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Biomedical subjects

R H Edwards

Publications and source records attributed to R H Edwards.

At least 235 records · Page 13Linked to original sources
PubMed1988

Hypotheses of peripheral and central mechanisms underlying occupational muscle pain and injury.

In an overview of the problem of occupational muscle pain the evidence indicates that injury is more common the greater the load and the worse the posture in which the work is performed. The commonest are backstrains or ligament or joint damage due to overuse. Fatigue is associated with alterations in energy metabolites in muscle while pain is often due to microscopical damage to the cellular architecture. The progress of pathological changes in muscle following occupational injury may be similar to those seen in primary fibromyalgia (fibrositis) because of a final common pathway involving calcium-induced secondary damage. Occupational muscle pain frequently occurs in the muscles supporting the upper limb girdle and head in workers engaged in repetitively performing skilled manipulations or activities requiring high or sustained mental concentration. It is suggested that both occupational myalgia of this kind may be due to an imbalance in the use of muscles for postural activity (holding or supporting fine movements) compared to phasic use in dynamic work. While there are undoubtedly muscular indications of damage these may be secondary to alterations in (unconscious) central motor control mechanisms.

Central Nervous System↗
PubMed1988

The gating of nucleotide-sensitive K+ channels in insulin-secreting cells can be modulated by changes in the ratio ATP4-/ADP3- and by nonhydrolyzable derivatives of both ATP and ADP.

The 31P-NMR technique has been used to assess the intracellular ratios and concentrations of mobile ATP and ADP and the intracellular pH in an insulin-secreting cell line, RINm5F. The single-channel current-recording technique has been used to investigate the effects of changes in the concentrations of ATP and ADP on the gating of nucleotide-dependent K+ channels. Adding ATP to the membrane inside closes these channels. However, in the continued presence of ATP adding ADP invariably leads to the reactivation of ATP-inhibited K+ channels, even at ATP4-/ADP3- concentration ratios greater than 7:1. Interactions between ATP4- and ADP3- seem competitive. An increase in the concentration ratio ATP4-/ADP3- consistently evoked a decrease in the open-state probability of K+ channels; conversely, a decrease in ATP4-/ADP3- increased the frequency of K+ channel opening events. Channel gating was also influenced by changes in the absolute concentrations of ATP4- and ADP3-, at constant free concentration ratios. ADP-evoked stimulation of ATP-inhibited channels did not result from phosphorylation of the channel, as ADP-beta-S, a nonhydrolyzable analog of ADP, not only stimulated but enhanced ADP-induced activation of K+ channels, in the presence of ATP. Similarly, ADP was able to activate K+ channels in the presence of two nonhydrolyzable derivatives of ATP, AMP-PNP and beta gamma methylene ATP.

Adenosine Diphosphate↗
PubMed1988

Effects of dietary-fish-oil feeding on muscle growth and damage in the rat.

1. Giving diets containing 100 g fully-refined, non-hydrogenated fish oil/kg to rats caused substantial modification of skeletal-muscle-membrane fatty acid composition compared with control animals fed on an equivalent diet containing 100 g maize oil/kg. 2. Total muscle arachidonic acid (20:4 omega 6) was reduced from 138 (SD 25) mg/g total fatty acids to 15 (SD 2) mg/g and phospholipid arachidonic acid content showed equivalent changes. 3. Reduction in muscle arachidonic acid content had no influence on the growth of individual muscles. 4. Variation in muscle fatty acid composition exacerbated the response of muscle to calcium-induced damage assessed by efflux of intracellular creatine kinase (EC 2.7.3.2). 5. It is concluded that metabolites of arachidonic acid are unlikely to be primary controlling factors of muscle growth or specific mediators of muscle sarcolemmal damage leading to enzyme efflux.

Aging↗
PubMed1988

Absence of excess peripheral muscle fatigue during beta-adrenoceptor blockade.

1. In eight normal volunteers, the adductor pollicis (AP) was fatigued using intermittent trains of programmed, supramaximal stimulation at 1, 10, 20, 50, 100 and 1 Hz. Activity protocols were performed both with and without circulatory occlusion, both without and during propranolol 80 mg thrice daily in order to investigate the effects of beta-adrenoceptor blockade on 'peripheral' fatigue mechanisms. 2. The degree of beta-adrenoceptor blockade was assessed by the reduction of exercise tachycardia during cycle ergometry, e.g. pulse rates at 210 watts were reduced from 190 +/- 15 to 127 +/- 5 beats min-1 (mean +/- 1 s.d.) indicating that beta-adrenoceptor blockade was substantial and highly significant (P less than 0.001). 3. Before, during and following fatiguing activity with circulatory occlusion force declines were identical during and without beta-adrenoceptor blockade. During and following activity without occlusion, there were slight declines in force which were questionably significantly different at 20 Hz (P less than 0.05). 4. The compound muscle action potential (CMAP) amplitude, measured from the skin surface over the muscle, was unaltered by beta-adrenoceptor blockade before, during or after activity whether with or without circulatory occlusion. 5. The maximal relaxation rate (MRR) was not significantly reduced in previously unfatigued muscle during beta-adrenoceptor blockade. During activity, both with and without circulatory occlusion, there was no evidence that MRR was reduced significantly more during beta-adrenoceptor blockade. 6. The absence of a convincing effect of beta-adrenoceptor blockade on peripheral fatigue mechanisms may indicate that central mechanisms are involved or that impairments of peripheral force production, of a specific nature or as a result of exacerbation of limitations of circulatory oxygen transport, though small are detected during voluntary exercise and give rise to increases in motor unit recruitment and/or firing rates, and hence increased perception of fatigue.

Adrenergic beta-Antagonists↗
PubMed1988

Mechanisms resisting fatigue in isometrically contracting human skeletal muscle.

Human adductor pollicis was fatigued during circulatory occlusion by supramaximal stimulation via the ulnar nerve using intermittent trains of stimuli in ascending (1, 10, 20, 50 and 100 Hz) and descending (100, 50, 20, 10 and 1 Hz) frequencies to investigate the contribution of relaxation rate slowing and post-tetanic potentiation (PTP) to fatigue resistance. At 50 and 100 Hz force was initially well maintained despite a marked loss of excitation as indicated by EMG, demonstrating the operation of a high-frequency 'safety factor' which appeared independent of the pattern of stimulation. At 10 Hz, force was initially potentiated before declining during both activity series. Potentiation was greater during the descending frequency series and the rate of decline of force, or fatigability, was reduced. The 'extra' low-frequency potentiation at 10 Hz was not simply the result of PTP of twitch force, since this declined more during the descending than during the ascending series, nor the result of maximal relaxation rate changes which were identical for both fatiguing series. It is hypothesized that the extra potentiation and reduced fatigability at low stimulation frequencies, when preceded by high frequency, is the result of increased myofibrillar Ca2+ availability and/or sensitivity. These findings may have important practical implications in relation to functional electrical stimulation techniques as used in paraplegia and in other areas of muscle research where fatigue is to be minimized.

Action Potentials↗
PubMed1988

Human muscle fatigue: frequency dependence of excitation and force generation.

1. Human adductor pollicis was fatigued using intermittent trains of programmed stimulation at 1, 10, 20, 50, 100 and 1 Hz, during activity with and without circulatory occlusion, to investigate the relationships between force generation, excitation and maximal relaxation rate (MRR). 2. The relationship between force generation and excitation was markedly dependent on stimulation frequency. Force loss was greatest at low frequencies, with little reduction in excitation, but as frequency increased force was well maintained despite marked loss of excitation. 3. Changes in MRR during activity and recovery were independent of stimulation frequency. 4. Marked increases of force at 1 Hz (pre-tetanic) and 10 Hz occurred, with little reduction in excitation, during activity with and without circulatory occlusion. This may be due to post-tetanic potentiation in addition to slowing of relaxation (MRR). 5. At high frequency a 'safety factor' may thus operate to maintain force, despite obvious loss of excitation, while at low frequencies there may be marked potentiation of force, despite unchanged excitation. These mechanisms could permit resistance to fatigue with muscle function remaining optimal over a range of conditions.

Action Potentials↗
PubMed1988

Processing and secretion of nerve growth factor: expression in mammalian cells with a vaccinia virus vector.

To study posttranslational mechanisms for the control of nerve growth factor (NGF), we used a recombinant vaccinia virus vector to independently express the two major NGF transcripts in a variety of mammalian cell lines. The two major transcripts contain NGF (12.5 kilodaltons [kDa]) at the C-terminus and differ by alternative splicing of an N-terminal exon, so that the large precursor (34 kDa) had 67 amino acids upstream of an internal signal peptide and the smaller precursor (27 kDa) had this signal peptide at its N-terminus. In L929 cells, expression of either NGF transcript with the vaccinia virus vector gave rise to an apparently identical intracellular 35-kDa glycosylated precursor formed by cleavage of the primary gene product after the signal peptide. These cells also secreted biologically active NGF. To determine whether NGF processing is restricted by cell type, we infected a variety of mammalian cell lines with both recombinant viruses; all accumulated the same 35-kDa precursor and secreted NGF. Thus, many types of cells have the machinery to process and secrete NGF. However, NGF accumulated intracellularly (presumably in secretory granules) in cells with a regulated pathway of secretion (e.g., AtT-20 and HIT cells). In these cells, a membrane-permeable cyclic AMP analog, 8-bromo-cyclic AMP, stimulated NGF secretion. This suggests a mechanism for the regulation of NGF levels in which specific secretagogues, e.g., neurotransmitters, control NGF secretion.

Animals↗
PubMed1988

The effect of mazindol on growth hormone secretion in boys with Duchenne muscular dystrophy.

Mazindol has been reported to improve muscle function in Duchenne muscular dystrophy (DMD) by virtue of its growth hormone (GH) suppression. The effects were studied on GH secretion (in response to growth hormone releasing factor and sleep) of mazindol 2 mg daily for 3 months in five boys with DMD. No consistent change was found following mazindol therapy. Adverse effects were noted in all the boys which may preclude long term use of mazindol in DMD.

Child↗
PubMed1988

Physiological characterisation of the "warm up" effect of activity in patients with myotonic dystrophy.

Contractile properties of adductor pollicis muscle were examined over a range of stimulation frequencies in patients with myotonic dystrophy and normal subjects. In patients, fresh muscle demonstrated impaired relaxation, weakness at all frequencies and selective loss of force and excitation at high frequencies. During stimulated "fatiguing" activity, patients showed improvements in force and relaxation which appeared to result from normalisation of membrane excitation. Normal twitch potentiation also occurred during activity suggesting intact excitation-contraction coupling. These electrophysiological findings help to characterise and explain the "warm up" effect described by patients.

Adult↗
PubMed1988

Hypoxemia during sleep in Duchenne muscular dystrophy.

Overnight polysomnography after acclimatization was performed on 14 patients with Duchenne muscular dystrophy (mean age, 18.3 yr; mean VC, 1.24 L). Despite their lack of sleep-related symptoms and normal daytime blood gas tensions, periods of hypopnea and/or apnea (H/A) were observed in all patients (mean frequency 9.6/h; range, 3.7 to 17.0; mean duration 23.1; range of means, 16 to 36 s). In 9 patients, between 0.5 and 12.3 oxygen desaturations of greater than 5% occurred per hour, with falls from a mean SaO2 baseline of 95.4 +/- 0.6% (SEM) to a mean nadir of 74.2 +/- 3.9% (range, 58 to 90). This desaturating group (n = 9) showed longer and more frequent H/A than did the 5 nondesaturators; the proportion of REM sleep occupied by H/A was 37.7 +/- 3.8% in the desaturating group compared with only 15.1 +/- 5.1% in the remainder (p less than 0.01). The severity of sleep-disordered breathing could not be reliably predicted from daytime pulmonary function test results, and only maximal static expiratory pressure appeared significantly lower in the desaturating group. Hypopneas were associated with reduced chest wall movement in all subjects, and with chest wall paradox in one; continued submental "inspiratory" EMG activity throughout "central" apneas in 2 subjects suggested that these episodes were not truly central in origin. Sleep hypoxemia is imputed in the progression of several chronic respiratory diseases, and its prevention in Duchenne and related neuromuscular diseases may influence morbidity and mortality.

Adolescent↗
PubMed1988

Use of vaccinia virus vectors to study protein processing in human disease. Normal nerve growth factor processing and secretion in cultured fibroblasts from patients with familial dysautonomia.

Familial dysautonomia is a hereditary disorder that affects autonomic and sensory neurons. Nerve growth factor (NGF) is required for the normal development of sympathetic and sensory neurons and it has been postulated that an abnormality involving NGF may be responsible for familial dysautonomia. Previous studies have shown that the beta-NGF gene is not linked to the disease. However, NGF appears to be abnormal by immunochemical assays; the putative altered form of NGF could result from a disturbance in the processing pathway. To study the processing of the 35-kD glycosylated NGF precursor and the secretion of NGF in familial dysautonomia, we have employed a recombinant vaccinia virus vector to express high levels of NGF mRNA in primary fibroblast cultures from patients with the disorder; the processing pathway was then studied directly. Cells from several unrelated patients all produce the same 35-kD NGF precursor, process this normally to NGF within the cell, and release NGF into the medium. There are no differences in the ability of cells from patients and from unaffected relatives to process and secrete NGF. The use of similar recombinant vaccinia virus vectors to express proteins at high level in primary cell lines should facilitate the detection of posttranslational processing defects in a variety of human disorders.

Cells, Cultured↗
PubMed1988

Technique for physiological examination of canine skeletal muscle in vivo.

A technique is described for studying the physiological function of canine skeletal muscle in vivo. The contractile properties of the tarsal flexor muscles were examined in three beagle dogs under general anaesthesia. The force responses to electrical stimulation of the common peroneal nerve were measured at various frequencies to determine the frequency:force relationship for this muscle group. Fatigue characteristics were also examined during intermittent stimulated activity delivered in a set pattern of frequencies. The results provide quantitative characterisation of muscle function which is repeatable. The technique described could be applied to other animals and is a potentially powerful tool for evaluating the effects of drugs on muscle performance.

Animals↗
PubMed1987

Effect of inhibitors of arachidonic acid metabolism on efflux of intracellular enzymes from skeletal muscle following experimental damage.

The role of arachidonic acid metabolism in the efflux of intracellular enzymes from damaged skeletal muscle has been examined in vitro using inhibitors of cyclo-oxygenase and lipoxygenase enzymes. Damage to skeletal muscle induced by either calcium ionophore A23187 (25 microM) or dinitrophenol (1 mM) caused an increase in the efflux of prostaglandins E2 and F2 alpha together with a large efflux of intracellular creatine kinase. Use of a cyclo-oxygenase inhibitor completely prevented the efflux of prostaglandins, but had no effect on creatine kinase efflux. However, several agents having the ability to inhibit lipoxygenase enzymes dramatically reduced creatine kinase efflux following damage. These data suggest that a product or products of lipoxygenase enzymes may be mediators of the changes in plasma membrane integrity which permit efflux of intracellular enzymes as a consequence of skeletal muscle damage.

2,4-Dinitrophenol↗