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Biomedical subjects

R B Stein

Publications and source records attributed to R B Stein.

At least 127 records · Page 7Linked to original sources

Length changes of intercostal muscles during respiration in the cat.

Sonomicrometry was used to measure the length changes of intercostal muscles throughout the rib cage of anesthetized cats. The motor unit discharge in the vicinity of the length measurement was monitored with bipolar electrodes. The external intercostal muscles in the rostral spaces and the parasternals actively shortened during inspiration. The external intercostals in the caudal spaces, which were inactive, either shortened or lengthened passively due to the forces imposed on the lower rib cage by the contraction of the diaphragm. The length changes of external intercostals of the mid-thoracic spaces, which were recruited during inspiration, were variable. The internal intercostals were usually inactive in our preparation and therefore their length excursions passively followed those of the external intercostals. The information regarding the length changes is correlated with that previously gathered for the role of muscle spindles in the intercostal muscles. It is suggested that gamma motoneurons are recruited to prevent the muscle spindles from being unloaded when the intercostal muscle shortens and to increase the sensitivity of the receptors during the phase of the respiratory cycle when the muscle is active.

Animals↗

Glyburide blocks the relaxation response to BRL 34915 (cromakalim), minoxidil sulfate and diazoxide in vascular smooth muscle.

BRL 34915 [6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidyl) 2H-benzo(b) pyran-3-ol], minoxidil sulfate and diazoxide may relax vascular smooth muscle via hyperpolarization due to an opening of membrane potassium channels. We therefore examined the effects of several potassium channel antagonists on the relaxation response to these vasodilators in isolated rat portal venous strips which were mounted in vitro for detecting changes in isometric force. BRL 34915 (IC50 = 4.7 X 10(-8) M), minoxidil sulfate (IC50 = 1.4 X 10(-7) M) and diazoxide (IC50 = 5 X 10(-6) M) elicited concentration-dependent relaxations of the spontaneous, myogenic contractions in venous strips. The relatively nonselective potassium channel antagonists tetraethylammonium ion (0.3-10 X 10(-3) M) and 4-aminopyridine (1-10 X 10(-3) M) caused concentration-dependent shifts (5- to 50-fold) in the relaxation responses to each vasodilator. Charybdotoxin (up to 10(-7) M) and apamin (up to 10(-7) M), known to be antagonists of high and low conductance calcium-activated potassium channels, respectively, had no inhibitory effect on the relaxation-response curves to BRL 34915, minoxidil sulfate or diazoxide. Glyburide (10(-7) to 3 X 10(-5) M), a sulfonylurea which has been shown to block the ATP-modulated potassium channel in insulin-secreting cells, caused concentration-dependent shifts to the right (up to 100-fold) of the IC50 value for BRL 34915 and diazoxide, and at 10(-6) M, abolished the relaxation response to minoxidil sulfate.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗

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↗

Microneurography for the recording and selective stimulation of afferents: an assessment.

The purpose of this study was to examine whether a microneurography electrode could record from and then selectively stimulate the same afferent fiber in cat sural and tibial nerves. Fiber activity was recorded distally with microneurography needle electrodes and proximally with hook electrodes. Records from the hook electrodes allowed the waveform shape and latency following natural stimulation to be compared with that produced by electrical stimuli delivered through the needle electrode. The action potentials from approximately 50% of the recorded fibers failed to propagate beyond the needle electrode. When propagation did occur and the comparison could be made, only 25% of the afferents recorded could be selectively stimulated. This relatively low success rate suggests that a typical microneurography needle is not particularly good for selectively stimulating identified afferents. Thus in human experiments, attempts to microstimulate identified afferents may often include stimulation of unidentified alternative, or additional, afferent fibers at thresholds of sensory perception.

Action Potentials↗

Comparison of force and stiffness in normal and dystrophic mouse muscles.

Isometric force and stiffness of fast- and slow-twitch muscles of affected and normal mice of the 129/ReJ dy/dy strain were studied at rest and during active contraction at a variety of lengths. Dystrophic muscles developed less force in response to stimulation, but the resting stiffness was not reduced as much, particularly at long muscle lengths. This is consistent with the replacement of muscle fibers by connective tissue that is considerably less elastic. When second and third stimuli are superimposed on the rising phase of a twitch in a normal muscle, a less-than-linear summation of force and stiffness generation (early depression) is followed by a more-than-linear summation (later facilitation). Dystrophic muscles showed a smaller early depression and a greater later facilitation of force and active muscle stiffness. Many of these phenomena can be predicted from a simple model of Ca2+ release and binding to troponin.

Animals↗

Oligopeptides inhibit the ribonucleotide reductase of herpes simplex virus by causing subunit separation.

It has recently been reported that a nonapeptide (H-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH) identical in sequence to the last nine amino acid residues of RR2, the small subunit of herpes simplex virus (HSV) ribonucleotide reductase (E.C. 1.17.4.1; RR), can inhibit HSV RR activity in vitro. It has been postulated that this peptide acts by interfering with the interaction of the large subunit, RR1, and RR2, but direct demonstration of its mechanism of action has not been reported. We present data which show that the inhibition of HSV RR by this oligopeptide is due to induced subunit dissociation.

Macromolecular Substances↗

The kinetics relating calcium and force in skeletal muscle.

The kinetics relating Ca2+ transients and muscle force were examined using data obtained with the photoprotein aequorin in skeletal muscles of the rat, barnacle, and frog. These data were fitted by various models using nonlinear methods for minimizing the least mean square errors. Models in which Ca2+ binding to troponin was rate limiting for force production did not produce good agreement with the observed data, except for a small twitch of the barnacle muscle. Models in which cross-bridge kinetics were rate limiting also did not produce good agreement with the observed data, unless the detachment rate constant was allowed to increase sharply on the falling phase of tension production. Increasing the number of cross-bridge states did not dramatically improve the agreement between predicted and observed force. We conclude that the dynamic relationship between Ca2+ transients and force production in intact muscle fibers under physiological conditions can be approximated by a model in which (a) two Ca2+ ions bind rapidly to each troponin molecule, (b) force production is limited by the rate of formation of tightly bound cross-bridges, and (c) the rate of cross-bridge detachment increases rapidly once tension begins to decline and free Ca2+ levels have fallen to low values after the last stimulus. Such a model can account not only for the pattern of force production during a twitch and tetanus, but also the complex, nonlinear pattern of summation which is observed during an unfused tetanus at intermediate rates of stimulation.

Actins↗

Novel uses of EMG to study normal and disordered motor control.

The electromyogram (EMG) is unique in that it gives the output of a single class of neurons, a-motoneurons, in a way that can be readily recorded and studied in normal subjects as well as in patients with a variety of disorders. Although the EMG has been used for many years, new applications continue to be found. This paper reviews in succession four recent approaches to EMG recording that have provided insight into the function of the normal and the disordered nervous system.

Electromyography↗

The trajectory of human wrist movements.

1. To determine the form of human movement trajectories and the factors that determine this form, normal subjects performed wrist flexion movements against various elastic, viscous, and inertial loads. The subjects were instructed with visual and auditory feedback to make a movement of prescribed amplitude in a present period of time, but were free to choose any trajectory that fulfilled these constraints. 2. The trajectories were examined critically to determine if they corresponded to those which would minimize the root mean square (RMS) value of some kinematic variable or of energy consumption. The data agreed better with the trajectory that minimized the RMS value of jerk (the third derivative of length) than that of acceleration. However, systematic deviations from the minimum jerk predictions were consistently observed whenever movements were made against elastic and viscous loads. 3. Improved agreement could generally be obtained by assuming that the velocity profile varied according to a normal (Gaussian) curve. We conclude that minimization of jerk is not a general principle used by the nervous system in organizing voluntary movements, although movements may approach the predicted form, particularly under inertial loading conditions. 4. The EMG of the agonist muscles consisted of relatively simple waveforms containing ramplike increases and approximately exponential decays. The form of the movements could often be predicted quite well by using the EMG as an input to a linear second-order model of the muscle plus load. Rather than rigorously minimizing a kinematic variable or energy consumption, the nervous system may generate simple waveforms and adjust the parameters of these waveforms by trial and error until a trajectory is achieved that meets the requirements for a given load.

Adult↗

Comparison of physiological and histochemical properties of motor units after cross-reinnervation of antagonistic muscles in the cat hindlimb.

1. Physiological and histochemical properties of the cat ankle extensor muscles, the lateral and medial gastrocnemius, and the soleus were studied after cross-reinnervation by flexor motoneurons. 2. Tibial and common peroneal nerves were cut and cross-united in the popliteal fossa of 2- to 6-mo-old cats. Eighteen to 24 mo later, single motor units were isolated by dissection and stimulation of ventral root filaments and classified into four types: fast-twitch, fatigable (FF), fast-twitch with intermediate fatigue resistance (FI), fast-twitch, fatigue-resistant (FR), and slow, fatigue-resistant (S). Muscle fibers were classified as fast glycolytic (FG), fast, oxidative glycolytic (FOG), and slow oxidative (SO) on the basis of histochemical staining. 3. Although motor-unit force was normally well correlated with the size of the innervating motor axon in the cross-reinnervated muscles, the force of different unit types overlapped considerably. The reinnervated motor units also showed a higher than normal degree of fatigability. 4. The range of muscle unit forces in cross-reinnervated triceps surae muscles was the same as in the normally innervated triceps surae muscles. This range is 2-3 times greater than the flexor muscles, which the common peroneal nerve normally supplies. The range of contraction speed of units in the cross-reinnervated extensor muscles was comparable to that in the flexor muscles, consistent with a motoneuron-specific determination of muscle speed (28). 5. SO and FOG muscle fibers were found in all reinnervated triceps surae muscles, but FG fibers were only found in reinnervated medial gastrocnemius (MG) and lateral gastrocnemius (LG) muscles, consistent with previous findings of the resistance of soleus muscles to complete conversion (10, 16, 20, 21). Type grouping of muscle fibers was characteristic of the reinnervated muscles. 6. Reinnervated SO muscle fibers were larger than the corresponding fibers in normally innervated muscles as were the estimated number of muscle fibers innervated by slow motor axons. Nonetheless, the force generated by the S motor units remained relatively smaller than FR and FF units. The relative contributions of the number, cross-sectional area and specific tension to the force generation of reinnervated motor units are discussed.

Adenosine Triphosphatases↗

Rehabilitation of musicians with upper limb amputations.

Three saxophone players with upper limb amputations have been successfully rehabilitated to play their musical instruments using skin-conductivity touch control. Each attained a standard of musicianship sufficient to perform the standard repertoire of the instrument in a concert setting. The mechanical and electrical modifications to the saxophone are described, as well as the principles of operation of the skin-conductivity touch control module. The touch control module is commercially available for prosthetists who wish to fit musicians or others with upper extremity amputations who require rapid accurate control of a number of channels of powered prosthetic function.

Amputation, Surgical↗

A method for simulating the reflex output of a motoneuron pool.

An analysis of the reflex output of a motoneuron pool in response to a Ia-afferent input is presented. The analysis is based upon a model of the motoneuron pool which includes the subthreshold behavior of motoneurons (integration of synaptic inputs) and the statistical distribution of the motoneurons according to their resting conductance. The latter feature allows for the orderly recruitment of the motoneurons in the order of low resting conductance to high resting conductance. The number of active motoneurons (i.e. the excitation level) is determined by the balance of the excitatory and inhibitory conductances acting on the pool. The reflex output in response to a Ia-EPSP is computed at various excitation levels and with different amounts of presynaptic inhibition. The reflex output is the same for a given excitation level, regardless of the mixture of excitatory and inhibitory postsynaptic conductances used to produce that excitation level. In contrast, presynaptic inhibition markedly affects the relation between reflex output and excitation level.

Action Potentials↗

Measurement of rate constants for the contractile cycle of intact mammalian muscle fibers.

Small, random length changes were applied to bundles of intact fibers from rat and mouse extensor digitorum longus (EDL) and soleus muscles, while they were being tetanically stimulated. With increasing frequency of length changes, EDL muscle stiffness (tension change per unit change in length) increased, then decreased and increased again. The decrease was not seen in the soleus muscles. The EDL frequency-response could be well fitted by three exponential components with apparent rate constants of approximately 25, 150, and 500 s-1 at 20 degrees C. All rate constants increased steadily with temperature and for each 10 degrees C increase in temperature, the rates in the mouse EDL increased by a factor (Q10) between 1.8 and 2.4. With tetanic stimulation, force increased nearly exponentially to a steady level with a rate constant of 24 s-1 at 20 degrees C in mouse EDL muscles, and a Q10 of 2.4. These values correspond closely to the lowest frequency rate constant measured with length perturbations, which suggests that this process may limit the rate of rise of force in intact muscle fibers. During fatigue the high frequency and intermediate frequency rate constants declined, but the low frequency rate constant remained unchanged. These results are discussed in relation to current biochemical models for cross-bridge cycling.

Animals↗

Polypoid tumor of the esophagus.

Five cases of an uncommon esophageal tumor consisting of a mucosal squamous cell carcinoma that surrounds a polypoid mass of spindle cells were examined. The spindle cell component was composed of elongated cells with blunt nuclei, admixed with multinucleated giant cells. Reticulin fibers enveloped individual cells, and abundant collagen was present. Thirteen to 69 mitotic figures occurred per 10 high-power fields. Electron microscopy showed dilated cisternae of rough endoplasmic reticulum and peripheral intermediate filaments within the cytoplasm. Intermediate-type junctions (zonulae adherens) and subplasmalemmal linear densities connected some cells. No tonofibrillar bundles or desmosomes (maculae adherens) were present. Immunoperoxidase stains detected no keratin in the spindle cells. Alpha-1-antichymotrypsin and alpha-1-antitrypsin were in the spindle cells in five of five and three of five cases, respectively. The absence of desmosomes, tonofibrillar bundles, and keratin and the presence of alpha-1-antitrypsin and alpha-1-antichymotrypsin favor fibrohistiocytic differentiation of the spindle cell component.

Carcinoma, Squamous Cell↗

Difference in the amplitude of the human soleus H reflex during walking and running.

1. The Hoffman reflex, or H reflex, was strongly modulated in the human soleus muscle during both walking (4 km/h) and running (8 km/h). It was relatively low at the time of heel contact, increased progressively during the stance phase, and reached its maximum amplitude late in the stance phase. During ankle dorsiflexion the H reflex was absent. 2. During running the peak e.m.g. level of the soleus was on average 2.4 times higher than during walking but the maximum amplitude of the H reflex was never larger than during walking. In fact, the H reflex was on average significantly (P less than 0.05 for one-tailed t test) smaller during running than during walking. Furthermore, the slope of the least-squares line fitted to the relation between the H reflex amplitude and the background e.m.g. was always steeper for the walking data than for the running data. 3. The difference in the H reflex in the two tasks is evidence that the size of the H reflex is not simply a passive consequence of the alpha-motoneurone excitation level, as indicated by the e.m.g., but is also influenced by other central neural mechanisms. We suggest that presynaptic inhibition is the most likely mechanism accounting for the change in the slope. 4. The modulation of the reflexes during walking and running can be interpreted in terms of the idea of automatic gain compensation. The decreased gain during running may be appropriate to reduce saturation of motor output and potential instability of the stretch reflex feed-back loop.

H-Reflex↗

Patterns of reinnervation and motor unit recruitment in human hand muscles after complete ulnar and median nerve section and resuture.

Following complete ulnar or above-elbow median nerve sections, there was no significant correlation between motor unit size (twitch amplitude) and recruitment threshold, as assessed by spike triggered averaging. This absence of orderly recruitment was attributed to misdirection of motor axons during regeneration. Following median nerve section at wrist level, where the reinnervated muscles have more synergistic actions, orderly recruitment by size appeared to be re-established. Thus, the size principle of motor unit recruitment can be re-established after nerve section in humans, if motor axons innervate their original muscles or ones with closely synergistic functions.

Action Potentials↗