Search PubMed⌕ Search

Biomedical subjects

D J Bennett

Publications and source records attributed to D J Bennett.

At least 55 records · Page 3Linked to original sources
PubMed1994

Stretch reflex responses in the human elbow joint during a voluntary movement.

1. The responsiveness of the stretch reflex is modulated during human voluntary limb movements. The influence of this modulation on the limb mechanical properties (stiffness) was investigated. 2. Subjects were taught to replicate accurately a rapid (4.0 rad s-1) targeted elbow flexion movement of 1 rad. From the onset of 12% of the trials a sinusoidal position disturbance (0.05 rad) was superimposed on the normal (trained) movement trajectory. The net joint torque (muscle torque) resisting these stretches was computed from measurements of applied torque, acceleration and limb inertia. Electromyographic (EMG) responses in the triceps brachii (TB), brachialis (Br) and biceps brachii (BB) were monitored. 3. The EMG responses to sinusoidal stretches applied early in the movement were less than those responses to perturbations applied when the arm neared the target (especially in the antagonist muscle TB). These EMG responses caused fluctuations in the resistance to the perturbation (stiffness), as described below. 4. When the perturbation frequency was low (< 4 Hz) the resistance of the elbow muscles to the stretch increased as the arm approached the target (48% increase). In contrast, when the stretch frequency was 7 Hz the resistance decreased by 63%. This decrease can be explained by the increased reflex response, since at 7 Hz the reflex response is probably timed so that it assists, rather than resists, the stretching as a result of loop delays. This reflex timing was confirmed by observing that, after abruptly stopping the sinusoidal stretch, the reflex response persisted for 100 ms and was indeed in a direction that would have reduced the resistance, had the perturbation continued. 5. The time course of the net muscle stiffness was estimated for frequencies ranging from 4 to 8 Hz and for each 40 ms interval a Nyquist plot was constructed, forming a C-shaped curve as frequency was varied. The size of this curve gave a measure of the stiffness resulting from reflex activity. When the arm neared the target this reflexive stiffness reached a maximum, and was probably comparable in size to the intrinsic (non-reflexive) muscle stiffness. Also, in four of the five subjects the viscous component of stiffness at 7 Hz dropped significantly below zero when the arm neared the target, again indicating that at this frequency the reflex was large and acted inappropriately.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Catching a ball: contributions of intrinsic muscle stiffness, reflexes, and higher order responses.

In three sets of experiments in nine normal subjects and a patient with a percutaneous wrist-stabilizing splint, we quantified the open-loop gain (OLG) of the stretch reflex acting about the elbow. The subjects exerted a steady mean flexing force and were instructed not to intervene (i.e., not to resist actively) when force or displacement perturbations were imposed on the forearm. The method was either to reconstruct transmission around the entire loop in a two-part experiment, or to use the attenuation of external perturbations in normal and electrically stimulated muscle to compute gain. Across all experiments, the mean magnitude of stretch reflex OLG was close to unity in the frequency range 1-2 Hz, and declined at higher frequencies, as required to ensure stability, given that the phase lag approached 180 degrees at 5 Hz. Inherent muscle stiffness was approximately equal to reflex stiffness. In functional terms, an OLG of 1 means that the yield caused by a force perturbation is approximately halved by reflex action (prevailing inherent muscle stiffness is doubled). Automatic scaling of reflex transmission at Ia/alpha-motoneuronal synapses ensures that the OLG remains close to unity as inherent stiffness increases. Trials in the patient with the wrist fixator gave similar results, indicating that the reflexes were proprioceptive ly mediated. In a fourth experiment in which the task was to catch a heavy ball, we compared the efficacy of inherent muscle stiffness and reflexes alone, with the subject's intentional reactions, which included predictive and voluntary components of response. The latter were far more effective in maintaining the position of the hand after the ball was caught than inherent and reflex stiffnesses alone. We conclude that stability requirements limit the extent to which stretch reflexes can augment inherent muscle stiffness. When inherent muscle stiffness is low, such as in our ball-catching task, the reflex stiffness is also low, and predictive and pre-programmed reactions predominate in load compensation, thus shifting the emphasis from automatic servo or equilibrium-point behaviour to higher order control.

Elbow Joint↗
PubMed1993

Torques generated at the human elbow joint in response to constant position errors imposed during voluntary movements.

The stiffness of the human elbow joint was investigated during targeted, 1.0-rad voluntary flexion movements at speeds ranging from slow (1.5 rad/s) to very fast (6.0 rad/s). A torque motor produced controlled step position errors in the execution of the movements. The steps began at the onset of movement, rose to an amplitude of 0.15 rad in 100 ms, and had a duration equal to movement duration. The net joint torque (muscle torque) resisting the step perturbation was computed from the applied torque, the joint acceleration, and the limb inertia. Subjects resisted the imposed step changes with approximately step changes in the net muscle torque. The mean resistance torque divided by the step amplitude was computed and is referred to as the stiffness. The stiffness increased with the voluntary movement speed, over the range of speeds (1.5-6 rad/s). The stiffness increased linearly with the magnitude of the net muscle torque on the unperturbed trials (referred to as "background torque"). The stiffness changed by only 20% when the step amplitude ranged from 0.05 to 0.15 rad. The mechanical resonant frequency (fr), estimated from the average stiffness estimates, ranged from 0.8 to 3.0 Hz. The resonant frequency approximately equaled the principal frequency component of the movement fm. On average: fr = 0.96 fm +0.46. During the fixed, 100-ms rise time of the step, the resistance was not linearly related to the background torque. At slower speeds the resistance was relatively greater during this rise time. However, when the imposed step perturbation was modified so that its rise time occurred in a time proportional to the movement duration (rather than in the fixed, 100-ms, time), the muscle torque resisting the motor during this rise time was proportional to the background torque. When these modified step responses were plotted on a time scale normalized to the movement duration, they all had approximately the same shape. Apparently the muscle viscosity scaled with the stiffness so as to maintain the constant response shape (constant damping ratio). The observed "tuning" of the mechanical properties to the movement speed is suggested to be important in the robust generation of smooth stereotyped voluntary movements.

Adult↗
PubMed1993

Electromyographic responses to constant position errors imposed during voluntary elbow joint movement in human.

The role of reflexes in the control of stiffness during human elbow joint movement was investigated for a wide range of movement speeds (1.5-6 rad/s). The electromyographic (EMG) responses of the elbow joint muscles to step position errors (step amplitude 0.15 rad; rise time 100 ms) imposed at the onset of targeted flexion movements (1.0 rad amplitude) were recorded. For all speeds of movement, the step position disturbance produced large modulations of the usual triphasic EMG activity, both excitatory and inhibitory, with an onset latency of 25 ms. In the muscles stretched by the perturbation, the early EMG response (25-60 ms latency) magnitude was greater than 50% of the activity during the unperturbed movements (background activity). In all muscles the EMG responses integrated over the entire movement were greater than 25% of the background activity. The responses were relatively greater for slower movements. Perturbations assisting the movement caused a short-latency (25-60 ms) reflex response (in the antagonist muscle) that increased with movement speed and was constant as a percentage of the background EMG activity. In contrast, perturbations resisting the movement caused a reflex response (in the agonist muscle) that was of the same absolute magnitude at all movement speeds, and thus decreased with movement speed as a percentage of the background EMG activity. There was a directional asymmetry in the reflex response, which produced an asymmetry in the mechanical response during slow movements. When the step perturbation occurred in a direction assisting the flexion movement, the antagonist muscle activity increased, but the main component of this response was delayed until the normal time of onset of the antagonist burst. When the step perturbation resisted the movement the agonist muscles responded briskly at short latency (25 ms). A reflex reversal occurred in two of six subjects. A fixed reflex response occurred in the antagonist muscle, regardless of the perturbation direction. For the extension direction perturbations (resisting movement), this response represented a reflex reversal (50 ms onset latency) and it caused the torque resisting the imposed step (stiffness) to drop markedly (below zero for one subject). Reflex responses were larger when the subject was prevented from reaching the target. That is, when the perturbation remained on until after the normal time of reaching the target, the EMG activity increased, with a parallel increase in stiffness. Similarly, when the perturbations prevented the subject from reaching the target during a 1-rad voluntary cyclic movement, the EMG and stiffness increased markedly.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

2-Oxoglutarate transport: a potential mechanism for regulating glutamate and tricarboxylic acid cycle intermediates in neurons.

2-Oxoglutarate (alpha-ketoglutarate) is transported into synaptosomal and synaptoneurosomal preparations by a Na(+)-dependent, high-affinity process that exhibits complex kinetics, and is differentially modulated by glutamate, glutamine, aspartate, malate, and a soluble, heat-labile substance of high molecular weight present in rat brain extracts. Glutamate and aspartate generally inhibit 2-oxoglutarate uptake, but under certain conditions may increase uptake. Glutamine generally increases 2-oxoglutarate uptake, but under certain conditions may inhibit uptake. One interpretation of our results is that 2-oxoglutarate uptake is mediated primarily by a transporter that exhibits negative cooperativity and possesses three regulatory sites that differentially modulate substrate affinity, Vmax, and negative cooperatively. Glutamate, aspartate, malate, and 2-oxoglutarate itself may interact with a site that reduces substrate affinity; whereas glutamine, and possibly glutamate and aspartate, appear to interact with another site that increases Vmax. A putative regulatory protein appears to abolish negative cooperativity and increases substrate affinity in the absence of glutamine. Based on the evidence that glutamatergic and GABAergic neurons depend on astrocytes to supply precursors to replenish their neurotransmitter and tricarboxylic acid cycle pools, the uptake of 2-oxoglutarate, presumably into synaptic terminals, may reflect a role for this metabolite in replenishing the transmitter and tricarboxylic acid pools, and a role for the transporter as a site at which these pools are regulated.

Ammonium Sulfate↗
PubMed1993

Implicit memory: effects of network size and interconnectivity on cued recall.

Previous findings have indicated that the recall of a recently studied word is affected by how many associates it has in long-term memory (set size). The purpose of these experiments was to determine whether recall is also affected by the connectivity of these associates. Studied words were preselected to represent combinations of set size and connectivity and, in different experiments, recall was cued with extralist or intralist cues and with cues sharing few or many associates with the studied words. Effects of study time, encoding context, and levels of processing were also investigated. The results indicated that recall was more likely for words with smaller associative sets and for words with more interconnected sets of associates. These findings demonstrate that the recall of a recently presented word in the presence of a retrieval cue is affected by both the size and organization of its implicitly activated associative structure.

Association↗
PubMed1992

Time-varying stiffness of human elbow joint during cyclic voluntary movement.

The objective of this study was to determine the extent to which subjects modulate their elbow joint mechanical properties during ongoing arm movement. Small pseudo-random force disturbances were applied to the wrist with an airjet actuator while subjects executed large (1 rad) elbow joint movements. Using a lumped parameter model of the muscle, tendon and proprioceptive feedback dynamics, a time-varying system identification technique was developed to analyze the phasic changes in the elbow joint's mechanical response. The mechanical properties were found to be time-varying, and well approximated by a quasi-linear second-order model. The stiffness of the arm was found to drop during movement. The arm was always underdamped, with the damping ratio changing during movement. Inertia estimates were constant and consistent with previous measurements. Overall, the moving arm was found to be very compliant, with a peak stiffness value less than the lowest value measured during posture, and a natural frequency of less than 3 Hz. Changing the speed of movement, or the load from gravity, changed the stiffness measured, but not in strict proportion to the change in net muscle torque.

Adult↗
PubMed1992

Proenkephalin A derivatives in lacrimal gland: occurrence and regulation of lacrimal function.

The derivatives of proenkephalin A were measured in acid extracts of rat lacrimal glands by specific radioimmunoassay. Glands from adult male rats contained all four derivatives of the opiate precursor. The content in the gland of proenkephalin A-derived peptides Met5-enkephalin, Leu5-enkephalin, Met5-enkephalin Arg6-Phe7 and Met5-enkephalin Arg6-Gly7-Leu8 indicates tissue specific processing with an enhancement of the heptapeptide. The effect of enkephalins on the activity of adenylate cyclase in lacrimal membranes was measured and compared with the effect of the synthetic enkephalin analogue D-ala2-methionine enkephalinamide (DALA) that inhibits both lacrimal protein secretion and lacrimal adenylate cyclase. In the presence of the peptidase inhibitors thiorphan and bestatin, the inhibition of forskolin-stimulated adenylate cyclase activity by Met5-enk, Leu5-enk, Met5-enk Arg6-Phe7 and DALA were identical. Maximum inhibition was approximately 35% at a dose of 50 microM enkephalin. Addition of the octapeptide, Met5-enk Arg6-Gly7-Leu8 resulted in decreased adenylate cyclase activity; however, the effect was not statistically significant. Activation of delta opioid receptors by the endogenous enkephalins is indicated by the reversal of adenylate cyclase inhibition in the presence of the delta-receptor antagonist ICI 174864. The data support the physiological significance of in vitro inhibition of lacrimal secretion by DALA and indicate a possible role for endogenous enkephalins in lacrimal function.

Adenylyl Cyclases↗
PubMed1992

Pertussis-toxin insensitive enkephalin inhibition of adenylyl cyclase in lacrimal acinar cells.

The mechanism by which the inhibitory effect of d-ala2-met-enkephalinamide (DALA) on lacrimal acinar adenylyl cyclase is exerted was assessed in membrane preparations by a cAMP protein binding assay. Inhibition by the analogue was GTP-dependent with a significant enhancement of the inhibitory effect by GTP. While pretreatment of membranes with either cholera or pertussis toxin resulted in stimulation of adenylyl cyclase activity, modification of the Gi alpha subunit by pertussis-toxin catalyzed ADP-ribosylation did not effect the hormonal inhibition of adenylyl cyclase. Incubation of membranes with manganese, however, prevented the inhibitory action of DALA in addition to enhancing basal and forskolin-stimulated adenylyl cyclase activity. The results suggest that the inhibitory effect of DALA in lacrimal acinar cells is exerted via a mechanism other than pertussis-toxin sensitive coupling of the receptor to adenylyl cyclase through Gi. The mechanism may be effected through a pertussis-toxin insensitive G protein, through an interaction with Gi that is pertussis-toxin insensitive, or through an interaction with the catalytic subunit of adenylyl cyclase.

Adenylate Cyclase Toxin↗
PubMed1992

Guanine nucleotide binding proteins in the dual regulation of lacrimal function.

The purpose of this study was to identify and characterize functional G proteins that couple regulatory peptides with lacrimal secretory functions. Membranes were prepared from isolated rat exorbital lacrimal gland acini, and guanosine 5'-triphosphate (GTP)-dependence of adenylyl cyclase activity, known to be coupled with regulation of secretion, was measured. The guanine nucleotide GTP produced a biphasic response in the activity of membrane-bound adenylyl cyclase during a 10 min incubation with a maximum stimulation at 10(-5) mol/l GTP. Significant inhibition occurred at a dose of 10(-3) mol/l GTP, with cyclic adenosine monophosphate (cAMP) production reduced to less than basal levels. The effect of ADP-ribosylation of membrane proteins by the toxins produced by Vibrio cholera or Bordetella pertussis on lacrimal adenylyl cyclase was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, autoradiography, and laser densitometry. Cholera toxin treatment of membranes resulted in dose-(0.5-100 micrograms/ml) and time-dependent (0-45 min) adenosine diphosphate (ADP)-ribosylation of two membrane proteins with M(r) values of 42,000 and 45,000. Pertussis toxin treatment resulted in the specific ADP-ribosylation of a single protein that migrates with an M(r) value of 41,000. This also was dose (0.5-25 micrograms/ml) and time dependent (0-30 min). Incorporation of 32P into the 45,000 M(r) and 42,000 M(r) proteins in the presence of 50 micrograms/ml cholera toxin was guanine nucleotide dependent, with a two- to threefold increase in labeling when the membranes were incubated with 1 or 0.5 mmol/l GTP. This effect was enhanced in the presence of the nonhydrolyzable GTP analog GTP gamma S.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate Ribose↗
PubMed1991

An airjet actuator system for identification of the human arm joint mechanical properties.

A system is described for determining the mechanical properties of the human arm during unconstrained posture and movement. An airjet perturbation device is attached to the wrist with a special cuff, and provides high-frequency stochastic perturbations in potentially three orthogonal directions. The airjet operates as a fluidic flip-flop utilizing the Coanda effect, and generates binary force sequences with a steady-state thrust of 4 N, a flat frequency response to 75 Hz, usable thrust to 150 Hz, and a rise time of 1 ms, when the static pressure at the nozzle inlet is 5.5 x 10(5) Pa (80 psi). These operating characteristics are adequate to identify the arm's mechanical properties efficiently and robustly.

Air↗
PubMed1991

Structure and function of non-enzymatically dissociated lacrimal gland acini.

Lacrimal gland acini were isolated utilizing a non-enzymatic dissociation procedure. This method resulted in the rapid isolation of an enriched population of acini from rat lacrimal gland with a complete absence of interlobular and rare occurrence of intralobular duct epithelium. The isolated acini had high viability and retained good histological organization. Alkaline phosphatase activity was present in the myoepithelial cells and capillaries associated with the periphery of the acini, indicating a relatively undisturbed basal surface. Secretion of peroxidase by the isolated acini in response to cholinergic and alpha-adrenergic stimulation indicated that the cell surface receptors in this preparation were retained and were physiologically functional. Thus, we report a dissociation protocol that eliminates enzymatic digestion, but results in a relatively enriched acinar preparation that is appropriate for the assessment of cellular biochemistry and physiology of lacrimal exocrine function of the acini.

Alkaline Phosphatase↗
PubMed1990

Peptidergic stimulation and inhibition of lacrimal gland adenylate cyclase.

Vasoactive intestinal peptide (VIP) and d-ala2-methionine enkephalinamide (DALA, a long-lasting enkephalin analogue) were used to investigate the peptidergic control of lacrimal gland function. To characterize the mechanism by which VIP stimulates and DALA inhibits lacrimal peroxidase secretion, the effect of these peptides on adenylate cyclase was measured. In addition, enzyme activity was measured in the presence of forskolin alone or in combination with DALA. VIP stimulated adenylate cyclase in a time- and dose-dependent manner. Negative control of adenylate cyclase was shown with the addition of DALA to membrane preparations. The enkephalin analogue inhibited basal activity approximately 65% at the maximum dose tested. The percent inhibition of VIP-stimulated activity by DALA was similar to the inhibition of basal activity. To determine if the inhibition of stimulated activity occurred at level of the VIP receptor, the effect of DALA on the response to forskolin was measured. Forskolin-stimulated adenylate cyclase activity was significantly reduced to approximately 50% in the presence of DALA. We conclude that lacrimal gland adenylate cyclase is subject to peptidergic regulation involving both stimulatory and inhibitory receptor-mediated controls.

Adenylyl Cyclase Inhibitors↗
PubMed1984

Human plasma oxalate concentration re-examined.

In an attempt to reconcile estimates of plasma oxalate concentration by in vitro and in vivo assays, the in vitro radioenzymatic isotope dilution assay (REIDA) for plasma oxalate concentration was modified by initiating precipitation of calcium oxalate from plasma ultrafiltrates within one hour of phlebotomy. Plasma oxalate concentration form normal males was 4.0 mumol/1, consistent with reported values of 3.0 mumol/1 and 2.3 mumol/1 by enzymatic methods, and 2.8 mumol/1 by a gas chromatographic technique, and lower than 10.0 mumol/1 reported previously by chemical/enzymatic methods. This lower estimate of oxalate results, at least in part, from avoiding in vitro conversion of ultrafilterable substances to oxalate, and from the use of 'fire-cleaned' glassware. No difference in plasma oxalate was observed between age-matched, apparently healthy black and white males or with blood collected in the presence and absence of inhibitors of the conversion of glyoxalate to oxalate.

Adult↗
PubMed1984

Educating the older cancer patient: obstacles and opportunities.

Cancer is a serious health problem among the elderly, with over 50% of all cancers occurring in the 11% of the population over age 65. Little research, however, has focused on the educational needs of elderly cancer patients and little is known about the emotional and psychological impact of cancer in this population. This paper describes two surveys which provide baseline data on the knowledge, attitudes, and beliefs of older people about cancer. These findings have implications for programs directed both at the healthy elderly and at older cancer patients.

Age Factors↗