determined by the RNase protection assay may serve as a molecular marker of heart failure.
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  • 167
    ISSN: 1432-0843
    Keywords: Key words Topoisomerase II ; Human ; Yeast ; Antitumour drugs ; Bisdioxopiperazine compounds ; ICRF-193
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To identify and characterize the specificity and potency of topoisomerase II-interacting antitumour drugs in an in vivo model utilizing the yeast Saccharomyces cerevisiae. Methods: Four yeast transformants were selected for the expression of either human or yeast DNA topoisomerase II at different, biologically relevant, levels under the tight control of promoters of various strengths. Results: Analyses of 24 drugs permitted their classification into three distinct groups, depending on whether they induced topoisomerase II-related cytotoxicity (etoposide), showed nonspecific cytotoxicity (camptothecin), or exerted no cytotoxicity at all (vinorelbine). Within the first group different patterns of action were distinguishable: (1) classical topoisomerase II expression-dependent cytotoxicity for both species of enzyme (e.g. etoposide, amsacrine, doxorubicin, actinomycin D), although amsacrine and TOP 53 were more active, respectively, on human and yeast topoisomerase II; and (2) compounds that appeared to poison only one species of topoisomerase II with, for example, genistein and the bisdioxopiperazine ICRF-193 lethally targeting only the human type, and mitoxantrone only the yeast isozyme. Three of the 16 known topoisomerase II inhibitors tested were not correctly identified with this assay, possibly owing to restricted cell wall permeability or to the absence of correct processing pathways such as, for example, in the case of the prodrug etopophos. Conclusion: This methodology, in vivo in yeast, selected for a large range of potent topoisomerase II-targeting anticancer agents. Of particular interest in this yeast model, and in contrast to yeast topoisomerase II, human topoisomerase II was shown to confer dominant sensitivity in the presence of the series of bisdioxopiperazine derivatives tested. This assay therefore has the potential easily to identify and characterize the potency and specificity of synthesized anticancer drugs with modified original chemical structures or those present, for example, in natural plant extracts or marine organisms.
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  • 168
    ISSN: 1432-2307
    Keywords: Key words Monoclonal antibody ; Multidrug resistance ; P-Glycoprotein peptide ; Mouse ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A novel immunization protocol together with stringent selection criteria have been employed to generate a new murine monoclonal antibody (’’D8’’, isotype IgG1, kappa) which specifically recognizes the human p170 drug resistance glycoprotein. This antibody is directed towards a defined peptide sequence located in the −COOH terminal region of the first external loop of the molecule. It is reactive with its epitope within the intact native glycoprotein in formalin-fixed and conventionally processed histological tissues, in flow-cytometric preparations and by Western blotting. The antibody precipitates its target peptide sequence from solution, and thus may be a useful reagent with which to establish an ELISA, RIMA or other similar assay. The peptide epitope recognized by this monoclonal antibody is restricted to the human MDR1 gene product and is not contained within the rodent homologue of the P-170 molecule. Immunohistochemistry has consistently failed to detect this epitope in rodent tissues, thus confirming that it does not exhibit the cross-reactivity of other currently available anti-P-glycoprotein monoclonal antibodies. The experience of this study emphasizes the value of the tuberculin-PPD (purified protein derivative) immunization protocol as a powerful strategy when generating monoclonal antibodies to small synthetic peptides. The resulting monoclonal antibody (D8) will be an invaluable reagent with which to analyse P-170 glycoprotein expression when assessing the role of multidrug resistance in human cancers.
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  • 169
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    Acta neuropathologica 96 (1998), S. 22-28 
    ISSN: 1432-0533
    Keywords: Key words Cerebral arteries ; Human ; Immunohistochemistry ; Vasa vasorum ; Atherosclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Vasa vasorum are adventitial vessels that play a role in pathogenesis of atherosclerosis, aneurysm, vasculitides, and graft vascular disease. The existence of vasa vasorum in human intracranial arteries is not yet well defined. The specific aims of this study are to determine whether the human intracranial arteries have vasa vasorum, whether their existence is related to the thickness of tunica media as is in systemic vessels, and whether they are acquired in reaction to pathological conditions, such as atherosclerosis and arterial occlusion. Human intracranial internal carotid (i-ICA), vertebral (i-VA), basilar (BA) and middle cerebral arteries (MCA) from adults, children and newborns were examined. Systemic vessels of comparable medial thickness were used as controls. Immunohistochemical staining for Factor VIII and CD 31 was used to identify the endothelial cells. Human intracranial arteries in neonates, children and adults do not have vasa vasorum, although their medial thickness is comparable to their systemic counterparts with vasa vasorum. Only in adults did the proximal intracranial segments of i-ICA and i-VA reveal a few vasa vasorum-like vessels with unusually large diameter. They were more frequently seen in atherosclerosis and thrombotic but again limited to the proximal segments of i-ICA and i-VA. Completely obstructed bilateral carotid arteries in a child with sickle cell disorder revealed a rich adventitial neovascularization in the proximal intracranial part of the vessel. It is not yet known whether obstruction of the distal segments may create similar neovascularizations. Adventitial neovascularizations seen in the proximal i-ICA and i-VA may represent a focal intracranial extension of the vascular pathologies involving the extracranial segments of major cerebral arteries.
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  • 170
    ISSN: 1432-0533
    Keywords: Key words B-50(GAP-43) ; Spinal cord ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract B-50(GAP-43) is a phosphoprotein mainly found in the nervous system which plays a major role in neurite growth during development and regeneration as well as in synaptic remodelling. In the mature intact central nervous system, intense B-50 immunoreactivity (B-50-IR) can still be detected in regions which maintain residual capacity for structural re-organization. B-50 expression has been studied extensively in laboratory animals; however, its distribution and regulation in the human spinal cord is largely unknown. As a first step to analyze lesion-induced structural alterations, we investigated the distribution of B-50 protein and mRNA in the normal adult human spinal cord and dorsal root ganglia. Intense B-50-IR was localized to the superficial laminae of the dorsal horn at all segmental levels, the intermediolateral nucleus at thoracic levels and Onuf’s nucleus at sacral levels. Scattered neurons, particularly in the ventral horn of lumbar and sacral segmental levels (and occasionally also in Clarke’s nucleus) displayed intense B-50-IR in close apposition to the perikaryal and proximal dendritic surfaces. Nonradioactive in situ hybridization indicated that B-50 mRNA could also be detected in neurons of the ventral horn and also in the intermediolateral nucleus. The distribution of B-50 mRNA and protein in the normal human spinal cord shows a marked similarity to that reported in experimental animals, including the selective labelling of Onuf’s nucleus. However, the strong B-50-IR on the surface of some large anterior horn motor neurons has not been observed in other mammals. This finding might reflect a particular state of readiness for synaptic plasticity.
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  • 171
    ISSN: 1432-0533
    Keywords: Key words Autoantibody ; Ganglioside ; Guillain-Barré ; Human ; Neuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A series of monoclonal IgM anti-GM1 ganglioside antibodies has been cloned from peripheral blood lymphocytes of patients with multifocal motor neuropathy and Guillain-Barré syndrome. In solid-phase immunoassay, the antibodies react with GM1, and also in differing degrees to the structurally related glycolipids asialo-GM1 (GA1) and GD1b. Here we describe the binding patterns of six human anti-GM1 antibodies to epitopes within the human nervous system. Antibodies were observed to bind to motor neurons and spinal grey matter, dorsal and ventral spinal roots, dorsal root ganglion neurons, nodes of Ranvier, neuromuscular junctions and skeletal muscle. The distribution of immunoreactive epitopes, which included sensory structures, extended beyond those sites conventionally regarded as pathologically affected in anti-GM1 antibody-associated motor nerve syndromes. This undermines a model of disease pathogenesis based solely on antigen distribution. Factors other than the presence or absence of antigen, such as the local ganglioside topography, antibody penetration into, and pathophysiological vulnerability of a particular site may also influence the clinicopathological outcome of anti-GM1 antibody-mediated autoimmune attack.
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  • 172
    ISSN: 1432-0533
    Keywords: Key words Non-astrocytic brain tumors ; p53 mutation ; Yeast functional assay ; Malignant lymphoma ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While it is established that p53 mutation plays a critical role in the carcinogenesis of astrocytic brain tumors, its role remains to be clarified for other types of tumors in the central nervous system (CNS). Using a yeast-based assay which tests the ability of human p53 to activate transcription, we analyzed p53 mutations in 85 non-astrocytic CNS tumors, including 4 benign neuronal tumors (3 central neurocytomas and 1 pineocytoma), 12 primitive neuroectodermal tumors, 14 germ cell tumors (7 germinomas, 7 non-germinomatous tumors), 4 craniopharyngiomas, 14 ependymomas, 22 schwannomas, 10 primary brain lymphomas in immunocompetent patients, and 5 bone tumors of the skull. The only tumors found to contain p53 mutations were 3 malignant lymphomas. The presence of mutations in these cases was confirmed by DNA sequencing. Given the high accuracy and sensitivity of the yeast assay and previous negative results using conventional techniques, this indicates that p53 mutation is a rare event in non-astrocytic CNS tumor types examined here.
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  • 173
    ISSN: 1432-0533
    Keywords: Key words Cytochrome c oxidase ; Fibre type ; Human ; Immunohistochemistry ; Myalgia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Muscular changes in male forest machine operators with work-related neck and shoulder myalgia were studied. Enzyme cyto- and immunohistochemical analysis was carried on muscle biopsies obtained from ten myalgic subjects (M), nine non-myalgic selected in the same work place (NM) and six healthy young men (C). The M group displayed a significant increase in type IIA fibres in comparison to the C group. This hypertrophy was accompanied by a parallel increase in the capillary bed. Both the M and NM groups exhibited an increase in fibres with a disorganised mitochondrial pattern. Interestingly, fibres lacking cytochrome c oxidase occurred in the M group (0.9%) but also in the NM group (0.5%), suggesting a mitochondrial defect. Central nuclei (5.2%) and developmental myosin (3%) were also more frequent in the M group. These changes are probably related to injury-regeneration cycles. These data support the association between the work conditions and muscle changes in work-related trapezius myalgia.
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  • 174
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    Surgical and radiologic anatomy 20 (1998), S. 185-189 
    ISSN: 1279-8517
    Keywords: Lateral pterygoid muscle ; Masticatory muscles ; Innervation ; Human ; Anatomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé L'organisation du muscle ptérygoïdien latéral (LPM) en un ou deux chefs a été analysée à travers l'étude de son innervation. Tous les muscles étudiés présentaient une innervation provenant directement du tronc terminal antérieur du nerf mandibulaire. Cette innervation était issue de 1 à 3 nerfs ptérygoïdiens qui se divisaient rapidement en 2 à 8 branches principales. A l'intérieur du muscle, les nerfs s'organisaient en plans verticaux, parallèles entre eux, de dehors en dedans. Ils émettaient des rameaux terminaux horizontaux parallèles aux fibres musculaires. Ce muscle apparaissait donc divisé par des plans nerveux sagittaux obliques et horizontaux, ces derniers reflétant son organisation penniforme. Les couches musculaires pourraient être sélectivement recrutées lors des mouvements mandibulaires. L'organisation nerveuse intra-musculaire montre que le muscle ptérygoïdien latéral doit être considéré comme un muscle constitué d'une seule entité anatomique formée par une alternance de couches musculo-aponévrotiques fonctionnellement indépendantes.
    Notes: Summary The one- or two-headed arrangement of the lateral pterygoid m. (LPM) was analysed by studying the motor nerve distribution within the muscular tissue. In all subjects, the main innervation of the lateral pterygoid m. came from the anterior trunk of the mandibular n. by one to three nerves. These nerves divided into five or six vertical branches which ramified into parallel horizontal tiny fibers. Consequently, the lateral pterygoid m. appeared to be divided into oblique sagittal planes and horizontal layers by the nerve branches, reflecting the multipennate organisation of the muscle. These layers can be selectively recruited during mandibular movements, ensuing a fine medial-lateral control. According to its nerve supply, the LPM has to be considered as a single unit made of independent functional musulo-aponeurotic layers even though its morphologic conformation is in one, two or three heads.
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  • 175
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    Immunogenetics 48 (1998), S. 40-46 
    ISSN: 1432-1211
    Keywords: Key words Immunoglobulin ; Genes ; Kappa light chain ; Human ; Antibody repertoire
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  We describe a hitherto unknown functional IGKV gene, VkLa, belonging to the IGKV1 subgroup with exon 2 having only 94% similarity to the closest known IGKV gene, 1–13/1D-13 (L4/L18a). Genomic DNA sequences spanning from 5’ of the decanucleotide box to 3’ of the heptamer (649 bp) were cloned and sequenced from four individuals. The new gene encodes the conserved amino acids in the exons and contains no apparent defects in known regulatory intron sequences such as pd-box, dc-box, TATA-box, CCCT-elements, splice-sequences, initiation codon, and heptamer sequence. VkLa is therefore potentially functional and, correspondingly, we found transcripts of properly rearranged VkLa with somatical hypermutations. VkLa was found in 12 of 57 (21%) healthy Caucasians by a nested polymerase chain reaction and subsequent sequencing of exon 2. This finding shows that there is more inter-individual variation in the available IGKV gene repertoire than was hitherto assumed. Finally, we describe a minor correction in the IGKV1D-43 (L23) gene sequence.
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  • 176
    ISSN: 1432-1211
    Keywords: Key words Antigen presenting cells ; Dendritic cells ; Cell surface molecule ; Antigen receptor ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Dendritic cells (DC) are specialist antigen presenting cells which capture antigens in the periphery, migrate centrally, and present the processed antigens in the context of major histocompatibility complex and appropriate co-stimulatory molecules to T lymphocytes for the initiation of an immune response. DEC-205 has been identified as a putative antigen-uptake receptor, which is expressed abundantly on mouse DC. The recently cloned mouse DEC-205 cDNA predicts a molecular structure which has a marked similarity to the macrophage mannose receptor. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and cDNA library screening, we obtained the full coding region of human DEC-205 cDNA from the Hodgkin’s disease-derived L428 cell line. The predicted protein structure is a type I transmembrane protein of 1722 amino acids consisting of a signal peptide, cysteine-rich domain, fibronectin type II domain, ten carbohydrate recognition-like domains, transmembrane domain, and a cytoplasmic tail. Human DEC-205 is 77% identical to the mouse protein with completely conserved cysteines. The DEC-205 gene (LY75) was mapped to chromosome band 2q24 by somatic cell hybrid panel analysis and fluorescent in situ hybridization. Northern blot analysis detected 7.8 and 9.5 kilobase DEC-205 transcripts in myeloid, B lymphoid, and Hodgkin’s disease-derived cell lines. RT-PCR analysis indicated that immature blood DC contain a barely detectable amount of DEC-205 transcripts but these were markedly increased upon differentiation/activation.
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  • 177
    ISSN: 1432-1238
    Keywords: Key words Intensive care ; Critical care ; Intensive care unit/organization and administration ; Respiration ; artificial/method ; Human ; Organizational policy ; Data collection ; Health care survey ; Questionnaire ; Length of stay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To determine whether there is variability in the structure and process of ventilatory care in intensive care units (ICUs) of the hospitals of Southwestern Ontario. Design: Self-administered questionnaire-based survey. Setting: ICUs of selected community and teaching hospitals of Southwestern Ontario. Participants: Head of respiratory therapy service of respective hospitals; in those hospitals without respiratory therapists, the ICU nurse manager. Intervention: Self-administered questionnaire. Outcome measure(s): The availability of different models of ventilators and respiratory therapist and physician coverage were assessed. In addition, the use of clinical practice guidelines, respiratory therapists, and the nursing role in ventilatory care were determined. Results: In general, the structure of ventilatory care, including availability of different modes of ventilation, and coverage by respiratory therapists and physicians was more comprehensive in larger hospitals. However, the availability of some modes of ventilation varied more than expected among hospitals of comparable size. Similarly, variability in the process of ventilatory care, defined by the availability of clinical practice guidelines and the roles of respiratory therapists varied both within and among hospitals of different size. Conclusions: The structure and process of ventilatory care in this sample of Southwestern Ontario ICUs was found to be variable. Not all this variability could be accounted for by hospital size, suggesting a potential for improvement in overall ventilatory care. Further study is required before any specific recommendations can be considered.
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  • 178
    ISSN: 1432-1238
    Keywords: Key words Hepatocyte growth factor (HGF) ; Pneumonectomy ; Lung growth ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Proliferation of alveolar type II cells is thought to be critical for the restoration of lung function after diffuse alveolar damage or pneumonectomy. However, the factors that regulate alveolar type II cell proliferation, and the mechanism that brings about compensatory lung growth are not well understood. Hepatocyte growth factor (HGF) has been shown to have hepatotrophic and nephrotrophic functions for regeneration of the liver and kidney. We have attempted to investigate the involvement of HGF in lung regeneration after lung resection. Desgin: A prospective, controlled study. Setting: Adult surgical patients in a university hospital. Patients and measurements: We measured serum HGF levels in eight patients undergoing major lung resection, and in five patients undergoing mastectomy as controls, by using radioimmunoassay and an enzyme-linked immunosorbent assay. Results: In all cases of pneumonectomy, the serum HGF levels increased 3- to 5-fold at 1–3 days (with a peak at 3 days) after operation, and then decreased to nearly basal levels in 2 weeks. However, these levels in patients undergoing mastectomy did not change much over the first 2 weeks, postoperatively. Conclusions: Serum HGF levels increased in patients after major lung resection, which suggests that HGF might play an important role in lung regeneration or compensatory lung growth in humans.
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  • 179
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    International journal of biometeorology 42 (1998), S. 84-88 
    ISSN: 1432-1254
    Keywords: Key words Mortality ; Human ; Seasonality ; Secular trend ; Temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract  Based on records from the Federal Bureau for Statistics of Germany, the seasonality of mortality was investigated for the period 1946–1995. Lowest mortality rates were found during summer (August or September) while highest values were found in winter (January through March). Non-linear regression of all monthly mortality data with the average monthly temperatures in Germany revealed a significant negative relationship (r=–0.739; n=600; P〈0.0001). The fact that the differences between the long-range monthly temperatures and the individual monthly temperatures also showed a distinct relationship to the mortality rates speaks against a mere coincidence of both parameters. The amplitude of this seasonal rhythm declined steadily within the observation period. It is concluded that low temperatures cause an increase in mortality rates and that this effect has become less important during recent decades due to the increased use of central heating and because of improvements in the public health system.
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  • 180
    ISSN: 1432-1106
    Keywords: Key words Cerebellar patients ; Double-step paradigm ; Pointing movement ; Kinematic analysis ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Three patients with cerebellar limb ataxia and three age-matched controls performed arm-pointing movements towards a visual stimulus during an experimental procedure using a double-step paradigm in a three-dimensional space. Four types of trajectories were defined: P1, single-step pointing movement towards the visual stimulus in the initial position S1; P2, double-step pointing movement towards S1; P3, double-step straight pointing movement towards the second position S2; and P4, double-step pointing movement towards S2 with an initial direction towards S1. We found that the cerebellar patients, as well as the controls, were able to modify their motor programs, but with impaired timing, severe anomalies in the direction and amplitude of the changed movement trajectories and alteration of the precision of the pointing movements.
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  • 181
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    Experimental brain research 119 (1998), S. 467-474 
    ISSN: 1432-1106
    Keywords: Key words Aging ; Feedback ; Vision ; Program control ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Young and elderly subjects performed aiming movements to a visual target with a manipulandum to determine whether the elderly reduce their reliance on visual feedback after extended practice. Reliance on visual feedback was assessed by performance on trials in which the cursor displaying arm movement was unpredictably extinguished. Movements were divided into two subcomponents: a primary, ballistic submovement and a secondary, corrective submovement. For both age groups, removal of visual feedback prior to practice resulted in a decrease in the distance covered in the primary submovement, an increase in the distance of the secondary submovement, and a decrease in endpoint accuracy. After extensive practice with the cursor present, the proportion of distance traveled with the primary submovement was again assessed under trial conditions in which the cursor randomly disappeared. Following practice, the young demonstrated that they were capable of extending the primary submovement distance closer to the target. In addition, primary submovement distance was unaffected by the removal of vision following practice. After practice the elderly did not show evidence of lengthening the primary submovement, and submovement distance and endpoint accuracy continued to be altered by the removal of vision. This suggests that, unlike the young, the elderly do not benefit from practice so that they can place a greater proportion of the movement under program control. Thus, on a relative basis, a greater proportion of their overall movement requires corrective adjustments.
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  • 182
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    Experimental brain research 119 (1998), S. 475-482 
    ISSN: 1432-1106
    Keywords: Key words Proprioception ; Eye position ; Botulinum toxin ; Strabismus ; Palisade ending ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Botulinum toxin is sometimes injected into human eye muscles as an alternative to surgery in the correction of strabismus. Within minutes of botulinum injections into ungulate eye muscles, proprioceptive discharge from muscle spindles decreases dramatically. It is only over 7–48 h, however, that surgically treated strabismus patients usually show an altered proprioceptive signal about eye position, presumably from the palisade endings attached to the global multiply innervated fibers. How quickly will botulinum toxin alter proprioceptive registration of eye position in humans? First, to examine the short-term effects, we measured open-loop pointing responses (which requires knowledge of eye position) in six strabismus patients preinjection and then over a 45 min postinjection period, and in six normal controls over the same time period. Second, to examine the long-term effects, 13 strabismus patients were tested preinjection and then daily over the next 3 weeks, and three normal controls over the same time period. We compared their open-loop pointing responses with the injected eye fixating the target to the photographically determined position of the occluded other eye (a measure of where the patient would point if eye position were determined by efference, not proprioception). There were three groups of patients: esotropes with no previous injection, exotropes with no previous injection, and exotropes with previous injection. First, all patients showed significant correction of their tropias. Second, over the short-term, there was no difference in pointing responses found between the patients and the controls (t(18) = –1.427, P = 0.1706). Third, over the long-term, however, the difference between the pointing responses and eye position information was compared among the four groups across four posttests and a significant difference found (F 3,12 = 58.988, P 〈 0.00001). Only in patients with no previous injections was there altered proprioceptive feedback about eye position. Also, injections into the medial rectus induced a significantly greater proprioceptive response than those injected into the lateral rectus. In humans, botulinum toxin alters proprioception from eye muscles only over the long-term. We suggest that the toxin temporarily affects proprioceptive feedback from palisade endings.
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  • 183
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    Experimental brain research 119 (1998), S. 483-492 
    ISSN: 1432-1106
    Keywords: Key words Cerebellar ataxia ; Limb movement ; Multijoint movement ; Kinematics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Kinematic abnormalities of fast multijoint movements in cerebellar ataxia include abnormally increased curvature of hand trajectories and an increased hand path and are thought to originate from an impairment in generating appropriate levels of muscle torques to support normal coordination between shoulder and elbow joints. Such a mechanism predicts that kinematic abnormalities are pronounced when fast movements are performed and large muscular torques are required. Experimental evidence that systematically explores the effects of increasing movement velocities on movement kinematics in cerebellar multijoint movements is limited and to some extent contradictory. We, therefore, investigated angular and hand kinematics of natural multijoint pointing movements in patients with cerebellar degenerative disorders and healthy controls. Subjects performed self-paced vertical pointing movements with their right arms at three different target velocities. Limb movements were recorded in three-dimensional space using a two-camera infrared tracking system. Differences between patients and healthy subjects were most prominent when the subjects performed fast movements. Peak hand acceleration and deceleration were similar to normals during slow and moderate velocity movements but were smaller for fast movements. While altering movement velocities had little or no effect on the length of the hand path and angular motion of elbow and shoulder joints in normal subjects, the patients exhibited overshooting motions (hypermetria) of the hand and at both joints as movement velocity increased. Hypermetria at one joint always accompanied hypermetria at the neighboring joint. Peak elbow angular deceleration was markedly delayed in patients compared with normals. Other temporal movement variables such as the relative timing of shoulder and elbow joint motion onsets were normal in patients. Kinematic abnormalities of multijoint arm movements in cerebellar ataxia include hypermetria at both the elbow and the shoulder joint and, as a consequence, irregular and enlarged paths of the hand, and they are marked with fast but not with slow movements. Our findings suggest that kinematic movement abnormalities that characterize cerebellar limb ataxia are related to an impairment in scaling movement variables such as joint acceleration and deceleration normally with movement speed. Most likely, increased hand paths and decomposition of movement during slow movements, as described earlier, result from compensatory mechanisms the patients may employ if maximum movement accuracy is required.
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  • 184
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    Experimental brain research 119 (1998), S. 504-510 
    ISSN: 1432-1106
    Keywords: Key words Clicks ; Galvanic stimulation ; Vestibular reflexes ; Vestibulospinal reflexes ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of this study was to demonstrate, if possible, vestibulospinal reflex responses in soleus using a stimulus known to be capable of exciting vestibular afferents, namely 100-dB (NHL) clicks. We were able to show short-latency electromyographic (EMG) responses after clicks in five of eight normal subjects, and then we compared these responses with those after transmastoid galvanic stimulation (12 normal subjects). Stimulation of the side towards which the head was rotated (i.e. the side facing backwards) with either clicks or the cathode (anode applied to the opposite side) gave an initial excitatory response in soleus, while click or cathodal stimulation of the opposite side (i.e. the side facing forwards) gave an initial inhibitory response. Onset latencies and modulation with changes in postural task were identical for both click- and galvanic-evoked responses. In addition, there was a significant correlation between the amplitudes of the responses in soleus after click and galvanic stimulation (R 2=0.72). These similarities suggest that the earliest reflex responses in soleus after clicks and galvanic stimulation may be mediated by a common central pathway. In contrast, there was no correlation between the amplitudes of responses evoked by 100-dB clicks in soleus and those evoked by the same stimulus in the sternocleidomastoid. We conclude that vestibular activation by clicks can evoke reflex responses in lower-limb muscles and these responses have similar characteristics to the earliest responses evoked by galvanic vestibular stimulation.
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  • 185
    ISSN: 1432-1106
    Keywords: Key words Cerebellar ataxia ; Limb movements ; Dynamics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In cerebellar ataxia, kinematic aberrations of multijoint movements are thought to originate from deficiencies in generating muscular torques that are adequate to control the mechanical consequences of dynamic interaction forces. At this point the exact mechanisms that lead to an abnormal control of interaction torques are not known. In principle, the generation of inadequate muscular torques may result from an impairment in generating sufficient levels of torques or from an inaccurate assessment and prediction of the mechanical consequences of movements of one limb segment on adjacent joints. We sought to differentiate the relative contribution of these two mechanisms and, therefore, analyzed intersegmental dynamics of multijoint pointing movements in healthy subjects and in patients with cerebellar degeneration. Unrestrained vertical arm movements were performed at three different target movement velocities and recorded using an optoelectronic tracking system. An inverse dynamics approach was employed to compute net joint torques, muscular torques, dynamic interaction torques and gravitational torques acting at the elbow and shoulder joint. In both groups, peak dynamic interaction forces and peak muscular forces were largest during fast movements. In contrast to normal subjects, patients produced hypermetric movements when executing fast movements. Hypermetric movements were associated with smaller peak muscular torques and smaller rates of torque change at elbow and shoulder joints. The patients’ deficit in generating appropriate levels of muscular force were prominent during two different phases of the pointing movement. Peak muscular forces at the elbow were reduced during the initial phase of the movement when simultaneous shoulder joint flexion generated an extensor influence upon the elbow joint. When attempting to terminate the movement, gravitational and dynamic interaction forces caused overshooting extension at the elbow joint. In normal subjects, muscular torque patterns at shoulder and elbow joint were synchronized in that peak flexor and extensor muscular torques occurred simultaneously at both joints. This temporal pattern of muscular torque generation at shoulder and elbow joint was preserved in patients. Our data suggest that an impairment in generating sufficient levels of phasic muscular torques significantly contributes to the patients’ difficulties in controlling the mechanical consequences of dynamic interaction forces during multijoint movements.
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  • 186
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    Experimental brain research 118 (1998), S. 352-360 
    ISSN: 1432-1106
    Keywords: Key words Attention ; Inhibition of return ; Crossmodal ; Orienting ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It is currently controversial whether auditory events produce inhibition of return (IOR). Although some authors argue that this can arise, others propose that peripheral auditory cues do not produce the characteristic IOR pattern of delayed detection latencies for ipsilaterally presented auditory or visual targets, unless a saccade is made to the cued location. We suggest that these previous discrepancies may depend on whether attention is reoriented centrally following the peripheral sound. We presented spatially uninformative peripheral auditory cues prior to visual targets requiring speeded detection responses. IOR was found in the absence of eye movements, provided an auditory reorienting event was presented at central fixation between onset of the peripheral cue and the subsequent target, but not when the central reorienting event was visual. A subsequent experiment demonstrated that auditory IOR between successive targets is similarly significantly reduced in the absence of an appropriate central reorienting event. These results imply that auditory stimuli can induce IOR directly. Previous failures to demonstrate IOR following auditory cues may have been due to an opposing influence of long-lasting attentional facilitation at the cued location, rather than to the putative inability of auditory stimuli to engage oculomotor processes generating IOR.
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  • 187
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    Experimental brain research 118 (1998), S. 415-420 
    ISSN: 1432-1106
    Keywords: Key words Vergence ; Depth perception ; Proprioception ; Limb position ; Pointing ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We sought to determine whether an increase in judged egocentric distance created by increasing vergence-specified distance would be negated when participants pointed at their own finger. It was found that ocular position dominates limb proprioception in the judgement of finger distance in the sagittal plane when vision is available. In contrast, an increase in perceived egocentric distance was largely attenuated by the presence of limb proprioception in reduced visual cue conditions. We conclude that the relative contribution of vergence to perceived distance depends upon the strength of the vergence effort signal when there are other cues present. Furthermore, if the distance percept includes a major contribution from retinal cues, then the visual component will dominate the limb proprioception component. If the visual component is largely determined by vergence information, limb proprioception will make a significant contribution and actually dominate when the vergence effort signal is weak. The results extend previous studies that have found a similar relationship between ocular position and limb proprioception in the perception of a finger′s location in the coronal plane.
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  • 188
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    Experimental brain research 118 (1998), S. 408-414 
    ISSN: 1432-1106
    Keywords: Key words Visual perception ; Visuomotor control ; Orientation ; Depth ; Binocular vision ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Normal human subjects were tested for their ability to discriminate the orientation of a square plaque tilted in depth, using two different tasks: a grasping task and a perceptual matching task. Both tasks were given under separate monocular and binocular conditions. Accuracy of performance was measured by use of an opto-electronic motion analysis system, which computed the hand orientation (specifically, a line joining the tips of the thumb and index finger) as the hand either approached the target during grasping or was used to match the target. In all cases there was a very strong statistical coupling between hand orientation and target orientation, irrespective of viewing conditions. However, the matching data differed from the grasping data in showing a consistent curvature in the hand-target relationship, whereby the rate of change of hand orientation as a function of object orientation was smaller for oblique orientations than for those near the horizontal or vertical. The results are interpreted as reflecting the operation of two different mechanisms for analysing orientation in depth: a visuomotor system (assumed to be located primarily in the dorsal cortical visual stream) and a perceptual system (assumed to be located in the ventral stream). It may be that the requirements of visuomotor control dictate a primary need for absolute orientation coding, whereas those of perception dictate a need for more categorical coding.
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  • 189
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    Experimental brain research 118 (1998), S. 427-430 
    ISSN: 1432-1106
    Keywords: Key words H-reflex ; Interlimb coordination ; Voluntary movement ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In 12 subjects, each sitting on an armchair with the right forearm prone, the H-reflex elicited in the resting flexor carpi radialis muscle underwent cyclic excitability changes correlated with rhythmic flexion-extension movements of the ipsilateral foot (frequency of oscillations between 1.5 and 2.5 Hz). During foot plantar flexion, the H-reflex underwent a clear-cut increase, the maximum facilitation falling, in most subjects, within the second half of that phase; then, a gradual reduction in size led the reflex amplitude back to the initial value at the end of foot dorsal extension. If present also when the wrist and the ankle are moved together, this facilitation should favour the in-phase (isodirectional) association between movements and, conversely, hinder the anti-phase coupling.
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  • 190
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    Experimental brain research 118 (1998), S. 421-426 
    ISSN: 1432-1106
    Keywords: Key words Intracortical inhibition ; Transcranial magnetic stimulation ; Motor exercise ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The motor-evoked potential (MEP) to transcranial magnetic stimulation (TMS) is inhibited when preceded by a subthreshold TMS stimulus at short intervals (1–6 ms; intracortical inhibition, ICI) and is facilitated when preceded by a subthreshold TMS at longer intervals (10–15 ms; intracortical facilitation, ICF). We studied changes in ICI and ICF associated with two motor tasks requiring a different selectivity in fine motor control of small hand muscles (abductor pollicis brevis muscle, APB, and fourth dorsal interosseous muscle, 4DIO). In experiment 1 (exp. 1), nine healthy subjects completed four sets (5 min duration each) of repetitive (1 Hz) thumb movements. In experiment 2 (exp. 2), the subjects produced the same number of thumb movements, but complete relaxation of 4DIO was demanded. Following free thumb movements (exp. 1), amplitudes of MEPs in response to both single and paired TMS showed a trend to increase with the number of exercise sets in both APB and 4DIO. By contrast, more focal, selective thumb movementsinvolving APB with relaxation of 4DIO (exp. 2) caused an increase in MEP amplitudes after single and paired pulses only in APB, while a marked decrease in MEPs after paired pulses, but not after single TMS, in the actively relaxed 4DIO. This effect was more prominent for the interstimulus interval (ISI) of 1–3 ms than for longer ISIs (8 ms, 10 ms, and 15 ms). F-wave amplitudes reflecting excitability of the alpha motoneuron pool were unaltered in APB and 4DIO, suggesting a supraspinal origin for the observed changes. We conclude that plastic changes of ICI and ICF within the hand representation vary according to the selective requirements of the motor program. Performance of more focal tasks may be associated with a decrease in ICI in muscles engaged in the training task, while at the same time ICI may be increased in an actively relaxed muscle, also required for a focal performance. Additionally, our data further supports the idea that ICI and ICF may be controlled independently.
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  • 191
    ISSN: 1432-1106
    Keywords: Key words Transcranial magnetic stimulation ; Interhemispheric transfer ; Simple reaction time ; Manual response ; Poffenberger paradigm ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We investigated the cerebral cortical route by which visual information reaches motor cortex when visual signals are used for manual responses. Subjects responded unimanually to photic stimuli delivered to the hemifield ipsilateral or contralateral to the moving hand. On some trials, trans-cranial magnetic stimulation (TMS) was applied unilaterally over the occiput, with the aim of stimulating extrastriate visual areas and thereby modifying transmission of visual input. In association with the side of a visual stimulus and a motor response, TMS could change inter- or intra-hemispheric transmission needed to convey visual information to motor areas. Reaction time differences following TMS suggested that TMS exerted an inhibitory effect only when visuo-motor information had to be transferred interhemispherically. This result reinforces evidence for an extrastriate pathway of interhemispheric transfer of visuomotor information.
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  • 192
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    Experimental brain research 118 (1998), S. 533-540 
    ISSN: 1432-1106
    Keywords: Key words Otolith ; Utricle ; Linear acceleration ; Vestibulo-ocular reflex ; Vestibular compensation ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied horizontal eye movements evoked by lateral whole body translation in nine patients who underwent vestibular nerve section. Preoperatively, all had preserved caloric function on both sides. Testing was performed before, 1 week and 6–10 weeks after surgery. Patients were seated upright in an electrically powered car running on a linear track. The car executed acceleration steps of 0.24 g, randomly to the left and right in the dark. The normal response consisted of a bidirectionally symmetrical nystagmus with compensatory slow phases. Response asymmetry of the slow-phase velocity of the desaccaded and averaged eye position signal was less than 13% in normals (n = 21). Before surgery, patients’ responses were mostly symmetrical. Postoperatively, responses were diminished or absent with head acceleration towards the operated ear in all patients, causing a marked asymmetry which averaged 56% after correction for spontaneous nystagmus. On follow-up, responses regained symmetry. Thus, early after vestibular nerve section, a single utricle produces a normal LVOR only with ipsilateral head translation. Therefore, afferents for the LVOR seem to originate from the mid-lateral area of the macula, where hair cells are stimulated in their on-direction during ipsilateral head translation. Compensation may depend on recovery of the off-directional responses from lateral hair cells of the remaining utricle.
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  • 193
    ISSN: 1432-1106
    Keywords: Key words Neglect ; Space perception ; Visual vertical ; Visual horizontal ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Current models of spatial neglect focus on deficits in the patients’ horizontal or midsagittal plane. However, other evidence suggests that patients with temporoparietal lesions centered on the parieto-insular-vestibular cortex show disturbed spatial perception of the subjective visual vertical and oblique orientation discrimination in another spatial plane, the frontal plane. As the relationship between neglect and spatial orientation deficits is unclear, we examined how patients with and without visual neglect perform visuospatial tasks in the roll plane and how their performance is related to neglect. Thirteen patients with predominantly right parietal lesions and left-sided neglect, 14 control patients without neglect after right-hemispheric cerebral lesions (RBD-controls), 11 patients without neglect after left-hemispheric lesions (LBD-controls), 3 patients with right-sided neglect after left parietal lesions, and 12 normal subjects were investigated. Constant errors and difference thresholds were measured with a PC-based system when the subjects had to adjust a luminous line to their subjective visual vertical, subjective visual horizontal, and in relation to an obliquely oriented reference line. Subjects were oriented with their head and body earth-vertical while sitting in a chair in total darkness. Patients with left-sided as well as those with right-sided neglect showed a significant, in most cases contraversive, tilt of the three spatial orientations (about 5° counterclockwise in the left neglect group and 5.5°–8.5° clockwise in the right neglect group). In contrast, the two patient groups without neglect as well as the normal subjects showed nearly perfect visuospatial judgements with constant errors of less than 0.8°. Difference thresholds were significantly elevated in patients with left neglect and in two of three patients with right-sided neglect, whereas normal control subjects and both control patient groups without neglect performed indistinguishably, having thresholds of one-tenth of those of the neglect patients. Tilt of all three spatial axes was significantly related to the severity of neglect (mean r for unsigned errors, 0.74; for difference thresholds, 0.40), indicating a significant contribution to the symptomatology of left and right spatial neglect. These results indicate a close although not necessarily causal link between spatial orientation deficits in the frontal plane and hemispatial neglect in patients with left or right parietal lesions, surpassing the well-documented impairments of these patients in the horizontal plane.
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    Experimental brain research 122 (1998), S. 131-138 
    ISSN: 1432-1106
    Keywords: Key words Synergy ; Isometric ; Finger ; Redundancy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Based on previous studies, we formulated a principle of error compensation as a major principle of synergy organization during motor tasks performed by a redundant set of effectors. Within the present study, we tested the principle by an investigation of the performance of individual fingers during isometric force production when another task was performed simultaneously. Subjects were asked to press at about 30% of the maximal contraction force with three fingers (index, middle, and ring) acting in parallel. Then, they were required to perform a series of taps at 2 Hz with one of the fingers. In all the tasks, nontapping fingers changed their force production without a time delay with the changes in the force by the tapping finger. During tapping with the index and with the middle finger, both nontapping fingers showed changes in their force negatively correlated with changes in force of the tapping finger. During tapping with the ring finger, two types of behavior could be seen in different subjects with the force of the middle finger going out of phase (group 1) or in phase (group 2) with the force of the ring finger. In both cases, the force of the index finger was out of phase with the force of the ring finger. These changes, on average, induced a compensation for the expected drop in finger force during tapping, ranging in different conditions from 94% to 102%. The ratio of forces produced by the nontapping fingers did not change during the tapping in all the cases except group 2 during ring-finger tapping, when the index finger started to generate significantly higher force as compared to the middle finger. We interpret the data as results of the action of a feed-forward central mechanism leading to parallel changes in forces produced by fingers united into a structural unit.
    Type of Medium: Electronic Resource
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  • 195
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    Experimental brain research 122 (1998), S. 185-195 
    ISSN: 1432-1106
    Keywords: Key words Posture ; Equilibrium ; Sway ; Posturography ; Sensory organization test ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Multivariate descriptors of sway were used to test whether altered sensory conditions result not only in changes in amount of sway but also in postural coordination. Eigenvalues and directions of eigenvectors of the covariance of shnk and hip angles were used as a set of multivariate descriptors. These quantities were measured in 14 healthy adult subjects performing the Sensory Organization test, which disrupts visual and somatosensory information used for spatial orientation. Multivariate analysis of variance and discriminant analysis showed that resulting sway changes were at least bivariate in character, with visual and somatosensory conditions producing distinct changes in postural coordination. The most significant changes were found when somatosensory information was disrupted by sway-referencing of the support surface (P=3.2·10−10). The resulting covariance measurements showed that subjects not only swayed more but also used increased hip motion analogous to the hip strategy. Disruption of vision, by either closing the eyes or sway-referencing the visual surround, also resulted in altered sway (P=1.7·10−10), with proportionately more motion of the center of mass than with platform sway-referencing. As shown by discriminant analysis, an optimal univariate measure could explain at most 90% of the behavior due to altered sensory conditions. The remaining 10%, while smaller, are highly significant changes in posture control that depend on sensory conditions. The results imply that normal postural coordination of the trunk and legs requires both somatosensory and visual information and that each sensory modality makes a unique contribution to posture control. Descending postural commands are multivariate in nature, and the motion at each joint is affected uniquely by input from multiple sensors.
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  • 196
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    Experimental brain research 122 (1998), S. 247-252 
    ISSN: 1432-1106
    Keywords: Key words Multisensory integration ; Saccade ; Reaction time ; Gaze shifts ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Information from the auditory and visual systems converges in the nervous system with physiological and behavioral consequences. Most of our knowledge about the rules governing such convergence has been obtained in experiments where the strength or the timing of the individual auditory and visual stimuli has been varied. Relatively little attention has been paid to the spatial relationship between different modalities of stimuli in multisensory experiments. We studied saccadic reaction times of human subjects to bimodal auditory and visual stimulus presentations under two conditions: first, with the targets spatially coincident and, second, with various degrees of spatial separation or disparity. In the first experiment, we found that the saccadic reaction times were consistently shorter than would be predicted by independent processing of information about the visual and auditory targets. These results suggest convergence of multimodal information at one or more loci within the nervous system. In the second experiment, we found that saccadic latency gradually increased as spatial distance between the auditory and visual targets increased. Evidence for neural summation was found over a wide range of spatial disparities. These results suggest that multisensory information can be integrated and have significant influences on behavior over a surprisingly large range of spatial disparity.
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  • 197
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    Experimental brain research 122 (1998), S. 235-246 
    ISSN: 1432-1106
    Keywords: Key words Gaze stabilization ; Head stability ; Posturography ; Vestibulo-ocular reflex ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Dynamic posturography by measurement of center of pressure (COP) is a widely employed technique for evaluating the vestibular system. However, the relationship of COP motion to vestibulo-ocular reflex (VOR) function and image stability on the retina has not been determined previously. To assess these relationships, we report gaze, head, and trunk stability during dynamic posturography in 11 normal volunteers, 7 subjects with unilateral vestibular lesions, and 3 subjects with bilateral vestibular lesions. Posturographic tasks consisted of standing still and standing on a platform that was sliding (0.2 Hz), tilting (0.1 Hz), or covered with a foam cushion 6 cm thick while tilting (0.1 Hz). Each perturbation was imposed in the anterior-posterior and repeated in the medial-lateral direction, in both light and darkness. Subjects viewed (or in darkness remembered) a target located 50, 100, or 500 cm distant. COP, angular eye position, and angular and linear orbit and trunk positions were measured using magnetic search coils and flux gate magnetometer sensors. With the target visible, the velocity of image motion on the retina was on average always less than 1°/s, well within the range consistent with high visual acuity. In darkness, gaze velocity increased for normal and vestibulopathic subjects. During tilt, vestibulopathic subjects had a significantly greater gaze velocity than controls. Gain of the angular VOR (eye velocity/head velocity) was significantly lower in darkness than in light and in vestibulopathic as compared to control subjects. Gain of the VOR was significantly correlated with gaze instability, but variation in VOR gain accounted for only 20–40% of the variance. In darkness, the velocity of the COP was significantly greater in vestibulopathic than control subjects for every condition tested. In light, this difference was small and often not significant. Although spectral analysis of the COP indicated frequencies above 1 Hz that were not observed in motion of the trunk and orbit, root mean square (RMS) velocities of the trunk and orbit in the horizontal plane were higher in darkness and in vestibulopathic subjects, mirroring COP findings. Only in vestibulopathic subjects tested in darkness was there a correlation between COP velocity and gaze velocity; COP velocity was otherwise uncorrelated with gaze. Gaze velocity was greater with near than with distant targets. Vertical VOR gain was higher with near targets. No other significant effects of target distance were found. Head movement strategy, VOR gain, and COP were all unaffected by target proximity. These data show that gaze velocity measurements during dynamic posturography in darkness are sensitive to vestibular loss. With a visible target, both COP and gaze stability of vestibulopathic subjects are difficult to distinguish from normal. During visual feedback, it is likely that image stabilization over the range of frequencies tested is achieved through better head stability and through visual tracking, allowing vestibulopathic subjects to maintain adequate visual acuity.
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  • 198
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    Experimental brain research 122 (1998), S. 260-274 
    ISSN: 1432-1106
    Keywords: Key words Eye-head coordination ; Bilateral vestibular loss ; Adaptation ; Vestibulo-ocular reflex ; Vestibulo-saccadic reflex ; Saccadic gaze shift ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Eye-head coordination during saccadic gaze shifts normally relies on vestibular information. A vestibulo-saccadic reflex (VSR) is thought to reduce the eye-in-head saccade to account for current head movement, and the vestibulo-ocular reflex (VOR) stabilizes postsaccadic gaze while the head movement is still going on. Acute bilateral loss of vestibular function is known to cause overshoot of gaze saccades and postsaccadic instability. We asked how patients suffering from chronic vestibular loss adapt to this situation. Eye and head movements were recorded from six patients and six normal control subjects. Subjects tracked a random sequence of horizontal target steps, with their heads (1) fixed in primary position, (2) free to move, or (3) preadjusted to different head-to-target offsets (to provoke head movements of different amplitudes). Patients made later and smaller head movements than normals and accepted correspondingly larger eye eccentricities. Targeting accuracy, in terms of the mean of the signed gaze error, was better in patients than in normals. However, unlike in normals, the errors of patients exhibited a large scatter and included many overshoots. These overshoots cannot be attributed to the loss of VSR because they also occurred when the head was not moving and were diminished when large head movements were provoked. Patients’ postsaccadic stability was, on average, almost as good as that of normals, but the individual responses again showed a large scatter. Also, there were many cases of inappropriate postsaccadic slow eye movements, e.g., in the absence of concurrent head movements, and correction saccades, e.g., although gaze was already on target. Performance in patients was affected only marginally when large head movements were provoked. Except for the larger lag of the head upon the eye, the temporal coupling of eye and head movements in patients was similar to that in normals. Our findings show that patients with chronic vestibular loss regain the ability to make functionally appropriate gaze saccades. We assume, in line with previous work, three main compensatory mechanisms: a head movement efference copy, an active cervico-ocular reflex (COR), and a preprogrammed backsliding of the eyes. However, the large trial-to-trial variability of targeting accuracy and postsaccadic stability indicates that the saccadic gaze system of patients does not regain the high precision that is observed in normals and which appears to require a vestibular head-in-space signal. Moreover, this variability also permeates their gaze performance in the absence of head movements.
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  • 199
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    Experimental brain research 119 (1998), S. 171-178 
    ISSN: 1432-1106
    Keywords: Key words Rapid body sway ; Leg muscle activity ; EMG pattern ; Ischemic nerve block ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Electromyographic (EMG) patterns of leg muscles associated with rapid body sway were studied in relation to displacement of the center of foot pressure (CFP). Standing subjects were instructed to shift the CFP by swaying their bodies, pivoting at the ankle as rapidly and accurately as possible after an auditory signal. CFP position was designated as N when the subject maintained a relaxed bending posture and as F when a maximally forward-leaning posture was maintained. A serial, stereotyped triphasic EMG pattern was observed in the rapid shift of CFP from N to F: cessation of EMG activity in the gastrocnemius (GC) muscle was followed by a burst in the tibialis anterior (TA) muscle (acceleration phase), and then resumed discharge occurred in the GC muscle with cessation of activity in the TA muscle (deceleration and stop). When the subject shifted the CFP from N to F to different degrees, the duration and amount of EMG activity in the TA muscle during acceleration and the GC muscle in deceleration were proportionate to the amount of CFP displacement associated with forward body sway. To determine the functional roles of sensory inputs from the foot on the triphasic EMG pattern, body sway was studied under the condition of sensory block in the feet induced by ischemia from tourniquets placed bilaterally just above the ankle joints. The triphasic EMG pattern persisted during ischemia. The time of GC cessation and the onset of TA burst at acceleration remained unchanged, but the times of TA cessation and resumption of GC discharge at deceleration were altered during ischemia. Moreover, subjects were unable to stop at F and eventually fell. These results indicate that both amount and duration of EMG activity associated with rapid body sway are functions of the amount of CFP displacement. Somatic sensation from the feet is important for control of burst and cessation timing and duration in leg muscle activity.
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  • 200
    ISSN: 1432-1106
    Keywords: Key words Cortical plasticity ; Phantom limb pain ; Traumatic amputation ; Congenital aplasia ; Neuromagnetic source imaging ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The relationship between phantom limb phenomena and cortical reorganization was examined in five subjects with congenital absence of an upper limb and nine traumatic amputees. Neuromagnetic source imaging revealed minimal reorganization of primary somatosensory cortex in the congenital amputees (M=0.69 cm, SD 0.24) and the traumatic amputees without phantom limb pain (M=0.27 cm, SD 0.25); the amputees with phantom limb pain showed massive cortical reorganization (M=2.22 cm, SD 0.78). Phantom limb pain and nonpainful phantom limb phenomena were absent in the congenital amputees. Whereas phantom limb pain was positively related to cortical reorganization (r=0.87), nonpainful phantom phenomena were not significantly correlated with cortical reorganization (r=0.34). Sensory discrimination was normal and mislocalization (referral of stimulation-induced sensation to a phantom limb) was absent in the congenital amputees. The role of peripheral and central factors in the understanding of phantom limb pain and phantom limb phenomena is discussed in view of these findings.
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