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Biomedical subjects

R H Edwards

Publications and source records attributed to R H Edwards.

At least 253 records · Page 14Linked to original sources

Cobra nerve growth factor: structure and evolutionary comparison.

We have cloned and sequenced an NGF cDNA from the cobra venom gland. The structure of the predicted cobra precursor resembles that of the mouse prohormone, with a highly conserved mature NGF protein at the C-terminus. In the non-NGF moiety, a putative signal peptide and two sets of basic residues presumably reflecting cleavage sites that are more conserved, while large interstitial regions are poorly conserved. This moiety may be involved in defining the folding of the precursor for subsequent proteolytic maturation and/or encode a bioactive polypeptide(s). Primer extension analysis indicates a single NGF transcript in the cobra venom gland.

Amino Acid Sequence↗

31P NMR studies on recovery from hypoxia of human tumor cells.

We describe the use of 31P NMR spectroscopy in the study of metabolic changes related to hypoxia in cultured human tumor cells in vitro. The 31P NMR spectrum can easily distinguish between metabolically active cells, metabolically inactive "dormant" cells, and necrotic cells. A crucial observation was that of the ability of the "dormant" cells to resume active metabolism on incubation with oxygen after long periods of hypoxia.

Adenocarcinoma↗

Practical analysis of variability of muscle function measurements in Duchenne muscular dystrophy.

To determine the possible sources of variation in performance indicators used in therapeutic trials, electrical stimulation techniques were used to measure contractile properties of the adductor pollicis and quadriceps muscles in boys with Duchenne muscular dystrophy. As no therapeutic effects were observed, longitudinal data obtained are taken to indicate changes in disease progress. Variance in voluntary contractions was found to be similar to that with electrically stimulated contractions; thus, variation could not be attributed to motivational changes, but rather to physiologic changes. Dystrophic muscle was slower to relax and less fatiguable than normal. However, such changes are of less significance to the overall disability compared to the loss of muscle bulk (cross-sectional area). Important variations in the function of individual muscles essential to complex performance, such as walking or getting up from the floor, could be masked by combining results from several muscle groups.

Adolescent↗

An examination of some factors influencing creatine kinase in the blood of patients with muscular dystrophy.

The natural variability of plasma creatine kinase activity has been examined in patients suffering from muscular dystrophy and in normal subjects. The coefficient of variation of the plasma creatine kinase activities was found to be large (approximately 35%) in both patients with Duchenne muscular dystrophy and normal control subjects. A comparison of the plasma activities of creatine kinase with other muscle-derived enzymes suggests that the cause of this variability is changes in the release of enzymes from muscle. Data obtained concerning the effect of physical activity on plasma creatine kinase activity are contradictory, but several young patients with Duchenne muscular dystrophy and a very high creatine kinase activity (greater than 5000 IU/liter) showed a decreased activity following admission to hospital. An estimate of the rate of efflux of certain kinase from muscle has been made, indicating that young ambulant patients with Duchenne muscular dystrophy have a grossly elevated muscle creatine kinase efflux (495.0 +/- 61.3 IU/kg muscle/hr) compared to control subjects (1.4 +/- 0.5 IU/kg muscle/hr).

Adolescent↗

Altered chromatin structure associated with a partial trisomy of chromosome 7 in the mouse.

The chromatin of a mouse that is trisomic for part of chromosome 7 was investigated. Chromatin from trisomic tissue has a smaller average nucleosome DNA repeat length than chromatin from tissue taken from normal diploid littermates. DNA of the nucleosome cores is the same size in both normal and trisomic tissues. Not all of the nucleosome monomers have different repeat lengths. Normal and trisomic mouse kidney cells in tissue culture maintained their nucleosome repeat-length differences.

Animals↗

Magnetic resonance spectroscopy in the recognition of metabolic disease.

Magnetic resonance (MR) is rapidly entering many fields of clinical medicine following a long history as a powerful tool in physics and chemistry. The non-invasive and non-destructive property of this technique has enabled the chemical shift in higher magnetic fields to be exploited to identify and quantitate metabolites in both in vitro and in vivo analysis. High resolution proton spectroscopy of body fluids has been shown to be complementary with established analytical techniques, while the development of whole body large bore magnets is enabling both the study of structure and metabolism in humans in vivo. Phosphorus MR spectroscopy has provided a method of monitoring ATP production and utilisation in situ in both perfused preparation and intact tissue. In human muscle it has been possible to test established theories of tissue energy metabolism. It provides a unique method with which to evaluate the state of tissue oxidative metabolism. The opportunities afforded by other nuclei are being studied, but the low sensitivity of the MR technique forces limitations. Recent technical advances in tissue localization have as yet only been applied in a limited way. The use of MR in metabolic disease will be considered with specific reference to disorders of skeletal muscle metabolism.

Adenosine Triphosphate↗

Development of changes in cation content of muscles from the 129 ReJ dystrophic mouse.

1. Muscle cation levels have been measured in severely affected and relatively unaffected muscles of dystrophic mice (129 ReJ strain) compared to control animals at various ages. 2. Muscle calcium levels were found to be elevated in the severely affected gastrocnemius muscles only at a late stage of the disease, calcium levels in mildly affected triceps muscles were unaffected. 3. Muscle sodium levels were elevated in both triceps and gastrocnemius muscles at all ages studied. 4. Muscle magnesium and potassium contents showed similar changes, being significantly reduced in the gastrocnemius from the time of development of the first signs of weakness (i.e. 3-5 weeks of age), this decrease becoming more marked with increasing age and showing a less marked, but significant, change in the triceps muscle at a later stage of the disease.

Aging↗

Knee moments in Duchenne muscular dystrophy.

The gait of 7 boys with Duchenne muscular dystrophy (DMD) who could walk unaided and 21 normal boys was analysed by means of a video recording technique linked to a Kistler force plate. An electronic device was used to superimpose the patient's ground reaction vector on the video recording of their walking. This recording was analysed to obtain sequential values for the moments developed around the knee during the walking cycle. The equinus gait of boys with DMD is shown to be a necessary adaptation to keep the forces about proximal joints, particularly the knee, within limits controllable by weakened muscles. These findings explain the observation that elongation of the Achilles tendon to correct contracture at the ankle can have irrevocably damaging effects on gait.

Adaptation, Physiological↗

Plasma creatine kinase changes after eccentric and concentric contractions.

This study was undertaken to determine whether the large delayed creatine kinase (CK) rise, previously only reported in normal subjects after stepping exercise, was caused by the eccentric or concentric contractions. On separate occasions, five normal subjects performed the same amount of total work by walking either up (mainly concentric contractions) or down (mainly eccentric contractions) a treadmill inclined at 13 degrees. After uphill walking, peak plasma CK values of 60-200 IU/liter occurred 24 hours after exercise. Downhill walking resulted in peak values of 700-1500 IU/liter 4-7 days later. It is concluded that it is the eccentric contractions that are responsible for the large enzyme efflux.

Adult↗

Skeletal muscle damage: a study of isotope uptake, enzyme efflux and pain after stepping.

We have studied the occurrence of skeletal muscle uptake of 99mtechnetium pyrophosphate (Tc-PYP), creatine kinase (CK) release and muscle pain in normal subjects after exercise. Five subjects stepped on and off a high bench in such a way that one leg stepped up and the other down. Pain only developed in the muscles used for descending: quadriceps, adductors and gluteal muscles of one leg and the calf muscle of the other. A large rise in plasma CK occurred in four subjects but no increased Tc-PYP muscle uptake was seen in the quadriceps. In the four subjects with high CK effluxes, increased isotope uptake was seen in the thigh adductors used when stepping down; in the two subjects with the largest CK effluxes there was extensive uptake into the gluteal muscles. Muscle pain preceded and was not well correlated with either the magnitude of the enzyme release or the amount and distribution of increased muscle isotope uptake. We conclude that delayed onset muscle pain, the cause of which remains unknown, is a poor indicator of muscle damage as indicated by circulating muscle enzymes and muscle isotope uptake. Tc-PYP uptake by skeletal muscle can provide useful information about the localisation and time course of muscle damage.

Adult↗

Treatment of carcinoma of the penis: the case for primary lymphadenectomy.

There were 65 patients with squamous cell carcinoma of the penis followed for a minimum of 5 years. Patients with stage I disease uniformly survived with local treatment only. Of the patients with stages II and III carcinoma of the penis 88 and 66 per cent, respectively, were free of disease if lymphadenectomy was performed shortly following treatment of the primary lesion, compared to only 38 and 0 per cent, respectively, if the primary lesion was treated locally and no lymphadenectomy was performed. These data support the concept that lymphadenectomy should be an integral part of the primary treatment in patients with stages II and III penile cancer.

Adult↗

The effect of marathon running on carnitine metabolism and on some aspects of muscle mitochondrial activities and antioxidant mechanisms.

Carnitine is an essential co-factor in the catabolism of fats as an energy source. The primary purpose of this study was to investigate the effect of running a marathon on the metabolism of carnitine by endurance-trained athletes, and to evaluate the effect of carnitine administration on the performance of such exercise. The effects of marathon running on mitochondrial enzymes and cellular anti-oxidants were also examined to assess whether the expression of these activities is altered by exercise. Subjects were 10 experienced male marathon runners aged between 19 and 25 years. Running a marathon caused a fall in the plasma content of unesterified carnitine (37%) and an increase in the level of acetylcarnitine present (288%). Loading of the athletes with L-carnitine for 10 days before running a marathon abolished the exercise-induced fall in plasma-free carnitine (P less than 0.05) whilst amplifying the production of acetylcarnitine (P less than 0.05). Carnitine loading of the athletes studied made no detectable improvement in performance of the marathon (P greater than 0.05). Cytochrome oxidase, succinate cytochrome C reductase and superoxide dismutase activities present in skeletal muscle were unaltered by marathon running. However, such exercise caused a large increase in the tissue content of oxidized glutathione (189%) at the expense of reduced glutathione (-18%).

Acetylcarnitine↗

Muscle fatigue and pain.

Muscle fatigue and pain are together common symptoms which can be analysed physiologically. For many patients attending a medical clinic the problem for the doctor is to decide whether the problem is "in the mind" or "in the muscle". A history of the symptoms occurring at rest without any exercise is a hint of psychological origin. Exercise fatigue or pain should ideally be reproduced by an appropriate provoking exercise test. Needle biopsy with histochemistry is cost-effective as a means of reaching a diagnosis while blood determinations of erythrocyte sedimentation rate and plasma creatine kinase and lactate are more specific but less sensitive indicators of a muscle cause. Fatigue is analysed by force and action potential measurements with electrically stimulated contractions. Pain worse after exercise can be related to muscle damage. A programme of therapeutic exercise may be tried as a further means of assessment of these symptoms.

Humans↗

Effect of aminophylline on fatigue of the sternomastoid muscle in man.

The effect of intravenous aminophylline on the contractility of the sternomastoid muscle was measured in the fresh state and after the induction of significant fatigue in five normal subjects. Fatigue was produced by repetitive isometric neck flexion, for two seconds every four seconds at 70% of the maximum voluntary contractile force, continued until exhaustion. Each subject performed three experiments, one to two weeks apart, in random order. In experiment 1 fatiguing exercise and recovery were completed without aminophylline; in experiment 2 intravenous aminophylline was started 30 minutes before exercise and continued throughout the 60 minute recovery period; and in experiment 3 intravenous aminophylline was started immediately after the end of exercise. Aminophylline did not influence the frequency-force relationships, relaxation rate, or maximum voluntary contractile force in the fresh muscle. After fatiguing exercise there was a relatively selective reduction in force response to stimulation frequencies of less than 30 Hz, with little alteration in forces at higher frequencies--that is, low frequency fatigue--and this effect was present for the entire one hour study period. Aminophylline given before or immediately after fatigue did not influence the recovery of either low frequency fatigue or maximum voluntary contractile force. Aminophylline at therapeutic concentrations had no significant effect on the contractility or fatiguability of the normal human sternomastoid muscle.

Adult↗

The effect of low frequency fatigue on endurance exercise in the sternomastoid muscle of normal humans.

It is not certain to what extent low frequency fatigue affects the performance of a muscle. We studied the endurance capacity of the sternomastoid muscle to undergo repetitive isometric neck flexion contractions for 2 s every 4 s at 35% of its maximal voluntary contraction force (MVC) in 5 normal subjects starting with different levels of fatigue. The endurance time, the duration the subjects were able to achieve the target force before exhaustion, was measured in each subject on 3 occasions: Study 1: in the fresh state, with a normal frequency/force curve and 20:50 ratio (ratio of force response at 20 Hz to that at 50 Hz) before the start of the endurance exercise; Study 2: with a moderately reduced 20:50 ratio before the start of endurance exercise (mean +/- SEM reduction in 20:50 ratio 11.4 +/- 0.8%); Study 3: with a substantially reduced 20:50 ratio before the start of the endurance exercise (29.2 +/- 3.7%). These reductions in 20:50 ratio were produced by the subjects performing 150 isometric neck flexion contractions at 50% of their MVC, followed by a period of rest to allow the 20:50 ratio to recover to approximately 10% of the starting value in Study 2, and to within 20 to 40% of the starting value in Study 3. Endurance exercise was then carried out.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗