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Biomedical subjects

A M Gordon

Publications and source records attributed to A M Gordon.

At least 37 records · Page 2Linked to original sources
PubMed2000

Specificity of internal representations underlying grasping.

The present study examines anticipatory control of fingertip forces during grasping based on the center of mass (CM) of a manipulated object. Subjects lifted an object using a precision grip while the fingertip forces and the angle about the vertical axis (roll) were measured. The object's CM could be shifted to the left or right of the object's center parallel to the grip axis without changing it's visual appearance. Subjects performed 20 lifts with the CM in the center, left, and right side of the object, respectively. Subjects were instructed to lift the object while preventing it from tilting. Within three to five lifts, subjects were able to asymmetrically partition the load force development before lift-off such that it was higher in the digit opposing the CM. This anticipatory load force partitioning prevented the object from rolling sideways at lift-off. To determine whether the internal representation underlying the anticipatory control is specific to the effectors used to form it, subjects performed five lifts with the right hand with the CM on one side. Following these lifts, they rotated the object 180 degrees around the vertical axis and performed one lift with the same hand or they translated the object to the left side of the body (with or without rotating it) and performed one lift with the left hand. Despite subjects' explicit knowledge of the new weight distribution, they were unable to appropriately scale the load forces at each digit, resulting in a subsequent large roll of the object. The findings suggest that within a few lifts subjects achieve a stable internal representation which accounts for the object's CM and is used to scale the fingertip forces in advance. They also suggest that this representation, which is used for anticipatory control of fingertip forces, is specific to the effectors used to form it. We propose that multiple internal representations may be used during the anticipatory control of grasping.

Adult↗
PubMed2000

Regulation of contraction in striated muscle.

Ca(2+) regulation of contraction in vertebrate striated muscle is exerted primarily through effects on the thin filament, which regulate strong cross-bridge binding to actin. Structural and biochemical studies suggest that the position of tropomyosin (Tm) and troponin (Tn) on the thin filament determines the interaction of myosin with the binding sites on actin. These binding sites can be characterized as blocked (unable to bind to cross bridges), closed (able to weakly bind cross bridges), or open (able to bind cross bridges so that they subsequently isomerize to become strongly bound and release ATP hydrolysis products). Flexibility of the Tm may allow variability in actin (A) affinity for myosin along the thin filament other than through a single 7 actin:1 tropomyosin:1 troponin (A(7)TmTn) regulatory unit. Tm position on the actin filament is regulated by the occupancy of NH-terminal Ca(2+) binding sites on TnC, conformational changes resulting from Ca(2+) binding, and changes in the interactions among Tn, Tm, and actin and as well as by strong S1 binding to actin. Ca(2+) binding to TnC enhances TnC-TnI interaction, weakens TnI attachment to its binding sites on 1-2 actins of the regulatory unit, increases Tm movement over the actin surface, and exposes myosin-binding sites on actin previously blocked by Tm. Adjacent Tm are coupled in their overlap regions where Tm movement is also controlled by interactions with TnT. TnT also interacts with TnC-TnI in a Ca(2+)-dependent manner. All these interactions may vary with the different protein isoforms. The movement of Tm over the actin surface increases the "open" probability of myosin binding sites on actins so that some are in the open configuration available for myosin binding and cross-bridge isomerization to strong binding, force-producing states. In skeletal muscle, strong binding of cycling cross bridges promotes additional Tm movement. This movement effectively stabilizes Tm in the open position and allows cooperative activation of additional actins in that and possibly neighboring A(7)TmTn regulatory units. The structural and biochemical findings support the physiological observations of steady-state and transient mechanical behavior. Physiological studies suggest the following. 1) Ca(2+) binding to Tn/Tm exposes sites on actin to which myosin can bind. 2) Ca(2+) regulates the strong binding of M.ADP.P(i) to actin, which precedes the production of force (and/or shortening) and release of hydrolysis products. 3) The initial rate of force development depends mostly on the extent of Ca(2+) activation of the thin filament and myosin kinetic properties but depends little on the initial force level. 4) A small number of strongly attached cross bridges within an A(7)TmTn regulatory unit can activate the actins in one unit and perhaps those in neighboring units. This results in additional myosin binding and isomerization to strongly bound states and force production. 5) The rates of the product release steps per se (as indicated by the unloaded shortening velocity) early in shortening are largely independent of the extent of thin filament activation ([Ca(2+)]) beyond a given baseline level. However, with a greater extent of shortening, the rates depend on the activation level. 6) The cooperativity between neighboring regulatory units contributes to the activation by strong cross bridges of steady-state force but does not affect the rate of force development. 7) Strongly attached, cycling cross bridges can delay relaxation in skeletal muscle in a cooperative manner. 8) Strongly attached and cycling cross bridges can enhance Ca(2+) binding to cardiac TnC, but influence skeletal TnC to a lesser extent. 9) Different Tn subunit isoforms can modulate the cross-bridge detachment rate as shown by studies with mutant regulatory proteins in myotubes and in in vitro motility assays. (ABSTRACT TRUNCATED)

Animals↗
PubMed2000

Gasless versus conventional laparoscopy.

The objective of our study was to evaluate the technical advantages of using the Laparolift device and examine the clinical benefits of gynecologic laparoscopy without pneumoperitoneum. A randomized single-blinded clinical trial was performed employing a sample of 30 consecutive patients undergoing laparoscopic gynecologic surgery with a primary outcome measure of visualization. Visualization was found to be inferior in gasless patients. The conclusion was that conventional laparoscopy employing pneumoperitoneum provides surgical exposure superior to that offered by the Laparolift device.

Adult↗
PubMed2000

Carisoprodol, meprobamate, and driving impairment.

This paper considers the pharmacology of the centrally acting muscle relaxant carisoprodol, and its metabolite meprobamate, which is also administered as an anxiolytic in its own right. Literature implicating these drugs in impaired driving is also reviewed. A series of 104 incidents in which these drugs were detected in the blood of drivers involved in accidents or arrested for impaired driving was considered, with respect to the analytical toxicology results, patterns of drug use in these subjects, the driving behaviors exhibited, and the symptoms observed in the drivers. Symptomatology and driving impairment were consistent with other CNS depressants, most notably alcohol. Reported driving behaviors included erratic lane travel, weaving, driving slowly, swerving, stopping in traffic, and hitting parked cars and other stationary objects. Drivers on contact by the police displayed poor balance and coordination, horizontal gaze nystagmus, bloodshot eyes, unsteadiness, slurred speech, slow responses, tendency to doze off or fall asleep, difficulty standing, walking or exiting their vehicles, and disorientation. Many of these cases had alcohol or other centrally acting drugs present also, making difficult the attribution of the documented impairment specifically to carisoprodol and meprobamate. In 21 cases, however, no other drugs were detected, and similar symptoms were present. Impairment appeared to be possible at any concentration of these two drugs; however, the most severe driving impairment and most overt symptoms of intoxication were noted when the combined concentration exceeded 10 mg/L, a level still within the normal therapeutic range.

Accidents, Traffic↗
PubMed1999

Ca2+ and cross-bridge-induced changes in troponin C in skinned skeletal muscle fibers: effects of force inhibition.

Changes in skeletal troponin C (sTnC) structure during thin filament activation by Ca2+ and strongly bound cross-bridge states were monitored by measuring the linear dichroism of the 5' isomer of iodoacetamidotetramethylrhodamine (5'IATR), attached to Cys98 (sTnC-5'ATR), in sTnC-5'ATR reconstituted single skinned fibers from rabbit psoas muscle. To isolate the effects of Ca2+ and cross-bridge binding on sTnC structure, maximum Ca2+-activated force was inhibited with 0.5 mM AlF4- or with 30 mM 2,3 butanedione-monoxime (BDM) during measurements of the Ca2+ dependence of force and dichroism. Dichroism was 0.08 +/- 0.01 (+/- SEM, n = 9) in relaxing solution (pCa 9.2) and decreased to 0.004 +/- 0.002 (+/- SEM, n = 9) at pCa 4.0. Force and dichroism had similar Ca2+ sensitivities. Force inhibition with BDM caused no change in the amplitude and Ca2+ sensitivity of dichroism. Similarly, inhibition of force at pCa 4.0 with 0.5 mM AlF4- decreased force to 0.04 +/- 0.01 of maximum (+/- SEM, n = 3), and dichroism was 0.04 +/- 0.03 (+/- SEM, n = 3) of the value at pCa 9.2 and unchanged relative to the corresponding normalized value at pCa 4.0 (0.11 +/- 0.05, +/- SEM; n = 3). Inhibition of force with AlF4- also had no effect when sTnC structure was monitored by labeling with either 5-dimethylamino-1-napthalenylsulfonylaziridine (DANZ) or 4-(N-(iodoacetoxy)ethyl-N-methyl)amino-7-nitrobenz-2-oxa-1,3-diazole (NBD). Increasing sarcomere length from 2.5 to 3.6 microm caused force (pCa 4.0) to decrease, but had no effect on dichroism. In contrast, rigor cross-bridge attachment caused dichroism at pCa 9.2 to decrease to 0.56 +/- 0.03 (+/- SEM, n = 5) of the value at pCa 9. 2, and force was 0.51 +/- 0.04 (+/- SEM, n = 6) of pCa 4.0 control. At pCa 4.0 in rigor, dichroism decreased further to 0.19 +/- 0.03 (+/- SEM, n = 6), slightly above the pCa 4.0 control level; force was 0.66 +/- 0.04 of pCa 4.0 control. These results indicate that cross-bridge binding in the rigor state alters sTnC structure, whereas cycling cross-bridges have little influence at either submaximum or maximum activating [Ca2+].

Actomyosin↗
PubMed1999

Fingertip forces during object manipulation in children with hemiplegic cerebral palsy. I: anticipatory scaling.

Previous studies of grasping and object manipulation in children with cerebral palsy (CP) have suggested a dichotomy in the ability to use anticipatory control (planning) of the fingertip force output, depending on the type of sensory information (tactile or proprioceptive) on which it is based. The present study further explores this issue by testing the ability of 15 children with hemiplegic CP aged between 8 and 14 years to scale the fingertip force output in advance during the lifting of small objects whose weight and surface texture are varied. The results indicate that children with hemiplegia can use anticipatory control based on both the weight and texture of the object, but require a greater number of trials than age-matched children without CP (control children) before they can do so. We suggest that the initial lack of anticipatory control results from an indistinct internal representation of the object's physical properties due to disturbed sensory mechanisms, which may have direct implications for therapeutic intervention.

Adolescent↗
PubMed1999

Fingertip forces during object manipulation in children with hemiplegic cerebral palsy. II: bilateral coordination.

The present study examines the coordination of fingertip forces during object manipulation in both the involved and non-involved hand of 14 children with hemiplegic cerebral palsy (CP) aged between 8 and 14 years. While no impairment could be observed in the non-involved hand, subtle deficits in the sequencing of the grip-lift movement were observed in all children tested in this hand. However, they were able to scale the fingertip force output of the non-involved hand in advance (use anticipatory control) based on the object's weight. In the second experiment in this paper, we tested whether the anticipatory control can be generalized across hands. The results indicate that sensory information from the non-involved hand can be used for anticipatory scaling of isometric force increase during subsequent lifts with the contralateral involved hand. These findings suggest that the initial lack of anticipatory control usually observed in the involved hand of children with hemiplegic CP is likely to be based on disturbed sensory input.

Adolescent↗
PubMed1999

Relation between clinical measures and fine manipulative control in children with hemiplegic cerebral palsy.

The present investigation examines the relation between various clinical measures and the performance of a functional precision grip-lift task. Fifteen children with hemiplegic cerebral palsy (CP), aged 8 to 14 years, and 15 age-matched control children grasped and lifted an object whose surface texture was varied while their fingertip forces were recorded. The force coordination was compared with tactile sensibility, grip strength, manual dexterity, and spasticity using correlational and regression analyses. The findings highlight the importance of tactile sensibility in this task. However, the manner in which sensibility was related varied for the sensory adaptation of fingertip forces, the anticipatory scaling of the force increase, and the smooth transitions between the temporal phases comprising the grip-lift task. The findings also indicate that spasticity affects some measures of the task, but not others, suggesting that the relation between spasticity and motor performance may not be absolute. The results further suggest that the impairments in grasping in children with hemiplegic CP are largely but not exclusively due to disturbed sensory mechanisms which may have direct implications for therapeutic intervention.

Adolescent↗
PubMed1998

Task-dependent deficits during object release in Parkinson's disease.

The present study examined fingertip forces during the replacement and release of an instrumented object on a table in eight subjects with Parkinson's disease (PD) both off and on medication and eight age-matched control subjects. Subjects performed the task at (1) their preferred speeds and (2) as fast as possible. During performance of the task at preferred speed, the duration of object replacement, the rate, and duration of force decrease following table contact for PD subjects were similar to that observed in the control subjects and were unaffected by medication. In contrast, the rates were significantly lower and durations longer in the PD subjects when the task was performed as fast as possible irrespective of medication. A similar result was obtained when subjects were asked to release their pinch force from predefined force levels while the object was fixed to the table surface. These results emphasize the importance of considering task requirements in order to delineate the specific task parameters associated with the movement impairments in Parkinson's disease.

Aged↗
PubMed1998

Skeletal muscle regulatory proteins enhance F-actin in vitro motility.

Using an in vitro motility assay, we have investigated the effects of rabbit skeletal muscle regulatory proteins, troponin and tropomyosin, on the gliding of F-actin filaments or F-actin filaments containing these regulatory proteins. We demonstrate that Ca2+ does not affect the motility of F-actin gliding on HMM, but does in the presence of skeletal muscle tropomyosin and troponin. We conclude that Ca2+ affects motility through troponin because, like F-actin, F-actin-Tm filaments show no Ca(2+)-dependence to their gliding speeds. Furthermore, there is a large enhancement of the gliding speed (about 75%) in the presence of skeletal muscle tropomyosin, troponin + saturating Ca2+ over that seen with F-actin filaments. This enhancement is not due to the action of tropomyosin alone as skeletal muscle tropomyosin without troponin enhances the speed little (about 5%) over that of F-actin. Thus troponin confers Ca2+ sensitivity to the motility and, additionally, potentiates motility greatly along with tropomyosin in the presence of saturating Ca2+. When [HMM] is varied, the decline in speed of F-actin seen at low HMM density is changed little by tropomyosin in the F-actin-Tm filaments. These data show that the skeletal regulatory proteins interact with F-actin to enhance the interaction with HMM particularly in the presence of troponin and saturating Ca2+ and enhance the gliding speed in the in vitro motility assay as they potentiate the ATPase activity in the isolated proteins. This enhancement of speed in the motility assay cannot be ascribed to tropomyosin alone.

Actins↗
PubMed1998

Functional magnetic resonance imaging of motor, sensory, and posterior parietal cortical areas during performance of sequential typing movements.

We investigated the activation of sensory and motor areas involved in the production of typing movements using functional magnetic resonance imaging (fMRI). Eleven experienced typists performed tasks, in which the spatial and temporal requirements as well as the number of digits involved were varied. These included a simple uni-digit repetitive task, a uni-digit sequential task, a dual-digit sequential task, a multi-digit sequential task, and typing text from memory. We found that the production of simple repetitive keypresses with the index finger primarily involved the activation of contralateral primary motor cortex (M1), although a small activation of the supplementary motor area (SMA) and other regions was sometimes observed as well. The sequencing of keypresses involved bilateral M1 and a stronger activation of the SMA and to a lesser extent the premotor area, cingulate gyrus, caudate, and lentiform nuclei. However, the activation of these areas did not exclusively depend on the complexity of the movements, since they were often activated during more simple movements, such as alternating two keypresses repeatedly. Somatosensory and parietal regions were also found to be activated during typing sequences. The activation of parietal areas did not exclusively depend on the spatial requirements of the task, since similar activation was observed during movements within intra-personal space (finger-thumb opposition) and may instead be related to the temporal requirements of the task. Our findings suggest that the assembly of well-learned, goal-directed finger movement sequences involves the SMA and other secondary motor areas as well as somatosensory and parietal areas.

Adult↗
PubMed1997

Object release in patients with Parkinson's disease.

Fingerstrip forces were examined in eight subjects with Parkinson's disease (PD) both OFF and ON medication and eight age-matched control subjects during the replacement and release of an instrumented object on a table. While the employed grip forces were similar in the PD subjects and controls, four PD subjects had greater than 25% increases in their grip forces ON compared to OFF medication. The PD subjects also had a greater reduction in their grip forces prior to table contact. However, the rate and duration of isometric force decrease following table contact were similar to the controls', and the forces were scaled according to the object's weight. This suggests that most aspects of object release are not greatly disrupted, and emphasizes the specificity of impairment in PD.

Adult↗
PubMed1997

A kinetic model for the binding of Ca2+ to the regulatory site of troponin from cardiac muscle.

The kinetics of the binding of Ca2+ to the single regulatory site of cardiac muscle troponin was investigated by using troponin reconstituted from the three subunits, using a monocysteine mutant of troponin C (cTnC) labeled with the fluorescent probe 2-[(4'-(iodoacetamido)anilino]naphthalene-6-sulfonic acid (IAANS) at Cys-35. The kinetic tracings of binding experiments for troponin determined at free [Ca2+] > 1 microM were resolved into two phases. The rate of the fast phase increased with increasing [Ca2+], reaching a maximum of about 35 s-1 at 4 degrees C, and the rate of the slow phase was approximately 5 s-1 and did not depend on [Ca2+]. Dissociation of bound Ca2+ occurred in two phases, with rates of about 23 and 4 s-1. The binding and dissociation results obtained with the binary complex formed between cardiac troponin I and the IAANS-labeled cTnC mutant were very similar to those obtained from reconstituted troponin. The kinetic data are consistent with a three-step sequential model similar to the previously reported mechanism for the binding of Ca2+ to a cTnC mutant labeled with the same probe at Cys-84 (Dong et al. (1996) J. Biol. Chem. 271, 688-694). In this model, the initial binding in the bimolecular step to form the Ca2+-troponin complex is assumed to be a rapid equilibrium, followed by two sequential first-order transitions. The apparent bimolecular rate constant is 5.1 x 10(7) M-1 s-1, a factor of 3 smaller than that for cTnC. The rates of the first-order transitions are an order of magnitude smaller for troponin than for cTnC. These kinetic differences form a basis for the enhanced Ca2+ affinity of troponin relative to the Ca2+ affinity of isolated cTnC. Phosphorylation of the monocysteine mutant of troponin I by protein kinase A resulted in a 3-fold decrease in the bimolecular rate constant but a 2-fold increase in the two observed Ca2+ dissociation rates. These changes in the kinetic parameters are responsible for a 5-fold reduction in Ca2+ affinity of phosphorylated troponin for the specific site.

Animals↗
PubMed1997

Anticipatory control of manipulative forces in Parkinson's disease.

In a previous study we found that subjects with Parkinson's disease (PD) had an impaired capability to initiate and sequence successive movement phases during lifts of small objects using the precision grip, and that they had regular oscillations in the force rates. The present study examined whether these subjects could use anticipatory control, in which the force output is scaled prior to liftoff, based on the object's physical properties. Subjects lifted an instrumented test object between the tips of the thumb and index finger while the employed grip force, load force (vertical lifting force), and corresponding time derivatives were recorded. In the first experiment, the object's weight was varied to assess its influence on the isometric force output. Subjects with PD scaled the isometric force increase according to the object's weight. In another experiment, the weight changed in proportion to the volume to determine whether subjects could make associative transformations between visual size information and the weight of the object. Subjects with PD still scaled the forces toward the expected weight, proportional to the volume of the object. Finally, programmed adjustments in force to sudden self-induced load changes were examined while subjects dropped a disk with one hand into a plate attached to the bottom of the grip instrument, held with the other hand. Subjects with PD had preparatory increases in the grip force prior to the disk contact, which matched the change in load, though may have been more dependent on visual feedback. We conclude that subjects with PD are capable of using anticipatory control to parameterize the isometric force output during a familiar lifting task.

Conditioning, Psychological↗
PubMed1997

Coordination of manipulative forces in Parkinson's disease.

The coordination of manipulative forces was examined in 10 subjects with Parkinson's disease (PD) both OFF and ON medication while they grasped and lifted a small object using the precision grip. The development of grip (squeeze) force and load (vertical lifting) force was recorded and compared to a group of age-matched control subjects. Subjects with PD often exhibited a prolonged delay between the first digit contact with the object and initiation of the lifting drive. These subjects also exhibited stepwise increases in force, with regular oscillations in the force rates. However, once the vertical drive began, the main increase in grip and load force generally was in parallel and most other temporal aspects of the force coordination were similar to those of the control subjects. The extent to which the movement initiation was delayed was related to the stage of the disease, and most subjects improved ON medication. When the object was held in the air, subjects with PD used a grip force level which was similar to that of the control subjects, and all subjects adjusted their grip force according to the surface texture. Furthermore, they exhibited proper reflexive corrections to sudden changes in load (object perturbations), suggesting intact sensorimotor integration. We conclude that the most obvious impairments in the coordination of this task were delayed initiation of the grip-lift sequence and tremor-like oscillations superimposed on otherwise normal force.

Adaptation, Physiological↗
PubMed1997

Disparate fluorescence properties of 2-[4'-(iodoacetamido)anilino]-naphthalene-6-sulfonic acid attached to Cys-84 and Cys-35 of troponin C in cardiac muscle troponin.

Two monocysteine mutants of cardiac muscle troponin C, cTnC(C35S) and cTnC(C84S), were genetically generated and labeled with the fluorescent probe 2-[4'-(iodoacetamido)anilino]naphthalene-6-sulfonic acid (IAANS) at Cys-84 and Cys-35, respectively. Cys-84 is located on helix D in the regulatory N-domain, and Cys-35 is at the -y position of the inactive 12-residue loop of site I. These labeled mutants were studied by a variety of steady-state and time-resolved fluorescence methods. In the absence of divalent cation, the fluorescence of the attached IAANS indicated an exposed environment at Cys-35 and a relatively less-exposed environment at Cys-84. The binding of Ca2+ to the single regulatory site elicited a large enhancement of the emission of IAANS attached to Cys-84, but only marginal fluorescence changes of the probe at Cys-35. Upon reconstitution of the labeled cTnC mutants with troponin I and troponin T to form the three-subunit troponin, the fluorescence of IAANS-Cys-84 in apo-troponin was spectrally similar to that observed with the Ca(2+)-loaded uncomplexed cTnC mutant. Only very moderate changes in the fluorescence of IAANS-Cys-84 were observed when the regulatory site in reconstituted troponin was saturated. The exposed Cys-35 environment of the uncomplexed cTnC mutant became considerably less exposed and less polar when the mutant was incorporated into apo-troponin. In contrast to the Cys-84 site, saturation of the regulatory site II by Ca2+ in reconstituted troponin resulted in a reversal of the environment of the Cys-35 site toward a more exposed and more polar environment. These results indicated involvement of the inactive loop I in the Ca2+ trigger mechanism in cardiac muscle. The fluorescence of IAANS at both Cys-84 and Cys-35 was sensitive to phosphorylation of cTnl in reconstituted troponin, and the sensitivity was observed with both apo-troponin and Ca(2+)-loaded troponin.

Animals↗
PubMed1997

Calcium regulation of skeletal muscle thin filament motility in vitro.

Using an in vitro motility assay, we have investigated Ca2+ regulation of individual, regulated thin filaments reconstituted from rabbit fast skeletal actin, troponin, and tropomyosin. Rhodamine-phalloidin labeling was used to visualize the filaments by epifluorescence, and assays were conducted at 30 degrees C and at ionic strengths near the physiological range. Regulated thin filaments exhibited well-regulated behavior when tropomyosin and troponin were added to the motility solutions because there was no directed motion in the absence of Ca2+. Unlike F-actin, the speed increased in a graded manner with increasing [Ca2+], whereas the number of regulated thin filaments moving was more steeply regulated. With increased ionic strength, Ca2+ sensitivity of both the number of filaments moving and their speed was shifted toward higher [Ca2+] and was steepest at the highest ionic strength studied (0.14 M gamma/2). Methylcellulose concentration (0.4% versus 0.7%) had no effect on the Ca2+ dependence of speed or number of filaments moving. These conclusions hold for five different methods used to analyze the data, indicating that the conclusions are robust. The force-pCa relationship (pCa = -log10[Ca2+]) for rabbit psoas skinned fibers taken under similar conditions of temperature and solution composition (0.14 M gamma/2) paralleled the speed-pCa relationship for the regulated filaments in the in vitro motility assay. Comparison of motility results with the force-pCa relationship in fibers suggests that relatively few cross-bridges are needed to make filaments move, but many have to be cycling to make the regulated filament move at maximum speed.

Actins↗