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Biomedical subjects

R B Stein

Publications and source records attributed to R B Stein.

At least 163 records · Page 9Linked to original sources

Suprasellar papillary squamous epithelioma ("papillary craniopharyngioma").

Six cases of a distinctive suprasellar papillary neoplasm are presented and the features of this lesion are contrasted with those of the classical adamantinomatous craniopharyngioma. Characteristics distinguishing the former from the latter include a predominate, and perhaps exclusive, occurrence in adulthood; frequent radiologic solidity and absence of calcification; macroscopic papillary nature; and, microscopically, a well-differentiated papillary squamous epithelium without calcification, palisaded cells, or keratoid nodules. We suggest that this papillary lesion is a clinicopathologic entity distinct from the classical adamantinomatous craniopharyngioma.

Adolescent↗

Photoaffinity labeling with GTP of viral p21 ras protein expressed in Escherichia coli.

The v-ras oncogene of Harvey murine sarcoma virus encodes a 21,000-dalton protein, p21, which mediates transformation produced by that virus. Previous work has shown that both p21v-rasH and the cellular homolog p21c-rasH appear to bind guanine nucleotides. We report here the expression in Escherichia coli of v-rasH to produce a biochemically active p21 fusion protein which retains both guanine nucleotide binding and autophosphorylating activity. Furthermore, direct interaction of this protein with GTP is unequivocally demonstrated by photoaffinity labeling it with [alpha-32P]GTP.

Affinity Labels↗

Synaptic transmission from muscle afferents during fictive locomotion in the mesencephalic cat.

Modulation of synaptic potentials produced by electrical stimulation of low-threshold muscle afferents in lumbar alpha-motoneurons innervating knee and ankle muscles was studied by intracellular recording during "fictive locomotion" induced by stimulating the mesencephalic locomotor region (MLR) in paralyzed, mesencephalic cats. Averaging postsynaptic potentials in different phases of the fictive step cycle indicated that relatively little amplitude modulation occurred. In nearly half of the 38 motoneurons analyzed, there was a statistically significant tendency for excitatory postsynaptic potentials (EPSPs) to increase in amplitude during the depolarized phase of the oscillation in the membrane potential produced during fictive locomotion (locomotor-drive potential). In 8% the EPSPs decreased under the same conditions, while the rest displayed a constant amplitude during all phases of the fictive step cycle. Only three cells showed a distinct second peak in the EPSP at a latency consistent with transmission in a di- or trisynaptic pathway. Late inhibitory postsynaptic potentials (IPSPs) were also rarely observed. Thus oligosynaptic pathways from muscle afferents to the motoneuron groups studied are not prominent during the locomotor cycle in this preparation. We suggest that the marked modulation of monosynaptic reflex amplitude observed in mesencephalic cats (1) arises mainly from the effects of the locomotor-drive potential in bringing the cells closer to threshold during some phases of locomotion. Specific modulation during fictive locomotion of transmission in pathways from muscle afferents, which has been demonstrated for cutaneous pathways (28), was not observed. The implications of these results for the control of locomotion are discussed briefly.

Animals↗

Phasic and tonic modulation of impulse rates in gamma-motoneurons during locomotion in premammillary cats.

To determine the role of gamma-motoneurons in the control of locomotion, we isolated single units from nerves to triceps surae muscles in the premammillary cat. The limb used for recording was largely denervated, except for the muscles of interest, and fixed in place, while the other three limbs walked on a treadmill. One type of gamma-motoneuron (13 units) had a high impulse rate at rest, which changed little on average during walking, but was deeply modulated with each step (phasically modulated gamma-motoneuron or gamma p). Another type (19 units) had a low impulse rate at rest, which increased greatly on average during walking, but was not highly modulated with each step (tonically modulated gamma-motoneuron or gamma t). Peak gamma p rates generally occurred after peak EMG, often near the peak of tension. In contrast, peak gamma t activity generally preceded peak electromyograms (EMG). No significant difference was observed in conduction velocities for the two types of units. At rest all gamma t units were excited by natural stimulation of the fur over a large part of the body surface, whereas 3 of 11 gamma p units were inhibited. During locomotion the same natural stimuli had no observable effect on either type of unit. By recording in continuity from fine branches of the lateral and medial gastrocnemius nerves and stimulating ventral root filaments in continuity, we identified dynamic and static gamma-motoneurons in terms of their effects on muscle spindle afferents. After cutting the nerve branch distally and other ventral root filaments supplying the muscle, the resting discharge of dynamic and static gamma-motoneurons was recorded and found to correspond to that of the gamma p and gamma t units, respectively. Other evidence is presented for a correspondence between phasically and tonically modulated units and dynamic and static gamma-motoneurons, contrary to some suggestions in the literature.

Action Potentials↗

Diagnostic applications of monoclonal antibodies to human cancer.

Monoclonal antibodies elicited to surface antigens on a wide variety of normal and neoplastic cell types have been used with increasing frequency in the diagnosis and classification of cancer. Their widest application so far has been in the in vitro analysis of leukemia and lymphoma using blood or bone marrow samples or tissue biopsy specimens. Although no true leukemia-specific marker has been found, the complex biologic nature of this group of tumors has been shown by monoclonal antibody studies. More recently, these antibodies were produced against solid tumor-associated antigens. The antibodies have helped to identify the tissue of origin of malignant neoplasms and, in some cases, to monitor the course of disease. Carefully chosen panels of monoclonal antibodies will become valuable additions to the diagnostic pathologist's arsenal.

Antibodies, Monoclonal↗

The relationship between axon diameter, myelin thickness and conduction velocity during atrophy of mammalian peripheral nerves.

The atrophy of cutaneous (sural) and muscle (medial gastrocnemius) nerves proximal to a ligation were studied in cats for periods up to 9 months, using light and electron microscopy, conduction velocity measurements and computer simulations. As atrophy proceeds, nerve fibres become increasingly non-circular. Cross-sectional areas of axons and fibres (axon + myelin) were measured. The diameters of equivalent circles (having the same axon and fibre cross-sectional area) were then calculated. A linear relation was found between axon diameter and fibre diameter, but the slope decreased as atrophy continued. This indicates that the axon cross-sectional area decreases relatively more than the total fibre area. Reduction in conduction velocity correlates more closely with reduction in axon diameter than fibre (axon + myelin) diameter. The ratio of the inner (axon) perimeter to the outer (myelin) perimeter remains constant at or near the optimal value of 0.6 for conduction in all groups of fibres at all periods of atrophy. Furthermore, the thickness of the myelin remains constant for a given perimeter over the entire period of atrophy studied. This suggests that the number of turns of myelin and the length of each turn remain unchanged during peripheral nerve atrophy. A simple geometric model explains how this can occur without gaps developing between the axon and myelin or between the turns of myelin. The Frankenhaeuser-Huxley equations for conduction in myelinated nerve fibres predict changes in conduction velocity similar to those observed, if the axons atrophy without changes in myelin. The advantages of this mode of atrophy are discussed.

Animals↗

Optimal control of antagonistic muscles.

Recently, a model for a pair of antagonistic muscles has been studied (Oğuztöreli and Stein, 1982). In the present paper we formulate and investigate the minimization of the costs associated with the time to complete the movement, the oscillation about the endpoint, the energy costs to the muscles to complete the movement, the cost to the nervous system to supply the inputs, and the cost of reliability in the face of perturbing forces. To solve these optimization problems the maximum principle of Pontryagin is employed. In all of these optimization problems, except the energy optimal problem, the optimal controls (active states or nervous inputs) are of the bang-bang type.

Animals↗

Functional comparison of upper extremity amputees using myoelectric and conventional prostheses.

Upper extremity amputees were tested on a standardized series of tasks using a myoelectric hand, a conventional prosthesis (cable-controlled hook), and their normal hand (unilateral amputees only). They answered also a questionnaire on activities of daily living (ADL) and provided other prosthetic information. Amputees who had been fitted only with a conventional prosthesis, and used their prosthesis regularly, tended to wear the prosthesis more hours per day (14 hours) than amputees fitted with a myoelectric hand (9.6 hours), some of whom continued to use a conventional prosthesis for some jobs. However, the amputees with myoelectric prostheses had a greater functional range of motion (ROM) than those with a conventional prosthesis, and many regular wearers of a myoelectric prosthesis had long since rejected a conventional prosthesis. Amputees took about 2.5 times as long to complete the tasks tested with a conventional prosthesis and about five times as long with a myoelectric prosthesis than with their normal hand. Despite the slower function, more than 60% of below-elbow (B-E) amputees accepted the myoelectric prosthesis in preference to a conventional prosthesis, which they had all been fitted with previously. Others preferred to continue using a conventional prosthesis to which they had become accustomed (13%) or no prosthesis (26%). The combination of function, ROM, and cosmetic appearance of a myoelectric prosthesis is preferred by most B-E amputees, despite its slower performance at the present time.

Activities of Daily Living↗

Analysis of a model for antagonistic muscles.

In the present work a linear model for a pair of antagonistic muscles is analysed. Each constituent muscle in this model is identical to ones considered previously (Stein and Oğuztöreli, 1976). Analytical properties of the antagonistic muscles and dynamics of the system are described and some numerical results are discussed. The natural modes of the system are determined by a fourth order polynomial, which most commonly has one pair of conjugate complex roots and two negative real roots. The filtering of neural inputs through the active state properties of the muscle increases the order of the system to fifth order for these inputs.

Animals↗

Slow changes and Wiener analysis of nonlinear summation in contractions in cat muscles.

With regular trains of stimuli at a high frequency, the contribution of each stimulus to the force generated over time declines from the second to about the tenth stimulus, but then begins to increase again. This late increase is referred to as tetanic potentiation in analogy with the post-tetanic potentiation of the twitch after such a period of stimulation. With regular trains of stimuli at a low frequency, a progressive decrease in the essentially unfused twitches (negative staircase) is observed in the slow soleus muscle of the cat, while a progressive increase (positive staircase) is observed for the fast plantaris muscle. The time constant for the approximately exponential changes observed is on the order of 10 s. Random trains of stimuli were applied at intermediate frequencies and analyzed in terms of general methods of analysis for nonlinear systems. Systematic decreases in the magnitude and increases in the time course of the average tension per stimulus were observed with increasing mean rates of stimulation. Similar changes were observed for short intervals between stimuli within a given random train at a constant mean rate. These changes can be described in terms of an early depression and a later facilitation described in the previous papers in this series.

Animals↗

Temperature dependence of mammalian muscle contractions and ATPase activities.

Isolated rat and mouse extensor digitorum longus (EDL) and soleus muscles were studied under isometric and isotonic conditions at temperatures from approximately 8 degrees -38 degrees C. The rate constant for the exponential rise of tension during an isometric tetanus had a Q10 of approximately 2.5 for all muscles (corresponding to an enthalpy of activation, delta H = 66 kJ/mol, if the rate was determined by a single chemical reaction). The half-contraction time, contraction time, and maximum rate of rise for tension in an isometric twitch and the maximum shortening velocity in an isotonic contraction all had a similar temperature dependence (i.e., delta H approximately 66 kJ/mol). The Mg++ ATPase rates of myofibrils prepared from rat EDL and soleus muscles had a steeper temperature dependence (delta H = 130 kJ/mol), but absolute rates at 20 degrees C were lower than the rate of rise of tension. This suggests that the Mg++ ATPase cycle rate is not limiting for force generation. A substantial fraction of cross-bridges may exist in a resting state that converts to the force-producing state at a rate faster than required to complete the cycle and repopulate the resting state. The temperature dependence for the rate constant of the exponential decay of tension during an isometric twitch or short tetanus (and the half-fall time of a twitch) had a break point at approximately 20 degrees C, with apparent enthalpy values of delta H = 117 kJ/mol below 20 degrees C and delta H = 70 kJ/mol above 20 degrees C. The break point and the values of delta H at high and low temperatures agree closely with published values for the delta H of the sarcoplasmic reticulum (SR) Ca++ ATPase. Thus, the temperature dependence for the relaxation rate of a twitch or a short tetanus is consistent with that for the reabsorption rate of Ca++ into the SR.

Adenosine Triphosphatases↗

Time course and extent of recovery in reinnervated motor units of cat triceps surae muscles.

1. Nerve and muscle properties were studied in single motor units of triceps surae muscles in the cat using chronic recording techniques and intramuscular microstimulation. Recordings were made before and at intervals up to 18 months after a nerve was sectioned and sutured either to its distal stump (nerve-nerve suture) or to a muscle directly (nerve-muscle suture). Thus, each nerve and muscle served as its own control for recovery after reinnervation.2. Following a delay all muscles recovered their preoperative tension after nerve-nerve suture with a single exponential having a time constant of 1-2 months. Only half the muscles recovered their preoperative tensions after nerve-muscle sutures. Muscles which did not recover fully also had a slower time course of recovery.3. The estimated number of motor units did not increase significantly later than 2 months after nerve section and suture. Further recovery of muscle tension is due to increased unit tension, rather than increasing numbers of reinnervated motor units. Unit tension recovered completely in all muscles, but did not become enlarged, even when muscles apparently remained partially denervated.4. The latency of compound nerve potentials often recovered completely, although the amplitude of the potential remained depressed. Single motor axonal potentials recovered to control levels after reinnervation of muscle with a time constant similar to that for the recovery of motor unit tension. Therefore, two distinct populations of motor axons contribute to the compound potential: reinnervating axons whose size recovers fully, and disconnected axons which remain atrophic. Incomplete recovery of the compound potential amplitude mainly results from a failure of all axons to remake peripheral connexions.5. Thus, formation of functional nerve-muscle connexions completely reverses the effects of axotomy on nerve and muscle. Reinnervated motor units recovered their preoperative size, whether or not much of the muscle remained denervated.

Action Potentials↗

Modulation of stretch reflexes during locomotion in the mesencephalic cat.

1. A cat preparation was used to study the modulation of stretch reflexes during locomotion. The brain stem was transected and locomotion was induced by electrical stimulation of the mesencephalic locomotor region below the level of transection. Three legs walked normally on a treadmill, while the fourth leg, which was denervated except for the soleus muscle, was held fixed. Brief length perturbations were applied to the soleus muscle at various phases of the stepping cycle.2. The stretch reflex in this muscle was deeply modulated during the step cycle, and reached its peak at or before the peak in soleus e.m.g. activity associated with the locomotion. A similar variation was observed when the sciatic nerve was stimulated electrically at a strength which elicited reflex activity (H wave), but did not directly elicit motor nerve activity (M wave). Variation in the reflex during electrical stimulation could not be accounted for by cyclic variation in fusimotor activity or in the afferent volley, but must be due to post-synaptic changes in alpha-motoneurones or in the presynaptic inputs to them.3. Large changes were also observed in intrinsic muscle stiffness during the step cycle. The maximum stiffness occurred near the time the limb would normally strike the ground during locomotion. A high stiffness would be useful in reducing the amount that the limb would yield under the weight of the body during the extension phase of the step cycle. The variation of the stretch reflex in parallel with stiffness suggests that reflexes could assist in this load compensation. The variation is not consistent with the idea that the stretch reflex is used to compensate for changes in intrinsic muscle properties, so that the total system behaves more like a spring of constant stiffness than does muscle alone.

Animals↗

Nonlinear properties of stretch reflex studied in the decerebrate cat.

1. Pairs of brief stretches or a series of stretches at random intervals (Poisson process) were applied to a slow (soleus) and a fast (plantaris) muscle in decerebrate cats to analyze the nonlinear effects of one stretch on the reflex responses to subsequent stretches. Neural activity, electromyogram (EMG), and force were recorded. The reflex responses due to stretch were compared with reflexes as a result of electrical stimulation of nerves. Nonlinearities of muscle were also examined in the absence of reflexes. Short-latency neural activity produced by the stimuli at all intervals studied was quite constant, so changes in sensory activity cannot account for the nonlinearities. Three phases of nonlinear interactions were observed, and mechanisms for these nonlinearities are suggested. 2. For short intervals (less than 100 ms) following a stretch the force and EMG produced by a second stretch is depressed. This early depression could be due to the after hyperpolarization of the motoneuron cel body or to synaptic mechanisms, since the depression of EMG is seen with electrical stimulation of Ia sensory, but not alpha-motor axons. In addition, a second stretch can disrupt the reflex contraction produced by the first stretch if it occurs at a time when new actomyosin bonds are not readily formed. Because of this force suppression, the total reflex force produced in response to two stretches may be less than the response to a single stretch. 3. For intervals between 100 and 300 ms the force and EMG produced by a second stretch is enhanced. This potentiation is also seen with electrical stimulation of large sensory but not motor axons and could result from a synchronization of motoneuronal excitability cycles. It is more prominent in the homogeneous (soleus) muscle than the mixed (plantaris) muscle, probably because the motoneuron cell bodies will reach a period of high excitability at more nearly the same time in the homogeneous muscle. 4. For longer intervals the force produced by a second stretch is reduced even when the EMG is close to control values. This late depression is also observed with electrical stimulation of cut motor axons and therefore arises from the contractile properties of muscles. 5. With a random series of stretches, the same time course of nonlinear interactions is observed. However, as the mean rate of the random stretches is increased, the average response of the reflex decreases. Thus, the stretch reflex will be most effective in correcting for occasional perturbations to a movement, rather than for continuously varying disturbances.

Animals↗