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  • 1995-1999  (164)
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  • 1998  (164)
  • Human  (163)
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  • 101
    Electronic Resource
    Electronic Resource
    Reach to grasp: the response to a simultaneous perturbation of object position and size (1998)
    Springer
    Experimental brain research 120 (1998), S. 31-40 
    Details
    ISSN: 1432-1106
    Keywords: Key words Reach to grasp ; Perturbation ; Kinematics ; Motor control ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study assessed the reach to grasp movement and its adaptive response to a simultaneous perturbation of object location and size. The aim was to clarify the means by which integration between the neural pathways modulating transport and manipulation is achieved. Participants (n = 11) were required to reach 30 cm to grasp a central illuminated cylinder of either small (0.7 cm) or large (8 cm) diameter. For a small percentage of trials (20/100) a visual perturbation was introduced unexpectedly at the onset of the reaching action. This consisted of a shift of illumination from the central cylinder to a cylinder of differing diameter (large in session A; small in session B) that was positioned 20° to the left (n = 10 trials) or to the right (n = 10) of the central cylinder. The subject was required to grasp the newly illuminated cylinder. Movement duration for these “double” (position and size) perturbed trials was much longer than those of control trials to the central cylinder (session A: by an average of 250 ms; session B: 180 ms), and the increased values were much greater than those reported previously in “single” perturbation studies where either size or location of the object was perturbed. Initial signs of a response to the “double” perturbation were seen almost simultaneously in the transport parameter of peak arm deceleration and in the manipulation parameter of maximum grip aperture, but these changes were not evident until more than 400 ms after movement onset, a response onset much later than that found in “single” perturbation studies. It is proposed that the visual change resultant from the double perturbation activates integration centres that at first gate the flow of information to the parallel channels of transport and manipulation. Following processing of this information, these centres act to instigate a synchronised and coordinated response in both components. These results add support to the existence of neural centres dedicated to the integration of parallel neural pathways, and which exercise flexibility in the degree to which these components are “coupled” functionally.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050375
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  • 102
    Electronic Resource
    Electronic Resource
    Changes in the symmetry of rapid movements Effects of velocity and viscosity (1998)
    Springer
    Experimental brain research 120 (1998), S. 52-60 
    Details
    ISSN: 1432-1106
    Keywords: Key words Movement symmetry ; Muscle viscosity ; Equilibrium-point hypotheses ; Load ; Muscle activation patterns ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Five subjects made rapid, discrete elbow flexion movements over different distances, against different inertial loads, as well as under distance and load combinations that kept movement time constant. The results demonstrated that an increase in peak movement velocity was associated with an increase in the temporal symmetry ratio of the movement (acceleration time divided by deceleration time), as well as with an increase in both agonist electromyographic (EMG) burst duration and antagonist EMG latency. Since an increase in peak movement velocity is associated with faster agonist muscle shortening, as well as with faster stretching of the antagonist muscle, we hypothesize that the velocity-related changes in movement symmetry can be viewed as, at least partially, a consequence of muscle viscosity. Viscosity increasingly resists the shortening agonist and assists the lengthening antagonist when movement velocity increases. Therefore, the agonist muscles require more time to produce the required impulse, while the antagonist muscle can brake the movement in a shorter period of time. In order to test the hypothesis that viscosity is responsible for the velocity-associated changes in the symmetry ratio, we performed a second experiment with distance and load combinations identical to those of the first experiment, but with different external viscous loads, which resisted the slower and assisted the faster movements. The results demonstrated that the movements became more symmetrical in the presence of the viscous load. There were also changes in agonist duration and antagonist latency. We conclude that changes in the symmetry associated with changes in movement velocity may be due to the effects of either muscle viscosity or changes in how muscles are activated to account for differences in viscous force.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050377
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  • 103
    Electronic Resource
    Electronic Resource
    Fast, anticipatory smooth-pursuit eye movements appear to depend on a short-term store (1998)
    Springer
    Experimental brain research 120 (1998), S. 129-133 
    Details
    ISSN: 1432-1106
    Keywords: Key words Eye movements ; Smooth pursuit ; Prediction ; Motor memory ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Anticipatory smooth pursuit before the expected appearance of a moving target can reduce the initial retinal blur caused by the 100-ms delay of visual feedback. Humans, though, can only voluntarily generate smooth velocities up to about 5°/s without a moving target. However, previous experiments have shown that repetitive brief presentations of a moving target every few seconds appear to charge an internal store, the contents of which can later be released to generate higher velocity anticipatory movements. This store’s longevity was assessed here by repetitively presenting a moving target for 500 ms at different known intervals up to 7.2 s. Target motion at 25°/s or 50°/s was tested, with presentations in alternate directions or the same direction. Anticipatory velocity, measured 100 ms after target onset, decreased with increasing interval for all target motion conditions. A decrease was still seen when accurate timing cues were given before each presentation, suggesting that the drive for anticipatory pursuit is held in a short-term store lasting a few seconds which can enhance the low velocities produced by volition alone. The results also demonstrate that high-velocity anticipatory pursuit helps to overcome the temporal delays in the system and allows target velocity to be matched at an earlier time.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050385
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  • 104
    Electronic Resource
    Electronic Resource
    Phase-dependent electromyographic activity of the lower-limb muscles of a patient with clinically complete spinal cord injury during orthotic gait (1998)
    Springer
    Experimental brain research 120 (1998), S. 139-142 
    Details
    ISSN: 1432-1106
    Keywords: Key words Orthotic gait ; Paraplegia ; Electromyography ; Locomotion ; Spinal stepping generator ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We examined the lower-limb electromyographic (EMG) activity from a patient with clinically complete spinal cord injury during orthotic gait. A newly developed gait orthosis was used to obtain bipedal locomotion. The surface EMG data during the gait together with the biomechanical variables were collected by way of a radio EMG system. A cyclic EMG activation pattern corresponding to the gait cycles were observed in each of the paralyzed lower-limb muscles during the orthotic gait. Although the EMG activation did not seem to contribute toward generating the gait, it showed some similarities to that of the infant stepping or immature gait. These results might be regarded as one of the indirect pieces of evidence that suggest the existence of a spinally originating motor mechanism underlying human locomotion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050387
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  • 105
    Electronic Resource
    Electronic Resource
    Gating of somatosensory evoked potentials during voluntary movement of the lower limb in man (1998)
    Springer
    Experimental brain research 120 (1998), S. 143-152 
    Details
    ISSN: 1432-1106
    Keywords: Key words Somatosensory evoked potential ; Gating ; H-reflex ; Voluntary movement ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Somatosensory evoked potentials (SEPs) evoked by stimulation of the tibial nerve (TN) in the popliteal fossa, the sural nerve (Sur) at the lateral malleole, and an Achilles tendon (Achilles) tap were recorded before and during voluntary plantarflexion, dorsiflexion, and cocontraction of the ipsi- and contralateral foot in normal subjects. Suppression (gating) of the TN-SEP began around 60 ms before the onset of electromyographic activity (EMG), and became maximal 50–100 ms after the onset of EMG. Similar gating was observed for the SEP evoked by activation of muscle afferents (Achilles) and cutaneous afferents (Sur). The TN-SEP was similarly depressed at the onset of a plantarflexion as at the onset of dorsiflexion. A depression, although much smaller, was also observed at the onset of movement of the contralateral limb. The depression of the TN-SEP after the onset of EMG decreased when fast-conducting afferents were blocked by ischemia below the knee joint. The TN-SEP was equally depressed during tonic dorsiflexion, plantarflexion, and cocontraction of dorsi- and plantarflexors. The TN-SEP was depressed for up to 300 ms when preceded by stimulation of Sur or a biceps femoris tendon tap. Gating of lower limb SEPs thus appears to have both central and peripheral components of which neither seems to be specific for the muscle being contracted or the sensory afferents being stimulated. We encourage that caution is taken when drawing functional conclusions regarding movement-specific modulation of afferent inflow to the somatosensory cortex based on observations of gating of lower limb SEP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050388
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  • 106
    Electronic Resource
    Electronic Resource
    Effects of anterior cingulate cortex lesions on ocular saccades in humans (1998)
    Springer
    Experimental brain research 120 (1998), S. 173-183 
    Details
    ISSN: 1432-1106
    Keywords: Key words Cingulate cortex ; Eye movements ; Saccades ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cerebral blood flow studies in humans suggest that the anterior cingulate cortex (ACC) could be involved in eye movement control. In two patients with a small infarction affecting the posterior part of this area (on the right side) and in ten control subjects, we studied several paradigms of saccadic eye movements: gap task, overlap task, antisaccades (using either a 5° or 25° lateral target), memory-guided saccades with a short (1 s) or long (7 s) delay, and sequences of memory-guided saccades. Compared with controls, patients had normal latency in the gap task but increased latency in the other tasks. The gain of memory-guided saccades was markedly decreased, bilaterally, whatever the duration of the delay. Patients made more errors than controls in the antisaccade task when the 5° lateral target was used, and a higher percentage of chronological errors in the sequences of saccades. These results show that the posterior part of the right ACC plays an important role in eye movement control and suggest that this area could correspond to a “cingulate eye field” (CEF). The role of this hypothetical CEF could be an early activation exerted on the frontal ocular motor areas involved in intentional saccades and also a direct action on brainstem ocular premotor structures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050391
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  • 107
    Electronic Resource
    Electronic Resource
    Context-dependent reflex control: some insights into the role of balance (1998)
    Springer
    Experimental brain research 119 (1998), S. 251-259 
    Details
    ISSN: 1432-1106
    Keywords: Key words Reflexes ; Control strategies ; Tripping ; Balance ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recent research suggests that the balance requirements of a task dictate the reflexive response. However, these observations were inferred indirectly from either different tasks or different phases of the same task. This study directly tested the hypothesis of balance-dependent control during recovery from an unexpected trip. The subjects were tripped in two different support conditions: unilimb support (provided by the stance limb) or trilimb support (provided by the stance limb and both arms placed on adjacent parallel bars). The subjects exhibited anticipatory changes: they biased the body center of mass toward the support limb in the mediolateral direction and elevated the swing limb higher when there was a possibility of being tripped. The electromyographic (EMG) latencies were not influenced by the threat to equilibrium. The magnitudes of the EMG reflexive response to the trip were clearly modulated as a function of the threat to stability, not in a simple manner, but rather in a complex manner, which optimized the recovery strategy. It is evident that the overriding concern, equilibrium control during locomotion, has a dominant influence on reflex modulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050339
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  • 108
    Electronic Resource
    Electronic Resource
    Magnetic transcranial stimulation at intensities below active motor threshold activates intracortical inhibitory circuits (1998)
    Springer
    Experimental brain research 119 (1998), S. 265-268 
    Details
    ISSN: 1432-1106
    Keywords: Key words Intracortical inhibitory circuits ; Brain stimulation ; Motor cortex ; descending volleys ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A magnetic transcranial conditioning stimulus given over the motor cortex at intensities below threshold for obtaining electromyographical (EMG) responses in active hand muscles can suppress responses evoked in the same muscles at rest by a suprathreshold magnetic test stimulus given 1–5 ms later. In order to define the mechanism of this inhibitory effect, we recorded descending volleys produced by single and paired magnetic transcranial stimulation of motor cortex through high cervical, epidural electrodes implanted for pain relief in two conscious subjects with no abnormality of the central nervous system. The conditioning stimulus evoked no recognisable descending activity in the spinal cord, whilst the test stimulus evoked 3–4 waves of activity (I-waves). Conditioning stimulation suppressed the size of both the descending spinal cord volleys and the EMG responses evoked by the test stimulus. Inhibition of the descending spinal volleys was most pronounced at ISI 1 ms and had disappeared by ISI 5 ms. It was evident for all components following the I1-wave, while the I1-wave itself was not inhibited at all. We conclude that a small conditioning magnetic stimulus can suppress the excitability of human motor cortex, probably by activating local cortico-cortical inhibitory circuits.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050341
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  • 109
    Electronic Resource
    Electronic Resource
    Force sharing among fingers as a model of the redundancy problem (1998)
    Springer
    Experimental brain research 119 (1998), S. 276-286 
    Details
    ISSN: 1432-1106
    Keywords: Key words Hand ; Finger forces ; Force sharing ; Motor redundancy ; Voluntary movement ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of this study was to test Bernstein’s idea that motor synergies provide solutions to the motor redundancy problem. Forces produced by individual fingers of one hand were recorded in one-, two-, three-, and four-finger tasks. The subjects (n=10) were asked to produce maximal total force (maximal voluntary contraction, MVC) and to match a ramp total force profile using different combinations of fingers. We found that individual finger forces were smaller in multifinger MVC tasks than in single-finger tasks. The deficit increased with the number of fingers involved. A saturation effect was observed: when several effectors were involved, adding a new effector did not significantly change the total force output. The data confirmed the idea that the central neural drive arriving at the level of synergies has a certain limit, a ceiling, that cannot be exceeded. The central nervous system cannot maximally activate the muscles serving all the fingers at the same time. Secondly, during the course of ramp trials, forces produced by individual fingers were linearly related to each other. Hence, a force sharing pattern was established at the beginning of the trial and did not change during the ramp period. A hypothesis is suggested that force distribution among fingers may be organized so as to minimize unnecessary rotational moment with respect to the functional longitudinal axis of the hand. Finally, in the four-finger trials, variance of the total maximal force output in ten consecutive attempts was smaller than the sum of variances of the maximal individual finger forces. The finding suggests that the control system of the motor tasks studied involves at least two levels, a central neural drive level and a synergy level. At the synergy level, an intercompensation in individual finger force production is observed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050343
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  • 110
    Electronic Resource
    Electronic Resource
    Tilt perception during dynamic linear acceleration (1998)
    Springer
    Experimental brain research 119 (1998), S. 307-314 
    Details
    ISSN: 1432-1106
    Keywords: Key words Tilt ; Otolith organs ; Vestibular system ; Perception ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Head tilt is a rotation of the head relative to gravity, as exemplified by head roll or pitch from the natural upright orientation. Tilt stimulates both the otolith organs, owing to shifts in gravitational orientation, and the semicircular canals in response to head rotation, which in turn drive a variety of behavioral and perceptual responses. Studies of tilt perception typically have not adequately isolated otolith and canal inputs or their dynamic contributions. True tilt cannot readily dissociate otolith from canal influences. Alternatively, centrifugation generates centripetal accelerations that simulate tilt, but still entails a rotatory (canal) stimulus during important periods of the stimulus profiles. We reevaluated the perception of head tilt in humans, but limited the stimulus to linear forces alone, thus isolating the influence of otolith inputs. This was accomplished by employing a centrifugation technique with a variable-radius spinning sled. This allowed us to accelerate the sled to a constant angular velocity (128°/s), with the subject centered, and then apply dynamic centripetal accelerations after all rotatory perceptions were extinguished. These stimuli were presented in the subjects’ naso-occipital axis by translating the subjects 50 cm eccentrically either forward or backward. Centripetal accelerations were thus induced (0.25 g), which combined with gravity to yield a dynamically shifting gravitoinertial force simulating pitch-tilt, but without actually rotating the head. A magnitude-estimation task was employed to characterize the dynamic perception of pitch-tilt. Tilt perception responded sluggishly to linear acceleration, typically reaching a peak after 10–30 s. Tilt perception also displayed an adaptation phenomenon. Adaptation was manifested as a per-stimulus decline in perceived tilt during prolonged stimulation and a reversal aftereffect upon return to zero acceleration (i.e., recentering the subject). We conclude that otolith inputs can produce tilt perception in the absence of canal stimulation, and that this perception is subject to an adaptation phenomenon and low-pass filtering of its otolith input.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050346
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  • 111
    Electronic Resource
    Electronic Resource
    Dipolar sources of the early scalp somatosensory evoked potentials to upper limb stimulation Effect of increasing stimulus rates (1998)
    Springer
    Experimental brain research 120 (1998), S. 306-315 
    Details
    ISSN: 1432-1106
    Keywords: Key words Somatosensory evoked potential generators ; Stimulus rates ; Brain electrical source analysis ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Brain electrical source analysis (BESA) of the scalp electroencephalographic activity is well adapted to distinguish neighbouring cerebral generators precisely. Therefore, we performed dipolar source modelling in scalp medium nerve somatosensory evoked potentials (SEPs) recorded at 1.5-Hz stimulation rate, where all the early components should be identifiable. We built a four-dipole model, which was issued from the grand average, and applied it also to recordings from single individuals. Our model included a dipole at the base of the skull and three other perirolandic dipoles. The first of the latter dipoles was tangentially oriented and was active at the same latencies as the N20/P20 potential and, with opposite polarity, the P24/N24 response. The second perirolandic dipole showed an initial peak of activity slightly earlier than that of the N20/P20 dipolar source and, later, it was active at the same latency as the central P22 potential. Lastly, the third perirolandic dipole exaplaining the fronto-central N30 potential scalp distribution was constantly more posterior than the first one. In order to evaluate the effect of an increasing repetition frequency on the activity of SEP dipolar sources, we applied the model built from 1.5-Hz SEPs to traces recorded at 3-Hz and 10-Hz repetition rates. We found that the 10-Hz stimulus frequency reduced selectively the later of the two activity phases of the first perirolandic dipole. The decrement in strength of this dipolar source can be explained if we assume that: (a) the later activity of the first perirolandic dipole can represent the inhibitory phase of a “primary response”; (b) two different clusters of cells generate the opposite activities of the tangential perirolandic dipole. An additional finding in our model was that two different perirolandic dipoles contribute to the centro-parietal N20 potential generation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050404
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  • 112
    Electronic Resource
    Electronic Resource
    Target anticipation and impairment of smooth pursuit eye movements in schizophrenia (1998)
    Springer
    Experimental brain research 120 (1998), S. 316-324 
    Details
    ISSN: 1432-1106
    Keywords: Key words Smooth pursuit ; Schizophrenia ; Prediction ; Monitor theory ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A reduced gain of smooth pursuit eye velocity has frequently been reported in schizophrenic patients. With respect to predictable stimuli, this could be due to a deficit in predicting the target path. To determine this contribution to smooth pursuit eye movement performance, we analyzed the ocular smooth pursuit response to a sinusoidally moving target that was suddenly stopped after some cycles of regular movement. Horizontal eye movements were recorded with infrared reflection oculography in a group of 17 schizophrenic in-patients and 16 age-matched healthy subjects for controls. The patients exhibited a reduced gain of smooth pursuit velocity, but phase lag was not different from the control group. After the unpredictable stop of target movement, predictive sinusoidal smooth pursuit was maintained for 150 to 200 ms in both groups. The resulting maximal position and velocity error was larger in the patient group. In conclusion, schizophrenic patients were able to generate a normal anticipatory component of smooth pursuit and to switch it off in response to external demands. They showed, however, an increased velocity of anticipatory pursuit, which might be used to compensate for the primary deficit of smooth pursuit velocity frequently found in schizophrenics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050405
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  • 113
    Electronic Resource
    Electronic Resource
    Timing variability of repetitive saccadic eye movements (1998)
    Springer
    Experimental brain research 120 (1998), S. 325-334 
    Details
    ISSN: 1432-1106
    Keywords: Key words Eye movements ; Timing ; Saccades ; Human ; Wing and Kristofferson model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We assessed the suitability of using the Wing and Kristofferson model for timing repetitive motor responses to analyse timing variability during repetitive saccadic eye movements. The model decomposes total timing variability (TV) into a central timing component (CV) and a peripheral motor delay component (MV). Eight normal subjects made voluntary horizontal saccades, in darkness, in synchrony with a regular auditory metronome. After 20 saccades had been produced, the metronome was switched off and subjects continued responding at the same frequency until 31 further saccades had been made. Inter-saccade intervals (ISIs) from the unpaced phase were used to calculate TV, CV and MV. Three different target intervals, paced by auditory cues, were used – 496 ms, 752 ms and 1000 ms. In the paced phase, subjects’ ISIs closely matched the auditory cue intervals. In the unpaced phase, subjects were clearly able to respond at three different frequencies. As predicted by the Wing and Kristofferson model, the durations of successive ISIs tended to be negatively correlated. As expected, TV and CV increased with increasing ISI. Contrary to the expectation of the model that MV would remain constant, we found that it increased with increasing interval. Our results do not conclusively demonstrate the validity of applying the Wing and Kristofferson model to the analysis of timing variability during repetitive saccadic eye movements. However, comparison with previous studies shows that, at least in normal subjects, it is equally valid to apply the model to the analysis of repetitive saccadic eye movements as it is to apply it to the analysis of data from other effectors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050406
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  • 114
    Electronic Resource
    Electronic Resource
    Effects of pre-cues on voluntary and reflexive saccade generation II. Pro-cues for anti-saccades (1998)
    Springer
    Experimental brain research 120 (1998), S. 417-431 
    Details
    ISSN: 1432-1106
    Keywords: Key words Attention ; Orienting ; Saccadic reaction time ; Express saccade ; Anti-saccade ; Gap effect ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The reaction times of saccades (SRT) to a suddenly presented visual stimulus (pro-saccade) can be decreased and a separate mode of express saccades can occur when a gap paradigm is used (i.e. fixation-point offset precedes target onset by 200 ms). A valid peripheral cue, presented briefly (100 ms) before target onset, has been found to facilitate the generation of saccades to the target, thereby increasing the frequency of express saccades and decreasing the mean latency. This facilitation occurs only for cues that correctly indicate the direction of the subsequent target presentation (valid cues). The present study investigates the effects of valid cues on SRTs and error rate in the anti-saccade task (saccades in the direction opposite to the stimulus) by systematically varying the cue lead time (CLT) and using the gap and overlap conditions, i.e. fixation point remains on throughout the trial. For a CLT of 100 ms, both reaction times and error rates were significantly increased. With increasing CLT (200–500 ms), both the reaction times of the anti-saccades and the error rates returned to approximately control level, with CLT more than 200 ms in both the gap and the overlap condition. Additional experiments using non-informative cues in the overlap task showed that the reaction times of correct anti-saccades and the error rate were decreased when cue and stimulus appeared at the same side. Analysis of the erratic pro-saccades revealed that almost all of them were corrected, i.e. they were followed by a second saccade towards the required location. It is found that the correction times were usually very short, with intersaccadic intervals between 0 and 150 ms. We suggest that the orienting mechanism, elicited by a transient peripheral cue, relates to the command and the decision to make a pro- rather than an anti-saccade. The cue elicits pro-orienting towards its position when a pro-saccade is required, and anti-orienting when an anti-saccade is required. The orienting effect is transient and decays with CLTs of more than 200 ms; this result holds for both anti-saccades and pro-saccades. Since subjects reported that they could not prevent the erratic pro-saccades or were often not aware of them, we conclude that this orienting mechanism occurs automatically, beyond voluntary control.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050415
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  • 115
    Electronic Resource
    Electronic Resource
    Isometric force-related activity in sensorimotor cortex measured with functional MRI (1998)
    Springer
    Experimental brain research 121 (1998), S. 59-64 
    Details
    ISSN: 1432-1106
    Keywords: Key words Functional MRI ; Isometric force ; Sensorimotor cortex ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Isometric force-related functional magnetic resonance imaging (fMRI) signals from primary sensorimotor cortex were investigated by imaging during a sustained finger flexion task at a number of force levels related to maximum voluntary contraction. With increasing levels of force, there was an increase in the extent along the central sulcus from which a fMRI signal could be detected and an increase in the summed signal across voxels, but these parameters were related in such a way that the signal from each voxel was similar for each level of force. The results suggest that increased neuronal firing and recruitment of corticomotor cells associated with increased voluntary isometric effort are reflected in an expansion of a relatively constant fMRI signal over a greater volume of cortex, rather than an increase in the magnitude of the response in a particular circumscribed region, possibly due to perfusion of an increase in oxygen-enriched blood over a wider region of the cortex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050437
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  • 116
    Electronic Resource
    Electronic Resource
    Latency of saccades during smooth-pursuit eye movement in man Directional asymmetries (1998)
    Springer
    Experimental brain research 121 (1998), S. 92-98 
    Details
    ISSN: 1432-1106
    Keywords: Key words Saccade ; Latency ; Fixation ; Smooth pursuit ; Gap ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To examine the effects of smooth-pursuit eye movements on the initiation of saccades, their latency was measured when subjects initially fixated or pursued a target. In half of the block of trials, the fixation or pursuit target was extinguished 200 ms before the saccade target was illuminated (gap trials). Reduction of the mean saccade latency in the gap trials (the “gap effect”) was evident even when the subjects were pursuing a moving target, consistent with previous observations. The effect of pursuit direction on saccade latency was also examined. Saccades in the same direction as the preceding pursuit (forward saccades) had shorter latencies than those in the opposite direction (backward saccades). This asymmetry was observed in both the gap and nongap trials. Although the forward-backward asymmetry was much smaller than the “gap effect”, it was statistically significant in six of eight cases. These results suggest that the preparation of saccades is affected by smooth-pursuit eye movements.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050440
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  • 117
    Electronic Resource
    Electronic Resource
    Inhibitory projections from pronator teres to biceps brachii motoneurones in human (1998)
    Springer
    Experimental brain research 121 (1998), S. 99-102 
    Details
    ISSN: 1432-1106
    Keywords: Key words Post-stimulus time histogram ; Biceps brachii ; Pronator teres ; Oligosynaptic group I inhibition ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Neural projections from the pronator teres (PT) muscle to biceps brachii (BB) motoneurones were studied in three healthy human subjects using a post-stimulus time histogram method. In 25 BB motor units, electrical stimulation to the PT nerve with intramuscular needle electrodes induced inhibition in nine units (36%), whereas facilitation was produced in 18 units (72%) by stimulation to the median nerve trunk with surface electrodes at the distal end of the intermuscular septum of the arm or in the cubital fossa. Six motor units (24%) received both inhibition (PT nerve stimulation) and facilitation (median nerve trunk stimulation). In the six, the latency of the inhibition was, on average, 1.2 ms longer than that of the facilitation. The stimulation site for the inhibition was, on average, 4.8 cm distal to that for the facilitation. The inhibition was evoked with an intensity well below the motor threshold. These findings suggest that BB motoneurones receive oligosynaptic inhibition of group I afferents from PT in human.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050441
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    Influence of head-to-trunk position on sound lateralization (1998)
    Springer
    Experimental brain research 121 (1998), S. 230-238 
    Details
    ISSN: 1432-1106
    Keywords: Key words Head position ; Eye position ; Interaural level difference ; Sound localization ; Spatial coordinates ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effect of horizontal head position on the lateralization of dichotic sound stimuli was investigated in four experiments. In experiment 1, subjects adjusted the interaural level difference (ILD) of a stimulus (band-pass noise) to the subjective auditory median plane (SAMP) while simultaneously directing the beam of a laser attached to the head to visual targets in various directions. The adjustments were significantly correlated with head position, shifting in a direction toward the side to which the head was turned. This result was replicated in experiment 2, which employed a two-alternative forced-choice method, in which stimuli of different ILD were presented and left/right judgments were made. In both experiments, the average magnitude of the shift of the SAMP was about 1 dB over the range of head positions from straight ahead to 60° to the side. The shift of the SAMP indicates that any shift in head position induces a change in sound lateralization in the opposite direction, i.e., the intracranial sound image is shifted slightly to the left when the head is directed to the right and to the right when the head is to the left. In experiments 3 and 4, the effect of head position was compared with that of eye position by using the same methods as in experiment 2. Both shifts in SAMP, induced by either head- or eye-position changes, are in the same direction and, on average, of about the same magnitude (experiment 3), and head- and eye-position effects compensate approximately for each other during variations of head position when the gaze remains fixed to a visual target in space (experiment 4).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050456
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    Tactile impairments cannot explain the effect of age on a grasp and lift task (1998)
    Springer
    Experimental brain research 121 (1998), S. 263-269 
    Details
    ISSN: 1432-1106
    Keywords: Key words Aging ; Hand ; Motor control ; Manipulation ; Prehension ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This experiment addressed the often-posed theory that age-related declines in manual dexterity result from diminished tactile function. We measured the time ’young’ subjects (n=33; mean=45 years) and ’old’ subjects (n=33; mean=74 years) needed to grip (thumb and index finger), lift, and transport a small metal sphere when vision was permitted and when blindfolded. Subjects began each trial by reaching for the sphere and were instructed to complete the entire task quickly. In the absence of visual information, placement of the finger and thumb for a secure grip and lift cannot be performed efficiently without tactile information. If age-related tactile changes are functionally significant for this task, then without visual information the ’old’ group should show a disproportionate increase in the duration of the grip and lift phase of the task compared to the ’young’ group. Perceptual thresholds for tactile pressure stimuli (Semmes-Weinstein filaments) confirmed well-known age-related changes. Age and vision effects were manifest mainly during the grip-lift phase (time from object contact to lift-off from its support surface), with the expected finding that the ’old’ group required more time than ’young’ group, regardless of visual condition. The main finding was that the ’grip-lift’ duration in the ’no-vision’ condition was about twice the duration observed in the ’vision’ condition for both age groups (ratios of 2.1 and 2.3 for ’young’ and ’old’, respectively). This similar relative slowing for the two groups fails to support the hypothesis that old adults’ ability to grip and lift the object was limited by changes in the availability or use of tactile information.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050459
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    Pain and Stroop interference tasks activate separate processing modules in anterior cingulate cortex (1998)
    Springer
    Experimental brain research 118 (1998), S. 52-60 
    Details
    ISSN: 1432-1106
    Keywords: Key words Affect ; Limbic system ; Cognition ; Functional imaging ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Investigations of pain using functional imaging techniques have revealed an extensive central network associated with nociception. This network includes the thalamus, insula, prefrontal cortex and anterior cingulate cortex (ACC) as well as the somatosensory cortices. Positron emission tomography (PET) of regional cerebral blood flow (rCBF) has demonstrated activation of the ACC during cognitively challenging tasks such as the Stroop interference task and divided attention. One interpretation of this research is that ACC is involved in the general features of attention and that it does not play a specific role in pain processing per se. Three-dimensional PET imaging provides a method for assessments of rCBF in a single individual during multiple tasks. In addition, coregistration of PET and magnetic resonance (MR) images allows for better localisation of the PET signals so that differences in cortical activation sites can be more accurately determined. This approach was used to assess rCBF during the experience of pain by subtracting images collected during heat from those during noxious heat stimulation. Two regions of the ACC had elevated rCBF, one in the perigenual region and one in the mid-rostrocaudal region (i.e. midcingulate cortex). During the execution of the Stroop task, the group result showed the midcingulate region overlapping with the site seen during the experience of pain. This group result, however, was not confirmed in the individual subject analysis, which revealed widespread and independent areas of ACC response to pain and Stroop. It is concluded that the ACC contributes to multiple cognitive procedures. It is inadequate to describe the primary contribution of ACC to pain processing as “attention” because it is unlikely that the multiple small and independent activation sites produced by pain and Stroop subserve attentive processing throughout the brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050254
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    Attentional coding for three-dimensional objects and two-dimensional shapes Differential interference effects (1998)
    Springer
    Experimental brain research 123 (1998), S. 289-297 
    Details
    ISSN: 1432-1106
    Keywords: Key words Kinematics ; Selective attention ; Reach to grasp ; Motor control ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The role played by the attentional mechanisms that enable dominance of relevant objects over distractor objects was investigated by measuring changes in the kinematics of the reach-to-grasp movement. Subjects reached towards three-dimensional (3D) stimuli while attention was diverted towards distracting information consisting of either two-dimensional (2D) projected shapes or 3D objects. Movement kinematics were influenced to a greater degree when a secondary task was performed involving a 3D object rather than a 2D projected shape. When the distractor was 3D, both the reaching and the grasping components were altered but, when it was 2D only, the reaching component was modified. It is suggested that, when attention is directed towards a distractor, it is associated with interference in the kinematics of the action towards the target. Further, the nature and dimensions of the distractor selectively influence the reach or the grasp component of a prehension movement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050571
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  • 122
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    Eye movements evoked by proprioceptive stimulation along the body axis in humans (1998)
    Springer
    Experimental brain research 120 (1998), S. 450-460 
    Details
    ISSN: 1432-1106
    Keywords: Key words Proprioceptive eye response ; Vestibulo-ocular reflex ; Cervico-ocular reflex ; Interaction ; Self-motion perception ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Proprioceptive input arising from torsional body movements elicits small reflexive eye movements. The functional relevance of these eye movements is still unknown so far. We evaluated their slow components as a function of stimulus frequency and velocity. The horizontal eye movements of seven adult subjects were recorded using an infrared device, while horizontal rotations were applied at three segmental levels of the body [i.e., between head and shoulders (neck stimulus), shoulders and pelvis (trunk stimulus), and pelvis and feet (leg stimulus)]. The following results were obtained: (1) Sinusoidal leg stimulation evoked an eye response with the slow component in the direction of the movement of the feet, while the response to trunk and neck stimulation was oriented in the opposite direction (i.e., in that of the head). (2) In contrast, the gain behavior of all three responses was similar, with very low gain at mid- to high frequencies (tested up to 0.4 Hz) but increasing gain at low frequencies (down to 0.0125 Hz). We show that this gain behavior is mainly due to a gain nonlinearity for low angular velocities. (3) The responses were compatible with linear summation when an interaction series was tested in which the leg stimulus was combined with a vestibular stimulus. (4) There was good correspondence of the median gain curves when eye responses were compared with psychophysical responses (perceived body rotation in space; additionally recorded in the interaction series). However, correlation of gain values on a single-trial basis was poor. (5) During transient neck stimulation (smoothed position ramp), the neck response noticeably consisted of two components – an initial head-directed eye shift (phasic component) followed by a shift in the opposite direction (compensatory tonic component). Both leg and neck responses can be described by one simple, dynamic model. In the model the proprioceptive input is fed into the gaze network via two pathways which differ in their dynamics and directional sign. The model simulates either leg or neck responses by selecting an appropriate weight for the gain of one of the pathways (phasic component). The interaction results can also be simulated when a vestibular path is added. This model has similarities to one we recently proposed for human self-motion perception and postural control. A major difference, though, is that the proprioceptive input to the gaze-stabilizing network is weak (restricted to low velocities), unlike that used for perception and postural control. We hold that the former undergoes involution during ontogenesis, as subjects depend on the functionally more appropriate vestibulo-ocular reflex. Yet, the weak proprioceptive eye responses that remain may have some functional relevance. Their tonic component tends to stabilize the eyes by slowly shifting them toward the primary head position relative to the body support. This applies solely to the earth-horizontal plane in which the vestibular signal has no static sensitivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050418
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    Differential effects of load stiffness on matching pinch force, finger span, and effort (1998)
    Springer
    Experimental brain research 120 (1998), S. 487-495 
    Details
    ISSN: 1432-1106
    Keywords: Key words Proprioception ; Pinch force ; Finger span ; Effort ; Motor command ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Disparities in load stiffness were used to differentiate and characterize pinch-force, finger-span, and pinch-effort matching in two experiments. All subjects squeezed a spring-loaded manipulandum in each hand using three-finger pinch. Subjects in the first experiment were instructed explicitly to match one of the three continua. Subjects matching force or span were told to attend carefully to sensations from the hand or arm and to ignore differences in the effort required to make the sensations equal. They had to achieve and hold a particular target force with the reference hand and then match force or span with the opposite hand, usually against a spring with a different stiffness. These subjects were given as much time as necessary to make their matches and were told which hand was serving as the reference in each trial. Effort-matching subjects were told to ignore peripheral sensations and to match effort or motor commands. These subjects were not told which hand was the reference and were given only 1 s to make a match, so they made matches by rapidly squeezing both manipulanda simultaneously and, presumably, with the same voluntary motor command. The matching behaviors of the three groups were clearly distinguishable and were consistent with instructions. Results were similar whether different subjects were assigned different instructions or the same subjects performed all three match types. In a second experiment, naïve subjects were given purposely ambiguous instructions without reference to a specific continuum and had no time or accuracy constraints. Subjects produced the same three sensorimotor behaviors obtained with explicit instructions, showing that the different behaviors were not artifacts of strict protocols. Taken together, the results show that force, span, and effort are distinct sensorimotor continua that can be judged reliably.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050422
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    Coordination among the body segments during reach-to-grasp action involving the trunk (1998)
    Springer
    Experimental brain research 123 (1998), S. 346-350 
    Details
    ISSN: 1432-1106
    Keywords: Key words Prehension ; Trunk ; Spatial coordination ; Human ; Motor control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To understand the internal representations used by the nervous system to coordinate multijoint movements, we examined the coordination among the body segments during reach-to-grasp movements which involve grasping by the hand and reaching by the arm and trunk. Subjects were asked to reach and grasp an object using the arm only, the trunk only, and some combinations of both arm and trunk. Results showed that kinematic parameters related to the transport component of the arm and the trunk, such as peak velocity and time to peak velocity, varied across conditions and that the coordination pattern between the arm and trunk was different across conditions. However, parameters related to the grasp component, such as peak aperture, time to peak aperture, and closing distance, were invariant, regardless of whether the hand was delivered to the target by the arm only, the trunk only, or both. We hypothesize that a hierarchy of motor control processes exists, in which the reach and grasp components are governed by independent neuromotor synergies, which in turn are coordinated temporally and spatially by a higher-level synergy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050578
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    Colour constancy impairments in patients with lesions of the prestriate cortex (1998)
    Springer
    Experimental brain research 123 (1998), S. 154-158 
    Details
    ISSN: 1432-1106
    Keywords: Key words Colour constancy ; Extrastriate cortex ; V4 ; Cortical lesions ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Colour matching and colour constancy were studied in seven patients and 46 control subjects. Subjects were required to match Munsell Colour Chips presented under either identical or different illumination. Three of the patients had deficits in colour constancy, i.e. failure to compensate for the change in the wavelength composition of the illumination. Two of the patients with defective constancy had suffered bilateral cortical damage to the poterior lingual and fusiform gyri, and one patient had a lesion restricted to the same regions of the right hemisphere. Our observations indicate that these cortical areas, which include part of putative human area V4, play an important role in colour constancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050556
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    Cortical control of saccades (1998)
    Springer
    Experimental brain research 123 (1998), S. 159-163 
    Details
    ISSN: 1432-1106
    Keywords: Key words Eye movements ; Saccade ; Cerebral cortex ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Saccadic eye movements are controlled by a cortical network composed of several oculomotor areas that are now accurately localized. Clinical and experimental studies have enabled us to understand their specific roles better. These areas are: (1) the parietal eye field (PEF) located in the intraparietal sulcus involved in visuospatial integration and in reflexive saccade triggering; (2) the frontal eye field (FEF), located in the precentral gyrus, involved in the preparation and the triggering of purposive saccades; and (3) the supplementary eye field (SEF) on the medial wall of the frontal lobe, probably involved in the temporal control of sequences of visually guided saccades and in eye-hand coordination. A putative cingulate eye field (CEF), located in the anterior cingulate cortex, would be involved in motivational modulation of voluntary saccades. Besides these motor areas, the dorsolateral prefrontal cortex (dlPFC) in the midfrontal gyrus is involved in reflexive saccade inhibition and visual shortterm memory.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050557
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    Idiothetic input into object-place configuration as the contribution to memory of the monkey and human hippocampus: a review (1998)
    Springer
    Experimental brain research 123 (1998), S. 201-209 
    Details
    ISSN: 1432-1106
    Keywords: Key words Object-place configuration ; Monkey ; Hippocampus ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Memory for object-place configurations appears to be a common function of the hippocampus in the human and monkey brain. The nature of the spatial information which enters into these object-configural memories in the primate, and the location of the memories themselves, have remained obscure, however. In the rat, much evidence indicates that the hippocampus processes idiothetic spatial information, an estimate of the animal’s current environmental location derived from path integration. I propose that in primates the hippocampus provides idiothetic information about the environmental location of body parts, and that the main function of this information in the primate brain is to become configured with object-identity information provided by temporal lobe cortex outside the hippocampus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050562
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    Load compensation during homologous and non-homologous coordination (1998)
    Springer
    Experimental brain research 121 (1998), S. 223-229 
    Details
    ISSN: 1432-1106
    Keywords: Key words Interlimb coordination ; Inertial load ; Human ; Motor control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two-limb coordination of homologous and non-homologous effectors was examined during isofrequency (1:1) and multifrequency (2:1) conditions. The coordination patterns involved flexion and extension movements in the sagittal plane and were performed under unloaded and single-limb (right arm) loaded conditions. Previous studies suggested that the lower degree of 1:1 synchronization observed during nonhomologous as compared to homologous coordination results from natural differences in biophysical (inertial) properties. Elaborating on this idea, adding weight to the right arm was hypothesized to modulate its inertial characteristics, rendering homologous limbs more dissimilar and nonhomologous limbs more similar by enhancing and decreasing their inertial differences, respectively. Therefore, the observations made during unloaded conditions were predicted to be completely reversed during loaded conditions. Findings revealed that during 1:1 coordination (experiment 1) single-limb loading resulted in a decreased relative phase stability, whereas relative phase accuracy depended upon the limb combination. In particular, phase-locking was more accurately maintained for loaded homologous than for nonhomologous limbs, whereas loading the nonhomologous limbs resulted in a deterioration of the quality of synchronization. These findings suggest that there is an additional explanation of differential coordination capabilities among limb combinations. It is hypothesized that the neural networks subserving the control centers of the homologous limbs are more tightly connected than those of the nonhomologous effectors, allowing 1:1 synchronization to be more successfully preserved in the face of (load) perturbations. During 2:1 coordination (experiment 2), the loading procedure disturbed the coordination dynamics across all limb combinations. That no differential effect of loading on effector combination was observed is possibly a result of the fact that only an initial level of practice was studied in which optimal relative phase dynamics are still being explored for both homologous and nonhomologous limbs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050455
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    Experimental jaw-muscle pain does not change heteronymous H-reflexes in the human temporalis muscle (1998)
    Springer
    Experimental brain research 121 (1998), S. 311-318 
    Details
    ISSN: 1432-1106
    Keywords: Key words Experimental muscle pain ; H-reflex ; M-response ; Jaw muscles ; Trigeminal reflexes ; Motoneuron excitability ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Muscle pain generally has an inhibitory effect on voluntary orofacial motor function. However, it is not known whether muscle pain causes direct or indirect changes in motoneuron excitability. In this study a monopolar needle stimulation technique was used to evoke the direct motor response (M-response) in the left masseter muscle and the heteronymous H-reflex in the left temporalis muscle as an indirect measure of motoneuron excitability. Series of 20 repeated electrical stimuli were delivered at 50% of maximal voluntary contraction (MVC) before, during, and after periods with experimental jaw-muscle pain in 11 healthy subjects. Pain was induced by standardized infusion of hypertonic (5%) saline into the mid-portion of the right masseter muscle. The mean pain intensity rating on a 100-mm visual analog scale was 42±5 mm. The short-latency responses (less than 6 ms) could be evoked in all subjects. Analysis of the latency and amplitude of the temporal H-reflex indicated no significant effect of jaw-muscle pain. The amplitude of the masseteric M-response was significantly smaller in the postpain condition than in the pain conditions (ANOVA, P=0.018), but no differences were found between the prepain and postpain conditions. In nine subjects, poststimulus periods (mean offset latency, 69.6±8.6 ms) with significantly (more than 50%) suppressed EMG activity were detected in the ipsilateral masseter muscle following the M-response (mean offset latency, 5.5±0.2 ms). These reflex responses did not show a systematic change during the pain conditions. In conclusion, acute contralateral jaw-muscle pain does not seem to modulate the motoneuron excitability as measured by the heteronymous H-reflex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050464
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    Neuroplasticity in the cat’s visual system Origin, termination, expansion, and increased coupling of the retino-geniculo-middle suprasylvian visual pathway following early ablations of areas 17 and 18 (1998)
    Springer
    Experimental brain research 121 (1998), S. 334-349 
    Details
    ISSN: 1432-1106
    Keywords: Key words Adaptive plasticity ; Behavioral sparing ; Extrastriate cortex ; Transsynaptic labeling ; Monkey ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We used anterograde and retrograde transsynaptic pathway tracing techniques to reveal the retinal origin and the cortical termination of the expanded retino-geniculo-middle suprasylvian (MS) cortex pathway in adult cats which sustained lesions of areas 17 and 18 on the day of birth (P1) or at 1 month of age (P28). Following anterograde transsynaptic transport of tritiated amino acids from the eye, four major results were obtained: (1) a strong and specific pathway from retina through dorsal lateral geniculate nucleus (dLGN) to the posterior half of MS cortex was identified; this pathway is a substantial expansion of an insignificant pathway present in intact cats; (2) the terminus of the pathway was lower layer III and layer IV; (3) contralateral projections were stronger than ipsilateral projections; (4) projections in P28 cats were stronger than those in P1 cats. Following retrograde transsynaptic transport of WGA-HRP from posterior MS cortex, four additional results were obtained: (1) the pathway was enlarged and visuotopically organized; (2) the pathway arose primarily from α- and γ-retinal ganglion cells; (3) a small number of β-cells in P1 cats and a modest number in P28 cats also contribute to the pathway; (4) the combined numbers of γ- and β-cells relative to α-cells was greater in temporal retina than in nasal retina. The combined demonstration of both origin and terminus of the pathway with transsynaptic tracers argued strongly for high levels of coupling between primary and secondary pathway limbs in both P1 and P28 cats. This level of coupling, as well as other features of the pathway, have much in common with the retino-geniculo-17/18 pathway of intact cats. However, the retino-geniculo-MS system in P1 cats transmits primarily Y and W signals, in P28 cats X, Y, and W signals; whereas the retino-geniculo-17/18 pathway transmits primarily X and Y signals. These results have implications for understanding the repercussions of early visual cortex lesions in monkeys and humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050466
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    Harvesting and preparation of cadaveric osseoligamentous lower cervical spine (C2-C7) for biomechanical testing (1998)
    Springer
    European spine journal 7 (1998), S. 66-68 
    Details
    ISSN: 1432-0932
    Keywords: Key words Autopsy ; Cadaver ; Cervical vertebrae ; Human ; Laboratory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cadaveric osseoligamentous lower cervical spines (C2-C7) are often used in the investigation of spinal biomechanics in vitro. Surprisingly, however, the techniques of harvesting at postmortem and preparation of cadaveric osseoligamentous lower cervical spine for biomechanical testing have not been described in detail. We describe a simple and effective method that can be readily integrated into the routine autopsy procedure. Points on the avoidance of disfiguring the cadaver and damaging the spinal osseoligamentous structures are highlighted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005860050030
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    Influence of the cytochrome P4502D6*4 allele on the pharmacokinetics of controlled-release metoprolol (1998)
    Springer
    European journal of clinical pharmacology 54 (1998), S. 469-474 
    Details
    ISSN: 1432-1041
    Keywords: Key words CYP2D6 ; Genetic polymorphism ; Metoprolol ; Pharmacokinetics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Aim: The aim of the present paper was to compare the pharmacokinetics of metoprolol in homozygous Caucasian volunteers for the wild-type CYP2D6 allele (CYP2D6*1/CYP2D6*1) and heterozygous (CYP2D6*1/CYP2D6*4) Caucasians. Methods: Thirty-six unrelated healthy male Caucasians were screened for two of the most frequently occurring mutant alleles (CYP2D6*3 and CYP2D6*4) using polymerase chain reaction (PCR). Twenty-four volunteers with a genotype suggesting a rapid hydroxylator phenotype were enrolled in a bioequivalence trial and each received in a randomized, cross-over fashion one of the three formulations compared. Each formulation contained 200 mg metoprolol tartrate/(tablet). In each of the three periods of the trial, one of the formulations was administered under fasting conditions in the morning on 4 consecutive days. Blood for quantification of metoprolol was drawn immediately before the last dose and in selected time intervals thereafter. A sensitive and specific high-performance liquid chromatography (HPLC) method with fluorescence detection was applied for the quantification of metoprolol. Pharmacokinetic parameters were determined for each subject and statistically compared in two groups of 16 homozygous (CYP2D6*1/CYP2D6*1) and six heterozygous (CYP2D6*1/CYP2D6*4) volunteers. Results: Significant differences between homozygous and heterozygous individuals were observed for all pharmacokinetic parameters. The AUC in the course of one those interval of 24 h (AUCτ), minium steady-state concentration (Cmin ss) and average steady-state concentration (Cav ss) values for heterozygous individuals were more than twice those of individuals. Significantly higher values for Css max , t1/2, half-value duration (HVD) and mean residence time (MRT) were also observed in heterozygous volunteers. The higher concentrations of metoprolol in heterozygous individuals also had pharmacodynamic consequences, namely, greater heart rate and blood pressure reduction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050495
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    Alternate-day buprenorphine dosing is preferred to daily dosing by opioid-dependent humans (1998)
    Springer
    Psychopharmacology 136 (1998), S. 217-225 
    Details
    ISSN: 1432-2072
    Keywords: Key words Buprenorphine ; Alternate-day dosing ; Heroin ; Methadone ; Human ; Reinforcer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Alternate-day buprenorphine dosing was compared to daily dosing in opioid-dependent outpatients and choice of alternate-day versus daily dosing was assessed. Four dosing schedules were presented in random order under blind and open dosing conditions. Subjects received two exposures to each dosing schedule. During daily dosing, subjects received maintenance doses every 24 h. During blind alternate-day dosing, subjects received double maintenance doses every 48 h; placebo was interposed on intervening days. During open alternate-day dosing, subjects received twice their maintenance dose on Monday, Wednesday and Friday and maintenance doses on Sunday. After completing two exposures to each dosing schedule, subjects chose either daily or alternate-day schedules each week for 1 month. Study participation was contingent on daily attendance and opioid abstinence. Ten subjects were exposed to the four conditions once. Seven subjects repeated these conditions and participated in the choice phase. The effects of daily versus alternate-day dosing were not influenced by blind or open dosing conditions. Subjects’ ratings of withdrawal, “sick” and sedation were lower during daily than during alternate-day dosing, but the difference between treatments was small. Nonetheless, subjects still chose alternate-day dosing on 96% of occasions, suggesting that the subject-rated differences between dosing schedules were not influential. These results extend prior findings to open-dosing conditions, and replicate the safety and acceptability of alternate-day buprenorphine treatment. Choice of alternate-day buprenorphine administration underscores the procedure’s clinical utility and potential use as a positive reinforcer to enhance opioid treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050559
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  • 134
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    Effects of pergolide on intravenous cocaine self-administration in men and women (1998)
    Springer
    Psychopharmacology 137 (1998), S. 15-24 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Human ; Self-administration ; Pergolide ; Sex differences ; Subjective effects ; Performance ; Cardiovascular effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clinical evidence suggests that pergolide, a D1/D2 dopamine receptor agonist, may be useful in maintaining cocaine abstinence. We investigated pergolide’s effects in a laboratory model of IV cocaine self-administration by humans. Twelve inpatient volunteers (7M, 5F), who reported spending an average of $170/ week on cocaine, received pergolide (0.05 mg BID) for 8 days and placebo for 8 days, with drug order balanced across subjects. Self-administration sessions occurred on the last 4 days of maintenance on each medication. A modified seven-trial progressive ratio choice procedure (0, 8, 16, 32 mg/70 kg cocaine versus $5) was utilized, with sessions consisting of: (a) two sample trials, where participants responded to receive the dose and tokens available that day, and (b) five choice trials, where participants chose between the available dose and tokens. Following each trial, the response requirement for the chosen option increased by 400. Maintenance on pergolide 1) decreased cocaine-induced increases in ratings of “High,”“Stimulated,” cocaine “Potency,” estimates of street value, and heart rate, 2) increased ratings of “I want cocaine,” and 3) had no effect on cocaine self-administration. The increased desire to use cocaine during pergolide maintenance suggests that it has limited treatment utility at this dose, but given the attenuation of cocaine’s subjective and cardiovascular effects, an investigation of a wider range of pergolide doses on cocaine self-administration and subjective effects is warranted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050588
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  • 135
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    Isradipine prevents global and regional cocaine-induced changes in brain blood flow: a preliminary study (1998)
    Springer
    Psychopharmacology 136 (1998), S. 335-341 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Brain blood flow ; Quantitative SPECT ; Ischemia ; Isradipine ; Stroke ; Calcium channel antagonist ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The L-type calcium channel antagonist, isradipine, reduces brain ischemia in animal models of ischemic stroke. These effects of isradipine appear more pronounced in dopamine (DA) rich brain regions. These same DA-rich brain regions have also been shown to be the areas most affected by cocaine-induced ischemic changes. Using a novel quantified approach to single photon emission computerized tomography, we demonstrated that isradipine pre-treatment prevented cocaine-induced ischemic changes, especially in these DA-rich brain regions. This is the first demonstration that any medication, including isradipine, can prevent the ischemic effects of cocaine on brain blood flow. Isradipine may, therefore, be a useful therapeutic agent for the prevention of brain ischemia in cocaine addicts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050575
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  • 136
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    Gender-dependent dissociation between oxytocin but not ACTH, cortisol or TSH responses to m-chlorophenylpiperazine in healthy subjects (1998)
    Springer
    Psychopharmacology 136 (1998), S. 342-348 
    Details
    ISSN: 1432-2072
    Keywords: Key words Adrenocorticotropic hormone (ACTH) ; Aldosterone ; Cortisol ; Human ; Meta-chlorophenylpiperazine (m-CPP) ; Thyrotropin (TSH) ; Oxytocin ; Serotonin agonist ; 5-HT2C receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract m-chlorophenylpiperazine (m-CPP), a serotonin (5-HT) agonist with some selectivity for the 5-HT2C receptor subtype, which is widely used to examine 5-HT receptor function in human subjects, has been found to induce oxytocin and thyrotropin (TSH) responses in rodents. This study examined whether m-CPP had any effect on plasma oxytocin, TSH and aldosterone concentration in healthy volunteers using a double-blind, placebo-controlled crossover design. Plasma adrenocorticorticotropic hormone (ACTH) and cortisol responses, two generally accepted markers of m-CPP-induced 5-HT receptor activation, were measured in parallel. Male subjects (n = 7) received placebo, 0.25 and 0.5 mg/kg oral m-CPP. In female subjects (n = 5), the effects of placebo and 0.25 mg/kg m-CPP were studied. After placebo, given in the morning, ACTH, cortisol, TSH and aldosterone concentrations decreased over time. m-CPP 0.25 mg/kg avoided decreases in ACTH, cortisol and TSH concentrations; these responses were significant. At the dose of 0.5 mg/kg, m-CPP caused increase in ACTH, cortisol, TSH and aldosterone concentrations. Significant plasma oxytocin responses were found in female subjects only; thus this effect of m-CPP was statistically significantly gender dependent. Other responses to m-CPP were similar in male and female subjects. The present results suggest that there are clear differences, including dose and gender-dependent dissociations, among the 5-HT receptor agonist m-CPP-induced neuroendocrine responses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050576
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  • 137
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    Effects of dynorphin A(1–13) on opiate withdrawal in humans (1998)
    Springer
    Psychopharmacology 137 (1998), S. 326-332 
    Details
    ISSN: 1432-2072
    Keywords: Key words Dynorphin ; Opiate withdrawal ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The objectives of the current study were to determine 1) the effects of various doses of dynorphin A (1–13) on opiate withdrawal in humans and 2) the safety of dynorphin at these doses. Opiate dependent subjects who had been stabilized on morphine received a single IV dose of placebo, 150, 500 or 1000μg/kg dynorphin after exhibiting spontaneous withdrawal using a randomized, double-blinded, between-subjects study design. Observer Withdrawal Scores were lower in the 150 and 1000μg/kg groups as compared to placebo (P〈0.05) but no significant differences were observed on the observer-rated Wang or Sickness Scales. Significant decreases were also found for self-reported symptoms of nervousness, runny nose, sneezing, and painful joints in the 500μg/kg group. Significant increases in serum prolactin levels were seen after all dynorphin doses; however, these were not dose-related. Dynorphin A (1–13) was well tolerated and safe, with no changes in physiologic parameters. We conclude that dynorphin A (1–13) has a modest effect in reducing mild opiate withdrawal in humans and is well tolerated at doses up to 1000μg/kg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050626
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  • 138
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    The effects of smoking on acoustic prepulse inhibition in healthy men and women (1998)
    Springer
    Psychopharmacology 137 (1998), S. 362-368 
    Details
    ISSN: 1432-2072
    Keywords: Key words Startle ; Prepulse inhibition ; Gating ; Human ; Smoking ; Nicotine ; Gender
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acoustic prepulse inhibition (PPI) refers to the reduction of the startle reflex to an intense stimulus if it is preceded by a weak stimulus. Nicotine and smoking have been reported to enhance PPI in rats and in healthy men, respectively. We studied the influence of smoking on PPI in healthy men and women, comparing non-smokers, deprived smokers, and smokers smoking during the test session after deprivation or after ad libitum smoking. Smoking during the session enhanced PPI, without affecting startle reaction or habituation over time. In addition, the effect of smoking on PPI was gender dependent. In men, ad libitum smoking enhanced PPI compared with non-smokers, while, in women, deprivation reduced PPI and smoking restored PPI to the level of non-smokers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050631
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  • 139
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    Buspirone is differentiated from diazepam in humans using a three-response drug discrimination procedure (1998)
    Springer
    Psychopharmacology 138 (1998), S. 16-26 
    Details
    ISSN: 1432-2072
    Keywords: Key words Buspirone ; Diazepam ; Benzodiazepine ; Discrimination ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The discriminative stimulus effects of buspirone and diazepam were examined in 12 healthy volunteers using a three-response drug discrimination procedure and a within-subject design. During an initial sampling phase, the training drug conditions (placebo, 15 mg/70 kg buspirone, and 10 mg/70 kg diazepam) were identified to subjects by letter codes before oral drug administration. During a subsequent training phase, subjects earned money for correct drug identifications made two hours after drug administration. Ten out of 12 subjects acquired the three-response discrimination. When lower doses of buspirone (3.75 and 7.5 mg/70 kg) and diazepam (2.5 and 5.0 mg/70 kg) were tested in a subsequent generalization testing phase, both buspirone and diazepam produced dose-related increases in appropriate drug identifications, without significant cross-generalization. Analyses of standardized and unstructured self report questionnaires revealed that buspirone and diazepam produced different profiles of effects, and that buspirone was associated with a number of “negative” subject-rated effects including tension, nausea, and dizziness. These results demonstrate a distinct profile of discriminative stimulus and subjective effects for buspirone relative to diazepam which is consistent with its distinct pharmacological profile, and provide evidence for the sensitivity of the three-response drug discrimination procedure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050640
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  • 140
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    Cerebral effects of nicotine during cognition in smokers and non-smokers (1998)
    Springer
    Psychopharmacology 136 (1998), S. 179-189 
    Details
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Positron emission tomography ; Regional cerebral blood flow ; Brain activation ; Human ; Cognition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  For the smoker, nicotine has a positive effect on attention, cognition and mood. Conversely, nicotine abstinence is characterized by uncomfortable psychological effects such as impaired attention, but also irritability. We postulated that nicotine exerts an effect on cerebral areas important for attention and mood. Regional cerebral blood flow (rCBF), as an index for cerebral activity, was measured in both smokers and non-smokers. They were scanned during performance of a psychometric task with and without IV infusion of nicotine (1-methyl-2-[3-pyridyl1] pyrrolidine). Nicotine induced rCBF decreases in the anterior cingulate cortex and the cerebellum, and concomitant increases in the occipital cortex. The changes were similar in nature and magnitude in smokers and non-smokers. Thus, specific changes were induced in areas pertaining to the anterior attention system and to higher order visual cortex. We conclude that these effects on cerebral activity provide insights into the desired positive effects of nicotine on cognition as well as the negative effects experienced during nicotine abstinence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050554
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  • 141
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    Discriminative stimulus properties of low doses of ethanol in humans (1998)
    Springer
    Psychopharmacology 136 (1998), S. 379-389 
    Details
    ISSN: 1432-2072
    Keywords: Key words Ethanol ; Drug discrimination ; Human ; Skin conductance ; Interoceptive stimulus ; Self-rating
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Discriminative stimulus properties of low doses of ethanol were evaluated in humans using established behavioural drug discrimination procedures. Twenty-five moderate drinkers (12 females and 13 males) were trained to discriminate placebo from 0.2 g/kg ethanol in 200 ml tonic water mixed with Tabasco sauce and drunk in portions of 50 ml every 15 s. Seventeen of the subjects (ten females and seven males) were able to reach criterion performance (at least 80% correct responses). Generalisation responding across ethanol doses of 0 (placebo), 0.025, 0.05, 0.1 and 0.2 g/kg was examined the day after training using a procedure in which subjects reported the extent to which the test stimulus resembled the training dose. At the end of each generalisation session, self ratings of mood changes, physiological responses and performance in a working memory and a time estimation task were evaluated. Subjects were able to distinguish the three higher doses of ethanol from placebo. Self ratings indicated that subjects' ability to distinguish ethanol from placebo was related, at the highest dose, to change of taste, but to feelings of light-headedness at the lower doses. Ethanol administration influenced skin conductance measurements but there was no relationship found between changes in skin conductance and the ethanol discriminative stimulus. These data suggest a difference in the nature of the discriminative stimulus of ethanol between high (training) and low (generalising) doses as indicated in the subjective reports.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050581
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  • 142
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    Effortful processing is a requirement for nicotine-induced improvements in memory (1998)
    Springer
    Psychopharmacology 138 (1998), S. 362-368 
    Details
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Human ; Memory ; Attention ; Consolidation ; Effortful processing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report two studies examining the effects of nicotine on memory in minimally deprived smokers. In experiment 1, semantically related words were recalled significantly better than unrelated words following nicotine, even when volunteers were explicitly instructed to target the unrelated word set for recall. Experiment 2 examined the effect of nicotine on two different types of lexical association: association by joint category membership (semantically related items), and association by derived meaning (”encapsulated” word pairs). Nicotine-induced improvements in recall were observed only for category associates and not for encapsulated word pairs. This implies that explicit, effortful processing of material in the presence of nicotine is necessary for improved recall performance to be observed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050682
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  • 143
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    Physical dependence increases the relative reinforcing effects of caffeine versus placebo (1998)
    Springer
    Psychopharmacology 139 (1998), S. 195-202 
    Details
    ISSN: 1432-2072
    Keywords: Key words Caffeine ; Reinforcement ; Drug choice ; Drug self-administration ; Physical dependence ; Withdrawal ; Multiple-choice procedure ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using a within-subject cross-over design, this study examined the role of physical dependence in caffeine reinforcement by experimentally manipulating physical dependence. Each subject was exposed to two chronic drug phases (300 mg/70 kg/day caffeine and placebo) for 9–12 days, with order of phases counterbalanced across subjects. On 2 separate days immediately following each of the chronic drug exposures, subjects received acute doses of either caffeine (300 mg/ 70 kg) or placebo in counterbalanced order. The reinforcing effects of these drugs were then determined by using a multiple-choice procedure in which subjects made a series of discrete choices between receiving varying amounts of money or receiving the drug again, and a choice between the two drugs. To ensure that subjects completed the form carefully, following exposure to both of the acute drug administrations, one of the subject’s previous choices from the multiple-choice form was randomly selected and the consequence of that choice was implemented. When subjects were maintained on chronic caffeine, they were willing to forfeit significantly more money and showed significant increases in typical withdrawal symptoms (e.g. fatigue, mood disturbance) after receiving placebo as compared to the other three conditions. When subjects were maintained on chronic caffeine, they also chose to receive caffeine over placebo twice as often than when they were maintained on chronic placebo. These findings provide the strongest evidence to date indicating that caffeine physical dependence increases the relative reinforcing effects of caffeine versus placebo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050704
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  • 144
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    Acute tryptophan depletion attenuates the prolactin response to d-fenfluramine challenge in healthy human subjects (1998)
    Springer
    Psychopharmacology 138 (1998), S. 9-15 
    Details
    ISSN: 1432-2072
    Keywords: Key wordsd-Fenfluramine ; Tryptophan ; Prolactin ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prolactin responses to d-fenfluramine (d-FEN) Challenge (0.5 mg/kg PO) were examined after pretreatment with and without acute tryptophan depletion (ATD) in six physically healthy male volunteers. Compared to pretreatment with SHAM-ATD, ATD pretreatment attenuated the PRL response to d-FEN Challenge in all subjects. These data suggest that PRL responses to d-FEN challenge reflect to a substantial degree the activity of newly synthesized 5-HT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050639
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  • 145
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    Rescue FK506 early conversion for refractory rejection after pediatric liver transplantation: experience in 20 children (1998)
    Springer
    Transplant international 11 (1998), S. S272 
    Details
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; Tacrolimus ; Human ; Child
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tacrolimus (FK506) is an effective and relatively safe novel immunosuppressant able to revert refractory rejection after pediatric liver transplantation (LTx). Between April 1993 and October 1996, 20 pediatric patients were converted to tacrolimus for biopsy-proven, steroid-resistant liver rejection. The mean follow-up was 18 months. The median time from LTx to switch was 20 days. Tacrolimus was administered per os at a mean dosage of 0.23 mg/kg per day to maintain median blood levels of 10.8 ng/ml at 1 week and 9.2 ng/ml at 1 year from the switch. Of the 20 patients, 15 are alive and they all recovered from rejection without the need of OKT3 after conversion. The major causes of death were: one multiorgan failure, two infections (cytomegalovirus Aspergillus), one bowel perforation, and one posttransplant lymphoproliferative disease. One patient experienced late side effects and was reconverted to cyclosporine when she was already rescued from hepatic allograft rejection. The results confirm that an earlier conversion to tacrolimus should be recommended after pediatric liver transplantation in order to revert hepatic allograft rejection with the best safety profile.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050477
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  • 146
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    Exocytosis in human salivary glands visualized by high-resolution scanning electron microscopy (1998)
    Springer
    Cell & tissue research 291 (1998), S. 325-336 
    Details
    ISSN: 1432-0878
    Keywords: Key words Salivary gland ; Secretion ; Granule docking ; Exocytosis-endocytosis coupling ; OsO4 maceration ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The luminal membrane of salivary acinar cells creates a specialized cell surface area that accepts exocytosis and undergoes dynamic changes during secretion. These changes were visualized three-dimensionally from both the inside and outside of the cell in human parotid and submandibular glands, by application of in vitro secretory stimulation and then of OsO4 maceration to remove cytoplasmic organelles by varying degrees. In control glands treated without secretagogues, the luminal surface of serous acinar cells bore well-developed microvilli with only an occasional incidence of exocytotic profiles. Following treatment with the β-adrenergic agonist, isoproterenol, considerable shortening and loss of microvilli occurred along the luminal membrane where, on its cytoplasmic side, many protuberances of sizes similar to or smaller than those of single secretory granules (∼1 μm in diameter) appeared. The cytoplasmic surface of these protuberances exhibited small vesicles (∼100–150 nm in diameter) that, by transmission electron microscopy, were shown to be coated pits or vesicles present on or around the exocytosed granule membranes. Treatment of tissues with the muscarinic agonist carbachol also caused a decrease of microvilli and the appearance of protrusions at the luminal membrane. However, unlike isoproterenol treatment, many of these protrusions were devoid of small pits or vesicles and were much larger than a single secretory granule. These results indicate that (1) secretory stimulation causes the dynamic transformation of microvilli at the luminal membrane, where granule docking and membrane fusion take place, and (2) after fusion, the exocytosed membranes are processed differently, by coated pit/vesicle mediated or non-mediated mechanisms, according to the autonomic receptor control.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051002
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  • 147
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    Monoclonal antibodies SMI 311 and SMI 312 as tools to investigate the maturation of nerve cells and axonal patterns in human fetal brain (1998)
    Springer
    Cell & tissue research 291 (1998), S. 433-443 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Neurofilaments ; Phosphorylation ; Differentiation ; Immunocytochemistry ; Brain storage ; Fixation ; Microwave ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Neurofilaments, which are exclusively found in nerve cells, are one of the earliest recognizable features of the maturing nervous system. The differential distribution of neurofilament proteins in varying degrees of phosphorylation within a neuron provides the possibility of selectively demonstrating either somata and dendrites or axons. Non-phosphorylated neurofilaments typical of somata and dendrites can be visualized with the aid of monoclonal antibody SMI 311, whereas antibody SMI 312 is directed against highly phosphorylated axonal epitopes of neurofilaments. The maturation of neuronal types, the development of area-specific axonal networks, and the gradients of maturation can thus be demonstrated. Optimal immunostaining with SMI 311 and SMI 312 is achieved when specimens are fixed in a mixture of paraformaldehyde and picric acid for up to 3 days and sections are incubated free-floating. Neurons, with their dendritic domains immunostained by SMI 311 in a Golgi-like manner, can be completely visualized in relatively thick sections. The limitations of Golgi-preparations, such as glia-labeling, artifacts, and the staining of only a small non-representative percentage of existing neurons, are not apparent in SMI preparations, which additionally provide the possibility of selectively staining axonal networks. The results achieved in normal fetal brain provide the basis for studies of developmental disturbances.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051013
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  • 148
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    Expression of insulin-like growth factor (IGF)-II in human prostate, breast, bladder, and paraganglioma tumors (1998)
    Springer
    Cell & tissue research 291 (1998), S. 469-479 
    Details
    ISSN: 1432-0878
    Keywords: Key words mRNA ; Cancerous epithelium ; Autocrine growth regulation ; In situ hybridization ; Immunohistochemistry ; Western blotting ; Benign prostate hyperplasia ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Insulin-like growth factors (IGFs) are potent mitogens for a variety of cancer cells in vitro. A paracrine/autocrine role of IGF-II in the growth of breast and prostate cancer cells has been suggested. Information on cell-type-specific IGF-II expression in vivo in the breast and prostate is, however, limited. Thus, cell types expressing IGF-II mRNA and protein in tumors were identified by in situ hybridization and immunohistochemistry. Of 36 prostate, 17 breast, and 10 bladder cancers, and 9 paraganglioma tissues examined, IGF-II was expressed in more than 50% of prostate, breast, and bladder tumors, and in 100% of paraganglioma tumors. Expression levels of IGF-II were highest in the paraganglioma and bladder followed by prostate and breast tumors. In all the tumors expressing IGF-II, both mRNA and protein were localized to malignant cells, expression in the stroma being minimal. Since previous studies had indicated that an incompletely processed form of 15-kDa IGF-II exhibited higher mitogenic potency than the completely processed 7.5-kDa IGF-II form, the quantity and size of IGF-II proteins expressed in these tumors were analyzed by Western immunoblotting. Greater expression of 15-kDa IGF-II relative to the 7.5-kDa IGF-II form was clearly demonstrated in all six prostate cancers and in half of the two breast and four bladder cancers examined. The results are consistent with the hypothesis that the 15-kDa form of IGF-II expressed in cancerous cells contributes to autocrine cancer cell growth in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051016
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  • 149
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    Effects of modulation of tyrosine phosphorylation on brush border enzyme activity in human Caco-2 intestinal epithelial cells (1998)
    Springer
    Cell & tissue research 292 (1998), S. 553-562 
    Details
    ISSN: 1432-0878
    Keywords: Key words Alkaline phosphatase ; Caco-2 intestinal epithelial cells ; Differentiation ; Dipeptidyl dipeptidase ; Proliferation ; Tyrosine kinase ; Tyrosine phosphoproteins ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Intestinal epithelial cell differentiation is closely regulated during normal cell renewal, maturation, and malignant transformation. Since tyrosine phosphorylation influences differentiation in other cell types and has been reported to vary between crypt cells to differentiated villus tip cells, we investigated the influence of tyrosine phosphorylation in colonocyte differentiation, by using human colonic Caco-2 cells as a model and expression of the brush border enzymes alkaline phosphatase (AKP) and dipeptidyl peptidase (DPDD) as differentiation markers. We studied three tyrosine kinase inhibitors with different modes of action and specificities, viz., genistein, erbstatin analog (EA), and tyrphostin, and the tyrosine phosphatase inhibitor sodium orthovanadate. AKP- and DPDD-specific activities were assayed in protein-matched cell lysates by synthetic substrate digestion. We also correlated the effects of these agents on brush border enzyme activity with tyrosine phosphorylation of phosphoproteins by Western blotting. Genistein (5–75 mg/ml) dose-dependently stimulated AKP and DPDD with a maximal stimulation at 75 mg/ml by 158.6± 17.5% and 228.6±37.1% of control values, respectively (n=12, P〈0.001). The inactive analog genistin had no effect. Tyrphostin (25 mM) similarly stimulated AKP and DPDD by 138.6±6.6% and 131.8±1.5% of control values (n=12, P〈0.001). Unexpectedly, EA (0.1–10 mM) had the opposite effect, inhibiting AKP- and DPDD-specific activity significantly at 10 mM with a maximal 14.8±6.4% and 26.5±2.5% of control values (n=12, each P〈0.001). Sodium orthovanadate had a discordant effect on these two differentiation markers. Orthovanadate dose-dependently increased AKP to a maximal 188.5±16.1% of basal activity at 1.5 mM but decreased DPDD activity at 1.5 mM to 47.2±3.8% (n=9, P〈0.001 each). The effects of each agent were preserved when proliferation was blocked with mitomycin C, suggesting that the modulation of phenotype by these agents was independent of any effects of proliferation. The tyrosine phosphorylation of several phosphoprotein bands was affected differently by these agents. In particular, the tyrosine phosphorylation of one 70-kDa to 71-kDa band was increased by genistein and tyrophostin but deceased by EA. The different effects of these modulators of tyrosine kinase activity raise the possibility that at least two independent enzymes or pathways regulating tyrosine phosphorylation modulate intestinal epithelial differentiation. Furthermore, tyrosine phosphorylation of the 70-kDa to 71-kDa phosphoprotein may be important in the intracellular signaling by which intestinal epithelial cell differentiation is controlled.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051084
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  • 150
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    The internal and external protein scaffold of the T-tubular system in cardiomyocytes (1998)
    Springer
    Cell & tissue research 294 (1998), S. 449-460 
    Details
    ISSN: 1432-0878
    Keywords: Key words Vinculin ; Talin ; Integrin ; Dystrophin ; Spectrin ; T-tubule ; Costamere ; Basal membrane ; Cardiac muscle cell ; Dilated cardiomyopathy ; Human ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The transverse tubule system of the cardiomyocyte remains undeformed despite the extreme forces it undergoes during the contraction-relaxation cycle, but the morphological basis for its stability remains unclear. Therefore, we have investigated the architecture and subcellular protein scaffold of the cardiac T-tubules and compared it with that of the costameres and of the free sarcolemma. Tissue samples from normal rat and monkey hearts, and left ventricular tissue from normal and cardiomyopathic human hearts obtained at transplantation surgery were investigated using immunocytochemistry and confocal microscopy and by electron microscopy. In addition, we used a re-differentiation model of isolated, cultured adult rat cardiomyocytes. The cell membrane of the cardiac T-tubules was found to contain the cell-matrix focal adhesion molecules (FAMs) vinculin, talin, the α5β1 integrin and the membrane-associated proteins (MAPs) dystrophin and spectrin. FAMs and MAPs were localized in the T-tubular membrane in a similar pattern: in longitudinally oriented myocytes as transverse punctate lines at the Z-level; in transversally cut myocytes a radial tubular network was found to extend throughout the interior of the cell. Immunolabeling for basement membrane components including collagen IV, fibronectin and laminin showed a colocalization with FAMs and MAPs parallel to the transverse T-tubules. The costameres of the sarcolemma showed a protein composition resembling that of the T-tubules but the intervening segments of free sarcolemma showed absence of FAMs and presence of MAPs. For the first time, we demonstrate the existence and protein composition of the T-tubular scaffold in the human heart. Furthermore, we show that cardiomyocytes from human failing hearts have less abundant but more dilated T-tubules than do experimental animals. These results indicate that the cardiac T-tubular system contains a subcellular scaffold closely resembling that of the costameres. It consists of FAMs, MAPs and basal lamina proteins that confer structural integrity to the cardiac T-tubular membrane during contraction/relaxation cycles.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051196
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  • 151
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    Distribution and submicroscopic immunogold localization of cellular prion protein (PrPc) in extracerebral tissues (1998)
    Springer
    Cell & tissue research 292 (1998), S. 77-84 
    Details
    ISSN: 1432-0878
    Keywords: Key words Prion protein (PrPc) ; Electron microscopy ; Secretory granules ; Membrane ; Extracerebral tissues ; Hamster ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  In transmissible spongiform encephalopathies (TSE), such as scrapie in animals and Creutzfeldt-Jakob disease in humans, the central event is the conversion of a host-encoded amyloidogenic protein (PrPc) into an abnormal isoform (PrPsc) that accumulates as amyloid in TSE brain. PrPc is a membrane sialoglycoprotein synthesized in the central nervous system and elsewhere. We have examined the ultrastructural localization of PrPc in numerous hamster and some human extracerebral tissues, by means of a post-embedding electron-microscopic method combined with immunogold labeling. In stomach, intestine, lung, and kidney from hamsters, and in stomach, kidney, and spleen from humans, immunogold labeling specific for PrPc is observed on various cellular substructures related to secretory pathways: Golgi apparatus, secretory globules, and plasma membrane. In mucous epithelial cells of stomach and intestine, PrPc appears to be concentrated in secretory globules, suggesting a role for PrPc in the secretory function of the digestive tract. The secretory aspect of PrPc may be a key to understanding the physiopathological mechanisms underlying TSE.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051036
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  • 152
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    Broad immunocytochemical localization of the formylpeptide receptor in human organs, tissues, and cells (1998)
    Springer
    Cell & tissue research 292 (1998), S. 129-135 
    Details
    ISSN: 1432-0878
    Keywords: Key words Neurons ; Brain ; Chemotaxis ; Endothelial cells ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The formylpeptide receptor (FPR), previously found only on polymorphonuclear leukocytes and monocytes/macrophages, responds to both synthetic N-formyl oligopeptides and those produced by bacteria. The cDNA for human FPR has been cloned and a rabbit polyclonal antiserum directed against a synthetic 11-amino-acid peptide corresponding to the deduced carboxy-terminus has been produced. We have now extensively characterized and used the antibody to detect FPR on normal human tissues and cell types. The receptor antigen is present on some epithelial cells, especially those with a secretory function, and on some endocrine cells, e.g., follicular cells of the thyroid and cortical cells of the adrenal. Liver hepatocytes and Kupffer cells are positive. Smooth muscle and endothelial cells are also generally positive. In the brain and spinal cord, the neurons of the motor, sensory, and cerebellar systems, and those of the parasympathetic and sympathetic systems stain positively. These data suggest that the putative endogenous agonist for FPR or an antigenically similar receptor reacts with cellular targets in the neuromuscular, vascular, endocrine, and immune systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051042
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  • 153
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    Establishment of oral mucosa phenotype in vitro in correlation to epithelial anchorage (1998)
    Springer
    Cell & tissue research 292 (1998), S. 355-366 
    Details
    ISSN: 1432-0878
    Keywords: Key words Organotypic cocultures ; Histodifferentiation ; Proliferation ; Basement membrane components ; Integrins ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Cell-matrix interactions and the ordered deposition of basement membrane (BM) components are of major importance for the maintenance of tissue homeostasis in complex epithelia. This aspect was studied in vitro in a coculture system designed as an oral mucosa model. As crucial epithelial features the kinetics of proliferation, expression of site-specific keratins as well as integrin patterns in correlation to synthesis of BM components were assessed by immunohistochemistry and in situ hybridization. Comparison with non-cornified gingiva as tissue of origin revealed different stages of epithelial development, eventually leading to complete reconstruction within a time frame of 1–3 weeks. First, the initial activated stage up to 1 week was characterized by (a) high keratinocyte proliferation, (b) extended expression of the basal cell-specific keratin K5 and (c) a patchy pattern of the differentiation-specific keratins K4 and K13. Second, after 2 weeks the improvement of histoarchitecture correlated to (a) predominant K5 expression in the basal and (b) extension of K4 and K13 within the suprabasal cell compartment, (c) high expression of integrins α3β1 and α6β4 including their ligand laminin-5 and (d) accumulating deposition of basement membrane components. Third, virtually complete tissue normalization at 3 weeks was indicated by (a) restriction of K5 to the basal cell area, (b) regular suprabasal localization of K4 and K13, (c) polarization of integrins to basal and parabasal cells and (d) linear codistribution of collagen IV, “classical” laminin (-1 or -10) and laminin-5 underneath the basal cells. Thus, these organotypic cocultures represent relevant equivalents for non-keratinized oral mucosa with typical gingival differentiation features and in addition suitable models for preclinical trials such as prospective dental material testing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051066
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  • 154
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    Secretory cell types and cell proliferation of human bronchial epithelial cells in an organ-culture system (1998)
    Springer
    Cell & tissue research 293 (1998), S. 573-577 
    Details
    ISSN: 1432-0878
    Keywords: Key words Airways ; Mucins ; Secretion ; Mini-organ culture ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  To study the secretory products and the proliferation of cells of the human respiratory surface epithelium, we established a miniorgan-culture system of bronchial tissue. Biopsies of large airways were grown on agar-coated dishes immersed in a serum-enriched medium. As determined by light and transmission electron microscopy, between 1 and 3 weeks, the organ cultures were covered by a differentiated epithelium consisting of secretory, ciliated, and basal cells. Immunohistochemistry, using antibodies to mucin and lysozyme, and lectin histochemistry revealed both mucous and serous secretory cells in the epithelium. Cell proliferation was studied in situ using antibodies to proliferating cell nuclear antigen (PCNA) and Ki-67. Whereas at the time of explantation the proliferation was low (2.5±1.7% of the epithelial cells were PCNA-positive, 1.7±0.6 were Ki-67-positive), at 24 h of cultivation, 30.4±5.1% or 25.2±4.9% of the epithelial cells were labeled with antibodies to PCNA or Ki-67. After 7 days, the number of dividing cells was low again. The results show that the organ-culture system of human respiratory surface epithelium produces a differentiated epithelium that is useful in the study of secretory processes, differentiation, and proliferation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051150
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  • 155
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    Differential expression of type XIV collagen/undulin by human mammary gland intralobular and interlobular fibroblasts (1998)
    Springer
    Cell & tissue research 291 (1998), S. 507-511 
    Details
    ISSN: 1432-0878
    Keywords: Key words Mammary gland ; Type XIV collagen ; Undulin ; Fibroblast ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Immunolocalisation of type XIV collagen/undulin in the human mammary gland revealed greater deposition in the interlobular stroma than in the intralobular stroma. The interlobular stroma is located between the breast lobules and their associated intralobular stroma. Fibroblasts isolated from the interlobular stroma synthesised 3- to 5-fold more type XIV collagen/undulin than intralobular fibroblasts, but synthesised type I and type IV collagens in similar amounts. The differential expression of type XIV collagen/undulin was maintained with passage in culture. The results suggest a role for type XIV collagen/undulin in stabilising dense collagen fibrils. The maintenance of two types of structurally distinct stromas may be important during developmental processes in the mammary gland.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051020
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  • 156
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    Distribution of endoglin in early human development reveals high levels on endocardial cushion tissue mesenchyme during valve formation (1998)
    Springer
    Cell & tissue research 292 (1998), S. 333-343 
    Details
    ISSN: 1432-0878
    Keywords: Key words TGF-β ; TGF-β receptors ; Vascular endothelium ; Heart ; Vascular disorders ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Endoglin is a component of the receptor complex for transforming growth factor (TGF)-β1 and TGF-β3. We analysed its expression by immunohistochemistry in human embryos at 4–8 weeks of gestation and in hearts ranging from 4–13 weeks old. We compared endoglin distribution with that of TGF-β receptors type I (TβR-I), type II (TβR-II) and betaglycan. Endoglin was found on endothelial cells in all tissues examined, consistent with its expression in adult blood vessels. TβR-I, TβR-II and betaglycan were observed on most cell types and had an overall similar pattern of distribution. Endoglin was detected on the endocardium as early as 4 weeks, but was absent from myocardium. It was present at high levels on the endocardial cushion tissue mesenchyme from 5–8 weeks’ gestation, during heart septation and valve formation, and subsequently decreased as the valves matured. Endoglin expression in heart extracts was confirmed by Western blot analysis. TβR-I, TβR-II and betaglycan were mostly found on cardiac myocytes, but were detectable at low levels on endocardium. They were expressed transiently on cushion mesenchyme, albeit at much lower levels than endoglin. All four components of the TGF-β receptor complex were detected by RT-PCR in embryonic heart. Thus transient up-regulation of the components of the TGF-β receptor complex, and particulartly of endoglin, is associated with heart septation and valve formation during early human development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051064
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  • 157
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    Galα1→4Gal-glycans are expressed on myofibrillar associated proteins (1998)
    Springer
    Cell & tissue research 293 (1998), S. 285-291 
    Details
    ISSN: 1432-0878
    Keywords: Key words Muscle ; Masseter ; Biceps ; P blood group ; CD77 ; Galactose ; Cat ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  There is evidence that glycans carrying terminal galactose residues are differently expressed in the sarcoplasm of different muscle fiber types. In this study monoclonal antibodies directed against P blood group antigens Pk: Galα1–4Galβ1–4Glcβ- and P1: Galα1–4Galβ1–4GlcNAcβ- were used to detect terminal α-galactosylated glycoconjugates on muscle proteins. Electrotransfer of proteins, extracted from human masseter and biceps muscles, to nitrocellulose after polyacrylamide gel electrophoresis (PAGE) and incubation with anti-Pk (CD77) consistently showed two bands with apparent molecular weights of 66 kDa and 64 kDa. In fresh frozen muscle sections from some humans there was endothelial reaction with anti-CD77 in capillaries, venules and veins but not in arterioles and arteries. In muscle samples from other humans there was no staining of endothelial cells. Formalin-fixed human muscle displayed a CD77 reaction with highest accumulation of reaction product at the periphery of the fibers. This may be explained by the presence of Pk glycoconjugates on intermediate filaments in muscle fibers. In preparations of cat masseter muscle proteins the antibodies against P1Pk antigens reacted with a 170 kDa and a 55 kDa band while in preparations of cat biceps brachii only a 55 kDa band was reactive. The specificities of the antibodies were investigated by fluorescence-activated cell sorter (FACS), α- and β-galactosidase digestion and inhibitory sugars. This study indicates that glycans carrying Galα1–4Galβ1- epitopes are expressed on myofibrillar associated proteins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051120
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  • 158
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    Presence and location of endothelin and endothelin-binding sites in human nasal mucosa under normal and metaplastic conditions (1998)
    Springer
    Cell & tissue research 293 (1998), S. 509-516 
    Details
    ISSN: 1432-0878
    Keywords: Key words Nose ; Endothelin ; Respiratory epithelium ; Metaplastic epithelium ; Nasal blood flow ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The presence and site of production of endothelin-1 (ET-1) was investigated in biopsies obtained from the nasal mucosa of 10 healthy human subjects and 10 patients affected by chronic rhinitis. The presence and localization of receptors for ET-1 was also investigated. Bioptic fragments were examined by scanning electron microscopy. ET-1 was present in the vessels and in the respiratory epithelium of normal subjects, whereas in patients affected by epithelial metaplasia induced by chronic rhinitis, it was absent in the metaplastic epithelium and present in the endothelium and vascular wall. Receptors for ET (A- and B-receptor subtypes) were localized in the vessels of the nasal mucosa, both in normal and in pathological subjects. In particular, A-receptors were identified in the vascular wall, whereas B-receptors were mainly distributed in the endothelium. We suggest that ET-1 is involved in the homeostasis of nasal blood flow (shunting the blood toward the deep cavernous plexus and inducing mucosal swelling) by an autocrine and/or paracrine mechanism. Normal epithelium seems to be important in this mechanism, since it is able to produce ET. However, when pathologic conditions induce squamous or cuboidal metaplasia, the epithelium is no longer able to play this role.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051143
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  • 159
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    Electron-microscopical evidence for heterogeneity of micronodular argyrophil cell growth in man (1998)
    Springer
    Cell & tissue research 292 (1998), S. 91-99 
    Details
    ISSN: 1432-0878
    Keywords: Key words Argyrophil cells ; Chronic gastritis ; Gastrinoma/Zollinger-Ellison syndrome ; Hypergastrinaemia ; Neuroendocrine complexes ; Pernicious anaemia ; Proton pump inhibitors ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Hypergastrinaemia-associated changes of non-antral argyrophil cells in man are of increasing interest, because of the development of potent inhibitors of gastric acid secretion. Using an antibody against chromogranin A, we identified micronodular endocrine cell hyperplasia of the oxyntic mucosa in gastric biopsy specimens of patients with hypergastrinaemia of different backgrounds. Consecutive ultrathin sections were examined at the electron-microscopical level. Endocrine cell types within the (extraepithelial) micronodules closely resembled those in the adjacent mucosa. Micronodules were classified into two groups. The first group was composed of endocrine cells only and predominated in patients with drug-induced hypergastrinaemia and/or chronic gastritis, and in a gastrinoma/MEN I patient. The second group represented “neuroendocrine complexes”, showing a close intermingling of non-myelinated nerve fibres with endocrine cells, and was found predominantly in pernicious anaemia. Micronodular argyrophil cell growth in man is therefore heterogeneous and depends on the background of the hypergastrinaemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051038
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  • 160
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    Temperature-sensitive regulation of epidermal morphogenesis and the expression of cornified envelope precursors by EGF and TGFα (1998)
    Springer
    Cell & tissue research 292 (1998), S. 107-114 
    Details
    ISSN: 1432-0878
    Keywords: Key words Reconstructed epidermis ; Differentiation ; Proliferation ; Migration ; Loricrin ; Involucrin ; SPRR ; EGF ; TGFα ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Epidermis reconstructed on de-epidermized dermis was used to investigate the effects of growth factors and culture temperature on epidermal morphogenesis and the expression of cornified envelope precursors. Cultures grown at 33°C or 37°C in the absence or presence of transforming growth factor alpha (TGFα), keratinocyte growth factor (KGF), basic fibroblast growth factor (bFGF), or insulin-like growth factor (IGF) show a similar morphology to that of native epidermis. Loricrin and SPRR2 are expressed in the stratum granulosum and SPRR3 is absent. Cultures grown in epidermal growth factor (EGF)-supplemented medium at 37°C have a normal morphology, whereas cultures grown at 33°C have a disorganized basal layer, no stratum granulosum, and nuclei are present in the stratum corneum. Loricrin is absent, and SPRR2 and SPRR3 expression extend into the spinous layers. Irrespective of the culture condition used, involucrin is aberrantly expressed in all suprabasal layers. EGF stimulated keratinocyte proliferation and migration to a greater degree than TGFα. Epidermis reconstructed on fibroblast-populated collagen gels at 33°C led to the same disturbances in keratinocyte differentiation as seen in cultures grown on de-epidermized dermis at 33°C in the presence of EGF, whereas parallel cultures grown at 37°C have a similar morphology to that of native epidermis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051040
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  • 161
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    Expression of SRY gene transcripts with a longer 3′ untranslated sequence in adult human male lymphocytes and tumor cells (1998)
    Springer
    Molecular genetics and genomics 257 (1998), S. 587-593 
    Details
    ISSN: 1617-4623
    Keywords: Key wordsSRY ; mRNA expression ; Human ; Lymphocytes ; Tumor ; Illegitimate transcripts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Using 3′ RACE PCR and the repeated nested-PCR method, the expression of transcripts of the sex-determining gene SRY was investigated in single lymphocytes from a human adult male and in male tumor cell lines. The gene is functionally transcribed in the early stages of embryogenesis and mRNA is also expressed in adult testes. However, in this study, SRY gene transcripts were also detected in somatic cells of adult male and in tumor cells. Moreover, this mRNA possessed a longer additional untranslated exon. Although expression of the transcripts might not have any functional meaning in these cells, these new findings support the hypothesis that any given human cell can contain illegitimate mRNAs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004380050686
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  • 162
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    Trends in mortality from major diseases in Europe, 1980–1993 (1998)
    Springer
    European journal of epidemiology 14 (1998), S. 1-8 
    Details
    ISSN: 1573-7284
    Keywords: Europe ; Geographical ; Human ; Mortality ; Neoplasms ; Temporal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Trends in age-standardized death certification rates from all causes, coronary heart disease (CHD), cerebrovascular diseases, all neoplasms and lung cancer were analysed over the period 1980–1993 in 20 major European countries. There were steady and substantial declines of overall mortality in all western European countries for both sexes, although appreciable geographic differences persisted. These favourable trends reflect a decline in CHD mortality in most western countries, besides a persisting fall in cerebrovascular disease, and a substantial stability (with some decline in a few northern and central European countries) in cancer mortality. In contrast, in eastern European countries appreciable rises were registered in mortality from major causes of death considered for males. For females, only moderate declines were observed in Eastern Europe. In the early 1990s, overall mortality was 30 to 100% higher for males and 20 to 100% higher for females as compared to Western Europe. As indicated by the trends in lung cancer death rates, this reflects a major impact of the tobacco-related disease epidemic in subsequent cohorts, as well as more unfavourable lifestyle factors (i.e. aspects of diet, other environmental factors), and a delayed control of hypertension in Eastern Europe, together with a substantial excess of suicides, (road) accidents, homicides and alcohol-related diseases, and the delayed introduction of rational treatment for some conditions. An indication of reversal of mortality trends was evident in the early 1990s only in Poland. In conclusion, there is ample scope for intervention on avoidable mortality in eastern European countries.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007440201137
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  • 163
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    Mixing in Stars and the Evolution of the 3He Abundance (1998)
    Springer
    Space science reviews 84 (1998), S. 199-206 
    Details
    ISSN: 1572-9672
    Keywords: Nuclear reactions ; Nucleosynthesis ; Abundances ; Stars:Evolution ; Interior ; Rotation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We first recall the observational and theoretical facts that constitute the so-called 3He problem. We then review the chemical anomalies that could be related to the destruction of 3He in red giants stars. We show how a simple consistent mechanism can lead to the destruction of 3He in low mass stars and simultaneously account for the low 12C/13C ratios and low lithium abundances observed in giant stars of different populations. This process should both naturally account for the recent measurements of 3He/H in galactic HII regions and allow for high values of 3He observed in some planetary nebulae. We propose a simple statistical estimation of the fraction of stars that may be affected by this process.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005027519798
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  • 164
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    Effects of nerve growth factor and glucocorticoid on cultured human pheochromocytoma cells (1998)
    Springer
    Medical molecular morphology 31 (1998), S. 24-30 
    Details
    ISSN: 1860-1499
    Keywords: Human ; Pheochromocytoma ; Nerve growth factor ; Cultured cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Primary cell cultures of two human pheochromocytomas (PC) that were associated with high serum levels of adrenaline and noradrenaline were developed to study the effects of nerve growth factor (NGF) and dexamethasone on the morphology and function of PC cells in vitro. By phase-contrast microscopy, cultured cells were small and hyperchromatic on the first day of culture; neurite-like processes that extended to other cells developed several days later and were maintained for more than 3 months. NGF (100ng/ml), dexamethasone (10−5M), or NGF + dexamethasone were added to the culture media 2 weeks after the cultured cells had stabilized. Catecholamine concentrations in the medium were maintained at higher levels after addition of NGF, dexamethasone, or NGF + dexamethasone as compared to control cells. In the presence of NGF, extension of neurite-like processes was clearly accelerated, while high levels of dexamethasone inhibited growth of processes. These in vitro studies showed that the addition of NGF or the removal of dexamethasone induces differentiation of adrenal neurons present in pheochromocytomas, suggesting that adrenocortical steroid hormones influence the morphological control of adrenal medullary cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01547945
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