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Biomedical subjects

D G Lloyd

Publications and source records attributed to D G Lloyd.

At least 19 recordsLinked to original sources
PubMed2004

A novel role for non-muscle gamma-actin in skeletal muscle sarcomere assembly.

Existing models describing sarcomere assembly have arisen primarily from studies using cardiac muscle. In contrast to cardiac muscle, skeletal muscle differentiation is characterised by dramatic changes in protein expression, from non-muscle to muscle-specific isoforms before organisation of the sarcomeres. Consequently, little is understood of the potential influence of non-muscle cytoskeletal proteins on skeletal sarcomere assembly. To address this issue, transfectant (gamma33-B1) and control mouse C2 myoblasts were differentiated to form myotubes, and various stages of skeletal sarcomere assembly were studied. Organisation of non-muscle gamma-actin and co-localisation with sarcomeric alpha-actinin, an early marker of sarcomere assembly and a major component of Z lines, was noted. gamma-Actin was also identified in young myotubes with developing sarcomeric myofibrils in regenerating adult mouse muscle. Localisation of gamma-actin in a different area of the myotube to the muscle-specific sarcomeric alpha-actin also indicated a distinct role for gamma-actin. The effects of aberrant gamma-actin expression in other myoblast lines, further suggested a sequestering role for gamma-actin. These observations make the novel suggestion that non-muscle gamma-actin plays a role in skeletal sarcomere assembly both in vitro and in vivo. Consequently, a modified model is proposed which describes the role of gamma-actin in skeletal sarcomere assembly.

Actinin↗
PubMed2004

Pre-surgery knee joint loading patterns during walking predict the presence and severity of anterior knee pain after total knee arthroplasty.

This study tested if abnormal sagittal knee joint loading patterns after total knee arthroplasty (TKA) were present pre-surgery, and if patterns with higher external knee flexion moments were related to the presence and severity of post-surgery anterior knee pain. Gait analysis and clinical evaluation were performed on 34 patients (41 arthroplasties) both before and 12-18 months after TKA, and on 20 healthy age-matched controls at matched velocities. The majority of knees with abnormal flexor or extensor sagittal knee joint loading patterns post-surgery (18 of 26, 69%) also displayed these patterns pre-surgery. Knee joint loading in the early mid-stance phase of walking prior to surgery was identified by stepwise regression as a significant predictor of the presence (exp(beta)=2.9, CI: 1.2-6.8, p=0.017) and severity of post-surgery anterior knee pain (R2=0.314, p=0.019). Therefore, the frequency and severity of anterior knee pain after TKA can be partially explained by retained pre-surgery gait patterns that had higher external flexion moments in the early mid-stance phase, which place higher forces on the patellofemoral joint.

Arthroplasty, Replacement, Knee↗
PubMed2003

Advances in the science of estrogen receptor modulation.

This work details recent advances in the science of estrogen receptor (ER) modulation, with emphasis on the discovery of novel ligands for the ER ligand binding domain (LBD). A detailed examination of structural studies of the ERs is presented with analysis of the impact of such works on contemporary ligand design and the molecular pharmacology of the ER. The various classes of ER modulators are discussed on the basis of stuctural similarities including selective estrogen receptor modulators (SERMs) and 'pure' non-steroidal antiestrogens. Additionally we review the emergence of a novel selective class of modulator which we have termed the selective estrogen receptor subtype modulators (SERSMs) and, in a departure from LBD strategies we examine the discovery of novel peptide inhibitors of the ER which inhibit transcriptional activiation of agonist liganded receptor through interaction with coactivator recruitment proteins, and offer unique insight to the mechanism of action of all classes of ER modulators. Through examination of patent and classical literature we present a thorough and informative cross-section of the contemporary state of the art in this exciting field of pharmaceutical research.

Animals↗
PubMed2002

Lack of correlation between different measurements of proprioception in the knee.

Current methods of measurement of proprioceptive function depend on the ability to detect passive movement (kinaesthesia) or the awareness of joint position (joint position sense, JPS). However, reports of proprioceptive function in healthy and pathological joints are quite variable, which may be due to the different methods used. We have compared the validity of several frequently used methods to quantify proprioception. Thirty healthy subjects aged between 24 and 72 years underwent five established tests of proprioception. Two tests were used for the measurement of kinaesthesia (KT1 and KT2). Three tests were used for the measurement of JPS, a passive reproduction test (JPS1), a relative reproduction test (JPS2) and a visual estimation test (JPS3). There was no correlation between the tests for kinaesthesia and JPS or between the different JPS tests. There was, however, a significant correlation between the tests for kinaesthesia (r = 0.86). We conclude therefore that a subject with a given result in one test will not automatically obtain a similar result in another test for proprioception. Since they describe different functional proprioceptive attributes, proprioceptive ability cannot be inferred from independent tests of either kinaesthesia or JPS.

Adult↗
PubMed2001

Flexible estrogen receptor modulators: design, synthesis, and antagonistic effects in human MCF-7 breast cancer cells.

Although many series of estrogen receptor antagonists continue to be produced, the majority are direct structural analogues of existing modulators. To examine the tolerance of the estrogen receptor toward flexible ligands, a series of novel flexible estrogen receptor antagonists were prepared and their antiproliferative effects on human MCF-7 breast tumor cells investigated. Each of these compounds deviated from the traditional triphenylethylene backbone associated with common tamoxifen analogues through the introduction of a flexible methylene (benzylic) spacing group between one of the aryl rings and the ethylene group and through variations in the basic side chain moiety. The compounds prepared, when assayed in conjunction with a tamoxifen standard, demonstrated high potency in antiproliferative assays against an MCF-7 human breast cancer cell line with low cytotoxicity and high binding affinity. A computational study was undertaken to investigate the compounds' potential interactions with specific residues within the human estrogen receptor alpha ligand-binding domain (ER-LBD), predicting these compounds bind in an antiestrogenic fashion within the ER-LBD and interact with those important residues previously identified in the structures of ER-LBD agonist/antagonist cocrystals. These compounds further illustrate the eclectic nature of the estrogen receptor in terms of ligand flexibility tolerance.

Animals↗
PubMed2001

Strategies of muscular support of varus and valgus isometric loads at the human knee.

In this paper we studied how subjects activate their muscles in response to static varus and valgus loads at the knee. The muscles' contributions to the external moments were estimated using an EMG driven biomechanical model of the knee. The individual muscle activation and loading patterns were examined to identify the strategies that the nervous system uses to support varus and valgus knee moments. It was found that the (1) co-contraction of the hamstrings and quadriceps, and (2) activation of the gracilis and tensor fascia lata increased with the increasing magnitude of the varus and valgus moments. These 2 activation patterns provided positive support of valgus and varus loads at the knee The sartorius appears to be activated to provide positive support of valgus loads at the knee, whereas during varus moments this muscle increases the varus load on the knee, i.e. provides negative support. Generally, the hamstrings and quadriceps co-contraction contributed to most of the muscular support of the varus and valgus moments. In addition, co-contraction supported 11-14% of the external moment in pure varus and pure valgus respectively. It appears that there are activation strategies with the specific purpose to support varus and valgus moments, albeit small, which suggest dual goals of the neuromotor system during the support of varus and valgus moments.

Adult↗
PubMed2001

External loading of the knee joint during running and cutting maneuvers.

PURPOSE: To investigate the external loads applied to the knee joint during dynamic cutting tasks and assess the potential for ligament loading. METHODS: A 50-Hz VICON motion analysis system was used to determine the lower limb kinematics of 11 healthy male subjects during running, sidestepping, and crossover cut. A kinematic model was used in conjunction with force place data to calculate the three-dimensional loads at the knee joint during stance phase. RESULTS: External flexion/extension loads at the knee joint were similar across tasks; however, the varus/valgus and internal/external rotation moments applied to the knee during sidestepping and crossover cutting were considerably larger than those measured during normal running (P < 0.05). Sidestepping tasks elicited combined loads of flexion, valgus, and internal rotation, whereas crossover cutting tasks elicited combined loads of flexion, varus, and external rotation. CONCLUSION: Compared with running, the potential for increased ligament loading during sidestepping and crossover cutting maneuvers is a result of the large increase in varus/valgus and internal/external rotation moments rather than any change in the external flexion moment. The combined external moments applied to the knee joint during stance phase of the cutting tasks are believed to place the ACL and collateral ligaments at risk of injury, particularly at knee flexion angles between 0 degrees and 40 degrees, if appropriate muscle activation strategies are not used to counter these moments.

Adolescent↗
PubMed2001

Anticipatory effects on knee joint loading during running and cutting maneuvers.

PURPOSE: To determine how unanticipated performance of cutting maneuvers in sport affects the external loads applied to the knee joint and the potential risk for ligament injury. METHODS: A 50-Hz VICON motion analysis system was used to determine the lower limb kinematics of 11 healthy male subjects during running and cutting tasks performed under preplanned (PP) and unanticipated (UN) conditions. Subjects performed the UN tasks in response to a light stimulus on a target board. A kinematic model was then used in conjunction with force place data to calculate the three-dimensional loads at the knee joint. RESULTS: External flexion/extension moments at the knee joint were similar between PP and UN conditions; however, the varus/valgus and internal/external rotation moments during the UN cutting tasks were up to twice the magnitude of the moments measured during the PP condition. CONCLUSION: Cutting maneuvers performed without adequate planning may increase the risk of noncontact knee ligament injury due to the increased external varus/valgus and internal/external rotation moments applied to the knee. These results are probably due to the small amount of time to make appropriate postural adjustments before performance of the task, such as the position of the foot on the ground relative to the body center of mass. Subsequently, training for the game situation should involve drills that familiarize players with making unanticipated changes of direction. Practice sessions should also incorporate plyometrics and should focus on better interpretation of visual cues to increase the time available to preplan a movement.

Adolescent↗
PubMed2001

Rationale for training programs to reduce anterior cruciate ligament injuries in Australian football.

This commentary presents the rationale for training programs to reduce the incidence of knee injuries. Our studies have revealed that the external knee loading patterns during sidestep cutting are what put the anterior cruciate ligament at greatest risk for injury. Compared to running, sidestep cutting involves similar levels of knee flexion loading but increased loading in varus-valgus and internal rotation of the knee, and these external loads need to be stabilized or supported by the internal structures of the knee. People use a generalized hamstrings and quadriceps co-contraction to stabilize these external loads, thereby reducing ligament loading. It is proposed that perturbation of the joint receptors reinforces the use of selective hamstrings and quadriceps co-contraction patterns superimposed on a generalized co-contraction pattern. This is not by immediate ligamento-muscular protective reflex, which is too slow to provide any adequate support, but by enhanced proprioceptive information that may be used in learning. In contrast, the immediate effect of muscle stretch reflexes would be to reduce co-contraction, a possibly negative outcome for joint stabilization. The effects of different types of training on the control of joint stability are examined. It is proposed that resistance training may not be appropriate because it enhances muscle stretch reflexes, which may reduce co-contraction, and produces no reductions in voluntary activation times and time to peak torque. However, stability and balance training is thought to suppress muscle stretch reflexes and, in turn, enhance co-contraction. Also, stability and balance training that stimulates the knee joint ligament and capsular receptors may reinforce co-contraction patterns to facilitate greater improvements in joint stabilization. Stability and balance training and plyometric training produce reductions in voluntary activation times and times to peak torque, which may decrease muscle response times so players are more able to perform rapid and unexpected sports maneuvers. Training programs that emphasize these neuromuscular mechanisms may enhance protection of the anterior cruciate ligament and reduce the incidence of injury.

Anterior Cruciate Ligament↗
PubMed2001

Ethyl side-chain modifications in novel flexible antiestrogens--design, synthesis and biological efficacy in assay against the MCF-7 breast tumor cell line.

To examine the efficacy of ethyl side-chain modifications in a family of flexible non-steroidal modulators of the estrogen receptor, a series of novel compounds was prepared and their antiproliferative effects on human MCF-7 breast tumor cells evaluated. These flexible antiestrogens consisted of members wherein the ethyl portion of the parent compound, a flexible analogue of tamoxifen, had been modified so as to introduce halogens or a nitro group, or to extend the side-chain length from ethyl to propyl or butyl. The compounds demonstrated potency at low micromolar concentrations in antiproliferative assays against an MCF-7 human breast cancer cell line with low associated cytotoxicity. Tested compounds exhibited nanomolar binding affinity (Ki) for the estrogen receptor (ER) as determined through displacement of radiolabelled estradiol. Semiempirical calculations predict an inherent lower oxidative potential at the allylic position, similar to that calculated for the established analogue toremifene, indicating a lesser propensity of such compounds towards metabolic oxidative carbocation generation and consequent DNA adduct formation. Computational studies predict these compounds to bind in a typical estrogen antagonist mode within the ER-ligand binding domain (LBD). Ethyl side-chain modification in this compound class is well tolerated within the ER and is not detrimental to compound efficacy, with additional potential anti-carcinogenic properties imbued to the molecule.

Adult↗
PubMed2000

Net forces during tethered simulation of underwater streamlined gliding and kicking techniques of the freestyle turn.

We assessed the net forces created when towing swimmers while gliding and kicking underwater to establish an appropriate speed for initiating underwater kicking, and the most effective gliding position and kicking technique to be applied after a turn. Sixteen experienced male swimmers of similar body shape were towed by a motorized winch and pulley system. A load cell measured net force (propulsive force - drag force) at speeds of 1.6, 1.9, 2.2, 2.5 and 3.1 m x s(-1). At each speed, the swimmers performed a prone streamline glide, a lateral streamline glide, a prone freestyle kick, a prone dolphin kick and a lateral dolphin kick. A two-way repeated-measures analysis of variance revealed significant differences between the gliding and kicking conditions at different speeds. The results demonstrated an optimal range of speeds (1.9 to 2.2 m x s(-1)) at which to begin underwater kicking to prevent energy loss from excessive active drag. No significant differences were found between the prone and lateral streamline glide positions or between the three underwater kicking techniques. Therefore, there appears to be no significant advantage in using one streamlining technique over another or in using one kicking style over another.

Adult↗
PubMed2000

An upper limb kinematic model for the examination of cricket bowling: a case study of Mutiah Muralitharan.

We show how biomechanics can be used to accurately assess spin-bowling techniques (offspin, legspin and topspin) in cricket, under controlled conditions, when the player is suspected of throwing. A 50 Hz six-camera Vicon Motion Analysis system was used to record the movements of markers strategically placed on the upper limb during each of the above bowling actions. A kinematic model of the upper limb, created using Vicon BodyBuilder software, enabled the movements of the upper arm and forearm to be described during each delivery. Selected physical characteristics of the upper limb were also measured. The present 'no ball' law in cricket with reference to throwing states that 'the arm should not be straightened in the part of the delivery that immediately precedes ball release'. The bowler, Mutiah Muralitharan, was shown to maintain a relatively constant elbow angle in the 0.06 s before ball release. Furthermore, this angle changed little from the time that the upper arm was angled vertically downward until ball release during the three spin-bowling actions.

Arm↗
PubMed2000

Simple 1,2-aminoalcohols as strain-specific antimalarial agents.

We report here the in vitro activity of a selection of 1, 2-aminoalcohol-containing compounds against cloned strains of human Plasmodium falciparum. These compounds exhibit moderate antimalarial activity but a high degree of strain specificity, preferentially inhibiting a chloroquine-resistant strain of the organism.

Animals↗
PubMed1997

Muscle activation at the human knee during isometric flexion-extension and varus-valgus loads.

We examined the role of muscles in counteracting static loads in the transverse plane at the knee to determine if (a) knee muscles are activated to counteract isometric varus or valgus loads, (b) muscle activity during varus and valgus loads changes with the angle of knee flexion, and (c) the direction of a muscle's activation can be predicted by its moment arm orientations. For seven subjects, muscle activity was recorded during isometric tasks using surface and intramuscular electrodes from 10 muscles that span the knee. A six-degree-of-freedom load cell was rigidly attached to each subject's lower leg just above the ankle, and the subjects were instructed to push against the load cell so as to produce moments in the flexion-extension-varus-valgus plane at the knee. Moments in this plane were all of equal magnitude and varied in direction the full 360 degrees in 20 degrees increments. Most muscles were not activated to stabilize the knee against varus-valgus loads, but the sartorius, gracilis, and tensor fasciae latae showed substantial electromyographic activation in these directions. The load directions where muscles were principally active were observed to be dependent on joint angle for some muscles. In particular, the principal directions of activation for these three muscles changed as the angle of knee flexion changed. Similarly, a muscle's moment arm orientation was a good predictor of direction of activation for some muscles and a poor one for others. These results suggest that different muscles may play different roles in providing joint stability and that these roles are complex functions of muscle moment arm orientations, joint angles, external load directions, and possibly other undetermined parameters.

Adult↗
PubMed1996

Sensori-motor function, gait patterns and falls in community-dwelling women.

Tests of vision, vestibular function, peripheral sensation, strength, reaction time, balance and gait were administered to 183 community-dwelling women aged 22-99 years. Walking speed, stride length and cadence declined with age with corresponding increases in stance duration and percentage of the stride in the stance phase. Visual acuity and contrast sensitivity, tactile and vibration sense in the lower limb, vestibular function (as assessed by the vestibular X Writing Test), quadriceps and ankle dorsiflexion strength and reaction time were significantly associated with all five gait parameters. Postural sway measures were associated with walking speed, stride length and percentage of the stride in the stance phase. Multiple regression analyses revealed seven sensori-motor measures as significant predictors for one or more of the gait parameters: low contrast visual acuity, tactile sensitivity, vibration sense, vestibular X-test writing performance, quadriceps strength, reaction time and sway. Quadriceps strength was included as a predictor variable for every gait parameter and in each case had the strongest beta weight. Women who fell on two or more occasions in a one-year prospective period had significantly reduced and more variable cadence and significantly increased stance duration (measured in absolute terms and as a percentage of stride) than those who did not fall or fell on one occasion only. The study findings elucidate the relative importance of specific physiological systems in the maintenance of normal gait and identify temporal gait measures that are associated with falling in older people.

Accidental Falls↗
PubMed1996

The effect of exercise on gait patterns in older women: a randomized controlled trial.

BACKGROUND: This study was undertaken to determine (a) whether a program of regular exercise can improve gait patterns in older women, and (b) whether any such improvement in gait is mediated by increased lower limb muscle strength. METHOD: A 22-week randomized controlled trial of exercise was conducted as part of the Randwick Falls and Fractures Study in Sydney, Australia. Subjects were 160 women aged 60-83 years (Mean age 71.1, SD = 5.2) who were randomly recruited from the community. Exercise and control subjects were tested prior to and at the end of the trial. At initial testing, exercisers and controls performed similarly in the strength and gait parameters. They were well matched in terms of age and a number of health and life-style characteristics. RESULTS: At the end of the trial, the exercise subjects showed improved strength in five lower limb muscle groups, increased walking speed, cadence, stride length, and shorter stride times as indicated by both reduced swing and stance duration. There were no significant improvements in any of the strength or gait parameters in the controls. Within the exercise group, increased cadence was associated with improved ankle dorsiflexion strength, and increased stride length was associated with improved hip extension strength. Exercise subjects with initial slow walking speed showed greater changes in velocity, stride length, cadence, and stance duration than those with initial fast walking speed. CONCLUSION: These findings show that exercise can increase gait velocity and related parameters in older persons, and that part of this increase may be mediated by improved lower limb muscle strength.

Aged↗