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Biomedical subjects

D Halliday

Publications and source records attributed to D Halliday.

At least 145 records · Page 8Linked to original sources
PubMed1985

In vivo estimation of muscle protein synthesis in myotonic dystrophy.

The rate of muscle protein synthesis in patients with myotonic dystrophy has been studied, and results correlated with total muscle mass. Whole body and skeletal muscle protein synthesis were estimated by stable isotope methodology with a primed, continuous infusion of 1-[13C]leucine with measurement of incorporation of [13C]leucine into muscle protein in biopsy samples. Whole body leucine flux, protein synthesis, and protein breakdown were only slightly depressed, but muscle protein synthesis was markedly decreased, in myotonic dystrophy. This depression of muscle protein synthesis in myotonic dystrophy correlates with previous observations of impaired insulin-induced muscle uptake of amino acids and supports the suggestion that muscle wasting in this disease is the consequence of defective anabolism in muscle.

Adolescent↗
PubMed1985

Elevated rates of whole body protein metabolism in patients with disseminated malignancy in the immediate postoperative period.

Protein metabolism after surgery in the presence of disseminated malignancy has been investigated and compared with results obtained from patients undergoing similar surgical procedures for benign disease and localized malignancy. Whole body nitrogen turnover, measured by primed continuous infusion of 15N glycine, was highest with disseminated malignancy. Similarly rates of whole body protein synthesis and breakdown, calculated from turnover and nitrogen excretion (nitrogen intake being zero), were elevated in the presence of disseminated malignant disease. The increased rates of protein metabolism may represent adaptation to the demands of inevitably growing malignant tissue.

Aged↗
PubMed1985

Analysis of (1-13C)leucine and (13C)KIC in plasma by capillary gas chromatography/mass spectrometry in protein turnover studies.

The methods used for the determination of the concentration and isotope enrichment of (1-13C)leucine and its metabolite (13C) alpha-ketoisocaproic acid (KIC) in plasma for the study of whole-body protein turnover are described. Leucine was analysed as its N-heptafluorobutyryl isobutyl ester and KIC as its quinoxalinol-TMS derivative, both by chemical ionization selected ion monitoring gas chromatography/mass spectrometry (GC/MS). The sensitivity of the leucine assay was improved 30 times by monitoring the negative ions under the conditions described. The coefficient of variation for enrichment and concentration measurements were 0.5% and 2%, respectively, with a minimum detectable enrichment of 0.1 at% excess for both assays.

Caproates↗
PubMed1985

Calculation of turnover rates in stable-isotope studies.

Tserng and Kalhan have raised the question of the appropriate equation to use for the measurement of turnover rate in a stable-isotope study. In a comparison of glucose turnover measured with 2H-glucose and with 13C-glucose they used five apparently different equations and obtained conflicting answers. There is, however, no difference in principle between the use of a stable isotope as a tracer and the use of a radioactive isotope, and the rate of appearance of tracee in a steady-state system (the turnover) can therefore be shown to be proportional to the equilibrium dilution of the infused tracer. Because the sensitivity of measurement of this dilution made using a gas chromatograph-mass spectrometer is lower than that made by radioactivity measurement, the contribution to the measured turnover rate due to the infusate cannot be neglected, as it usually is in radioisotope work. A convenient calibration curve to establish this dilution is the mole ratio of the pure infusate against the area ratio for the relevant ions. Tserng and Kalhan's apparently conflicting results for glucose turnover using 13C-glucose as the tracer can all be shown to amount to approximately 11.6 mumol min-1 kg-1. This value is only slightly lower (0.05 less than P less than 0.1) than that obtained using 2H-glucose as the tracer and supports the use of 13C-glucose as an alternative.

Blood Glucose↗
PubMed1985

Direct determination of leucine metabolism and protein breakdown in humans using L-[1-13C, 15N]-leucine and the forearm model.

We have used the forearm model to study protein metabolism in six normal healthy subjects in the fed state using L-[1-13C, 15N]-leucine as the substrate tracer. Deep venous and arterialized venous blood samples from the forearm were collected at 10-min intervals 2.5 h into a primed-continuous infusion of the dilabelled tracer. Arterialized venous blood was obtained using a 'hot-box' technique and forearm blood flow was measured by mercury strain-gauge plethysmography. The concentration and isotope enrichment of leucine and its metabolites, alpha-ketoisocaproic acid and CO2, in deep venous and arterialized venous blood were measured by gas chromatography-mass spectrometry and isotope ratio-mass spectrometry. The rates of leucine deamination and reamination were 388 +/- 24 (mean +/- SEM) and 330 +/- 23 nmol (100 ml)-1 min-1 respectively, whilst protein synthesis and breakdown rates were 127 +/- 11 and 87 +/- 10 nmol (100 ml)-1 min-1 respectively across the forearm in the fed state. We have demonstrated that the use of doubly labelled leucine as tracer and application of the mathematical model developed in this study, permits the comprehensive quantification of leucine kinetics including protein breakdown.

Adult↗
PubMed1984

Protein synthesis in muscle measured in vivo in cachectic patients with cancer.

Rates of synthesis of protein were measured in vivo in skeletal muscle and in the whole body of cachectic patients with cancer and in normal healthy men, using a tracer infusion of leucine labelled with a stable isotope. Synthesis of protein in muscle was significantly reduced in the patients with cancer (0.030 v 0.198%/hour; p less than 0.01), whereas whole body rates of protein synthesis and degradation did not differ significantly between the two groups. Thus depression of synthesis of protein in muscle appeared to be the immediate cause of muscle wasting in cancerous cachexia. Any therapeutic intervention that aims at preventing the onset of cachexia should be designed to stimulate the synthesis of protein in muscle, and measurement of turnover of protein may be used to evaluate such treatment provided that rates of protein synthesis are measured directly in specific tissues.

Aged↗
PubMed1984

Preparation of CO2 from blood and protein-bound amino acid carboxyl groups for quantification and 13C-isotope measurements.

Measurements of protein and amino acid metabolism in man using stable isotopes and selected ion monitoring gas chromatographic/mass spectrometric techniques are limited by the requirement of relatively high levels of labelling for adequate precision (greater than 0.05 at % excess). We describe here a means of extending the scope of such studies by measurement of lower levels of enrichment achieved in gaseous CO2 derived from whole blood or protein-bound amino acids following the administration of tracer amounts of appropriately labelled substrates. Construction and operation of a novel glass vacuum line required for this work are described in detail and specific applications relevant to clinical investigations are outlined. Measurements of both the total amount of CO2 and its 13C enrichment are performed in an isotope-ratio mass spectrometer which provides acceptable levels of accuracy and reproducibility for both measurements (+/- 0.1% and +/- 0.0001 at % excess respectively).

Amino Acids↗
PubMed1984

Increased energy expenditure in poorly controlled Type 1 (insulin-dependent) diabetic patients.

The basal energy expenditure of 10 Type 1 (insulin-dependent) C-peptide-negative diabetic patients (2042 +/- 62 kcal/24 h) was found to be significantly higher than the 1774 +/- 52 kcal/24 h predicted from their age, sex and body surface area (p less than 0.01). Intravenous insulin treatment significantly reduced energy expenditure to 1728 +/- 19 kcal/24h (p less than 0.01), which matched predicted values. The observed increase in metabolic rate in uncontrolled diabetic patients is associated with increased protein turnover, increased plasma glucagon, but no significant increase in cortisol, growth hormone or triiodothyronine concentrations in plasma. It may be accounted for by the energy cost of protein synthesis, or gluconeogenesis, or possibly increased sympathetic activity. This increased energy expenditure will contribute to the weight loss seen in Type 1 diabetic patients.

Adult↗
PubMed1984

The measurement of whole body protein turnover in the preterm infant with intragastric infusion of L-[1-13C]leucine and sampling of the urinary leucine pool.

The measurement of whole body protein turnover in the preterm infant has been investigated with an intragastric infusion of L-[1-13C]-leucine and with sampling of the urinary leucine pool. Measurements have been made in seven preterm infants with body weights averaging 1733 g, fed with either human breast milk (n = 3) or proprietary formulae (n = 4), giving intakes of 541 (+/- 25) kJ/kg and 465 (+/- 42) mg of N day-1 kg-1 and growing satisfactorily (14.7 +/- 2.6 g day-1 kg-1). The measurement of the enrichment of urinary leucine was well within the capability of gas chromatography-spectrometry, and similar values for the enrichment of plasma and urinary leucine were observed (plasma/urinary ratio was 0.93 +/- 0.04, mean +/- 1 SEM, n = 13). Isotopic equilibrium, as indicated by a plateau in the urinary leucine and expired CO2 enrichment, was obtained within 8 h and was maintained for at least 48 h. Nitrogen retention, measured by nitrogen balance, was similar to that calculated from the leucine retention (determined as the leucine intake--oxidation), i.e. 310 +/- 45 and 301 +/- 38 mg of N day-1 kg-1 (means +/- 1 SEM). Because of this it is suggested that in this specific type of study the direct measurement of nitrogen retention dispenses with the need for measurement of leucine oxidation, thereby simplifying the measurements. From the leucine flux, leucine intake and nitrogen retention, rates of whole body protein synthesis and degradation were shown to be 11.32 (+/- 0.78) and 9.54 (+/- 0.55) g day-1 kg-1.

Body Weight↗
PubMed1983

Effect of poor diabetic control and obesity on whole body protein metabolism in man.

We have investigated whole body protein turnover in the fasted state in five normal men, five male Type 1 diabetic patients off insulin therapy, and five obese women, using IV 13C-leucine as a tracer. In diabetic patients, there was, as expected, a greater net loss of protein in the fasted state than in normal subjects. However, contrary to animal and studies in vitro, our diabetic patients in the fasted state showed a greater rate of protein synthesis than normal subjects (p less than 0.01). The increased net loss of protein in diabetic patients compared with normal subjects arose because, in the diabetic patients, protein breakdown was increased even more than protein synthesis under the conditions of this study. Plasma leucine concentration was higher in diabetic and in insulin-insensitive obese patients than in normal subjects (p less than 0.01), and higher in diabetic than in obese patients (p less than 0.05). The rate of protein synthesis per kg lean body mass was also higher in diabetic patients than in obese or normal subjects (p less than 0.01), and higher in obese than normal subjects (p less than 0.05). We conclude that, in human subjects, whole body leucine and protein metabolism are very sensitive to the action of insulin.

Adult↗
PubMed1983

Thermic response to isoenergetic protein, carbohydrate or fat meals in lean and obese subjects.

The thermic response of five lean and five obese subjects was measured by indirect calorimetry before, and for 157.5 min after a meal of protein, carbohydrate or fat, each of which provided 1.25 MJ. The change in plasma glucose, insulin and (in the case of the carbohydrate meal) the rate of exogenous glucose oxidation was also measured. There was no significant difference between the lean and obese groups in the magnitude of the thermic response to any of the three meals. In both weight groups the response was largest and most prolonged after the protein meal (P less than 0.01). The obese group showed a higher concentration of fasting plasma insulin (P less than 0.01) and a larger increase in plasma glucose (P less than 0.05) after the carbohydrate meal, but there was no significant difference in the oxidation of exogenous glucose when compared with the lean group. Previous studies on dietary-induced thermogenesis in lean and obese subjects have given conflicting results. In general reports of decreased thermogenesis in obese subjects are characterized by either (a) high pre-meal metabolic rates in the obese group, especially in diabetic subjects, or (b) a group classified as 'normal' who have been selected for their high thermogenic capacity.

Adult↗
PubMed1983

Depressed protein synthesis is the dominant characteristic of muscle wasting and cachexia.

Wasting of skeletal muscle is a characteristic of many conditions besides those involving primary muscle disease, for example, cancer, cachexia and postoperative catabolism. There is now strong evidence from studies in animals, normal men and in patients with a variety of diseases to suggest that the muscle mass is regulated primarily by alterations in the protein synthetic rate and that changes in muscle protein degradation are largely secondary and adaptive. If this is so, attention should be focused on possible means of therapeutic intervention to increase protein synthesis rather than on ways of decreasing protein degradation.

Animals↗
PubMed1983

A study of 'starch blockers' in man using 13C-enriched starch as a tracer.

It is claimed that commercial preparations of an alpha-amylase inhibitor, taken in tablet form 10 min before a meal, will inhibit the digestion of up to 100 g starch in the following meal. This was tested by giving five obese women three meals each containing cornflour enriched with 13C after a tablet of 'Starchex' or 'Calorex' or a placebo, in randomized sequence. The response to the meal in the rate of evolution of 13CO2, the increase in plasma insulin and the increase in blood sugar did not differ with the type of tablet which preceded the meal. We conclude that these starch-blocker tablets do not affect starch digestion or absorption in vivo.

Adult↗