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Biomedical subjects

P W Emery

Publications and source records attributed to P W Emery.

At least 19 recordsLinked to original sources
PubMed2005

Influence of folate status on genomic DNA methylation in colonic mucosa of subjects without colorectal adenoma or cancer.

DNA hypomethylation may increase the risk of colorectal cancer. The main aim of this study was to assess the influence of folate status (serum and erythrocyte folate and plasma homocysteine concentrations) on DNA methylation. Methylenetetrahydrofolate reductase (MTHFR 677C --> T and 1298A --> C), methionine synthase (MS 2756A --> G) and cystathionine synthase (CBS 844ins68) polymorphisms were measured to account for potential confounding effects on folate status and DNA methylation. A total of 68 subjects (33 men and 35 women, 36-78 years) free from colorectal polyps or cancer were recruited in a cross-sectional study. Tissue biopsies were obtained at colonoscopy for the determination of DNA methylation in colonic mucosa using an in vitro radiolabelled methyl acceptance assay. Serum and erythrocyte folate were inversely correlated with plasma homocysteine (r=-0.573, P<0.001 and r=-0.307, P=0.01 respectively) and DNA hypomethylation in colonic mucosa (r=-0.311, P=0.01 and r=-0.356, P=0.03). After adjusting for gender, age, body mass index, smoking and genotype, there were weak negative associations between serum and erythrocyte folate and colonic DNA hypomethylation (P=0.07 and P=0.08, respectively).

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2005

Metabolic changes in malnutrition.

This paper is concerned with malnutrition caused by inadequate intake of all the major nutrients rather than deficiency diseases relating to a single micronutrient. Three common situations are recognised: young children in third world countries with protein-energy malnutrition; adults in the same countries who are chronically adapted to subsisting on marginally inadequate diets; and patients who become malnourished as a result of chronic diseases. In all these situations infectious diseases are often also present, and this complicates the interpretation of biochemical and physiological observations. The metabolic response to starvation is primarily concerned with maintaining a supply of water-soluble substrates to supply energy to the brain. Thus there is an initial rise in metabolic rate, reflecting gluconeogenic activity. As fasting progresses, gluconeogenesis is suppressed to minimise muscle protein breakdown and ketones become the main fuel for the brain. With chronic underfeeding the basal metabolic rate per cell appears to fall, but the mechanistic basis for this is not clear. The main adaptation to chronic energy deficiency is slow growth and low adult body size, although the reduction in energy requirement achieved by this is partially offset by the preservation of the more metabolically active organs at the expense of muscle, which has a lower metabolic rate. The interaction between malnutrition and the metabolic response to trauma has been studied using an animal model. The rise in energy expenditure and urinary nitrogen excretion following surgery were significantly attenuated in malnourished rats, suggesting that malnutrition impairs the ability of the body to mobilise substrates to support inflammatory and reparative processes. However, the healing process in wounded muscle remained unimpaired in malnutrition, suggesting that this process has a high biological priority.

Adult↗
PubMed2005

Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma.

BACKGROUND AND AIMS: A low dietary folate intake can cause genomic DNA hypomethylation and may increase the risk of colorectal neoplasia. The hypothesis that folic acid supplementation increases DNA methylation in leucocytes and colorectal mucosa was tested in 31 patients with histologically confirmed colorectal adenoma using a randomised, double blind, placebo controlled, parallel design. METHODS: Subjects were randomised to receive either 400 microg/day folic acid supplement (n = 15) or placebo (n = 16) for 10 weeks. Genomic DNA methylation, serum and erythrocyte folate, and plasma homocysteine concentrations were measured at baseline and post intervention. RESULTS: Folic acid supplementation increased serum and erythrocyte folate concentrations by 81% (95% confidence interval (CI) 57-104%; p<0.001 v placebo) and 57% (95% CI 40-74%; p<0.001 v placebo), respectively, and decreased plasma homocysteine concentration by 12% (95% CI 4-20%; p = 0.01 v placebo). Folic acid supplementation resulted in increases in DNA methylation of 31% (95% CI 16-47%; p = 0.05 v placebo) in leucocytes and 25% (95% CI 11-39%; p = 0.09 v placebo) in colonic mucosa. CONCLUSIONS: These results suggest that DNA hypomethylation can be reversed by physiological intakes of folic acid.

Adenoma↗
PubMed2004

Plasma taurine and cysteine levels following an oral methionine load: relationship with coronary heart disease.

OBJECTIVE: To test the hypothesis that endogenous synthesis of taurine from methionine is impaired in people with coronary heart disease (CHD). DESIGN: Nested case-control. SUBJECTS: Indian Asian and white European males aged 35-60 y. Both racial group included patients with CHD and healthy controls. Samples from 20 subjects in each of the four groups were selected at random. INTERVENTION: Fasting blood samples were taken before and 6 h after consumption of methionine (100 mg/kg body weight) MEASUREMENTS: Plasma concentrations of taurine, cysteine, pyridoxal-5-phosphate and 4-pyridoxic acid. RESULTS: Fasting plasma taurine values were higher in Indian Asian cases than controls, but not significantly different between European cases and controls. Postload taurine values were higher in cases than controls in both racial groups (P=0.002). Fasting plasma cysteine was higher in cases than controls (P=0.002) and higher in Indian Asians than Europeans (0.007), but there were no significant differences between any of the groups in postload cysteine values, nor in plasma pyridoxal-5-phosphate or 4-pyridoxic acid. CONCLUSIONS: Taurine production from methionine was not impaired in patients with CHD, but fasting plasma cysteine was higher in CHD cases than controls.

Adult↗
PubMed2001

Separation and identification of rat skeletal muscle proteins using two-dimensional gel electrophoresis and mass spectrometry.

Skeletal muscle plays a major role in whole body protein metabolism, and changes in the rates of synthesis and degradation of proteins are likely to lead to characteristic changes in the amounts of different proteins in muscle under various physiological and pathological conditions. This paper demonstrates the feasibility of a proteomic approach to analyzing the protein composition of skeletal muscle. We report here the initial establishment of two-dimensional gel electrophoresis (2-D PAGE) reference maps for mixed skeletal muscle taken from the abdominal wall of a normal adult rat. We used immobilized pH gradients of 3-10 (non-linear) and 4-7 (linear), and matrix assisted laser desorption/ionization--time of flight mass spectrometry for protein identification by peptide mass fingerprinting. More than 600 protein spots were detected on each gel, of which 100 were excised and characterized. In-gel digestion followed by peptide mass fingerprinting enabled tentative identification of 74 of these, which included a wide range of myofibrillary and sarcoplasmic proteins. This database should provide the nucleus of a valuable resource for investigation of the biochemical basis of skeletal muscle pathologies in general and such specific disorders as alcoholic myopathy and injury.

Animals↗
PubMed2000

The postprandial rates of glycogen and lipid synthesis of lean and obese female Zucker rats.

OBJECTIVE: To determine the relative rates of glycogenesis and lipogenesis following administration of a test meal in lean and obese Zucker rats. PROTOCOL: Nine-week-old lean and obese Zucker rats were fasted overnight, then tube-fed a test meal of balanced composition amounting to 16kJ (lean rats and one group of obese rats) or 24kJ (one group of obese rats) and containing 200 mg 1-(13)C glucose. Immediately after the meal the rats were injected intraperitoneally with 5 mCi of 3H2O and killed 1 h later. METHODS: Glycogenesis was calculated from the incorporation of 3H into liver glycogen divided by the specific activity of plasma water. Lipogenesis was calculated similarly from the incorporation of 3H into saponifiable lipids in liver and perirenal adipose tissue. The proportion of glycogen synthesized by the indirect pathway via pyruvate was determined from the ratio of 3H labelling at positions C6 and C2 in the glycogen glucose residues. Glycogen synthesis from glucose was determined from the ratio of 13C enrichment in liver glycogen to that in plasma glucose. RESULTS: The rate of synthesis of glycogen was considerably lower in the livers of obese rats than those of lean controls, with the larger meal causing a small but significant increase in glycogenesis. The proportion of glycogen synthesized via pyruvate showed a non-significant increase in the obese rats, while the amount of glycogen synthesized from glucose was significantly decreased. Hepatic lipogenic rates were about five times higher in both groups of obese rats than the lean controls. In adipose tissue, lipogenesis per g tissue was slightly reduced in the obese rats, although there was clearly an increase in adipose tissue lipogenic activity per whole animal. The larger meal caused a greater rise in plasma glucose and insulin concentrations but did not affect lipogenic rates, although it did cause a greater suppression of lipolysis, as indicated by a lower plasma glycerol concentration. CONCLUSION: Ingested carbohydrate is partitioned predominantly into hepatic fatty acid synthesis in obese Zucker rats. Hepatic glycogen synthesis is suppressed and comes mainly from precursors other than glucose. The suppression of hepatic glycogen synthesis may contribute to the increased energetic efficiency of obese Zucker rats.

Animals↗
PubMed1999

The effect of malnutrition on the metabolic response to surgery.

The effect of previous malnutrition on the metabolic response to surgical hysterectomy was investigated in adult female rats. Malnutrition was achieved by feeding a 20 g protein/kg diet and restricting food intake to 50% of normal. This dietary regimen was maintained for 3 weeks before surgery and for 4 d after surgery. Unoperated control rats were pair-fed with the hysterectomized rats after surgery. Energy balance was measured by the comparative carcass technique and, in a second experiment, urinary N excretion was measured. Surgery caused energy expenditure to increase by 37% in ad libitum-fed rats but in malnourished rats it increased by only 22%. Urinary N excretion rose immediately after surgery. In the ad libitum-fed rats it was on average 85% greater in hysterectomized rats than controls for the first 3 d after surgery, whereas in the restricted rats it was 74% greater on the first day and not significantly elevated thereafter. Thus, malnutrition attenuated the metabolic response to surgery but did not abolish it completely.

Animals↗
PubMed1998

The effect of meal size on postprandial carbohydrate metabolism in normal and tumor-bearing rats.

Doubling the size of a meal causes less than a two-fold increase in the thermic effect of feeding. One possible reason for this is that larger meals may be associated with a change in the pathway of postprandial hepatic glycogen synthesis from the indirect pathway, involving gluconeogenesis, to the more energetically efficient direct pathway. We have therefore investigated the effect of meal size on the relative contributions of those two pathways both in normal rats and in tumor-bearing rats, which have previously been shown to utilize the indirect pathway to a greater extent. Rats bearing a transplantable Leydig cell tumor and freely fed controls were fasted overnight and given a test meal amounting to 12 or 24 kJ of their normal diet. They were then injected with 3H2O and 14C-glycerol and killed one hour later. The total amount of 3H incorporated into liver glycogen was not affected by meal size, although it was greater in tumor-bearing rats than controls. Analysis of the 3H labelling at different positions in the glycogen glucose residues showed that the proportion of glycogen synthesized via pyruvate, which tended to be greater in tumor-bearing rats, was significantly reduced by increasing the size of the meal. Glycogen synthesis from glycerol was not affected by either meal size or tumor growth. Increasing the size of the meal increased the rate of fatty acid synthesis in both the liver and the epididymal fat pad, but not the tumor. Thus increasing the size of the meal appeared to increase the proportion of glycogen synthesized by the direct pathway from glucose in both tumor-bearing and control animals.

Animals↗
PubMed1998

Glycogen synthesis in tumor-bearing rats after ingestion of a high-glycerol meal.

Tumor-bearing rats have a high rate of postprandial hepatic glycogen synthesis by the indirect pathway that involves gluconeogenesis. This study was designed to investigate the role of glycerol as a precursor for postprandial glycogen synthesis in tumor-bearing rats. Rats bearing a Leydig cell tumor and freely fed controls were fasted overnight, then fed a 16-kJ meal with or without 50 mg of glycerol by gavage. [U-14C]glycerol (1 microCi) was also administered intragastrically, and 7 mCi of 3H2O were injected intraperitoneally. The rats were killed one hour later, and the specific activities at different positions within the glycogen glucose residues in the liver were measured. Increasing the glycerol content of the meal had no significant effect on the overall incorporation of 3H into liver glycogen or on the proportion of glycogen synthesized via pyruvate in tumor-bearing or control rats. There was no difference between tumor-bearing and control rats in the amount of glycerol incorporated into glycogen, although this was increased by the high-glycerol meal. Thus glycerol appeared to make a small contribution to postprandial glycogen synthesis in tumor-bearing and control rats.

Animals↗
PubMed1997

Effect of acute acipimox administration on the rates of lipid and glycogen synthesis in cachectic tumor-bearing rats.

Increased energy expenditure in cancer cachexia may be associated with increased postprandial glycogen synthesis via an indirect pathway involving gluconeogenesis. The possible beneficial effect of acipimox, a nicotinic acid analogue that suppresses lipolysis and may also inhibit gluconeogenesis, were therefore examined. Rats bearing a transplantable Leydig cell tumor and freely fed controls were fasted overnight, then given a test meal with or without 10 mg of acipimox. The meal included 200 mg of [1-13C]glucose, and the rats were injected simultaneously with 7 mCi of 3H2O and 1 microCi of [14C]glycerol. The rats were killed one hour later. The rate of incorporation of 3H2O into hepatic glycogen was increased in the tumor-bearing rats and suppressed by acipimox. Positional analysis of the tritium incorporated into glycogen indicated that a greater proportion of the glycogen was synthesized via pyruvate in the tumor-bearing rats. Acipimox tended to reduce this proportion, although the effect was not statistically significant. Neither tumor growth nor acipimox significantly affected the proportion of 13C incorporated into different positions in the glycogen glucose. Glycogen synthesis from glycerol tended to decrease when lipolysis was suppressed by acipimox, although the statistical significance of this effect was marginal. Fatty acid synthesis in liver and adipose tissue was reduced in tumor-bearing rats, but acipimox had no effect. It is concluded that acipimox does suppress gluconeogenesis and glycogenesis in the postprandial state, but it does not normalize all the metabolic abnormalities observed in cancer cachexia.

Animals↗
PubMed1997

Two phase randomised controlled clinical trial of postoperative oral dietary supplements in surgical patients.

BACKGROUND: Previous work has shown that the administration of oral dietary supplements to patients who have undergone gastrointestinal surgery results in clinically significant short term benefits. AIMS: This study aimed firstly to re-evaluate these short term effects, and secondly to establish whether there are any long term benefits. SUBJECTS: One hundred patients admitted for elective moderate or major gastrointestinal surgery. METHODS: In the inpatient phase, patients were randomised to receive a normal ward diet postoperatively, or the same diet supplemented with an oral dietary supplement. In the outpatient phase, patients were further randomised to receive their home diet, or their home diet supplemented with the oral dietary supplement for four months. RESULTS: During the inpatient phase, patients treated with oral supplements had a significantly improved nutritional intake and lost less weight (2.2, 95% confidence interval (95% CI) 0.9 kg) compared with control patients (4.2 (0.78) kg, p < 0.001). Supplemented patients maintained their hand grip strength whereas control patients showed a significant reduction in grip strength (p < 0.01). Subjective levels of fatigue increased significantly above preoperative levels in control patients (p < 0.01) but not in the supplemented group. Twelve patients in the control group developed complications compared with four in the supplemented group (p < 0.05). In the outpatient phase, supplemented patients had improved nutrient intakes but there were no significant differences in indices of nutritional status or wellbeing between the groups. CONCLUSIONS: The prescription of oral dietary supplements to patients who have undergone gastrointestinal surgery results in clinically significant benefits. These benefits, however, are restricted to the inpatient phase.

Adult↗
PubMed1995

The local and systemic effects of minor injury on muscle protein synthesis in the rat.

Massive physical trauma has marked effects on metabolism of body tissues. At present, however, there is little data available on the effect of minor injury on protein metabolism. In this study we examined the effects of a minor muscle injury on the rate of protein synthesis in injured muscle as well as its contralateral control. Rats were injured by removing a small piece of tissue from the interior of one gastrocnemius muscle. Muscle protein synthesis was measured in vivo by a flooding dose technique. The injury had no significant effect on food intake, body weight, muscle protein content or plasma insulin concentration at any time during the following 48 hr. However the rate of protein synthesis in the injured muscle increased 48 hr after injury (mean value in injured muscle 16.1 +/- 1.8 (SEM, n = 18) % per day, uninjured muscle in the same animals 13.1 +/- 1.3% per day, P < 0.05 by paired t-test). These results indicate that even a minor injury causes a local increase in the rate of protein synthesis 48 hr later. This may be an obligatory part of the process of repair and regrowth of muscle tissue.

Animals↗
PubMed1995

Effect of dietary restriction on protein synthesis and wound healing after surgery in the rat.

1. The healing of an abdominal muscle wound after surgery is associated with a considerable increase in the rate of protein synthesis. We have investigated whether this increase in protein synthesis is affected by chronic undernutrition, and whether this causes a delay in wound healing. 2. A group of rats was fed 58% of the voluntary food intake of a matched control group. After 7 days half the rats in each group underwent abdominal surgery. Forty-eight hours later all the rats were killed and muscle protein synthesis rate was measured by the flooding dose technique. 3. In a second experiment using the same dietary regimen rats were placed in metabolic cages after surgery and killed 7 days later. In addition to measurements of muscle protein synthesis, wound breaking strength was measured with a tensiometer and collagen content was also measured at the wound site. 4. Dietary restriction caused a loss of body weight, a decrease in nitrogen balance and a deficit in muscle protein mass. It also caused a decrease in protein synthesis rate in gastrocnemius muscle and in parts of the abdominal muscle distant from the site of the wound. However, it had no effect on the rate of muscle protein synthesis at the site of the wound either 2 or 7 days after surgery. The tensile strength and the collagen content of the wound were also unaffected by food restriction. 5. It is concluded that the wound healing process is uniquely protected from the effects of moderate undernutrition such as might be experienced by a chronically ill patient.

Abdominal Muscles↗
PubMed1994

Effect of surgical trauma on muscle protein synthesis in the rat.

The rate of protein synthesis in skeletal muscle was measured in vivo in rats at various times during the first 2 days after abdominal surgery. Protein synthesis in abdominal muscle at the site of the wound was slightly reduced 2 h after operation, had returned to normal by 24 h and was massively increased by 48 h after surgery. In contrast, there was no change at any time in the rate of protein synthesis in either the gastrocnemius muscle or abdominal muscle distant from the wound site. Surgery had no effect on the weight or protein content of the gastrocnemius muscle, although urinary nitrogen excretion was increased relative to food intake, indicating the presence of a net catabolic response. Changes in whole-body protein turnover in response to uncomplicated abdominal surgery are thus likely to reflect the anabolic processes of wound healing and repair as well as any catabolic response in uninjured tissues.

Abdominal Muscles↗
PubMed1993

Lipid metabolism in cachectic tumor-bearing rats at different stages of tumor growth.

Rates of lipogenesis and lipoprotein lipase (LPL) activity were measured in liver, adipose tissue, heart, and tumor at several stages during 10 days of palpable growth of a transplantable Leydig cell tumor in rats. This model showed the same characteristics as human cancer cachexia, including anorexia, weight loss, and muscle wasting. Comparison with pair-fed controls showed that the rate of loss of body fat was greater than could be explained by anorexia alone. The rate of lipogenesis tended to decrease during the later stages of tumor growth, particularly in the liver, where there was a statistically significant reduction on Days 5 and 10. This may be largely attributable to decreased availability of substrates caused by decreasing food intake and increasing glucose uptake by the tumor. There was a significant decrease in plasma glucose concentration by Day 10. In contrast, LPL activity in adipose tissue was depressed from the earliest stage of tumor growth, and this is likely to be a major cause of lipid depletion in cancer. There was no difference in adipose tissue LPL activity between the fed and postabsorptive states in the tumor-bearing rats, indicating that the normal response to nutrient intake was impaired. Thus, treatment of cancer cachexia should concentrate on normalizing the metabolic response to nutrient ingestion.

Animals↗
PubMed1993

Alterations in postprandial glycogen and lipid synthesis in cachectic tumor-bearing rats.

Alterations in the postprandial metabolism of glucose were investigated in groups of tumor-bearing rats and freely fed controls and in groups of normal rats whose food intake had been restricted to match that of the tumor-bearing rats. A standard mixed meal was administered by gavage, and the rate of incorporation of 3H from 3H2O into hepatic glycogen and into saponifiable lipids in the liver and adipose tissue was measured at intervals up to three hours after the meal. In tumor-bearing rats, the rate of glycogen synthesis rose by more than twice as much as normal after the meal, while the normal rise in rates of fatty acid synthesis was suppressed. In contrast, in the rats whose food intake had been restricted, the postprandial rise in hepatic glycogenesis was suppressed and the rates of postprandial lipogenesis in liver and adipose tissue were increased. Thus the changes that were observed in the tumor-bearing animals did not represent a normal response to reduced food intake. Increased postprandial glycogenesis in tumor-bearing rats is likely to be associated with increased gluconeogenesis, thereby increasing energy expenditure. The prolonged high rate of hepatic glycogen synthesis may also delay the initiation of the next meal and thus contribute to the decrease in food intake in cancer cachexia.

Animals↗
PubMed1991

Influx and incorporation into protein of L-phenylalanine in the perfused rat pancreas: effects of amino acid deprivation and carbachol.

The rate of protein synthesis in the isolated perfused rat pancreas was measured from the rate of incorporation of L-[3H]phenylalanine into total protein, and was compared with the transport of this amino acid into the epithelium. Unidirectional (15 s) and net (15-30 min) uptake of L-[3H]phenylalanine was measured relative to D-[14C]mannitol (extracellular marker) using a cell loading technique. The fractional rate of protein synthesis in the pancreas was also measured in vivo using a flooding dose technique and found to be 118 +/- 10% day-1 (corresponding to an absolute rate of incorporation of L-Phe into protein of 36.1 +/- 3 nmol min-1 g-1) in overnight fasted rats. Compared with the in vivo rate, the perfused pancreas exhibited a markedly lower rate of protein synthesis which increased significantly when amino acids were added to the perfusate (15.6 +/- 1.9 vs. 22.5 +/- 0.9% day-1 or 4.7 +/- 0.6 vs. 6.9 +/- 0.3 nmol L-Phe min-1 g-1). Carbachol (3 x 10(-7) M) stimulated protein synthesis provided amino acids were also supplied in the perfusate. Protein synthesis rates measured under all conditions in vivo and in vitro were at least an order of magnitude lower than the unidirectional influx (121 +/- 14 nmol min-1 g-1) of L-phenylalanine into the pancreatic epithelium. These results demonstrate that amino acid transport across the basolateral membrane of the epithelium is not rate-limiting for pancreatic protein synthesis.

Amino Acids↗