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Biomedical subjects

A M Moseley

Publications and source records attributed to A M Moseley.

12 recordsLinked to original sources
PubMed2002

Change in length of relaxed muscle fascicles and tendons with knee and ankle movement in humans.

Ultrasonography was used to measure changes in length of muscle fascicles in relaxed human tibialis anterior and gastrocnemius during passively imposed changes in joint angle. Changes in the length of muscle fascicles were compared to changes in the length of the whole muscle-tendon units calculated from joint angles and anthropometric data. Relaxed muscle fascicles underwent much smaller changes in length than their muscle-tendon units. On average, muscle fascicles in tibialis anterior 'saw' 55 +/- 13 % (mean +/- S.D.) of the total change in muscle-tendon length. This indicates nearly half of the total change in muscle-tendon length was taken up by stretch of tendon. In gastrocnemius, which has relatively long tendons, only 27 +/- 9 % of the total change in muscle-tendon length was transmitted to muscle fascicles. Thus, the tendency for passive movement to be taken up by the tendon was greater for gastrocnemius than tibialis anterior (P = 0.002). For these muscles, the relatively large changes in tendon length across much of the physiological range of muscle-tendon lengths could not wholly be explained by tendon slackness, changes in fibre pennation, or stretch or contraction history of the muscle. Our data confirm that when joints are moved passively, length changes 'seen' by muscle fascicles can be much less than changes in the distance between muscle origin and insertion. This occurs because tendons undergo significant changes in length, even at very low forces.

Adult↗
PubMed2001

Normative data for passive ankle plantarflexion--dorsiflexion flexibility.

OBJECTIVE: To describe the normal distribution parameters for measures of passive ankle plantarflexion-dorsiflexion flexibility obtained from a large sample of able-bodied young adult subjects. DESIGN: Seven variables were assessed and descriptive analyses were conducted. BACKGROUND: While assessment of plantarflexion-dorsiflexion flexibility is an important component of a clinical examination of plantarflexion contracture, there is limited normative data available that can be used as a reference for clinical decision-making. METHODS: Data were collected from 300 able-bodied male and female subjects aged between 15 and 34 years. Both ankles were measured. Load-displacement curves were collected using a manually controlled instrumented footplate. Six variables were extracted from these curves: passive torque at zero and 10 deg, passive stiffness at zero and 10 deg, and two coefficients from an equation fitted to the curve (i.e., k and b). The seventh variable, passive dorsiflexion range of motion, was quantified using a clinical procedure. RESULTS: Flexibility variables did not differ between the left and right ankles, nor between the dominant and non-dominant legs. All variables were normally distributed. These distributions can, therefore, be adequately described using their mean and standard deviation values. CONCLUSIONS: This study has substantially increased the available database on plantarflexion-dorsiflexion flexibility and forms the basis of norm-referenced clinical tests.

Adolescent↗
PubMed2001

Time course of stress relaxation and recovery in human ankles.

OBJECTIVE: To characterise the time course of stress relaxation and recovery from stress relaxation in human ankles. DESIGN: Two experiments were conducted. The first used a randomised within-subjects design, and the second used a randomised between-subjects regression design. BACKGROUND: Several studies have described the time course of stress relaxation in human joints, but most have looked only at the effects of short durations of stretch. The time course of recovery from stretch in human ankles has not been documented. METHODS: In the first experiment, one ankle of each of eight subjects was stretched to a fixed dorsiflexion angle for 20 min. The ankle was then released for 2 min (during which time subjects either remained relaxed or performed isometric contractions), then stretched again. In a second experiment, on 24 subjects, the ankle was stretched for 20 min, then released between 0 and 20 min, then stretched again. In both experiments, subjects remain relaxed and ankle torque was measured continuously. RESULTS: When a constant-angle stretch was applied to the ankle, torque declined bi-exponentially towards an asymptote that was 58% of the initial torque. Nearly 5 min of stretch were required to obtain half of the maximal possible stress relaxation. Torque had recovered by 43% within 2 min of the release of stretch, but the degree of recovery did not appear to depend on whether subjects remained relaxed or performed isometric contractions. The time course of recovery was similar to the time course of stress relaxation. CONCLUSIONS: Long duration stretches are required to produce a large proportion of the maximal possible stress relaxation. Recovery is initially rapid when the stretch is released. RELEVANCE: These data provide a description of the time course of the effects of stretch, and of the subsequent relief of stretch, on mechanical properties of human ankles.

Adult↗
PubMed2000

Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep.

Mesenchymal stem cells are multipotent cells that can be isolated from adult bone marrow and can be induced in vitro and in vivo to differentiate into a variety of mesenchymal tissues, including bone, cartilage, tendon, fat, bone marrow stroma, and muscle. Despite their potential clinical utility for cellular and gene therapy, the fate of mesenchymal stem cells after systemic administration is mostly unknown. To address this, we transplanted a well-characterized human mesenchymal stem cell population into fetal sheep early in gestation, before and after the expected development of immunologic competence. In this xenogeneic system, human mesenchymal stem cells engrafted and persisted in multiple tissues for as long as 13 months after transplantation. Transplanted human cells underwent site-specific differentiation into chondrocytes, adipocytes, myocytes and cardiomyocytes, bone marrow stromal cells and thymic stroma. Unexpectedly, there was long-term engraftment even when cells were transplanted after the expected development of immunocompetence. Thus, mesenchymal stem cells maintain their multipotential capacity after transplantation, and seem to have unique immunologic characteristics that allow persistence in a xenogeneic environment. Our data support the possibility of the transplantability of mesenchymal stem cells and their potential utility in tissue engineering, and cellular and gene therapy applications.

Adipocytes↗
PubMed2000

PEDro. A database of randomized trials and systematic reviews in physiotherapy.

This paper describes PEDro, the Physiotherapy Evidence Database. PEDro is a web-based database of randomized controlled trials and systematic reviews in physiotherapy. It can be accessed free of charge at http://ptwww.cchs.usyd.edu.au/pedro. The database contains bibliographic details and abstracts of most English-language randomized trials and systematic reviews in physiotherapy, and of many trials and reviews in other languages. Trials on the database are rated on the basis of their methodological quality so that users of the database can quickly identify trials of high quality. Trials and systematic reviews are extensively indexed to facilitate searching. PEDro provides an important information resource to support evidence-based clinical practice.

Databases, Bibliographic↗
PubMed1997

The effect of casting combined with stretching on passive ankle dorsiflexion in adults with traumatic head injuries.

BACKGROUND AND PURPOSE: Ankle plantar-flexion contractures are a common problem following traumatic head injury. Although serial casting is used to correct and prevent ankle plantar-flexion contractures, treatment efficacy has not been evaluated using an experimental design. The aim of this research was to establish the effect of a regimen of casting combined with stretching on passive ankle dorsiflexion motion. SUBJECTS: Nine people who had sustained traumatic closed head injuries and had limited dorsiflexion motion participated in the study. METHODS: A crossover design was used in the study. Subjects were assigned to both experimental and control groups. Torque-controlled measurements of passive ankle dorsiflexion motion were obtained for all subjects before and after 1 week of casting combined with stretching, as well as before and after a 1-week control period. The order of the experimental and control conditions was randomized. RESULTS: Passive ankle dorsiflexion increased by a mean of 13.5 degrees (SD = 9.3) during the experimental condition, as compared with a mean decrease of 1.9 degrees (SD = 10.2) during the control condition. The difference between the experimental and control conditions was statistically significant. CONCLUSION AND DISCUSSION: These findings suggest that casting combined with stretching is an effective method of correcting ankle plantar-flexion contractures in patients with traumatic head injuries.

Adolescent↗
PubMed1993

3-Acyl-4-hydroxyquinolin-2(1H)-ones. Systemically active anticonvulsants acting by antagonism at the glycine site of the N-methyl-D-aspartate receptor complex.

Most full antagonists at the glycine site of the NMDA receptor contain a carboxylic acid, which we believe to be detrimental to penetration of the blood-brain barrier. By consideration of a pharmacophore, novel antagonists at this site have been designed in which the anionic functionality is a vinylogous acid, in the form of a 4-hydroxyquinolin-2(1H)-one. In this series, a 3-substituent is necessary for binding, and correct manipulation of this group leads to compounds such as the 3-(3-hydroxyphenyl)propargyl ester 24 (L-701,273), with an IC50 for displacement of [3H]-L-689,560 binding of 0.17 microM and Kb against NMDA in the cortical slice of 1.39 microM. Compounds were tested for their ability to prevent audiogenic seizure in DBA/2 mice; the most potent compound in this series is the cyclopropyl ketone 42 (L-701,252), with an ED50 of 4.1 mg/kg ip. A model is proposed for binding to the glycine site, in which an important interaction is of a putative receptor cation with the pi-system of the 3-substituent.

Acylation↗
PubMed1992

2-Carboxytetrahydroquinolines. Conformational and stereochemical requirements for antagonism of the glycine site on the NMDA receptor.

2-Carboxy-1,2,3,4-tetrahydroquinoline derivatives, derived from kynurenic acid, have been synthesized and evaluated for in vitro antagonist activity at the glycine site on the NMDA receptor. 2,3-Dihydrokynurenic acids show reduced potency relative to the parent lead compounds (Table I) possibly as a result of conformational effects. Removal of the 4-oxo group results in further reduced potency, but introduction of a cis-carboxymethyl group to the 4-position restores antagonist activity (Tables III and IV). Replacement of the keto group of 5,7-dichloro-2,3-dihydrokynurenic acid with other alternative H-bonding groups, for example cis- and trans-benzyloxycarbonyl and cis- and trans-carboxamido (Table V), gives comparable activity, but there is negligible stereoselectivity. A significant increase in potency and stereoselectivity is seen within the 4-acetate series (Table VI). The trans-4-acetic acid is significantly more potent than the corresponding lead kynurenic acid and has 100-fold greater affinity than the cis isomer. The results are consistent with a requirement in binding for a pseudoequatorially placed 2-carboxylate and clearly demonstrate the importance for binding of a correctly positioned hydrogen-bond-accepting group at the 4-position. The high-affinity binding of an anionic group in the 4-substituent binding pocket suggests that the glycine site and the neurotransmitter recognition (NMDA) site may have some features in common.

Animals↗
PubMed1992

4-Amido-2-carboxytetrahydroquinolines. Structure-activity relationships for antagonism at the glycine site of the NMDA receptor.

trans-2-Carboxy-5,7-dichloro-4-amidotetrahydroquinolines, evolved from the lead 5,7-dichlorokynurenic acid, have been synthesized and tested for in vitro antagonist activity at the glycine site on the N-methyl-D-aspartate (NMDA) receptor. Optimization of the 4-substituent has provided antagonists having nanomolar affinity, including the urea trans-2-carboxy-5,7-dichloro-4[[(phenylamino)carbonyl]amino]-1,2,3, 4-tetrahydroquinoline (35; IC50 = 7.4 nM vs [3H]glycine binding; Kb = 130 nM for block of NMDA responses in the rat cortical slice), which is one of the most potent NMDA antagonists yet found. The absolute stereochemical requirements for binding were found to be 2S,4R, showing that, in common with other glycine-site NMDA receptor ligands, the unnatural configuration at the alpha-amino acid center is required. The preferred conformation of the trans-2,4-disubstituted tetrahydroquinoline system, as shown by X-ray crystallography and 1H NMR studies, places the 2-carboxyl pseudoequatorial and the 4-substituent pseudoaxial. Modifications of the 4-amide show that bulky substituents are tolerated and reveal the critical importance for activity of correct positioning of the carbonyl group. The high affinity of trans-2-carboxy-5,7-dichloro-4-[1-(3-phenyl-2-oxoimidazolidinyl)]- 1,2,3,4-tetrahydroquinoline (55; IC50 = 6 nM) suggests that the Z,Z conformer of the phenyl urea moiety in 35 is recognized by the receptor. Molecular modeling studies show that the 4-carbonyl groups of the kynurenic acids, the tetrahydroquinolines, and related antagonists based on N-(chlorophenyl)glycine, can interact with a single putative H-bond donor on the receptor. The results allow the establishment of a three-dimensional pharmacophore of the glycine receptor antagonist site, incorporating a newly defined bulk tolerance/hydrophobic region.

Aminoquinolines↗
PubMed1992

Characterization of the binding of [3H]L-689,560, an antagonist for the glycine site on the N-methyl-D-aspartate receptor, to rat brain membranes.

The binding characteristics of [3H]L-689,560 [(+/-)-4-(trans)-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino -1,2,3,4- tetrahydroquinoline], a selective antagonist for the glycine site on the N-methyl-D-aspartate receptor, have been evaluated using rat cortex/hippocampus P2 membranes. Specific [3H]L-689,560 binding was saturable, having a Kd of 2.97 nM and a Bmax of 4.15 pmol/mg of protein. The Bmax value was not significantly different from that obtained for [3H]glycine in the same membrane preparation, and L-689,560 and glycine were found to be mutually competitive. The specific binding of [3H]L-689,560 (1 nM) represented 96 +/- 0.02% (four experiments) of total binding. Association experiments at 4 degrees revealed that [3H]L-689,560 reached equilibrium in 120 min, with a t1/2 of 40 min. The dissociation of [3H]L-689,560 was slow at 4 degrees (t1/2 = 118 min), allowing the use of filtration to separate free from bound radioactivity. Both association and dissociation curves were best fitted by a double-exponential function, suggesting the presence of two components. Comparison of IC50 values obtained using [3H]glycine and [3H]L-689,560 binding for 21 glycine site ligands (including agonists, partial agonists, and antagonists, with affinities spanning 5 orders of magnitude) showed a 1:1 correlation, with a correlation coefficient of 0.97. This suggests that efficacy does not have a large influence on the affinity of glycine site ligands when an agonist or antagonist radioligand is used. Ligands for other amino acid recognition sites did not directly inhibit [3H]L-689,560 binding. [3H]L-689,560 is an improved radioligand for the glycine site that will facilitate further investigations of its properties.

Aminoquinolines↗