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Biomedical subjects

W Berger

Publications and source records attributed to W Berger.

At least 109 records · Page 6Linked to original sources
PubMed1995

Adaptational and learning processes during human split-belt locomotion: interaction between central mechanisms and afferent input.

Split-belt locomotion (i.e., walking with unequal leg speeds) requires a rapid adaptation of biomechanical parameters and therefore of leg muscle electromyographic (EMG) activity. This adaptational process during the first strides of asymmetric gait as well as learning effects induced by repetition were studied in 11 healthy volunteers. Subjects were switched from slow (0.5 m/s) symmetric gait to split-belt locomotion with speeds of 0.5 m/s and 1.5 m/s, respectively. All subjects were observed to adapt in a similar way: (1) during the first trial, adaptation required about 12-15 strides. This was achieved by an increase in stride cycle duration, i.e., an increase in swing duration on the fast side and an increase in support duration on the slow side. (2) Adaptation of leg extensor and flexor EMG activity paralleled the changes of biomechanical parameters. During the first strides, muscle activity was enhanced with no increase in coactivity of antagonistic leg muscles. (3) A motor learning effect was seen when the same paradigm was repeated a few minutes later--interrupted by symmetric locomotion--as adaptation to the split-belt speeds was achieved within 1-3 strides. (4) This short-time learning effect did not occur in the "mirror" condition when the slow and fast sides were inverted. In this case adaptation again required 12-15 strides. A close link between central and proprioceptive mechanisms of interlimb coordination is suggested to underlie the adaptational processes during split-belt conditions. It can be assumed that, as in quadrupedal locomotion of the cat, human bipedal locomotion involves separate locomotor generators to provide the flexibility demanded. The present results suggest that side-specific proprioceptive information regarding the dynamics of the movement is necessary to adjust the centrally generated locomotor activity for both legs to the actual needs for controlled locomotion. Although the required pattern is quickly learned, this learning effect cannot be transferred to the contralateral side.

Adaptation, Physiological↗
PubMed1995

Gating of sensation and evoked potentials following foot stimulation during human gait.

To investigate how gait influences the perceived intensity of cutaneous input from the skin of the foot, the tibial or sural nerves were stimulated at the ankle during walking or running on a treadmill. As compared to standing, the detection threshold for these stimuli was raised by more than 30% during the locomotion tasks. During walking, there was a phase-dependent modulation in perceived intensity of suprathreshold stimuli (1.5, 2, or 2.5 x PT). Stimuli given just prior to footfall were perceived as significantly above average (Wilcoxon signed-rank test). In contrast there was a significant phasic decrease in sensitivity for shocks delivered immediately after ipsi- and contralateral footfall. The amplitude of somatosensory evoked potentials (P50-N80 complex), simultaneously evoked from pulse trains to the sural nerve and recorded at scalp level, was, on average, 62% of the level during standing. During gait, the amplitude of this complex was significantly smaller just after footfall than the amplitude during late swing (MANOVA). It is suggested that the reduced sensation and the decreased evoked potentials after touchdown may be due to occlusion or masking by concomitant afferent input from the feet. On the other hand, the phasic increase in sensitivity at the end of swing is thought to result from a centrally generated facilitation of sensory transmission of signals in anticipation of foot-placing.

Adult↗
PubMed1995

Modulation of sural nerve somatosensory evoked potentials during stance and different phases of the step-cycle.

In order to investigate the modulation of somatosensory processing during stance and locomotion, sural nerve somatosensory evoked potentials were recorded during both stance and different phases of the step-cycle. Characteristic sequences of negative-positive waves were elicited, consisting of an early component, N40, presumably of subcortical origin, followed by a P50-N80-P220 complex of cortical origin. The N40 and N40-P50 components had similar amplitudes in both gait and stance. However, the P50-N80 component was attenuated whereas the N80-P220 complex became biphasic during gait. Within the step-cycle, amplitudes of the cortical components P50-N80 and N80-P110 were larger prior to footfall and smaller at the beginning of the support phase. The results demonstrate that locomotion produces a modulatory effect on somatosensory input at a cortical level. Within the step-cycle, excitability of the somatosensory cortex is increased during the middle and late swing phases and decreased during the support phase. Such modulation may contribute to an improved detection of foot contact at touchdown.

Adult↗
PubMed1995

Leg muscle activation during gait in Parkinson's disease: adaptation and interlimb coordination.

Adaptation in leg muscle activity and coordination between lower limbs were studied during walking on a treadmill with split belts in one group of parkinsonian patients and one of age-matched healthy subjects. Four different belt speeds (0.25/0.5/0.75/1.0 m/sec) were applied in selected combinations to the left and right leg. While these walking conditions were easily tolerated by the healthy subjects, the parkinsonian patients usually reached the limits of their walking capabilities. Both groups adapted automatically to a change in belt speed within approximately 20 stride cycles. Healthy subjects adapted by reorganizing their stride cycle with a relative shortening of duration of support and lengthening of the swing phase of the "fast" leg and vice versa on the "slow" leg. The patients showed a restricted range of stride frequencies for the various belt speeds during normal and split-belt walking with consequent deviations in the reorganization of the stride cycle. In both healthy subjects and patients, ipsilateral gastrocnemius and contralateral tibialis anterior electromyographic (EMG) activity increased predominantly with an ipsilateral increase in belt speed. Two main differences were observed in the EMG patterns: (1) In the patients leg muscle EMG activity was less modulated and gastrocnemius EMG amplitude was small during normal and split-belt walking. However, there was no significant difference between the two groups in respect to the reorganization of the EMG pattern required for the various split-belt walking conditions. (2) The amount of co-activation of antagonistic leg muscles during the support phase of the stride cycle was greater in the patients compared to the healthy subjects during normal and split-belt walking. It is suggested that reduced EMG modulation and recruitment in the leg extensors may contribute to the impaired walking of the patients. This in turn is a result of an impaired proprioceptive feedback from extensor load receptors. This defective control is partially compensated for in parkinsonian patients by a greater amount of leg flexor activation which leads to a higher degree of co-activation. Visual input plays a role in the control of this increased activation.

Adaptation, Physiological↗
PubMed1995

Protein content of the evening meal and nocturnal plasma glucose regulation in type-I diabetic subjects.

The effect of two isocaloric evening meals (low protein-high fat vs. high protein-low fat content) on plasma glucose regulation during the night were compared. Eight C-peptide-deficient type-I diabetic subjects without autonomic neuropathy were treated with fixed doses of continuous infusions of insulin during 2 nights. At 7 p.m. they received in random order either a low protein-high fat (5% of total energy protein, 60% fat, 35% carbohydrate) or a high protein-low fat (35% protein, 30% fat, 35% carbohydrate) evening meal. Venous plasma samples were drawn hourly thereafter. Plasma glucose concentrations were similar postprandially during the 2 nights between 7 p.m. and 11 p.m., but they were higher in the early morning hours after the high protein meal (p < 0.02 vs. the low protein meal). Two subjects developed symptomatic hypoglycemia after the low protein meal. Plasma glucagon concentrations were higher (p = 0.023) and serum free insulin lower (p < 0.05) after the high protein-low fat meal. Plasma cortisol and growth hormone were not significantly different between the two diets. Therefore, an increase in the protein content of the evening meal (fat content diminished) increases plasma glucose concentrations several hours later in the night, possibly due to protein-induced glucagon secretion and to lower plasma free insulin levels. Patients with type-I diabetes with a tendency to develop hypoglycemia during the night may avoid this problem by increasing the protein content of the evening meal.

Blood Glucose↗
PubMed1995

The effect of activated alveolar macrophages on experimental lung emphysema development. II. The study of fibroblast and alveolar macrophage co-culture.

The cell-cell interaction between fibroblasts and alveolar macrophages was examined using a co-culture system. Alveolar macrophages (AM) were harvested from the bronchoalveolar lavages (BAL) of rats with papain induced lung emphysema. The BCG-vaccine was applied as a macrophage mobilizing and activating agent. The morphological examinations carried out in scanning electron microscope (SEM) as well as the evaluation of the uptake of 3H-thymidine did not show any significant differences between respective co-cultures of fibroblasts and AM isolated both from the lungs of control and experimental animals (treated with BCG or papain, and BCG+papain). However, significant growth were noted in 3H-thymidine uptake between fibroblast cultures done with or without cells isolated from the lungs. The results obtained suggest that AM can promote fibroblast proliferation during the progression of experimental lung emphysema.

Animals↗
PubMed1994

Intrinsic MDR-1 gene and P-glycoprotein expression in human melanoma cell lines.

Metastatic malignant melanoma is considered a chemotherapy-refractory malignancy. A few previous studies have delivered contradictory results regarding the presence and functionality of P-glycoprotein (P-gp), a transmembranous protein associated with the classical multidrug resistance (cMDR), in malignant melanoma. Therefore we have investigated this issue on 33 cell lines established from primary and metastatic lesions of human malignant melanoma, comparing different cMDR detection methods. Immunocytochemically 33% of the cell lines stained positive for P-gp. The data correlated with those of a P-gp-radioimmunometric (antibody-binding) assay. When RT-PCR was used for MDR-1 mRNA determination, 76% of the melanoma cell lines scored positive. Slot-blot analysis was seen to be less sensitive than RT-PCR. Results from the functional P-gp assays, using daunomycin (DM) as MDR-substrate, showed no influence of P-gp expression on drug accumulation and cytotoxicity. However, the cMDR-modifier verapamil (VP) significantly increased both parameters in those melanoma cells with the highest P-gp levels. We conclude that cMDR is apparently not the decisive but probably a complementary protective mechanism against toxic agents in malignant melanoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Complex molecular mechanism for dihydropyridine binding to L-type Ca(2+)-channels as revealed by fluorescence resonance energy transfer.

We analyzed binding-induced changes in the fluorescence properties of the 1,4-dihydropyridine (DHP), DMBODIPY-DHP [(-)-1,4-dihydro-2,6-dimethyl-4-(2-trifluromethylphenyl)- 3,5-pyridinedicarboxylic acid 2-[4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-3- (s-indacene)propionylamino]ethylethyl ester)], to study the molecular mechanisms underlying the interaction of DHPs with the alpha 1-subunit of skeletal muscle L-type Ca2+ channels. The quantum yield of the fluorophore DMBODIPY was similar in solvents of different polarity. In contrast, the quantum yield of DMBODIPY-DHP was low in buffer but increased with solvent polarity and upon specific binding. This indicates the existence of binding-induced changes of intramolecular quenching of the fluorophore by the DHP moiety. Specific ligand binding also induced fluorescence resonance energy transfer (FRET) between one or more tryptophanes of the channel protein and the DMBODIPY-DHP fluorophore. The specific FRET signal was successfully used to directly measure DHP binding at high time resolution. It revealed complex association and dissociation kinetics of DMBODIPY-DHP although no site heterogeneity was detected in equilibrium experiments. We therefore fitted our data to a binding scheme considering one or more intermediate conformational states for the formation of the ligand-receptor complex. Such a step-wise binding mechanism explains previously observed differences in the binding site densities and the kinetic constants determined for different DHPs using conventional binding (for example filtration) assays.

Animals↗
PubMed1994

Memantine inhibits [3H]MK-801 binding to human hippocampal NMDA receptors.

The antispastic agent and N-methyl-D-aspartate (NMDA) receptor antagonist memantine has recently been proposed as a neuroprotective drug for use in patients with dementia syndromes with primarily temporal lobe pathology, e.g. senile dementia of Alzheimer type or dementia in Parkinson's disease. In a quantitative autoradiographic study in human post mortem hippocampus, memantine was able to inhibit binding of the noncompetitive NMDA-antagonist [3H]MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate) with inhibition constants between 3 and 10 microM, being about a factor of 10 more potent than the dissociative anaesthetic and NMDA receptor antagonist (+/-)ketamine. As these inhibition constants are well within the therapeutic concentration range of memantine, antagonism of endogenous glutamate at limbic NMDA receptors may be one molecular mechanism by which memantine is beneficial in dementia syndromes.

Aged↗
PubMed1994

Rhythmic oscillations with a wavelength of 0.5-2 min in transcranial Doppler recordings.

We have studied intracranial pressure (ICP) B-waves and their association with rhythmic changes in blood flow velocity (B-wave equivalents) by transcranial Doppler sonography (TCD) monitoring. In overnight TCD recordings in 10 normal young adults, these rhythmic changes in blood flow velocity were higher and more frequent during REM sleep and sleep stage 1 than during other sleep stages. B-wave equivalents also had a longer wavelength during REM sleep. Their relative frequency in these normal subjects over one night ranged from 35 to 73%. Peripheral resistance (assessed by the Pourcelot index) was lower and heart rate was higher at the peak of these oscillations. These results support the hypothesis that ICP B-waves are caused by vasodilation. A non-linear relationship between ICP and blood flow velocity was found during B-waves in 9 of 11 patients with suspected NPH. Our results throw doubt on the suggestion that a relative frequency of less than 80% B-wave activity can be a valid indicator for shunt responsiveness in patients with suspected normal pressure hydrocephalus (NPH). ICP recordings in suspected NPH should be accompanied by polysomnography to avoid misleading results due to variability of B-wave appearance dependent on sleep pattern.

Adult↗
PubMed1993

A light stabilizer (Tinuvin 770) that elutes from polypropylene plastic tubes is a potent L-type Ca(2+)-channel blocker.

A pharmacologically active agent was easily extracted by aqueous or organic solvents from laboratory plastic tubes (Falcon Blue Max) and has been chemically identified as bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate. This compound (approximately 12 micrograms per tube approximately 25 nmol) blocked 1,4-dihydropyridine-sensitive 45Ca2+ uptake into GH3 cells with an IC50 value of 3.6 microM, inhibited Sr2+ currents through L-type Ca2+ channels in A7r5 smooth-muscle cells in whole-cell patch-clamp experiments after extracellular application, and affected the high-affinity binding of Ca2+ entry-blocker ligands to a variety of preparations. Bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate is a highly potent (IC50 values < 10 nM) inhibitor at the phenylalkylamine- and benzothiazepine-selective drug-binding domains of the alpha 1 subunit of L-type Ca2+ channels. This compound behaves as a heterotropic allosteric regulator for the 1,4-dihydropyridine-selective domain in purified Ca(2+)-channel preparations from rabbit skeletal muscle. (+)-Tetrandrine stimulation of 1,4-dihydropyridine binding to the membrane-bound L-type Ca2+ channel is inhibited by the compound in a competitive manner (Ki value = 6.8 nM). Bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate is therefore classified as the prototype of another class of L-type Ca(2+)-channel blockers that binds to the alpha 1 subunit at the drug-binding domains selective for (+)-tetrandrine or (+)-cis-diltiazem. This compound is identical to Tinuvin 770, which is used worldwide as a light stabilizer for polyolefins.

Alkaloids↗
PubMed1993

Localization of X chromosome short arm markers relative to synovial sarcoma- and renal adenocarcinoma-associated translocation breakpoints.

A series of thirteen different DNA markers was mapped relative to papillary renal cell carcinoma- and synovial sarcoma-associated translocation breakpoints in Xp11.2 using a panel of tumor-derived somatic cell hybrids in conjunction with Southern blot analysis. Our results indicate that the two translocation breakpoints differ from each other and that the chromosomal break in t(X;1)-positive papillary renal cell carcinoma is located between the markers PFC-TIMP-OATL1-SYP-TFE3 and DXS226-DXS146-DXS255-OATL2-DXS14. In addition, our current breakpoint analysis has resulted in a revision of the regional localization of the proximal Xp marker DXS226.

Animals↗