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Biomedical subjects

R B Stein

Publications and source records attributed to R B Stein.

At least 145 records · Page 8Linked to original sources
PubMed1987

The effects of pH on force and stiffness development in mouse muscles.

Changes in force and stiffness during contractions of mouse extensor digitorum longus and soleus muscles were measured over a range of extracellular pH from 6.4 to 7.4. Muscle stiffness was measured using small amplitude (less than 0.1% of muscle length), high frequency (1.5 kHz) oscillations in length. Twitch force was not significantly affected by changes in pH, but the peak force during repetitive stimulation (2, 3, and 20 pulses) was decreased significantly as the pH was reduced. Changes in muscle stiffness with pH were in the same direction, but smaller in extent. If the number of attached cross-bridges in the muscle can be determined from the measurement of small amplitude, high frequency muscle stiffness, then these findings suggest that (a) the number of cross-bridges between thick and thin filaments declines in low pH and (b) the average force per cross-bridge also declines in low pH. The decline in force per cross-bridge could arise from a reduction in the ability of cross-bridges to generate force during their state of active force production and (or) in an increased percentage of bonds in a low force, "rigor" state.

Animals↗
PubMed1987

[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↗
PubMed1986

Statistical limits for detecting change in the cumulative sum derivative of the peristimulus time histogram.

The peristimulus time histogram (psth) provides a means of correlating the discharges of neurones with other events. The cumulative sum (cusum) derived from the psth facilitates the detection of small changes in the psth that may be obscured by random fluctuations in counts. The cusum integrates differences from the mean control level of counts in the psth. Any signal in the data that is related to the stimulus appears as a slope in the cusum. Psth's constructed from the rhythmic discharges of single neurones are shown to contain periodical fluctuations in counts that arise from refractoriness. This periodicity results in a cusum which deviates less from the horizontal line than predicted from a Poisson distribution of points. The more regular the spike train, i.e., the lower the coefficient of variation of the distribution of interspike intervals, the flatter is the cusum. The theory of stochastic point processes is used to derive an algorithm for calculating the best approximation of variance of the cusum. Significance limits set at 3 standard deviations of the cusum are shown to provide a good fit to cusums for unit discharges over a wide range of coefficients of variation (0.09-0.60).

Action Potentials↗
PubMed1986

Innervation and function of hind-limb muscles in the cat after cross-union of the tibial and peroneal nerves.

Peripheral nerves to flexor (common peroneal) and extensor (tibial) nerves in a hind limb of seven 2-6 month old cats were cut and cross-united to study the plasticity in the spinal cord. The extent to which motoneurones from extensor and flexor motor pools were misdirected to their antagonistic muscles was determined by measuring the potentials generated at the spinal roots from the crossed nerves. The axons contributing to the extensor nerves normally leave the cord in the L7 and S1 ventral and dorsal roots while the axons contributing to the flexor nerves normally leave the cord in the L6 and L7 ventral and dorsal roots. Following cross-union, medial gastrocnemius (m.g.) and lateral gastrocnemius-soleus (l.g.s.) nerves were primarily supplied by L6 and L7 ventral and dorsal roots, and common peroneal (c.p.) nerves were primarily supplied by L7 and S1 ventral and dorsal roots. A method for quantifying the completeness of cross-reinnervation was developed. The pattern of e.m.g. activity in cross-reinnervated muscles during locomotion was primarily determined by the innervating nerve with the reinnervated flexor muscles being activated during the extensor phase. However, the cross-reinnervated extensor muscles showed evidence of extensor activity in addition to the double-burst pattern typical of flexor nerves. This extensor activity was more prominent when the nerve cross was less complete. We conclude that during locomotion the activity of spinal motoneurones was not substantially modified by inappropriate peripheral connexions, even when the nerve cross was carried out in young animals. This conclusion is discussed in relation to previous studies which suggested some degree of functional modification.

Action Potentials↗
PubMed1986

Organization of motor units following cross-reinnervation of antagonistic muscles in the cat hind limb.

Peripheral reorganization of nerve and muscle properties was studied following misdirection of regenerating axons to foreign muscles. The tibial nerve, which innervates all of the distal extensor muscles, was cross-united with the common peroneal nerve, which innervates all of the distal flexor muscles, in one hind limb of seven 2-6 month old cats. After 18-24 months the properties of the motor units in the reinnervated triceps surae muscles were studied by dissection and stimulation of the ventral root filaments. The normal size relationships were re-established in reinnervated medial gastrocnemius (m.g.) and lateral gastrocnemius-soleus (l.g.s.) muscles in so far as motor unit force was directly correlated with the extracellularly recorded amplitude of the axon potential and with contractile speed. The range of sizes of motor units in reinnervated m.g. and l.g.s. muscles was similar to normal, both in terms of the muscle unit size (determined by measuring tetanic tension) and axon size (determined from the amplitude of the extracellularly recorded action potential). The amplitude of the axon potentials in the crossed nerves was weakly correlated with calculated conduction velocities because of the variation in the conduction delays across the suture line. As axon potential amplitude is a direct function of axon size at the recording site, it provided a reliable measure of regenerating axon size. Motor units were classified as slow (s.), fast fatigue resistant (f.r.), fast intermediate (f.i.) or fast fatigable (f.f.) by their contractile speed and fatigue properties. Tetanic tensions generally increased from slow to fast units with s. less than f.r. less than f.i. less than f.f. in reinnervated and normally innervated muscles, but the overlap between different unit types was considerably greater in reinnervated muscles. Thus, peripheral reorganization of nerve and muscle properties according to size can occur in reinnervated muscles, irrespective of the source of the regenerating nerves.

Action Potentials↗
PubMed1986

Molecular cloning of the temperature-sensitive 371 Kirsten murine sarcoma virus and expression in Escherichia coli of the mutant and wild-type viral Kirsten ras p21 proteins.

Rodent fibroblasts infected with the ts371 Kirsten murine sarcoma virus (KiMuSV) are temperature sensitive for the maintenance of transformation because of the production of an abnormal p21 protein. We cloned the ts371 KiMuSV provirus from the genome of a conditionally transformed nonproducer cell line, ts371 KiMuSV NRK clone 5 (T. Y. Shih, M. O. Weeks, H. A. Young, and E. M. Scolnick, J. Virol. 31:546-556, 1979). The molecularly cloned virus had 1,000-fold lower transformed focus-forming activity at 39 degrees C than at 34 degrees C. The ts371-v-Ki-ras gene differed from the wild type (wt) by a single point mutation, resulting in the substitution of arginine for glutamine at amino acid residue 43 of the encoded p21. A second difference from the published sequence for wt v-Ki-ras (N. Tsuchida, T. Ryder, and E. Ohtsubo, Science 217:937-939, 1982) at amino acid residue 37 was found. However, on sequencing the wt v-Ki-ras in this region, we found that it also contained a glutamate at residue 37. Preliminary characterization of bacterially expressed wt and ts371-v-Ki-ras p21 proteins is discussed.

Amino Acid Sequence↗
PubMed1986

Nonlinear stiffness--force relationships in whole mammalian skeletal muscles.

Small, sinusoidal length changes were superimposed on isometric contractions of fast- and slow-twitch mouse muscles, which were stimulated maximally via their nerves. Stiffness increased with increasing frequency of sinusoidal stimulation, but the relative time course of force and stiffness changes during twitch, tetanic, or partially fused contractions was quite invariant over a range of frequencies in both muscles. Typically, stiffness increases more rapidly than force during contraction and decreases less rapidly during relaxation. This pattern was observed at various temperatures and with various numbers of stimuli. It can be described by a nonlinear relation between stiffness and force with some hysteresis. The presence in the muscle of parallel and series elastic elements, whose stiffness varies with force, may account for the nonlinear relation. This nonlinearity can be used to relate the patterns for summation of force and stiffness observed with brief trains of stimuli under a variety of conditions.

Animals↗
PubMed1986

Motor-unit recruitment in human first dorsal interosseous muscle for static contractions in three different directions.

Spike-triggered averaging was used to extract the twitch tensions and contraction times of 144 motor units from the first dorsal interosseous muscle of four subjects for three different directions of static contraction: abduction of the index finger, flexion of the index finger, and adduction of the thumb coupled with flexion of the index finger (hereafter referred to as adduction). Although the twitch tensions were generally largest for the abduction contraction, all units contributed tension to all three directions of contraction. A linear correlation was found for twitch tensions of motor units for the three directions of static contractions. Linear correlations were also found between twitch tension and threshold force of these motor units for each direction, which suggests that an orderly pattern of recruitment, according to increasing twitch size, adequately describes the function of human first dorsal interosseous muscle for all contraction directions. No clear evidence was found for separate groups of motor units in the muscle that were selectively activated for the different tasks. Rank order of recruitment for motor units in the three directions of contraction was correlated, but was not identical. The scatter in our data is discussed in relation to earlier reports of altered motor-unit recruitment during different movements.

Action Potentials↗
PubMed1986

Malignant transformation of a preneoplastic hamster epidermal cell line by the EJ c-Ha-ras-oncogene.

We have investigated whether the activation of endogenous ras genes is associated with the immortalization or malignant transformation of primary hamster epidermal cells by chemical carcinogens. We have also asked whether transfection of a cloned c-Ha-ras oncogene (pEJ) into a nontumorigenic cell line established from hamster epidermal cells by N-methyl-N'-nitro-N-nitrosoguanidine treatment can induce conversion to a malignant phenotype. DNA from the nontumorigenic epidermal cell line (H5-MNNG) and from two neoplastic cell lines transformed by benzo(a)pyrene was not capable of transforming NIH/3T3 cells. This result suggests that these cells do not contain an activated (mutated) ras gene. However, when H5-MNNG cells were cotransfected with pEJ and pSV2-gpt, a plasmid containing the dominant selectable marker gene Ecogpt, seven of nine clones of Ecogpt transformants formed carcinomas in nude mice and colonies in soft agar. Southern blot analysis of BamHl-digested genomic DNA from the Ecogpt-transformed clones indicated that rapid malignant transformation was associated with integration of a complete copy of the 6.6-kilobase fragment of pEJ containing the activated c-Ha-ras gene. Furthermore, DNA from the malignant clones transformed NIH/3T3 cells in a secondary transfection assay. These studies demonstrate that a mutated c-Ha-ras gene, under the transcriptional control of its normal cellular promoter, can rapidly transform a nontumorigenic epidermal cell line. This result suggests that activation of an endogenous c-ras gene can function as the final completing event in the progression of epithelial cells to the malignant phenotype. Thus, preneoplastic cell lines of both mesenchymal and epithelial origin have now been shown to be susceptible to malignant conversion by a single mutation in a c-Ha-ras proto-oncogene.

Animals↗
PubMed1986

Amplitude modulation of the soleus H-reflex in the human during walking and standing.

Experiments were done to determine the amplitude of the monosynaptically mediated H-reflex of the soleus muscle at various phases of the step cycle, using a computer-based analysis procedure. In all subjects tested the amplitude of the H-reflex was strongly modulated in amplitude during the walking cycle and was highest during the stance phase. In many subjects the peak reflex amplitude occurred at about the same time as the peak soleus electromyographic (EMG) activity, but in others it occurred earlier. The form of the reflex variation (i.e., envelope of H-reflex amplitude versus phase in cycle) during the step cycle could also be quite different from that of the EMG produced during stepping. At an equal stimulus strength and EMG level, the H-reflex was always much larger, up to 3.5 X, during steadily maintained contractions while standing than during walking. The large reflexes when subjects were standing are consistent with the control of position required to maintain a stable posture in this task. Similarly, the reflexes during walking are greatest during the stance phase, when they will assist in maintaining the upright position of the body against gravity. The reflexes are smallest during the swing phase when they would oppose ankle flexion. However, since the reflex amplitude is task-dependent (i.e., greater during standing than during walking at the same EMG and stimulus levels) and is not always closely related to the EMG produced during a given task such as walking, the strong modulation of H-reflex during walking is not simply a passive consequence of the alpha-motoneuron excitation level.(ABSTRACT TRUNCATED AT 250 WORDS)

Ankle↗
PubMed1986

Improved ankle-foot system for above-knee amputees.

Above-knee amputees were studied while wearing a prosthesis containing either a standard or a modified single axis foot. The modified foot allowed 12-15 degrees of dorsiflexion and reduced stiffness in the area of the metatarsal-phalangeal (MTP) joint. The amputees were allowed to vary the stiffness at the two joints to obtain what "felt best." The amputees agreed that in comparison to the standard single-axis foot, the modified foot: a) offered a more comfortable gait while walking on level ground; b) made walking up inclines easier; c) affected knee stability while walking on declines; and d) made foot placement on stairs and ladders more critical due to potential knee instability. As well as qualitative reactions, changes in the gait cycle were measured quantitatively for different speeds and inclinations of walking on a treadmill. Measurements from normal subjects matched by age and sex were used for control purposes. All participants wore soft-soled shoes. The amputees selected a stiffness that allowed a degree of dorsiflexion which precisely matched on average that of the normal subjects. In contrast, they selected a stiffness at the MTP joint which allowed very little flexion of the toes. Significant changes also occurred in the pattern of hip movements, so that they became much more symmetrical on the two sides, although substantial differences remained between the hip movements of the amputees and the normal subjects. If modifications in the ankle joint can be coupled with improvements in the knee joint to prevent potential instability, a much improved gait should be possible for above-knee amputees.

Adult↗
PubMed1985

Viral Harvey ras p21 expressed in Escherichia coli purifies as a binary one-to-one complex with GDP.

The ras oncogene of Harvey murine sarcoma virus encodes a 21,000-dalton protein, p21, which mediates transformation. Viral Harvey ras p21, cloned into Escherichia coli HB101 lambda/pRAS1, has been purified to homogeneity by a three-step procedure. The purified E. coli p21 can be bound by a monoclonal antibody to viral Harvey ras p21 and has an amino acid composition consistent with that predicted from its DNA sequence. Purified E. coli p21 has been shown by HPLC analysis on an ion-exchange column to contain near stoichiometric amounts of GDP. This noncovalently associated GDP is seen in the UV absorption spectrum of the purified protein. The noncovalently associated GDP acts as a competitive inhibitor of the interaction of added guanine nucleotides with p21.

Amino Acids↗
PubMed1985

Temperature effects on the kinetics of force generation in normal and dystrophic mouse muscles.

The kinetics of isolated extensor digitorum longus and soleus muscles from normal and genetically dystrophic (129/ReJ dy/dy) mice were studied at temperatures from 8 to 38 degrees C. The rate constants for the exponential rise of tetanic force and for the exponential decay of force during an isometric twitch or short tetanus were similar in normal and dystrophic soleus muscles, but the decay rates were significantly reduced in dystrophic extensor digitorum longus muscles. The temperature dependence for several rate constants for isometric twitches and tetani was similar in all muscles studied, suggesting that the same rate limiting processes apply to fast and slow, normal and dystrophic muscles. Thus, the contractile proteins and those in the sarcoplasmic reticulum of dystrophic muscle are probably normal. The slower relaxation phase in dystrophic extensor digitorum longus muscles is compatible with a reduction in Ca2+-pumping sites in the sarcoplasmic reticulum, perhaps secondary to a change in motor unit composition. Some changes in the temperature dependence for measured times, toward those of soleus muscles, is consistent with the increased proportion of slow twitch motor units in dystrophic extensor digitorum longus muscles.

Animals↗
PubMed1985

Microinjected ras family oncogenes stimulate DNA synthesis in quiescent mammalian cells.

Oncogenes of the ras family stimulate DNA synthesis when microinjected into quiescent mouse and hamster fibroblasts, as detected by in situ autoradiography. The molecularly cloned genomes of Harvey and Kirsten sarcoma viruses, the cloned Harvey ras gene, and the product of the v-ras gene, the p21v-rasH protein, stimulate DNA synthesis in quiescent cells. This stimulation is comparable to the stimulatory activity of the microinjected SV40 T-antigen-coding gene. The demonstration that these oncogenes can stimulate transient DNA synthesis in quiescent cells is relevant to understanding the mechanism by which these genes are able to transform cells in vitro and induce tumors in animals.

Animals↗
PubMed1985

Model of a pattern generator for locomotion in mammals.

This paper presents an analytic model of a limb pattern generator that can produce complex muscle activation patterns such as those shown to control the limbs of cats. The limb pattern generator is considered to have a tonic input and six outputs; this provides for flexion and extension of representative muscles for each of the three joints of the limb. The pattern generator functions as a community of labile synthesized relaxation oscillators that alters its output in response to input. This model was studied using electromyographic data from an experiment conducted on an acute postmammillary cat preparation. The results suggest that the limb pattern generator can be represented as three subsystems: an oscillator that produces the fundamental frequency of the output in response to the tonic signal, nonlinear shaping functions that mold the oscillator output into the basic complex pattern, and appropriate weighting functions that generate the muscle activity pattern from basic waveforms. The model can account for speed changes in locomotion with a relatively smooth change of system parameters. The pattern generator model is generative, amenable to simulation studies, and can be realized by a neural network.

Animals↗
PubMed1985

Impulse rates and sensitivity to stretch of soleus muscle spindle afferent fibers during locomotion in premammillary cats.

Impulse from soleus muscle afferents were recorded in premammillary cats that were walking on a treadmill. In normal walking the effects of gamma-motoneurons on impulse rates of muscle spindle afferents are confounded by the effects of the large length changes that occur. To isolate the effects of gamma-motoneurons the leg was fixed in place for recording and denervated except for soleus muscle. Because gamma-motoneurons produce marked effects on the stretch sensitivity of muscle afferents, soleus muscle was oscillated about a present length so the stretch sensitivity of its afferents could be determined. The impulse rate of secondary muscle spindle afferents in soleus muscle was generally increased at all phases of the step cycle. The mean rate approximately doubled during walking (82 imp/s), compared with nonwalking (rest) periods (44 imp/s). The sensitivity to sinusoidal length changes was generally reduced throughout the step cycle (mean reduction = 33%). Primary muscle spindle afferents also showed an increased mean rate during walking (47 imp/s) compared with rest (24 imp/s). The impulse rate peaked after the muscle reached its maximum force and often showed a second peak before the maximum electromyogram (EMG) activity. The sensitivity to sinusoidal stretches varied cyclically during locomotion. During the extension phase it sometimes exceeded the resting value, but was greatly reduced during the flexion phase (mean reduction = 49% over whole cycle). Control experiments were carried out in which static and dynamic gamma-motoneurons were stimulated and activity from muscle spindle afferents was recorded in anesthetized cats. With the amplitude and frequency of stretch applied, stimulation of dynamic gamma-motoneurons usually increased and stimulation of static gamma-motoneurons usually decreased the sensitivity of primary muscle spindle afferents to sinusoidal stretch. The patterns observed in muscle spindle afferents suggest a strong, maintained activation of static gamma-motoneurons throughout the step cycle and a phasic activation of dynamic gamma-motoneurons, which is consistent with previous direct recordings from gamma-motoneurons. With this pattern of activating gamma-motoneurons, the secondary muscle spindle afferents will provide a good feedback signal of the large length changes that normally occur in the muscle during locomotion. The changes in sensitivity of primary muscle spindle afferents will complement central changes so the gain of the stretch reflex from extensors is high during extension (when required to help support the weight of the body) and low during flexion (when a high gain would be counterproductive).

Anesthesia, General↗
PubMed1984

Modification of muscle responses by spinal circuitry.

Recently, we developed a model based on experimental data, which includes a pair of antagonistic muscles, a general load against which the muscles act, feedback pathways from muscle sense organs and spinal inhibitory circuits involving 1A interneurons and Renshaw cells. Descending inputs can activate the model through combinations of inputs to alpha-motoneurons, gamma-motoneurons (via intrafusal muscles and their feedback pathways) or the 1A interneurons. The role of each of these connections is analysed here in terms of its effect on the response of the muscles to impulse inputs, with particular interest in the effects on the overall stability of the systems. Increasing muscle stiffness or feedback from muscle receptors tends to produce high frequency oscillations. Coactivation of alpha- and gamma-motoneurons can lead to cancellation of oscillations, because of delays in the effects of gamma-motoneurons on contraction. Connections of 1A inhibitory interneurons onto antagonist motoneurons accentuate the oscillations. Inhibitory connections from Renshaw cells onto alpha-motoneurons tend to prevent oscillations, whereas the concentrations onto gamma-motoneurons may produce them.

Animals↗