Biomedical subjects

R B Stein

Publications and source records attributed to R B Stein.

At least 91 records · Page 5Linked to original sources

PubMed1993

Recovery potential of muscle after partial denervation: a comparison between rats and humans.

The response to partial denervation is compared for the tibialis anterior muscle in the rat and the thenar muscle group in the human. Partial denervation in the human was a result of spinal cord injury, while partial denervation in the rat was induced by sectioning of the L4 ventral root. In some animals, a spinal cord transection at the T12-13 level was also performed to determine whether spinal cord injury affected the sprouting capability of motoneurons caudal to the injury site. Motor units were isolated by intramuscular microstimulation in the human and by ventral root splitting in a terminal experiment in the rat. Motor unit numbers were estimated by dividing the amplitude of the electromyogram (EMG) and the peak twitch force in response to maximum stimulation of the muscle nerve by the average unit EMG and twitch force, respectively. In both the rat and the human, surviving motor units enlarged as a function of the degree of partial denervation. Moreover, all surviving motor units appeared to enlarge proportionately. The limit to sprouting was tested systematically in the rat. On average, single motor units enlarged up to about five times their original size, resulting in the ability to compensate for up to 80% of motoneuron loss. The reason for this limit remains unclear, but histological data suggest that sprouting may be confined to the more distal regions of the motor axon, such that reinnervation of denervated muscle fibers is confined to the territory of the original motor unit.

Animals↗

PubMed1993

Modification of reflexes in normal and abnormal movements.

The trajectories observed for the limb during human locomotion are determined by a mixture of influences, some arising from neural circuits entirely within the central nervous system and others arising from a variety of sensory receptors. Muscle reflexes are highly modulated during locomotion in an adaptive manner within each phase of the step cycle. Furthermore, the modulation can be modified quickly for different tasks such as standing, walking and running, probably by changes in presynaptic inhibition. This modulation is often lost or severely reduced in patients with spasticity after spinal cord or head injury. In normal subjects cutaneous reflexes can be completely reversed from exciting to inhibiting a muscle during each step cycle, particularly in muscles that normally show two bursts of activity per cycle (e.g., tibialis anterior). In some patients stimulation of a mixed nerve (e.g., common peroneal) can directly produce muscle contraction, generate a reflex response (flexor reflex) and transiently reduce spasticity in antagonist (extensor) muscles. Thus, simple systems employing stimulation can enhance gait to a certain extent in patients with incomplete injuries.

Electric Stimulation↗

PubMed1993

A linear time-varying model of force generation in skeletal muscle.

A model of isometric force production by skeletal muscle was developed in which the response to each stimulus in a train was described by a critically damped, linear second-order system. The parameters describing the system were constrained to be constant within an interstimulus interval, but were allowed to vary between interstimulus intervals. The ability of this model to match experimental data, and the time variation in the parameters (low-frequency gain and natural frequency) required to do so were examined in soleus and plantaris muscles of the cat stimulated by synchronous whole-nerve stimulation. The model produced good fits across firing rates from twitch to tetanus for slow and fast muscle, rested and fatigued muscle, and maximal submaximal stimulation. Both gain and natural frequency generally varied smoothly and predictably under all conditions. Gain increased at intermediate stimulation rates and in potentiated muscle, and decreased with fatigue and submaximal stimulation. Natural frequency was higher in fast muscle, and decreased with stimulation rate and fatigue. This modeling approach may provide a useful alternative to current models of skeletal muscle force, as its implementation is simple and it can describe force under conditions (fatigue, potentiation) where the muscle dynamics change with time.

Animals↗

PubMed1993

Sensory nerve recording for closed-loop control to restore motor functions.

A method is developed for using neural recordings to control functional electrical stimulation (FES) to nerves and muscles. Experiments were done in chronic cats with a goal of designing a rule-based controller to generate rhythmic movements of the ankle joint during treadmill locomotion. Neural signals from the tibial and superficial peroneal nerves were recorded with cuff electrodes and processed simultaneously with muscular signals from ankle flexors and extensors in the cat's hind limb. Cuff electrodes are an effective method for long-term chronic recording in peripheral nerves without causing discomfort or damage to the nerve. For real-time operation we designed a low-noise amplifier with a blanking circuit to minimize stimulation artifacts. We used threshold detection to design a simple rule-based control and compared its output to the pattern determined using adaptive neural networks. Both the threshold detection and adaptive networks are robust enough to accommodate the variability in neural recordings. The adaptive logic network used for this study is effective in mapping transfer functions and therefore applicable for determination of gait invariants to be used for closed-loop control in an FES system. Simple rule-bases will probably be chosen for initial applications to human patients. However, more complex FES applications require more complex rule-bases and better mapping of continuous neural recordings and muscular activity. Adaptive neural networks have promise for these more complex applications.

Action Potentials↗

PubMed1993

Electrical systems for improving locomotion after incomplete spinal cord injury: an assessment.

Simple systems for electrical stimulation (1-4 channels) with either surface, percutaneous, or implanted electrodes during locomotion were assessed in 10 subjects who had chronic, incomplete spinal cord injury (SCI). On average, the speed of locomotion was increased by 4 m/min independently of the subject's speed of locomotion without stimulation (0-50 m/min) while oxygen consumption was reduced somewhat. These simple systems can provide practical help, particularly for incomplete SCI subjects who can stand but are lacking or have very limited ability to walk. Further improvement in locomotion requires stabilization and reduction in the duration of the stance phase of locomotion.

Adult↗

PubMed1993

Fatigue in human jaw muscles: a review.

Muscle fatigue has been thought to be one of the causes of pain associated with temporomandibular disorders. A multitude of variables could contribute to neuromuscular fatigue when a subject attempts to sustain a given force. In studies of jaw muscles the endurance limit has been related to a failure in electrical conductivity (transmission fatigue), an increasing imbalance in the intracellular contents of muscle fibers (contraction fatigue), and the onset of pain. This review describes the principles that underlie fatigue and the results of studies of jaw muscle fatigue. Attempts are made to explain why various studies may have produced different results.

Adenosine Triphosphate↗

PubMed1992

9-cis retinoic acid is a high affinity ligand for the retinoid X receptor.

All-trans retinoic acid (RA) has previously been shown to modulate the transcriptional properties of the retinoic acid receptor (RAR) and retinoid X receptor (RXR). The inability of all-trans RA to bind to RXR suggests that it may be metabolized to a more active high affinity ligand. We report here an experimental approach that has identified 9-cis RA as an RXR ligand. It is up to 40-fold more potent than all-trans RA in transfection assays and binds with high affinity. The production of 9-cis RA in cultured cells and the identification of this molecule in liver and kidney demonstrates the existence of this molecule in living organisms. The discovery of this novel hormone points to the key role retinoid metabolism may have in generating new signaling pathways.

Carrier Proteins↗

PubMed1992

A comparison of intact and in-vitro locomotion in an adult amphibian.

Locomotion was compared in an intact and in-vitro preparation of the adult mudpuppy (Necturus maculatus). The intact animals walked on an aquatic treadmill while in-vitro preparations were made to walk with a bath application of the excitatory amino acid NMA (N-methyl DL-aspartate). EMG recordings of shoulder muscles (pectoralis, latissimus dorsi, dorsalis scapulae, and procoracohumeralis) and elbow muscles (brachialis and extensor ulnae) were obtained from intact animals while recordings were made from only the elbow muscles in-vitro. The in-vitro preparation required magnesium in the bath to initiate and maintain locomotion, consistent with an NMDA mediated response. Also consistent with an NMDA response was the finding that glycine potentiated the NMA induced locomotion in-vitro. The range of cycle durations seen in-vitro was well within the range seen in the intact animal, while gait analysis demonstrated the similarity of intact and in-vitro locomotor cycles. In spite of these very similar locomotor patterns there are interesting differences in the patterned output seen in-vitro, such as the absence of a second burst in the brachialis muscle in-vitro.

Animals↗

PubMed1992

An in vitro preparation of the mudpuppy for simultaneous intracellular and electromyographic recording during locomotion.

In this report we describe the development of an in vitro preparation of the mudpuppy (Necturus maculatus) used to investigate locomotion in walking vertebrates. The preparation consists of the first 5 segments of the cervical spinal cord and the attached forelimb. The preparation is bathed in a cooled (15 degrees C) and oxygenated spinal cord Ringers solution and remains viable for 36-100 h. Locomotion can be elicited during the first 36-48 h by applying the excitatory amino acid N-methyl D-aspartate (NMDA) to the bath. Cutaneous and dorsal root reflexes remain unchanged for much longer periods of time (72-100 h). During locomotion, intracellular recordings can be made from interneurons and motoneurons while simultaneous electromyographic (EMG) recordings are made from forelimb muscles. Rhythmically active interneurons can be classified according to their phase of activity during the step cycle. Further classification of interneurons involves both monitoring the afferent input to these cells from dorsal root and cutaneous afferents as well as using their action potentials as a trigger for averaging the ongoing locomotor EMG activity. In this way some of the input and output characteristics of the interneurons can be monitored. The ability to record simultaneously from interneurons and muscles offers distinct advantages over current in vitro preparations.

Animals↗

PubMed1992

Interaction of glucocorticoid analogues with the human glucocorticoid receptor.

Transient co-transfection of receptor cDNA and suitable reporter genes was used to study human glucocorticoid receptor (hGR) function in a neutral mammalian cell background. A variety of natural and synthetic steroids were analyzed for their ability to activate gene expression through the hGR and to bind to extracts of cells expressing the hGR cDNA. There was very good correlation between these two in vitro parameters for these compounds. Furthermore, correlation of these data with reported in vivo anti-inflammatory potencies was surprisingly close, with two exceptions. The in vitro data suggest an explanation for the discrepant compounds, consistent with published data on their metabolic fate in vivo. The co-transfection assay has utility as a quantitative predictor of in vivo glucocorticoid pharmacology.

Animals↗

PubMed1992

Optimal stimulation of paralyzed muscle after human spinal cord injury.

Muscle properties change profoundly as a result of disuse after spinal cord injury. To study the extent to which these changes can be reversed by electrical stimulation, tibialis anterior muscles in complete spinal cord-injured subjects were stimulated for progressively longer times (15 min, 45 min, 2 h, and 8 h/day) in 6-wk intervals. An index of muscle endurance to repetitive stimulation doubled (from 0.4 to 0.8), contraction and half-relaxation times increased markedly (from 70 to approximately 100 ms), but little or no change was measured in twitch or tetanic tension with increasing amounts of stimulation. The changes observed with 2 h/day of stimulation brought the physiological values close to those for normal (control) subjects. A decrease in the stimulation period produced a reversal of the changes. No effects were observed in the contralateral (unstimulated) muscle at any time, nor was there evidence of decreased numbers of motor units in these subjects secondary to spinal cord injury. Motor unit properties changed in parallel with those of the whole muscle. The occasional spasms occurring in these subjects are not sufficient to maintain normal muscle properties, but these properties can largely be restored by 1-2 h/day of electrical stimulation.

Adaptation, Physiological↗

PubMed1992

Influence of electrical stimulation on the morphological and metabolic properties of paralyzed muscle.

Selected morphological and metabolic properties of single fibers were studied in biopsy samples from the tibialis anterior of normal control and spinal cord-injured (SCI) subjects. In the SCI subjects, one muscle was electrically stimulated progressively over 24 wk, in 6-wk blocks for less than or equal to 8 h/day, while the contralateral muscle remained untreated. The percentage of fibers classified as type I [qualitative alkaline preincubation myofibrillar adenosinetriphosphatase (ATPase)] was significantly less in the unstimulated paralyzed muscles than in the muscles of normal control subjects. Electrical stimulation increased the proportion of type I fibers in the SCI subjects. For both type I and type II fibers, the cross-sectional area, activities of myofibrillar ATPase and succinate dehydrogenase, and the capillary-to-fiber ratio were also significantly less in the paralyzed muscles than in the normal control muscles. Electrical stimulation increased only the activity of succinate dehydrogenase in both fiber types of the SCI subjects. These data are discussed in relation to the electromechanical properties of the respective muscles described in an accompanying paper (J. Appl. Physiol. 72: 1393-1400, 1992). In general, the electrical stimulation protocol used in this study enhanced the oxidative capacity and endurance properties of the paralyzed muscles but had no effect on fiber size and strength.

Adenosine Triphosphatases↗

PubMed1992

The size and distribution of fiber types in jaw muscles: a review.

Histochemical enzyme reactions and physiological recordings of limb and jaw muscles have independently revealed three to five types of muscle fibers. Surprisingly, type II fibers are smaller than type I fibers in major human jaw muscles. This is the opposite of the situation in limb muscles. Human jaw muscles contain mixed fiber types. Type I fibers predominate in lateral pterygoid and type II fibers in digastric muscles. The masseters in carnivorans and rodents contain mainly type II fibers, whereas those of some herbivorans, including rabbits and bovids, contain mainly type I fibers. Attempts were made to describe the functional significance of some observations.

Animals↗

PubMed1991

Alternative splicing contributes to K+ channel diversity in the mammalian central nervous system.

In an attempt to define the molecular basis of the functional diversity of K+ channels, we have isolated overlapping rat brain cDNAs that encoded a neuronal delayed rectifier K+ channel, K,4, that is structurally related to the Drosophila Shaw protein. Unlike previously characterized mammalian K+ channel genes, which each contain a single protein-coding exon, K,4 arises from alternative exon usage at a locus that also encodes another mammalian Shaw homolog, NGK2. Thus, the enormous diversity of K+ channels in mammals can be generated not just through gene duplication and divergence but also through alternative splicing of RNA.

Amino Acid Sequence↗

PubMed1991

The bovine endothelin receptor has an apparent molecular weight of 43,000.

In crosslinking experiments, [125I]endothelin-1 was treated with N-hydroxysuccinimidyl-4-azidobenzoate, purified by HPLC, allowed to bind to bovine aortic membranes and then photoactivated. Autoradiography of sodium dodecyl sulfate polyacrylamide gel electrophoretograms of the products of this reaction showed that a component of apparent Mr = 42,000 was specifically labelled by endothelin-1 under reducing conditions. Under nonreducing conditions, a small amount of 125I-labelled endothelin-1 specifically labelled a component of apparent Mr = 45,900 in the absence of crosslinking agent. Non-radiolabelled endothelin analogues with a wide range of binding affinities inhibited specific labelling of the Mr = 42,000 and 45,900 components in parallel over the concentration ranges which inhibited binding of radiolabelled endothelin. Specific labelling of these components was also observed in parallel in membranes from bovine heart and kidney. The components labelled in the presence and absence of crosslinker appear to be the same, and the small difference in apparent Mr in the labelled components is likely due to a difference in conformational constraints arising from the two labelling processes, with a true, corrected Mr of 43,400. Since the specific labelling of this component is related to physiologically relevant binding in several bovine tissues, we conclude that it is a component of the bovine endothelin receptor.

Affinity Labels↗

PubMed1991

Contribution of peripheral afferents to the activation of the soleus muscle during walking in humans.

Small, rapid stretches were applied to the soleus muscle during the stance phase of walking by lifting the forefoot with a pneumatic device. Stretch responses were induced in the soleus muscle by the disturbance. The amplitude and time course of the responses from the soleus muscle were a function of both the kinematics of the disturbance and the time in the step cycle when the disturbance was applied. The step cycle was divided into 16 equal time parts, and data obtained within each of these parts were averaged together. The electromyographic (EMG) response of the soleus muscle showed a time course that was similar to the time course of the angular velocity induced by the disturbance at the ankle. Three linear equations were used to predict the EMG response from the soleus muscle as a function of the angular kinematics of the disturbance: 1) velocity, 2) velocity and displacement, 3) velocity, displacement and acceleration. Introduction of a pure delay between the EMG and the kinematics substantially improved the predictions. Most of the variance (70%) in the EMG response could be accounted for by the velocity of the disturbance alone with an optimal delay (average 38 ms). Inclusion of a displacement term significantly increased the variance accounted for (85%), but further addition of an acceleration term did not. Since the velocity of the disturbance accounted for most of the variance, the reflex gain was estimated from the velocity coefficient. This coefficient increased in a ramp-like fashion through the early part of the stance phase, qualitatively similar to the increase in the H-reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

PubMed1991

The effect of variable mechanical impedance on the control of antagonistic muscles.

Most models of muscle have assumed that the series elastic element has a constant stiffness, although experimentally this is not true, either at the level of individual cross-bridges or that of the whole muscle. In this paper elastic and viscous elements are introduced whose properties vary systematically with activity levels as has been found experimentally. The effects of these nonlinear variations on the methods for optimally controlling a pair of antagonistic muscles are calculated. Although the nonlinearities add some complexity to the derivation and are important to the mechanism of force generation in the muscle, they do not qualitatively change the overall control of movement.

Animals↗

PubMed1991

Optimal control for the active above-knee prosthesis.

Control of an active above-knee prosthesis has been simulated for a selected gait activity using a hierarchical closed-loop method. An extension of finite-state control, referred to as artificial reflex control, was adopted at the strategic level of control. At the actuator level of control an optimal tracking method, based on dynamic programming, is applied. This deals mainly with the actuator level of control, but considers the interaction of the leg dynamics and the switching effects of artificial reflex control. Optimal tracking at the actuator level of the above-knee prosthesis reduces the on-off effects of finite-state methods, such as artificial reflex control. The proposed method can also be used for the design of prosthetic elements. Specific attention is paid to the limited torque and power in the prosthetic joint actuator, which are imposed by the principle of self-containment in the artificial leg. The hierarchical structure, integrating artificial reflex control and optimal tracking, can be used in real time, as estimated from the number of computer operations required for the suggested method.

Artificial Limbs↗