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Biomedical subjects

D J Taylor

Publications and source records attributed to D J Taylor.

At least 145 records · Page 8Linked to original sources
PubMed1995

ATP production and mechanical work in exercising skeletal muscle: a theoretical analysis applied to 31P magnetic resonance spectroscopic studies of dialyzed uremic patients.

31P magnetic resonance spectroscopy (31P MRS) can yield much information about bioenergetics in skeletal muscle. During mixed aerobic/glycolytic exercise, changes in phosphocreatine (PCr) concentration and pH may be abnormal because of reduced muscle mass or reduced efficiency (which the authors combine here as "effective muscle mass") or because of reduced oxidative capacity. The authors show how these can be distinguished by calculating the nonoxidative and oxidative costs of mechanical work, and also of work per unit of effective muscle mass (measured using the initial rate of ATP turnover). These quantities are substantially time-independent during incremental exercise, and so can be used to compare exercise studies of differing duration. The authors illustrate this analysis by showing that in dialyzed patients with chronic renal failure, the substantial exercise abnormalities seen by 31P MRS are due mainly to a decrease in effective muscle mass, which outweighs the oxidative defect implied by the abnormal PCr recovery kinetics.

Adenosine Triphosphate↗
PubMed1995

A relationship between impaired fetal growth and reduced muscle glycolysis revealed by 31P magnetic resonance spectroscopy.

Thinness at birth is associated with insulin resistance and an increased prevalence of non-insulin-dependent diabetes mellitus in adult life. As muscle is an important site of insulin resistance, and because thin babies have reduced muscle mass, thinness at birth may affect muscle structure and function and impair carbohydrate metabolism. We have therefore used 31P magnetic resonance spectroscopy to investigate the bioenergetics of gastrocnemius and flexor digitorum superficialis muscles in 16 normoglycaemic women who had a low ( < or = 23 kg/m3) and 9 women who had a high (> 23 kg/m3) ponderal index at birth. In the flexor digitorum superficialis study anaerobic metabolism was stressed with a constant heavy workload. Low ponderal index subjects fatigued more rapidly (3.3 vs 5.8 min); as phosphocreatine decreased, the accompanying drop in muscle pH was less than in the high ponderal index group. In the first minute of exercise phosphocreatine fell and adenosine diphosphate rose more rapidly (p=0.04 and 0.03, respectively). Gastrocnemius showed a similar trend late in exercise (this exercise was more oxidative, becoming more anaerobic with increasing workload). These changes were not explained by differences in body composition, muscle mass or blood flow. The findings are consistent with a decreased lactic acid and glycolytic adenosine triphosphate production in the low ponderal index group and suggest the possibility that the mechanisms which control substrate utilisation and metabolism in adult life be programmed during prenatal life.

Adenosine Diphosphate↗
PubMed1995

Calf muscle mitochondrial and glycogenolytic ATP synthesis in patients with claudication due to peripheral vascular disease analysed using 31P magnetic resonance spectroscopy.

1. We set out to define abnormalities of oxidative ATP synthesis, cellular proton efflux and the efficiency of ATP usage in gastrocnemius muscle of patients with claudication due to peripheral vascular disease, using data obtained by 31P magnetic resonance spectroscopy during aerobic exercise and recovery. 2. Eleven patients with moderate claudication were studied and results were compared with 25 age-matched control subjects. Changes in pH and phosphocreatine concentration during recovery were used to calculate the maximum rate of oxidative ATP synthesis (Qmax.) and the capacity of net proton efflux. Changes in pH and phosphocreatine concentration were used to estimate rates of non-oxidative and (indirectly) oxidative ATP synthesis throughout exercise, taking account of abnormalities in proton efflux during exercise. 3. In patients with claudication, slow post-exercise phosphocreatine recovery showed a 42 +/- 9% decrease in Qmax., and the slow ADP recovery was consistent with this. pH recovery was slow, showing a 77 +/- 9% decrease in the capacity for proton efflux. Both abnormalities are compatible with a substantial reduction in muscle blood flow. 4. During exercise, increased phosphocreatine depletion and intracellular acidification were a consequence of impaired oxidative ATP synthesis and the consequent increase in non-oxidative ATP synthesis, compounded by reduced proton efflux. The acidification prevented an increase in ADP concentration which could otherwise partially compensate for the oxidative defect. All these abnormalities are compatible with a reduced muscle blood flow. 5. In addition, initial-exercise changes in pH and phosphocreatine concentration implied a 44 +/- 5% reduction in 'effective muscle mass', necessitating an ATP turnover (per litre of muscle water) twice as high for given power output as in control muscle. Some of this is probably due to a localized loss of muscle fibres, but the rest appears to reflect reduced metabolic efficiency of the muscle. This is not a direct consequence of reduced blood flow, and may be related to change in muscle fibre type.

Adenosine Triphosphate↗
PubMed1995

Antenatal diagnosis and management of meconium peritonitis: a case report and review of the literature.

We present a case of meconium peritonitis which was associated with a short bowel and complicated by progressive bowel distension and difficulty in making a definitive diagnosis of cystic fibrosis. Treatment was by bowel resection and an ileostomy (and later bowel anastomosis), followed by parenteral nutrition which was complicated by hepatitis. The literature is reviewed and management dilemmas and options are discussed.

Adult↗
PubMed1994

Bioenergetics of skeletal muscle in mitochondrial myopathy.

31Phosphorus nuclear magnetic resonance spectroscopy was used to examine skeletal muscle in 29 patients with mitochondrial myopathy, 9 male and 20 female. Gastrocnemius was investigated in 15 patients and 30 normal subjects and finger flexor muscle (flexor digitorum superficialis, fds) in 24 patients and 35 normal controls. Both muscles were studied in 10 of the patients. Results were abnormal (outside the full range of normal values) in all but 2 patients. In 86% of patients (25/29) abnormalities were detected in resting muscle. In most cases there was a low phosphocreatine/ATP ratio, high calculated free [ADP] and low phosphorylation potential. At rest, abnormality was detected with equal ease in fds and gastrocnemius. Exercise and recovery increased the sensitivity of MRS in detecting abnormal metabolism. Finger flexion was better tolerated by patients than plantar flexion and gave bigger changes in metabolite concentrations and intracellular pH. Thus, results from fds were more easily differentiated from normal. Exercise duration was significantly shorter than in controls while phosphocreatine depletion was more rapid than normal, consistent with a shortfall in mitochondrial ATP synthesis. Nearly all patients (25/27, 93%) showed abnormalities during recovery from exercise. [ADP] was high during exercise and its recovery was delayed, providing increased drive for oxidative phosphorylation. Phosphocreatine resynthesis during recovery (which reflects oxidative ATP synthesis) was slow both in absolute terms and in relation to [ADP]. Recovery of intracellular pH after exercise was significantly more rapid than normal, consistent with an upregulation of proton efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1994

Mast cell proteinases activate precursor forms of collagenase and stromelysin, but not of gelatinases A and B.

Mast cell activation in vivo is often associated with areas of oedema and connective-tissue degradation. Tryptase and chymase are the major serine proteinases released by mast cells, but they appear to have little activity on most components of the extracellular matrix. The matrix metalloproteinases (MMP) are purported to degrade almost all connective tissue elements and are secreted by cells in the form of inactive precursors. Since the mechanisms of MMP activation in vivo are poorly understood we have examined the potential of mast cell proteinases to activate the precursor forms of human collagenase (MMP-1), stromelysin (MMP-3), gelatinase A (MMP-2) and gelatinase B (MMP-9). Mast cell proteinases prepared from purified dog mastocytoma cells were shown to process and activate purified precursor forms of both MMP-1 and MMP-3. Using antipain and chymostatin, inhibitors for tryptase and chymase, respectively, it was demonstrated that both pMMP-1 and pMMP-3 were effectively processed and activated by the chymase component. By contrast, tryptase activated only pMMP-3. The mast cell proteinases were unable to process or activate purified precursor forms of MMP-2 and MMP-9. However, MMP-3 previously activated by mast cell proteinases was shown to activate pMMP-9, but not pMMP-2. Since we have no evidence that mast cells express these four metalloenzymes, the release of mast cell serine proteinases following activation/degranulation could contribute to local metalloproteinase activation and subsequent matrix degradation.

Amino Acid Sequence↗
PubMed1994

Cytokine combinations increase p75 tumor necrosis factor receptor binding and stimulate receptor shedding in rheumatoid synovial fibroblasts.

OBJECTIVE: To identify cytokines responsible for the increased levels of tumor necrosis factor receptor (TNFR) in the joints of patients with rheumatoid arthritis. METHODS: Antibodies to TNFR types were used both to inhibit ligand cell binding and to quantify released receptors in rheumatoid synovial fibroblasts. RESULTS: Binding by and shedding of the p75 TNFR was affected by interleukin-1 (IL-1), IL-4, and interferon-gamma. CONCLUSION: IL-1 could cause increased TNF alpha binding and TNFR shedding in inflamed joints.

Arthritis, Rheumatoid↗
PubMed1994

Interleukin-4 (IL-4) induces down-modulation and shedding of the p55 tumour necrosis factor receptor and inhibits TNF alpha's effect on rheumatoid synovial fibroblasts.

Recombinant human interleukin-4 (rhIL-4) and rhIL-1 alpha each produced a rapid down-modulation of tumour necrosis factor receptor (TNFR) on rheumatoid synovial fibroblasts (RSF) in vitro. This was associated with a staurosporine-resistant increase in p55 soluble TNFR levels, in culture media, suggesting that down-modulation was due to enhanced receptor shedding via a protein kinase C-independent mechanism. Pretreatment with rhIL-4 reduced the subsequent tumour necrosis factor alpha (TNF alpha) stimulation of prostaglandin E (PGE) and matrix metalloproteinase-3 (MMP-3) production by RSF. Thus, the potential anti-synovial monokine properties of rhIL-4 are not confined to inhibiting monokine production but also include the ability to interfere with their action on cells that constitute a substantial proportion of the rheumatoid synovium.

Alkaloids↗
PubMed1994

Apparent cerebellar ectopia: a reappraisal using volumetric MRI.

Cerebellar ectopia, once considered rare, is apparently extremely common on magnetic resonance imaging (MRI). However, assessment of cerebellar position relative to the foramen magnum is usually made from thick sagittal sections and therefore may not be as reliable as sometimes believed. Volumetric MRI, acquired in the coronal plane with section thickness 1.5 mm, was used to assess the position of the cerebellum in 144 subjects who also had two-dimensional sagittal imaging using 5.0 mm thick sections. On these images, the frequency of cerebellar ectopia appeared to be 19% (27 cases), but volumetric coronal images indicated that the biventral lobules protruded below the foramen magnum in only 3 (2%), and the cerebellar tonsils lay well above in all cases. Hence the actual frequency of cerebellar tonsillar ectopia in this sample was zero. We concluded that cerebellar ectopia really is rare.

Adolescent↗
PubMed1994

A 31P magnetic resonance spectroscopy study of mitochondrial function in skeletal muscle of patients with Parkinson's disease.

The activity of complex I of the respiratory chain is decreased in the substantia nigra of patients with Parkinson's disease (PD) but the presence of this defect in skeletal muscle is controversial. Therefore, the mitochondrial function of skeletal muscle in patients with PD was investigated in vivo using 31P magnetic resonance spectroscopy. Results from 7 PD patients, 11 age matched controls and 9 mitochondrial myopathy patients with proven complex I deficiency were obtained from finger flexor muscle at rest, during exercise and in recovery from exercise. In resting muscle, the patients with mitochondrial myopathy showed a low PCr/ATP ratio, a low phosphorylation potential, a high P(i)/PCr ratio and a high calculated free [ADP]. During exercise, stores of high energy phosphate were depleted more rapidly than normal, while in recovery, the concentration of phosphocreatine and free ADP returned to pre-exercise values more slowly than normal. In contrast, the patients with PD were not significantly different from normal for any of these variables, and no abnormality of muscle energetics was detected. Three of the PD patients also had mitochondrial function assessed biochemically in muscle biopsies. No respiratory chain defect was identified in any of these patients by polarography or enzyme analysis when compared with age-matched controls. These results suggest that skeletal muscle is not a suitable tissue for the investigation and identification of the biochemical basis of the nigral complex I deficiency in PD.

Adolescent↗
PubMed1994

Plasma disposition of amikacin and interactions with gastrointestinal microflora in Equidae following intravenous and oral administration.

Amikacin was detectable (> 0.02 micrograms/ml) in plasma for 12 h in horses and donkeys and for 8 h in ponies following intravenous (i.v.) administration at a dose rate of 6 mg/kg bodyweight. The elimination half-life (harmonic mean) of amikacin was 2.8, 1.6 and 1.9 h in horses, ponies and donkeys, respectively, and the mean body clearance was relatively slow (45.2, 82.4 and 58.0 ml/h.kg, respectively). A suitable dosage interval for the i.v. administration of amikacin sulphate to horses, ponies and donkeys, at a dose rate of 6 mg/kg, would be every 8 h in horses, and every 6 h in ponies and donkeys. Following i.v. administration there were no marked alterations in caecal liquor pH, the number of viable bacteria isolated, or the short chain fatty acid (SCFA) concentrations in caecal liquor and faeces. Amikacin was not detected (< 0.02 micrograms/ml) in plasma following administration by nasogastric tube to ponies with cannulated caecal fistulae; however, there were high concentrations of amikacin measured in caecal liquor (maximum 16.2-99.4 micrograms/ml). Despite the high drug concentrations in caecal liquor, there were only slight alterations in the number of viable bacteria isolated. However, there was a reduction in caecal liquor pH to < 6.6, but few changes in caecal liquor SCFA concentrations. Faecal SCFA concentrations, dry matter content and consistency did not alter markedly.

Administration, Oral↗
PubMed1994

Increased serum proMMP-3 in inflammatory arthritides: a potential indicator of synovial inflammatory monokine activity.

OBJECTIVE: To investigate if the increased concentrations of stromelysin (MMP-3) found in the synovial fluid (SF) of patients with various arthritides reflect the concentrations in the circulation. METHODS: Using a double antibody ELISA, we have measured proMMP-3 concentrations in sera from these patient groups and in others with a heightened acute phase response (APR) as a result of multiple organ failure. RESULTS: The median serum concentration of proMMP-3 was increased by up to ninefold in the inflammatory arthritides, but not in osteoarthritis or in patients with a heightened APR resulting from a non-chronic inflammatory condition. CONCLUSION: In chronic inflammatory diseases such as rheumatoid arthritis, serum proMMP-3 may prove to be a more specific indicator of monokine activity than currently available serum markers.

Acute-Phase Reaction↗
PubMed1994

Uraemic muscle metabolism at rest and during exercise.

The effect of chronic renal failure and the accompanying hyperphosphataemia on muscle metabolism at rest and during exercise was examined in a group of undialysed patients suffering from chronic renal failure. 31P magnetic resonance spectroscopy was used to measure intracellular high-energy phosphates in resting muscle as well as changes in the concentrations of these metabolites during exercise and recovery from exercise. In resting muscle, cell [Pi] rose with plasma [Pi], and free [ADP] changed such that the phosphorylation potential ([ATP]/([ADP] x [Pi])), which probably controls mitochondrial oxidation in resting muscle, was preserved despite a wide variation in cell [Pi]. The maximal oxidative capacity of the muscle was calculated from the kinetics of phosphocreatine recovery after exercise. There was no reduction in uraemic muscle oxidative capacity compared to control muscle. This contrasts with our finding of a reduction in the mitochondrial oxidative capacity in the muscle of patients established on dialysis, suggesting that a substance crucial for mitochondrial function or substrate supply to mitochondria is removed by dialysis.

Adenosine Diphosphate↗
PubMed1994

The relation between antenatal care and birth weight.

The relation between gestational age at first antenatal visit and infant's birth weight was investigated in a cohort study of 846 primiparas living in the City of Dundee, Scotland, whose first antenatal visit was between 1 May 1985 and 30 April 1986. The earlier in pregnancy the first antenatal visit the greater the infants' birth weights tended to be (p < 0.01). The relation was independent of gestational age at birth, mother's age and height, social class, tobacco and alcohol consumption and the child's sex. The result supports similar findings elsewhere, but is more robust in that, in contrast to other studies, all birth weights were measured on a single electronic scale and the effects of maternal tobacco and alcohol consumption on birth weight were taken into account in the analysis. The mechanism of the effect remains to be determined but needs to be identified as it may indicate possible preventive measures for the benefit of future children.

Adult↗
PubMed1993

A phase I study of the left-shifting agent BW12C79 plus mitomycin C and the effect on the skeletal muscle metabolism using 31P magnetic resonance spectroscopy.

BW12C79 stabilizes the oxyhemoglobin molecule resulting in a reversible left-shift of the oxygen saturation curve. The activity of a number of bioreductive anticancer drugs, such as mitomycin C, may be enhanced under hypoxic conditions. Twenty-four patients with various malignancies received BW12C79 and mitomycin C. BW12C79 was administered i.v. with a loading dose (20-50 mg/kg) over 1 h followed by a maintenance infusion of 4 mg/kg/h for 5 h. Percentage modification of the oxyhemoglobin (degree of left-shift) was dose related with maximum modification of 56% and was maintained for the duration of maintenance infusion of BW12C79. Hemoglobin electrophoresis showed a fast moving band consistent with the BW12C79-oxyhemoglobin complex. Side effects at the top dose level comprised headache, nausea/vomiting, vein irritation, and myocardial ischemia. One other patient suffered from an acute encephalopathy of unknown etiology a few days following BW12C79. 31P magnetic resonance spectroscopy of exercising calf muscles showed increased breakdown of high energy phosphate stores and a greater reduction in pH. Recovery of the high energy phosphate stores after exercise was slow. These results were consistent with reduced oxygen supply due to either a left shift of the oxygen saturation curve and/or reduced muscle blood flow. BW12C79 did not interfere with the pharmacokinetics of mitomycin C. In conclusion, this phase I study demonstrates the feasibility of achieving a significant left shift in the oxygen saturation curve in cancer patients which is maintained for at least 5 h with acceptable toxicity. The maximum tolerated dose of BW12C79 was 50 mg/kg loading infusion followed by a maintenance infusion of 4 mg/kg/h. Magnetic resonance spectroscopy results were consistent with reduced supply of oxygen to exercising skeletal muscle. BW12C79 may be of potential benefit as an adjunct to bioreductive drugs in the treatment of solid tumors.

Adult↗
PubMed1993

16 kDa envelope proteins in non-Serpulina hyodysenteriae spirochaetes isolated from pigs.

Spirochaetes isolated from field samples of diarrhoea, 'colitis' and mucoid diarrhoea from pigs were examined by a series of cultural, biochemical and serological tests. In addition sodium dodecyl sulphate polyacrylamide gel electrophoresis was used to determine whether the organisms possessed a 16 kDa protein thought to distinguish Serpulina hyodysenteriae from S innocens. Spirochaetal isolates which differed culturally and biochemically from S hyodysenteriae were found to possess a 16 kDa protein. One of these isolates was examined by electron microscopy and found to have an ultrastructure differing from that of S hyodysenteriae. Antiserum to the 16 kDa antigen of S hyodysenteriae reacted with isolate S80/5, the homologous strain, and with B78, the type species, but not with the 16 kDa antigens of the field isolates considered to be S hyodysenteriae or with the non-S hyodysenteriae spirochaetes. It was concluded that there may be a family of 16 kDa proteins located on the envelope of various spirochaetes responsible for diarrhoea in pigs.

Animals↗