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  • 1
    Electronic Resource
    Electronic Resource
    Human tissue levels and plasma pharmacokinetics of temoporfin (Foscan®, mTHPC) (1996)
    Springer
    Lasers in medical science 11 (1996), S. 267-272 
    Details
    ISSN: 1435-604X
    Keywords: Photosensitizer ; Photodynamic therapy ; mTHPC ; Temoporfin ; Pharmacokinetics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract A Phase I photodynamic therapy (PDT) clinical trial was carried out with Temoporfin (Foscan®, mTHPC) at the Departments of Otolaryngology at Orebro Medical Center (OMC) and Long Island Jewish Medical Center (LIJMC). A range of drug doses, consisting of 0.3, 0.15, 0.075 and 0.0375 mg kg−1, were utilized. Light treatment was performed on the sixth day after injection of the photosensitizer mTHPC. Photodynamic therapy was done on prostate cancer (six cases), bronchial cancer (one case), nasopharyngeal cancer (three cases), laryngeal cancer (eight cases), mesothelioma (one case), laryngeal papilloma (five cases) and basal cell nevus syndrome (one case). A number of patients were treated more than once. Plasma was collected and analysed at 1, 24, 48, 72, 96, 120 and 144 h and at 2 weeks post-injection, to follow the loading and clearance rate of the photosensitizer. Normal and malignant tissues were collected immediately prior to PDT, chemically extracted, and analysed for drug content spectrofluorometrically. Plasma drug levels were proportional to the dose. The half-life of the drug was 45.4 h across the entire dose range. The ratio of the drug in the tumour compared to normal adjacent mucosa was in the range of 2–3. There were no significant adverse effects. These data establish the basis for full clinical trials.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02134918
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  • 2
    Electronic Resource
    Electronic Resource
    Early features of zidovudine-associated myopathy: histopathological findings and clinical correlations (1995)
    Springer
    Acta neuropathologica 90 (1995), S. 1-6 
    Details
    ISSN: 1432-0533
    Keywords: Key words Myopathy ; Zidovudine ; Human ; immunodeficiency virus ; Mitochondria ; Nucleoside analogue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Zidovudine-induced myopathy is characterized by reversible muscle weakness, wasting, myalgia, fatigue, and elevated creatine kinase (CK). Some zidovudine-treated patients with normal muscle strength experience excessive fatigue, myalgia, or transient mild CK elevations that improve when zidovudine is stopped. To determine the cause of these symptoms, we studied 13 physically fit, HIV-infected men who developed fatigue, myalgia, and reduced endurance, while taking zidovudine for a mean period of 20 months (2–39 months), with neurological evaluation and muscle biopsy processed for enzyme histochemistry and electron microscopy (EM). All subjects had normal muscle strength. In 6 of the 13 patients, muscle biopsies were normal by enzyme histochemistry. EM, however, demonstrated proliferation of normal or abnormal mitochondria, and increased amounts of lipid, glycogen, and lipofuscin. Electromyographic (EMG) studies (5/5) and serum CK (6/6) were normal. The other 7 individuals had signs of moderate to severe mitochondrial abnormalities shown by both light microscopy and EM, characterized by severe destruction, vacuolization, and rare paracrystalline inclusions. Most had elevated CK (4 out of 7) and normal EMG (5 out of 7). The severity of morphological abnormalities did not correlate with duration of HIV infection, zidovudine therapy, or zidovudine dosage. We conclude that in zidovudine-treated patients, symptoms of fatigue, myalgia, reduced endurance, and exercise intolerance represent early signs of zidovudine-induced mitochondriotoxicity, which causes an energy shortage within the muscle fibers even when muscle strength is still normal. Zidovudine, a DNA chain terminator, results in overt myopathy when a critical threshold of molecular, histological, and biochemical dysfunction of mitochondria is crossed, which seems to vary between individuals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00294452
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  • 3
    Electronic Resource
    Electronic Resource
    Epidermal growth factor receptor in adult human dorsal root ganglia (1996)
    Springer
    Anatomy and embryology 194 (1996), S. 253-257 
    Details
    ISSN: 1432-0568
    Keywords: Epidermal growth factor receptor ; Dorsal root ganglia ; Immunoblotting ; Immunohistochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Transforming growth factor-α (TGFα) enhances neuronal survival and neurite outgrowth in cultured dorsal root ganglia (DRG) sensory neurons. It binds a membrane protein, denominated epidermal growth factor receptor (EGFr). EGFr has been localized in developing and adult human DRG. However, it remains to be elucidated whether all DRG neurons express EGFr or whether differences exist among neuronal subtypes. This study was undertaken to investigate these topics in adult human DRG using immunoblotting, and combined immunohistochemistry and image analysis techniques. A mouse monoclonal antibody (clone F4) mapping within the intracytoplasmic domain of EGFr was used. Immunoblotting revealed two main proteins with estimated molecular masses of ∼- 65 kDa and 170 kDa, and thus consistent with the full-length EGFr. Additional protein bands were also encountered. Light immunohistochemistry revealed specific immunoreactivity (IR) for EGFr-like proteins in most (86%) primary sensory neurons, the intensity of immunostaining being stronger in the small- and intermediate-sized ones. Furthermore, EGFr-like IR was also observed in the satellite glial cells of the ganglia as well as in the intraganglionic and dorsal root Schwann cells. Taken together, our findings demonstrate that EGFr, and other related proteins containing the epitope labeled with the antibody F4, are responsible for the EGFr IR reported in DRG. Furthermore, we demonstrated heterogeneity in the expression of EGFr-like IR in adult human primary sensory neurons, which suggests different responsiveness to their ligands.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00187136
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  • 4
    Electronic Resource
    Electronic Resource
    Calretinin immunoreactivity in human sympathetic ganglia (1996)
    Springer
    Anatomy and embryology 194 (1996), S. 373-378 
    Details
    ISSN: 1432-0568
    Keywords: Paravertebral sympathetic ganglia ; Calretinin ; Aging ; Immunoblotting ; Immunohistochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Calretinin is an “EF-hand” calcium-binding protein involved in the maintenance of intracellular calcium ion homeostasis. This study was understaken to investigate the presence of calretinin in human lumbar paravertebral sympathetic ganglia from subjects of different ages (26–85 years) using immunohistochemical and immunoblotting methods. Calretinin-like immunoreactivity was found in a subpopulation of postganglionic sympathetic neurons, whose percentage decreased progressively with aging by about 50% (63% of immunoreactive neurons at ≤40 years; 29% at ≥81 years) whereas the neuronal density remained basically unchanged. Calretinin-like immunoreactivity showed a granular pattern of cytoplasmic distribution suggesting preferential localization of this protein associated with intracellular membranes. Occasionally diffuse cytosolic labelling was also observed. The immunoblotting demonstrated a protein band with an estimated molecular weight of 30 kDa, approximately. Present results provide, for the first time, evidence for the presence of calretinin in human paravertebral sympathetic ganglia. Since the number of calretinin-like immunoreactive neurons decreased significantly with aging our findings suggest an involvement of this protein in the age-dependent impairment of sympathetic function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00198539
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  • 5
    Electronic Resource
    Electronic Resource
    Stochastic processes in postural center-of-pressure profiles (1997)
    Springer
    Experimental brain research 113 (1997), S. 158-164 
    Details
    ISSN: 1432-1106
    Keywords: Posture ; Center of pressure ; Stochastic processes ; Development ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The stochastic processes of postural center-of-pressure profiles were examined in 3- and 5-year-old children, young adult students (mean 20 years), and an elderly age group (mean 67 years). Subjects stood still in an upright bipedal stance on a force platform under vision and nonvision conditions. The time evolutionary properties of the center-of-pressure dynamic were examined using basic stochastic process models. The amount of motion of the center of pressure decreased with increments of age from 3 to 5 years to young adult but increased again in the elderly age group. The availability of vision decreased the amount of motion of the center of pressure in all groups except the 3-year-old group, where there was less motion of the center of pressure with no vision. The stochastic properties of the center-of-pressure dynamic were assessed using both a two-process, random-walk model of Collins and De Luca and an Ornstein-Uhlenbeck model that is linear and has displacement governed only by a single stiffness term in the random walk. The two-process open- and closed-loop model accounted for about 96% and the Ornstein-Uhlenbeck model 92% of the variance of the diffusion term. Diffusion parameters in both models showed that the data were correlated and that they varied with age in a fashion consistent with developmental accounts of the changing regulation of the degrees of freedom in action. The findings suggest that it is premature to consider the trajectory of the center-of-pressure as a two-process, open- and closed-loop random-walk model given that: (a) the linear Ornstein-Uhlenbeck dynamic equation with only two parameters accommodates almost as much of the variance of the random walk; and (b) the linkage of a discontinuity in the diffusion process with the transition of open- to closed-loop processes is poorly founded. It appears that the nature of the stochastic properties of the random walk of the center-of-pressure trajectory in quiet, upright standing remains to be elucidated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02454152
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  • 6
    Electronic Resource
    Electronic Resource
    Changes in the force-sharing pattern induced by modifications of visual feedback during force production by a set of fingers (1998)
    Springer
    Experimental brain research 123 (1998), S. 255-262 
    Details
    ISSN: 1432-1106
    Keywords: Key words Synergy ; Force production ; Finger ; Redundancy ; Feedback ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We investigated force-sharing among three fingers which acted in parallel and produced ramp profiles of total force from zero to the maximal voluntary force. The feedback to the subject was provided by a visual signal on the monitor and could correspond to the sum of forces of all the fingers or to the sum of forces of two fingers, while the force of the third finger was added with a coefficient 2 or 0.5. If the subjects did not know about the distorted feedback, they showed a template-sharing pattern within the whole range of total force values. This pattern did not depend on which finger force was multiplied and by which coefficient. If the subjects knew in advance how the feedback signal would be calculated, they tried to perform the task using either only the finger whose force was multiplied by 2 or two fingers when the force of the third one was multiplied by 0.5. Further into the trial, however, they were unable to track the ramp pattern using only one or two fingers and demonstrated a search activity that could continue until the end of the trial or lead eventually to a three-finger sharing pattern similar to the template pattern used in cases of undistorted feedback. We conclude that the limited number of preferred sharing pattern within the studied task reflects an organization of the fingers into a structural unit (involving one, two, or all three fingers) by the central nervous system. The availability of structural units defines the presence of stable solutions available for the system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050567
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  • 7
    Electronic Resource
    Electronic Resource
    Optically induced plasticity of the cervico-ocular reflex in patients with bilateral absence of vestibular function (1996)
    Springer
    Experimental brain research 112 (1996), S. 372-380 
    Details
    ISSN: 1432-1106
    Keywords: Cervico-ocular reflex ; Adaptation ; Vestibular loss ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The horizontal cervico-ocular reflex (COR) was examined in five labyrinthine-defictive subjects (LDS), during both passive oscillations of the head on the trunk (HTexam) and of the trunk under the earthfixed head (THexam) at 0.1–0.5 Hz, peak angular displacement ±30°. Subjects were tested in the dark, before and immediately after adaptation to binocular magnifying (x1.9) and reducing (x0.6) lenses. During long-term adaptation, the LDS were exposed to the normal environment for 5 h while wearing lenses. Short-term adaptation experiments (15–20 min) consisted of sustained ocular following of a small LED in an otherwise dark room and in full-room illumination. This LED was either stationary in space whilst the subjects moved their head actively, or fixed on the chair and rotating with the trunk during head-fixed stimulation. In all five patients, magnifying lenses increased COR gain (peak slow-phase eye velocity/peak stimulus velocity), whereas reducing lenses reduced the gain. Under HTexam the gain changes were greater, more consistent and the phases approximately compensatory to head displacement, whereas during THexam the gain decreased and phase increased at higher frequencies. COR adaptation was observed during foveal stimulation alone, but the effects were stronger with added background illumination. Results during an imaginary target task showed that the gain can be influenced strongly by mental set. Our findings indicate a highly modifiable COR in subjects with loss of vestibular function. Both peripheral and foveal retinal information contribute to the plastic changes in COR gain. Somatosensory cues from the trunk as well as cognitive/perceptual factors may be involved in the modification of the COR, by providing information about the relevance of eye movements, and contribute to the stabilisation of gaze in space.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227943
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  • 8
    Electronic Resource
    Electronic Resource
    Brain activity related to serial cognitive performance resembles circuitry of higher order motor control (1996)
    Springer
    Experimental brain research 109 (1996), S. 136-140 
    Details
    ISSN: 1432-1106
    Keywords: Cognitive performance ; Positron emission tomography ; Supplementary motor area ; Parietal cortex ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Differences between two states of cerebral activation were studied in eight subjects by positron emission tomography (PET) of regional cerebral blood flow (rCBF) and subsequent statistical parameter mapping. Subjects had to respond to a row of numbers presented on tape. In one condition they had to repeat each number. In the other condition the last heard number had to be added to the number presented before. Cerebral activity specifically related to the serial addition task was distributed over supplementary motor area (SMA), left premotor cortex and superior dorsal parietal cortex bilaterally, without significant involvement of prefrontal cortex. This indicated circuitry related to mental performance characterised by a fixed strategy of executing serial manipulation of numbers within “internal space”. The main aim of this communication is to discuss the similarity between circuitry underlying higher order motor control and pure cognitive performance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228634
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  • 9
    Electronic Resource
    Electronic Resource
    Coordination between posture and movement in a bimanual load-lifting task: is there a transfer? (1996)
    Springer
    Experimental brain research 109 (1996), S. 450-456 
    Details
    ISSN: 1432-1106
    Keywords: Posture ; Movement ; Bimanual coordination ; Motor learning ; Learning transfer ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present experimental series was designed to test the possibility that an anticipatory postural adjustment learned during the performance of a bimanual load lifting task may be transferred between the upper extremities. Eight seated subjects were asked to maintain horizontally one forearm (postural arm) loaded with a 1kg load, which was fixed to the arm by means of an electromagnet. The unloading was triggered either by the experimenter pressing a switch (control) or by the subjects making a voluntary movement with their other arm (moving arm). In the latter case, the subject lifted a 1-kg load resting on a force platform with the moving hand, and the switching off was triggered when the force level reached a threshold of 0.5 kg. The maximum amplitude (MA) and the maximum velocity (MV) of the postural forearm elbow joint rotation occuring after the unloading were measured at each trial. The learning process was estimated by performing a regression analysis on each series of trials, using an exponential model, and from the intercept of the regression curve with the ordinate. 1. During the original learning session (three series of 20 trials), a decrease in MA and MV was found to occur both within the series and between the series during a session. 2. After the initial learning session, the sides of the postural and moving arm were interchanged to test whether any transfer had occurred. The first series of trials in the second session (transfer) and the last series of trials in the original learning session were compared and found to be significantly different in terms of the intercept (seven subjects in the case of MA, five subjects in the case of MV) and the slope (five subjects), indicating a lack of transfer. 3. The data recorded during the second transfer learning session indicated that learning occurred in all eight subjects in the case of MA and in six subjects in the case of MV. It was observed that the original learning session did not facilitate the second one. 4. The lack of transfer of the anticipatory postural adjustment observed in this task is discussed with reference to the data in the literature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00229629
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  • 10
    Electronic Resource
    Electronic Resource
    The preparation, execution and suppression of copied movements in the human brain (1998)
    Springer
    Experimental brain research 120 (1998), S. 386-398 
    Details
    ISSN: 1432-1106
    Keywords: Key words Broca’s area ; Ventral prefrontal cortex ; Supramarginal gyrus ; Cingulate ; Cerebellum ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We used positron emission tomography (PET) to measure movement set-related changes in regional cerebral blood flow (rCBF) when human subjects were asked to copy hand movements. Movement set-related activity in the brain is thought to reflect the processes of movement selection, preparation and inhibition. Four conditions were used. In the first condition, prepare and execute (PE), the hand stimulus to be copied was shown to subjects 3 s before an auditory “go”-cue instructed subjects to execute the movement; a large part of the scanning time was therefore spent in preparing to move. In the immediate execution condition (E), the hand stimulus and the go cue were presented simultaneously. The prepare-only condition (P) was similar to PE, except subjects only prepared to make the movement and did not actually execute any movement when they heard the auditory go-cue. The same stimuli were presented in a baseline condition (B), but the subjects were instructed to neither prepare nor execute movements. There were 5 principle findings: (1) In contrast to a previous study of human set-related activity in which movements were instructed by an arbitrary pattern of LEDs, preparing to make a copied movement causes rCBF changes in area 44 in posterior Broca’s area; (2) set-related activity can be recorded in the cerebellar hemispheres and midline; (3) we confirmed that the supramarginal gyrus has a general role in preparing movements – there was more rCBF in the P than the E condition; (4) the cerebellar nuclei and the basal ganglia may be particularly involved in the initiation and execution of a planned movement; these regions were more active in the PE condition than the P condition; (5) the ventrolateral prefrontal cortex and a left anterior cingulate area are part of a distributed system involved in the suppression of a motor response; these areas were significantly more active in the P than the PE condition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050412
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