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Biomedical subjects

R Dengler

Publications and source records attributed to R Dengler.

At least 145 records · Page 8Linked to original sources

[The dependence of rapid voluntary contractions on the tremor phase in parkinsonism].

Parkinsonian patients sometimes have problems to produce really fast motor responses. Often, these are significantly delayed in comparison to those of normal controls. In patients with tremor-at-rest, this delay might be induced by some attraction of the movement execution to the tremor oscillator, according to a hypothesis of Hallet et al. (1977). This study now examined the phase relationship between the on-going tremor and the onset of fast voluntary contractions in Parkinson's disease (PD), quantitatively. Five patients with prominent tremor-at-rest performed rapid isometric index finger abductions under self paced (SP) and reaction time (RT) conditions, and force and surface EMG signals from the FDI muscle were analyzed. In both conditions the SP and the RT, data showed that the onset of the contraction mostly occurs during the descending phase of the tremor oscillation and, accordingly, the phasic EMG burst synchronously with the tremor bursts confirming the above mentioned hypothesis.

Aged↗

Mechanical implications of paired motor unit discharges in pathological and voluntary tremor.

Paired motor unit discharges (PDs), i.e., two discharges of the same motor unit (MU) with short interval, and their relation to tremor amplitude were studied in the first dorsal interosseous muscle (FDI) of patients with parkinsonian or essential tremor and in normal subjects mimicking tremor. In both pathological and voluntary tremor, interdischarge intervals of PDs were inversely correlated with the amplitude of the subsequent tremor beat, i.e., PDs with shorter intervals were followed by higher tremor beats. To further assess their mechanical impact, PDs were simulated by applying paired stimuli to MUs of the FDI in normal subjects using intramuscular microstimulation. Following paired stimuli, summation of twitch responses was more than linear. This was also the case with the paired stimuli applied at a tremor-like repetition rate (5 Hz). These findings stress the importance of PDs for tremor expression.

Adult↗

Detection of cathepsin B in tumor cytosol and urine of breast cancer patients.

In order to evaluate the role of cathepsin B (CB) as a proteinase involved in mammary tumor progression and its potential role as a tumor marker, we have measured the CB activity in cytosols of breast cancer tumor tissue using Z-Arg-Arg-AMC as the substrate and found a 23fold increase when compared to distantly located breast tissue from the same patient. In addition, urine of breast cancer patients under adjuvant chemotherapy was screened for CB immunoreactivity with a sandwich type enzyme immunoassay which revealed significant interindividual differences in concentrations with some urines containing immunoreactivity comparable to healthy controls. The urines were also investigated for CB activity but no differences between patients and controls were observed. However, urine contains thiol activatable proteinases causing substrate hydrolysis, which is to a varying extent inhibited by E-64 or Z-Phe-Phe-CHN2.

Adult↗

[Changes in the responses of motor units to transcranial magnetic stimulation in patients with multiple sclerosis and stroke].

In multiple sclerosis and stroke the muscle responses to transcranial magnetic stimulation are frequently delayed, reduced in amplitude or absent. To investigate the underlying pathophysiological mechanisms, responses of single motor units to transcranial magnetic stimulation were analysed using peri-stimulus time histograms. The following response patterns were detected: 1. prolongation of latency and duration of the primary peak which occurs in healthy controls 17 to 30 ms after the stimulus and has a duration of 2 to 8 ms, 2. lack of an excitatory response, 3. prolongation of the interval between sub-peaks within the primary peak and 4. multimodal responses. Possible mechanisms for these changes are: reduction and dispersion of conduction velocities in corticospinal axons associated with impaired summation of excitatory post-synaptic potentials at the spinal motoneurone, frequency-dependent or complete conduction block in corticospinal neurones and compensatory activation of other descending motor pathways.

Adult↗

[Hyp3]-bradykinin and [Hyp3]-Lys-bradykinin interact with B2-bradykinin receptors and stimulate inositol phosphate production in cultured human fibroblasts.

The recently isolated, naturally occurring peptide hormones [Hyp3]-bradykinin and [Hyp3]-Lys-bradykinin were investigated for their agonist activity on solubilized binding sites from human fibroblasts. Both ligands competed with [3H]bradykinin binding in a dose-dependent fashion with potencies similar to bradykinin (BK) and Lys-BK. Biological activity was assessed by determination of inositol phosphate accumulation and cyclic 3',5'-adenosine monophosphate synthesis in intact cultured cells. Stimulation by the hydroxylated peptides resulted in a pronounced accumulation of both parameters with similar effectiveness as BK and Lys-BK. These results indicate that [Hyp3]-BK and [Hyp3]-Lys-BK are agonists at the bradykinin receptor system with properties comparable to their non-hydroxylated analogues. This suggests that hydroxylation of kinins does not alter receptor interaction or signal transduction in cultured human fibroblasts.

Bradykinin↗

Amyotrophic lateral sclerosis: macro-EMG and twitch forces of single motor units.

Macro-EMG potentials (MEP)s and twitch contractions (spike-triggered-averaging) of single motor units (MUs) have been recorded in the first dorsal interosseus muscle (FDI) of 10 control subjects and 20 patients with amyotrophic lateral sclerosis (ALS). MUs over the full range of voluntary recruitment thresholds were studied. Patients with slightly affected FDIs (5) mainly showed MUs with enlarged MEPs and increased twitch forces. In contrast, the patients with more severely affected FDIs (15) revealed decreased twitch forces, especially in the MUs with higher thresholds. The corresponding MEPs could be enlarged as well as normal. It appears that MU sprouting and the resulting increase of twitch force can compensate for the loss of motoneuron in early stages of ALS. In more advanced stages, however, a decline of the force of the surviving MUs, especially of those with higher thresholds, seems to contribute to the progressive muscle weakness, in addition to the corticospinal degeneration and the reduction in the number of motoneurons.

Action Potentials↗

Regulation of bradykinin action at the receptor level.

Intact cultured human foreskin fibroblasts can be used as an in vitro system to study the regulatory events related to kinin receptor function. Specific bradykinin (BK) receptor sites (B2 subtype) were measured by direct binding study and correlated with BK-induced biological effects such as the release of inositol phosphates, formation of prostacyclin (PGI2), and accumulation of cyclic 3'5' adenosine monophosphate (cAMP). Depending on the ambient concentration of BK in the culture medium, homologous receptor downregulation accompanied by a reduction in BK-stimulated PGI2 release occurred. These events were transient and followed by the recovery of both BK binding sites and BK responsiveness that was related to destruction of BK by highly active degradation systems. The fate of receptor-bound [3H]BK was studied by the acetic acid "stripping technique" that completely removes surface-bound [3H]BK while leaving internalized material with the remaining cells. Kinetic analysis of inside/surface ratios of 3H radioactivity revealed data consistent with the hypothesis of internalization of BK-receptor complexes. High-performance liquid chromatography (HPLC) analysis of internalized 3H counts showed significant quantities of intact [3H]BK occurring in an intracellular compartment. Compounds or drugs that enhance intracellular cAMP levels or inhibit generation of eicosanoids were shown to modify the BK response by indirect means. BK-receptor binding sites appear to be under tight regulatory control by both the mechanisms influencing the ambient concentration of BK and the interaction between multiple mediators.

Biological Availability↗

Collateral nerve sprouting and twitch forces of single motor units in conditions with partial denervation in man.

Single motor units (MUs) were studied in the first dorsal interosseus muscle of 7 patients with slight partial denervation and in 10 controls. MU action potentials were recorded using the macro-EMG technique and their size was taken to assess collateral nerve sprouting. Simultaneously, the muscle force was monitored to determine the voluntary recruitment thresholds of the MUs and spike-triggered-averaging was applied to measure their twitch forces. At comparable force recruitment thresholds, both macro-EMG potentials and twitch forces were increased in the patients. We conclude, that collateral nerve sprouting increases MU force and can compensate for MU loss.

Adult↗

The impact of paired motor unit discharges on tremor.

We studied paired discharges (PDs) of single motor units (MUs) of the first dorsal interosseus muscle in parkinsonian and essential tremor. The number of PDs increased with increasing tremor strength and the duration of their intervals shortened. The amplitudes of the single tremor beats showed a significant negative correlation to the duration of the intervals of the preceding PDs. It is concluded that PDs play an important role as tremor amplifiers. The basic mechanism is probably the more than linear summation of two twitch contractions with short interval which is known from animal experiments.

Adult↗

Axonal conduction velocity and force of single human motor units.

Tungsten microelectrodes of the type used for microneurography have been used to record motor units selectively from the first dorsal interosseous and abductor pollicis brevis muscles of normal subjects and patients who had had complete sections of the ulnar or median nerve. After determining the recruitment threshold and the twitch tension (spike-triggered averaging) of a single unit, its nerve was stimulated at the wrist and the elbow using surface electrodes. By adjusting the position of the surface electrode and the stimulus intensity and by using computerized subtraction of responses just above and below threshold for a given unit, the same motor unit could often be identified in response to stimulation at both sites and its conduction velocity determined. The twitch tension and recruitment threshold of the motor units were closely correlated with the conduction velocity of the motor axons in normal subjects. Preliminary data from patients suggests that this method should be applicable to patients with a number of neuromuscular disorders.

Adult↗

Silent periods in single orbicularis oculi motoneurones.

The activity of single motor units (MUs) of the orbicularis oculi muscle was recorded in normal volunteers. While the subject maintained a constant firing rate, electrical stimuli were applied to the ipsilateral supraorbital nerve. Peristimulus histograms were constructed showing 2 periods of discharge accumulation at times corresponding to the R1 and R2 component of the blink reflex, each followed by a silent period, called SP1 and SP2, respectively. Whereas SP1 may merely result from the synchronisation of discharges in the preceding R1, SP2 can only be explained by an inhibition of the motoneurone activity. These findings confirm the existence of silent periods in the orbicularis oculi muscle in spite of the absence of mechanisms probably responsible for silent periods in load-bearing muscles.

Adult↗

[Double discharges of motor units and tremor strength].

The relationship between the double-discharges (DDs) of single motor units (MUs) and the tremor strength was studied in 7 patients with parkinsonism and 3 with essential tremor. The potentials of single MUs and the force of the first dorsal interosseus muscle were recorded during slight isometric contractions. The rate of DDs and their interval duration were correlated with the global tremor strength and the amplitudes of the single tremor beats. With increasing tremor strength, the rate of DDs increased and the duration of their intervals decreased. It is concluded that DDs act as tremor amplifiers. This effect is probably accounted for by a more than linear summation of two consecutive MU contractions with short interval which is known from animal experiments.

Adult↗

[Direct measurement of the conduction velocity of single motor axons in man].

The conduction velocity (CV) of single motor axons was measured in the ulnar and median nerve. Stimuli of submaximal intensities were delivered at the wrist and at the elbow using surface electrodes. The responses of single motor units were recorded by tungsten or steel microelectrodes. Changes of the stimulus intensity and of the position of the stimulation electrodes and subtraction of the responses frequently allowed the potential of the same motor unit to be identified following stimulation at both sites and to calculate its axonal CV. In all individuals, axonal CV's from the low to the high velocity range (40 to 63 m/s) could be measured. The method may provide a new approach to the investigation of various disorders of the peripheral nerve.

Adult↗

Discharge pattern of single motor units in basal ganglia disorders.

We studied the discharge pattern of motor units (MUs) from the first dorsal interosseous muscle during slight stationary isometric contraction. In six controls, seven patients with parkinsonism, and five patients with choreic disorders, we analyzed 78 MUs. About one-half of the MUs in both patient groups fired irregularly as shown by interval histograms, joint interval histograms, and corresponding statistical calculations. Cross-correlation techniques revealed a characteristic type of MU synchronization in parkinsonism. Analysis of the MU discharge pattern can be useful in clinical assessment of these disorders.

Adult↗

[Disorders of motor unit discharge activity in parkinsonism].

The discharge activity of single motor units (MUs) of the first dorsal interosseus muscle was recorded in slight stationary isometric contractions. Normal subjects and patients with parkinsonism of various degrees were investigated. The purpose was to study disturbances of the discharge pattern in the patients and their potential diagnostic role. Automatic signal recognition and statistical analysis of the interval distribution were used. Most MUs of the patients revealed considerable irregularities of their discharge sequences best marked by the so called "floating standard deviation". All patients, also 2 without tremor, showed a characteristic synchronization of their MU discharges ("broad-peak" type). Since the above changes were also seen in the patients with only slight symptoms, these investigations, if methodically simplified, could be of diagnostic value.

Action Potentials↗