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Biomedical subjects

G C Ford

Publications and source records attributed to G C Ford.

At least 37 records · Page 2Linked to original sources
PubMed1990

Aspects of protein metabolism after elective surgery in patients receiving constant nutritional support.

1. The present study was designed in an attempt to resolve conflicting views currently in the literature relating to the effect of surgery on various aspects of protein metabolism. 2. Sequential post-operative (2, 4 and 6 days) changes in whole-body protein turnover, forearm arteriovenous difference of plasma amino acids, glucose, lactate and free fatty acids, muscle concentration of free amino acids, RNA and protein, urinary nitrogen and 3-methylhistidine, plasma concentrations of insulin, cortisol and growth hormone, and resting metabolic rate, were measured in six patients undergoing uncomplicated elective total abdominal hysterectomy. 3. All patients received a constant daily diet, either orally or intravenously, based on 0.1 g of nitrogen/kg and an energy content of 1.1 times the resting metabolic rate for 7 days before and 6 days after surgery. 4. Whole-body protein turnover, synthesis and breakdown increased significantly 2 days after surgery (P less than 0.05) and returned towards pre-operative levels thereafter. 5. Forearm release of branched-chain amino acids and alanine, and efflux of glucose and lactate, were enhanced 4 days after surgery (P less than 0.05). Muscle glutamine and alanine concentrations were decreased on the fourth and sixth days after surgery (P less than 0.05). The RNA/protein ratio (indicating the capacity for protein synthesis) was unaltered. 6. A significant increase in urinary nitrogen and 3-methylhistidine was observed on days 3 and 4 after surgery (P less than 0.05). Thereafter, these parameters remained elevated, although failing to reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effect of general anaesthesia on whole body protein turnover in patients undergoing elective surgery.

To determine if general anaesthesia alone or in conjunction with surgery alters body protein turnover, we studied six healthy, unpremedicated females undergoing elective total abdominal hysterectomy. Changes in protein metabolism, synthesis and breakdown were estimated by an isotope dilution technique using a continuous infusion of the stable isotope tracer, L-[1-13C]leucine, before anaesthesia (4 h), during anaesthesia alone (1 h), during anaesthesia and surgery (1 h) and in the recovery period (2 h). General anaesthesia comprised thiopentone, pancuronium, enflurane (1 MAC) and oxygen-enriched air. An isotopic steady state in plasma 13C-alpha-ketoisocaproate (13C alpha-KIC) and expired 13C-carbon dioxide were obtained during the four periods. Collections of plasma and expired air were made during the steady state periods and plasma alpha-KIC enrichment measured to indicate precursor pool labelling from which leucine flux (equal to protein breakdown in the post-absorptive state) and oxidation were calculated, and whole body protein synthesis was derived. Whole body protein breakdown did not change with anaesthesia, but decreased with both surgery and during the acute recovery period (P less than 0.05). Protein synthesis did not change with anaesthesia and surgery, but decreased significantly after surgery (P less than 0.05).

Adult↗
PubMed1989

Molecular size and symmetry of the bacterioferritin of Escherichia coli. X-ray crystallographic characterization of four crystal forms.

X-ray crystallographic data from four crystal forms of Escherichia coli bacterioferritin show that the molecule has a diameter in the range 119 to 128 A. Molecules are composed of 24 subunits arranged in 432 symmetry. In both size and symmetry the molecule resembles ferritin from eukaryotes. The four crystal forms are monoclinic, space group P2(1) with unit cell dimensions a = 118.7 A, b = 211.6 A, c = 123.3 A and beta = 119.1 degrees; orthorhombic, C222(1), a = 128.7 A, b = 197.1 A, c = 202.8 A; tetragonal, P4(2)2(1)2, a = b = 210.6 A, c = 145.0 A and cubic, I432, a = 146.9 A.

Bacterial Proteins↗
PubMed1989

Practical considerations in the use of stable isotope labelled compounds as tracers in clinical studies.

Increasingly widespread usage of stable isotope tracers to aid clinical diagnosis and support basic research has stemmed from both advances in mass spectrometry and the availability of competitively priced labelled compounds. Stable isotopes have been used generally to investigate normal and abnormal metabolic pathways, to estimate energy expenditure and body composition and to quantitate substrate flux and oxidation rates. Despite the fact that the underlying principles relating to the use of stable isotopes for in vivo studies are straightforward, careful consideration must be given to all aspects of human studies. This review highlights some of these, including choice of label and tracer molecule, mode of tracer administration and sampling site, analytical instrumentation, interpretation of data and ethical constraints.

Carbon Isotopes↗
PubMed1989

Substrate disposal in metabolic disease: a comparison between rates of in vivo propionate oxidation and urinary metabolite excretion in children with methylmalonic acidemia.

The relative importance of endogenous metabolism and urinary metabolite excretion was assessed in vivo in six children with methylmalonic acidemia by examining the kinetics of the immediate precursor to methylmalonate, propionate. Total production and oxidation of propionate were measured by means of a continuous infusion of (1-13C)propionate and were compared with the urinary excretion of propionate metabolites. Propionate oxidation was substantial (mean 48.9 mumol/kg/hr +/- SD 18.0) and, in four children, exceeded urinary metabolite excretion (mean urinary excretion in all subjects 40 mumol/kg/hr +/- 25). The sum of urinary excretion and oxidation rates (88 mumol/kg/hr +/- 29) approximated the total propionate production (93.4 +/- 37.0), suggesting that these routes together constitute the major mechanisms of propionate disposal. These results suggest that propionate oxidation is an important route of disposal in methylmalonic acidemia. Variations in the relative proportions of propionate disposal through oxidation and urinary excretion may be one reason for the often poor correlation between clinical status and urinary metabolite excretion. Measurement of urinary metabolite concentration alone may not always reflect clinical status and responses to treatment accurately.

Humans↗
PubMed1989

Rapid measurement of whole body and forearm protein turnover using a [2H5]phenylalanine model.

Whole body protein turnover was measured in six normal adults using a model based on a primed constant infusion of [2H5]phenylalanine and, independently, by an established method of a primed constant infusion of [1-13C]leucine. Isotopic plateau in plasma was achieved within 2 h for [2H5]phenylalanine and, in four of the subjects who received a priming dose of [2H4]tyrosine, for [2H4]tyrosine. In all subjects whole body protein turnover measured with the phenylalanine model (mean protein synthesis, 2.65 +/- (SD) 0.16 g.kg-1.24 h-1; catabolism, 3.58 +/- 0.26 g.kg-1.24 h-1) was similar to that measured using the leucine model (synthesis, 3.09 +/- 0.27 g.kg-1.24 h-1; catabolism, 3.70 +/- 0.35 g.kg-1.24 h-1). Mean forearm fractional muscle protein synthesis calculated by the phenylalanine model was 0.06 +/- 0.03%/h, which compares closely with literature values derived by other methods. The phenylalanine model allows the rapid assessment of whole body and muscle protein turnover from plasma samples alone, obviating the need for measurement of expired air CO2 production or enrichment.

Adult↗
PubMed1989

Effect of triiodothyronine on leucine kinetics, metabolic rate, glucose concentration and insulin secretion rate during two weeks of fasting in obese women.

We investigated the effect of the fasting-induced reduction in triiodothyronine (T3) on metabolic changes that occur during fasting. In five obese women (T3 group) the serum T3 level during a 2200 kcal/day diet was 3.34 +/- 0.23 nmol/l while taking 20 micrograms T3 8-hourly, 0.65 +/- 0.04 after one week of fasting while not taking T3, and 2.9 +/- 0.3 after a second week of fasting while taking T3 20 micrograms 8-hourly. In three other obese women (control group) who did not take T3, T3 concentrations decreased during fasting and remained low at the end of both the first and second week of fasting. In the T3 group, resting metabolic rate (RMR) (O2 ml/min) decreased 11.7 percent at the end of one week of fasting, but then increased by 5.3 percent at the end of the second week of fasting, whereas in the control group RMR decreased by 13.1 percent after one week of fasting and a further fall of 13.3 percent occurred by the end of the second week of fasting. The RMR at the end of 2 weeks of fasting of the control group was significantly lower (P less than 0.05) than predicted using the equation of Dore, whereas that of the T3 group was as predicted using the same equation. The changes in leucine flux, leucine oxidation and non-oxidative portion of leucine flux were not different during fasting between the T3 group and the control group. Plasma concentrations of glucose, insulin and C-peptide increased from the end of one week of fasting to the end of 2 weeks of fasting in the T3 group, whereas they decreased in the control group. It is concluded that the changes in T3 concentration during fasting affected RMR, glucose metabolism and insulin secretion but failed to influence leucine metabolism.

Adult↗
PubMed1988

The identity of Escherichia coli bacterioferritin and cytochrome b1.

Two different procedures were used to prepare pure samples of 'cytochrome b1' (column chromatography) and 'bacterioferritin' (immunoprecipitation) from Escherichia coli K-12 strain CA265. Both were crystallized, and X-ray-crystallographic data were compared with those from the bacterioferritin of E. coli strain W3300 used as a standard. We conclude that 'cytochrome b1' and 'bacterioferritin' are identical.

Bacterial Proteins↗
PubMed1988

Influence of amino acid administration on whole-body leucine kinetics and resting metabolic rate in postabsorptive normal subjects.

1. We have investigated the effect of an amino acid mixture (Vamin 14; 57.4 +/- 10.2 mumol h-1 kg-1) on whole-body leucine kinetics, calculated by a steady-state reciprocal pool model, and resting metabolic rate in eight postabsorptive normal subjects. 2. Vamin 14 infusion increased whole-body leucine flux (P less than 0.001), leucine employed for protein synthesis (P less than 0.001), leucine oxidation (P less than 0.001), metabolic clearance rate of alpha-ketoisocaproic acid (P less than 0.05) and levels of all three branched-chain amino acids (P less than 0.001) compared with the basal situation. In contrast, whole-body proteolysis was reduced (P less than 0.05). 3. Resting metabolic rate was increased during Vamin 14 infusion (P less than 0.05) and was positively correlated with whole-body protein synthesis (n = 16, r = 0.6342, P less than 0.01; y = 0.605x + 173.7), as was the change in metabolic rate with the change in protein synthesis (n = 8, r = 0.772, P less than 0.05; y = 0.493x - 10.85). 4. Overall, Vamin 14 infusion was associated with increased blood glucose (P less than 0.001), although the observed increase in plasma glucagon (t = 2.012) and plasma insulin (t = 1.683) failed to reach statistical significance. 5. These data lend a measure of support to the hypothesis that the apparent increase in whole-body protein synthesis in insulin-dependent diabetic (type I) subjects during insulin withdrawal may be substrate related.

Adult↗
PubMed1988

Relationships between plasma isotope enrichments of leucine and alpha-ketoisocaproic acid during continuous infusion of labelled leucine.

The ratio at steady-state of alpha-ketoisocaproic acid (KIC) to leucine 13C enrichments in plasma during continuous infusion of [13C]leucine was examined in 58 studies under a variety of conditions. The ratio was lower (P less than 0.001) in 'arterialized' venous plasma (mean +/- SD 0.85 +/- 0.09) than in deep venous plasma (0.95 +/- 0.08), the sampling site enrichment differences being greater for leucine than for KIC. Variation in the ratio between the various conditions studied was largely explained by analytical variation. Three normal subjects were given an intravenous bolus dose of L-[1-13C, 15N]leucine. Both [13C]KIC and [13C]leucine appeared quantitatively in plasma within 10 min, indicating that both transamination of leucine and KIC, and their equilibration between intracellular fluid and plasma, is rapid. This study suggests that changes in sampling site, rather than in study conditions, are more likely to lead to variation in the KIC:leucine enrichment ratio. The lesser variation for KIC, and the rapid equilibration of the [13C]leucine bolus, favour KIC as tracee for [13C]leucine protein turnover studies.

Adult↗
PubMed1987

Effect of intravenous insulin treatment on in vivo whole body leucine kinetics and oxygen consumption in insulin-deprived type I diabetic patients.

In vivo leucine metabolism was studied after an overnight fast in nine type I diabetic patients and nine healthy control subjects using L-[1-13C] leucine as a tracer. In the insulin-deprived state, leucine flux (reflecting proteolysis), leucine oxidation, and plasma leucine concentrations were higher in the diabetic patients than in the control subjects (P less than .001). In 4 of the 9 insulin-deprived diabetic patients, a four-hour intravenous insulin treatment decreased plasma glucose and leucine concentrations and leucine flux, but failed to decrease leucine oxidation. In the remaining 5 of the 9 diabetic patients, uninterrupted insulin treatment prior to the study and a seven-hour intravenous insulin treatment during the study period decreased not only the concentrations of plasma glucose and leucine and leucine flux, but also leucine oxidation (P less than .01). In all 9 diabetic patients the nonoxidative portion of leucine flux (reflecting protein synthesis) decreased during insulin treatment (P less than .01), but this decrease was lower than that of leucine flux (reflecting proteolysis), and therefore protein was conserved during insulin treatment. We conclude that the effect of insulin on proteolysis (reflected by leucine flux) is more rapid than its effect on leucine oxidation, but on aggressive insulin treatment accelerated leucine oxidation also was decreased in type I diabetic patients.

Adult↗
PubMed1987

Influence of fasting on leucine and muscle protein metabolism across the human forearm determined using L-[1-13C,15N]leucine as the tracer.

1. We have used L-[1-13C,15N]leucine as the substrate tracer to study leucine and muscle protein metabolism across the forearm of eight normal fasting adults. 2. The rates of protein synthesis and breakdown, de- and re-amination of leucine, and the oxidative decarboxylation of its keto acid were calculated directly from the arteriovenous metabolite balances and isotope dilutions as described by the metabolic model. 3. The results were compared with those obtained previously when subjects were fed. The effects of fasting on protein and leucine metabolism were a significant decrease in protein synthesis from 127 (SEM 11; n = 6) to 70 (SEM 6; n = 12) nmol of leucine min-1 100 ml-1 of forearm tissue (P less than 0.001) and a marked decrease in leucine catabolism in the forearm muscle. 4. This model has demonstrated that each subject was in negative protein balance across the forearm during fasting while positive during feeding, the mean values being -29(SEM 5; n = 12) and +39(SEM 9; n = 6) nmol of leucine min-1 100 ml-1 of forearm tissue respectively. 5. These results are sufficiently encouraging to suggest a role for this model in future studies on muscle protein metabolism.

Adult↗
PubMed1987

Failure of carbohydrate to spare leucine oxidation in obese subjects.

Leucine kinetics were studied in six obese subjects (W/H2 = 39 +/- 4) and six normal subjects (W/H2 = 21 +/- 3) before and after an oral load of 150 g glucose. An intravenous infusion of 1(-13)C leucine was given to the fasting subjects for 450 min: a steady state of plasma leucine enrichment was established 90 min after the start of the infusion, and the glucose load was given 220 min after the start of the infusion. Compared with the lean controls the obese subjects showed a greater area under the curve of blood glucose after the glucose load (P less than 0.025) and higher insulin and glucagon levels both before and after the meal (P less than 0.05), thus indicating the well-known insulin insensitivity of obese (but not diabetic) subjects with respect to glucose metabolism. After the glucose load the lean subjects showed a significant and sustained decrease in leucine oxidation (from 20.0 +/- 2.2 to 13.3 +/- 1.5 mumol/kg LBM/h: P less than 0.01). This response is similar to that observed when insulin-dependent diabetic subjects are given insulin. However the obese subjects showed no decrease in leucine oxidation after the glucose meal (20.3 +/- 1.9 before, and 21.2 +/- 3.6 after). This indicates that obese subjects show insensitivity to the action of insulin with respect to protein metabolism as well as carbohydrate metabolism.

Administration, Oral↗
PubMed1985

Structural homology between mouse liver and horse spleen ferritins.

Mouse liver ferritin is composed almost exclusively of polypeptide chains similar in molecular mass (22 kDa) to that characteristic of the major chain (H) found in heart ferritin isolated from human, horse or rat. In these species the predominant polypeptide of liver (L) is smaller (about 20 kDa). Here we show that mouse liver and horse spleen ferritins and apoferritins exhibit extensive structural homology as judged by the similarity in the diffraction patterns of their crystals grown from cadmium sulphate solutions. Implications of this finding are discussed.

Animals↗
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

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↗