Search PubMed⌕ Search

Biomedical subjects

R H Edwards

Publications and source records attributed to R H Edwards.

At least 163 records · Page 9Linked to original sources

Relationship between ammonia, heart rate, and exertion in McArdle's disease.

We studied plasma ammonia and exercise tolerance in six patients with McArdle's disease (myophosphorylase deficiency, type V glycogenosis) during incremental cycle ergometry. Tests were performed either in the postabsorptive state or after supplementation with branched-chain amino and 2-oxoacids and glucose. Glucose and branched-chain 2-oxoacid combined increased total work performed from control 49 +/- 22 to 80 +/- 36 kJ (P less than 0.05). Glucose alone also improved total work performed from 49 +/- 22 to 64 +/- 33 kJ (P less than 0.05). Branched-chain 2-oxoacids alone had a variable effect, and branched-chain amino acids were of no benefit. Correlations between plasma ammonia and heart rate for individual patients were r = 0.99, P less than 0.01; r = 0.95, P less than 0.01; r = 0.84, P less than 0.01; r = 0.76, P less than 0.01; r = 0.73, P less than 0.01; and r = 0.63, P less than 0.05 and between ammonia and perceived exertion for all patients combined was r = 0.70, P less than 0.0001. In two patients, correlation of ammonia with heart rate at a power output of 60 W was r = 0.91, P less than 0.001 and at 40 W was r = 0.77, P less than 0.001. We conclude that ammonia is either a mediator or a marker of the metabolic events leading to fatigue.

Adolescent↗

Energy metabolism during damaging contractile activity in isolated skeletal muscle: a 31P-NMR study.

Creatine kinase (CK) release in response to excessive electrically stimulated contractile activity has been studied in isolated rat soleus muscles. The exacerbation of CK release induced by contractile activity was found to be directly related to the length of time for which the muscle was stimulated and indirectly related to the recovery of force following the end of stimulation. 31P-NMR studies were undertaken using a recirculating superfused muscle preparation and demonstrated that muscles subjected to two different stimulation protocols (stimulation for 0.5 s every 2 s in oxygenated medium or for 1.5 s every 2 s in anoxic medium) had similar falls in ATP content and pH despite a substantially greater release of CK from the muscles stimulated under anoxia. However, stimulated muscles under anoxia showed a more rapid fall and reduced recovery of phosphocreatine and a greater sustained elevation of inorganic phosphate than muscles in oxygenated medium. It is concluded that only part of the increased loss of CK from muscles stimulated in anoxic medium can be explained by release from cells which have lost energy supplies and therefore that other mechanisms must exist which allow release of CK and other cytosolic enzymes from muscle cells.

Adenosine Triphosphate↗

The effect of vitamin E analogues and long hydrocarbon chain compounds on calcium-induced muscle damage. A novel role for alpha-tocopherol?

Previous studies have demonstrated that supplemental alpha-tocopherol inhibited calcium-induced cytosolic enzyme efflux from normal rat skeletal muscles incubated in vitro and suggested that the protective action was mediated by the phytyl chain of alpha-tocopherol [1]. In order to investigate this further a number of hydrocarbon chain analogues of tocopherol (7,8-dimethyl tocol, 5,7-dimethyl tocol, tocol, alpha-tocotrienol, alpha-tocopherol [10], vitamin K1, vitamin K1 [10], vitamin K1 diacetate, vitamin K2 [20], phytyl ubiquinone and retinol) were tested for any ability to inhibit calcium ionophore, A23187, induced creatine kinase (CK) enzyme efflux. Some compounds were found to be very effective inhibitors and comparison of their structures and ability to inhibit TBARS production in muscle homogenates revealed that the effects did not appear related to antioxidant capacity or chromanol methyl groups, but rather the length and structure of the hydrocarbon chain was the important mediator of the effects seen.

Animals↗

Acute effects of phorbol esters on the protein-synthetic rate and carbohydrate metabolism of normal and mdx mouse muscles.

1. mdx mice do not express dystrophin, the product of the gene which is defective in Duchenne and Becker muscular dystrophy. We have previously shown that protein-synthetic rates (ks) are increased in mdx mouse muscles [MacLennan & Edwards (1990) Biochem. J. 268, 795-797]. 2. The tumour-promoting stereoisomer of phorbol 12,13-didecanoate (4 beta-PDD) acutely increased the ks of muscles from mdx and wild-type (C57BL/10) mice incubated in vitro in the absence of insulin. The effects of 4 beta-PDD are presumably mediated by activation of protein kinase C (PKC). 3. The muscle glycogen concentrations of mdx mice were higher than those of C57BL/10 mice. Studies performed in vivo and in vitro suggested that the effect might be at least partially due to increased rate of glycogen synthesis in mdx muscle. 4. 4 beta-PDD increased the glycogen-synthetic rates rates of C57BL/10, but not mdx, muscles incubated in vitro in the absence of insulin. 5. In muscles from both species incubated in the absence of insulin, treatment with 4 beta-PDD also induced increased rates of glucose uptake and lactate production. Kinetic studies of C57BL/10 and mdx muscles suggested that 4 beta-PDD raised the Vmax. of glucose uptake, but did not alter the Km for the process. 6. The possible role of PKC in controlling the protein and carbohydrate metabolism of normal and mdx mouse muscles is discussed.

Animals↗

The nature of the proteins lost from isolated rat skeletal muscle during experimental damage.

Sodium dodecyl sulfate-polyacrylamide gel analysis of the incubation media surrounding isolated rat soleus muscles has been used to determine the nature of the proteins lost from skeletal muscle during damage. Following various forms of experimental trauma only selected proteins are lost to the medium when compared to the protein composition of the muscle cytosol. The proteins released do not appear to be released in a size dependent manner and their release is partly inhibited by an absence of calcium in the extracellular medium. alpha-Tocopherol entirely prevents the release of cytosolic enzymes induced by intracellular calcium overload.

2,4-Dinitrophenol↗

Cardiac cachexia.

Explore the source record for details and available documents.

Cachexia↗

Epidermal growth factor and transforming growth factor alpha induce c-fos gene expression in retinal Muller cells in vivo.

Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) are peptides that act at a common receptor and are mitogenic for immature astrocytes and trophic for developing brain neurons in vitro. However, a role for these growth factors in the mature nervous system has not been established. To investigate the actions of EGF and TGF alpha in the adult central nervous system (CNS) in vivo, the growth factors were injected into the vitreous cavity of adult male rabbits. After varying intervals, the retinas were examined for c-fos mRNA by Northern blot hybridization or Fos (and Fos-related antigen) protein by immunocytochemistry. EGF induction of c-fos mRNA occurs within 30 min and persists more than 4 hr. Fos nuclear immunostaining is induced selectively in nuclei of Muller cells by both EGF and TGF alpha. Fos-like immunoreactivity appears within 1 hr and persists more than 9 hr after EGF injection. These observations demonstrate that mature retinal Muller cells respond to exogenously applied EGF and TGF alpha in vivo, although the effect of the growth factors is not necessarily direct. The expression of c-fos and other immediate early genes provides a short-term marker that can be used to investigate the role of growth factors in normal retinal physiology and responses to injury.

Animals↗

Quantitative magnetic resonance studies of lumbar vertebral marrow in patients with refractory or relapsed Hodgkin's disease.

Lumbar vertebral (LV) bone marrow proton relaxation times were measured from midline sagittal magnetic resonance images of the lumbar spine of 20 patients with refractory or relapsed Hodgkin's disease (HD) referred for autologous bone marrow transplantation (ABMT) and 18 aged-matched normal volunteers. Two patients with positive bone marrow biopsies had markedly elevated mean LV marrow T1 and T1 variation. Elevated mean LV marrow T1 or T1 variation, consistent with bone marrow involvement with HD, was also seen in four other patients with negative bilateral posterior iliac crest bone marrow biopsies. Four patients with abnormal quantitative MR studies were examined serially following treatment. Mean LV marrow T1 and T1 variation normalised post ABMT, consistent with a good response to treatment. Quantitative MR studies of LV marrow may improve the detection of bone marrow involvement with lymphoma and be a complementary examination to bone marrow biopsy. Serial studies allow an objective and non-invasive assessment of treatment response.

Adult↗

Lumbar muscularity and its relationship with age, occupation and low back pain.

This paper considers an internal standard of lumbar muscularity. The cross-sectional areas (Acs) of the intervertebral disc and paraspinal muscles were measured in 147 working men from an axial magnetic resonance image passing through the L3-4 disc. Lumbar muscularity was expressed by two ratios; the ratio between the Acs of the right psoas and the Acs of the intervertebral disc (P:disc), and the ratio between the combined Acs values of the right erector spinae and quadratus lumborum and the Acs of the disc (ESQL:disc). When the subjects were divided into two age groups (76 aged 20-30 years and 71 aged 31-58 years) lumbar muscularity was found to be significantly greater (P less than 0.001) in the younger age group (P:disc = 0.8, SD 0.2; ESQL:disc = 2.0, SD 0.3) than in the older age group (P:disc = 0.7, SD 0.2; ESQL:disc = 1.8, SD 0.3). Lumbar muscularity was not significantly affected by occupation or by a history of low back pain.

Adult↗

The application of total vertical projections for the unbiased estimation of the length of blood vessels and other structures by magnetic resonance imaging.

A new stereological method has recently been developed to estimate the total length of a bounded curve in 3D from a sample of projections about a vertical axis. Unlike other methods based on serial section reconstructions, the new method is unbiased (i.e., it has zero systematic error). A basic requirement, not difficult to fulfill in many cases, is that the masking of one structure by another is not appreciable. The application of the new method to real curvilinear structures using a clinical magnetic resonance (MR) imager is illustrated. The first structure measured was a twisted water-filled glass tube of known length. The accuracy of the method was assessed: With six vertical projections, the tube length was measured to within 2% of the true value. The second example was a living bonsai tree, and the third was a clinical application of MR angiography. The possibility of applying the method to other scientific disciplines, for example, the monitoring of plant root growth, is discussed.

Blood Vessels↗

A comparative psychiatric assessment of patients with chronic fatigue syndrome and muscle disease.

The psychiatric status of patients with chronic fatigue syndrome (N = 34) and muscle disease (N = 24) attending a general medical clinic was studied. Among fatigue patients 14 (41.2%) were cases and a further 9 (26.5%) were subcases of psychiatric disorder as defined by CATEGO. A variety of diagnoses was found. Significantly fewer of the muscle patients had a psychiatric disorder with 3 (12.5%) being cases and 1 (4%) a subcase. The relative risk of psychiatric disorder in patients with chronic fatigue syndrome compared to patients with muscle disease was 3.3:1.

Adult↗

Effects of contractile activity on muscle damage in the dystrophin-deficient mdx mouse.

1. Isolated extensor digitorum longus muscles from control C57BL/10 and mutant dystrophin-deficient C57BL/10 mdx mice have been studied in vitro to determine whether dystrophin deficiency influences the susceptibility of muscle to contractile activity-induced damage. 2. mdx muscles were found to release reduced amounts of intracellular creatine kinase compared with control tissue in response to excessive contractile activity with or without simultaneous stretching of the muscle to 130% of its resting length. 3. In contrast, prostaglandin E2 release from mdx muscle was elevated compared with control tissue in response to either form of contractile activity or to treatment with the calcium ionophore A23187. 4. These results do not support the hypothesis that dystrophin-deficient muscle is more susceptible to damage induced by contractile activity, but suggest that dystrophin deficiency influences the activity of muscle membrane phospholipase enzymes.

Animals↗

Glutathione depletion during experimental damage to rat skeletal muscle and its relevance to Duchenne muscular dystrophy.

1. The release of glutathione has been studied in comparison with the release of creatine kinase from isolated rat soleus muscles subjected to certain forms of experimental damage. 2. Excessive electrically stimulated contractile activity or treatment of muscles with the mitochondrial inhibitor, 2,4-dinitrophenol, induced a substantial release of both creatine kinase and glutathione and a reduction in the total glutathione content of the muscle. The time course of this release and depletion indicates that the efflux of the two molecules is not directly related and that a reduction in muscle glutathione content does not occur before cytosolic enzyme release. 3. 2,4-Dinitrophenol-stimulated release of creatine kinase was significantly reduced by the omission of external calcium from the incubation media, but glutathione release and depletion was relatively unaffected by this. Deliberate elevation of the muscle intracellular calcium content with the calcium ionophore, A23187, induced a substantial loss of creatine kinase, but had no significant effect on the release of glutathione. 4. Muscle biopsies from patients with Duchenne muscular dystrophy were found to have an elevated content of glutathione and an equivalent protein-thiol content compared with control subjects. 5. We conclude that, although release of glutathione from skeletal muscle occurs after excessive contractile activity or inhibition of mitochondrial metabolism, this is not a key step in the damaging processes leading to cytosolic enzyme release, neither is it relevant to the ongoing damage to skeletal muscle which occurs in patients with Duchenne muscular dystrophy.

2,4-Dinitrophenol↗