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Biomedical subjects

D Halliday

Publications and source records attributed to D Halliday.

At least 181 records · Page 10Linked to original sources

Changes in fat, fat-free mass and body water in human normal pregnancy.

Measurements of body weight, total body water and total body potassium (40K) were made serially on three occasions during pregnancy and once post partum in 27 normal pregnant women. Skinfold thickness and fat cell diameter were also measured. A model of body composition was formulated to permit the estimation of changes in fat, lean tissue and water content of the maternal body. Total maternal body fat increased during pregnancy, reaching a peak towards the end of the second trimester before diminishing. Serial measurements of fat cell diameter showed poor correlation, whilst total body fat calculated from skinfold thickness correlated well with our estimated values for total body fat in pregnancy.

Adipose Tissue↗

3-Methylhistidine excretion as an index of myofibrillar protein catabolism in neuromuscular disease.

Myofibrillar protein catabolism has been calculated in a variety of neuromuscular diseases from the amount of 3-methylhistidine excreted in the urine. It was found to be significantly raised in Duchenne type muscular dystrophy, motor neurone disease, polymyositis, and thyrotoxic myopathy. In Becker type muscular dystrophy the level was slightly raised. It was normal in scapuloperoneal and limb girdle dystrophy, dystrophia myotonica, extrapyramidal disease, and multiple sclerosis. It was significantly decreased in hypothyroid myopathy.

Histidine↗

Resting metabolic rate, weight, surface area and body composition in obese women.

Resting metabolic rate was measured in 22 women with varying degrees of obesity. Body composition was estimated from total body potassium and from total body water, and creatinine excretion in urine was measured over a period of three weeks while the patients were on a creatinine and creatine-free reducing diet. Resting metabolic rate was highly significantly correlated with body weight, surface area, creatinine excretion and lean body mass calculated either from potassium or water measurements (P less than 0.001). Correlation with adipose tissue was less strong, and when multiple regression of both fat and lean on metabolic rate was performed, the relationship was seen to depend mostly on the mass of lean rather than adipose tissue. In obese people the water content of fat-free tissue is greater than that in normal subjects, so it is not valid to assume that fat content can be calculated accurately from a measurement of total body water.

Adipose Tissue↗

Sources of ammonia for mammalian urea synthesis.

The initial rate of incorporation of [15N]alanine into the 6-amino group of the adenine nucleotides in rat hepatocytes was about one-eighteenth of the rate of incorporation into urea. Thus the purine nucleotide cycle cannot provide most of the ammonia needed in urea synthesis for the carbamoyl phosphate synthase reaction (EC 2.7.2.5). On the other hand, contrary to the view expressed by McGivan & Chappell [(1975) FEBS Lett. 52, 1--7], the experiments support the view that hepatic glutamate dehydrogenase can supply the required ammonia.

Adenine Nucleotides↗

Comparison of human myofibrillar protein catabolic rate derived from 3-methylhistidine excretion with synthetic rate from muscle biopsies during L-[alpha-15N]lysine infusion.

1. Urine was collected in five healthy men over 10--14 days, with fasting blood samples on days 1, 5 and 10, whilst they consumed a standard creatine-free diet, which was quantitatively related to their body surface area. 2. The urinary excretion of 3-methylhistidine fell to a plateau by day 5 in all subjects. Myofibrillar protein catabolic rate calculated from the mean value of 3-methylhistidine excretion from day 5 to day 10 averaged 1.21 g day-1 kg-1 body weight. The average turnover of muscle myofibrillar protein was calculated to be 2.16%/day. 3. From a previous study using continuous intravenous infusion of L-[alpha-15N]lysine with serial muscle biopsies on the same subjects, the mean myofibrillar protein synthetic rate was calculated to be 0.82 g day-1 kg-1 body weight, and the mean turnover rate was 1.47%/day of total muscle myofibrillar protein. 4. The estimations of myofibrillar protein turnover rate derived from the two methods are compared and the differences discussed.

Adult↗

Metabolic studies with keto acid diets.

Five patients with chronic renal failure taking a diet containing approximately 5 g N throughout were studied during two periods of 1 month each. Nitrogen balance, urea metabolism, and incorporation of 15N from urea into albumin on diet alone or with a keto acid/essential amino acid supplement were measured. Keto acids produced a reduction of plasma urea, urea synthesis, and urea excretion and an improvement in nitrogen balance. In patients who demonstrated the greatest change on ketoacids, 15N incorporation also increased, but their total incorporation of urea nitrogen was not nearly sufficient to account for the improvement in nitrogen balance. The role of keto acids in protein anabolism is not solely or even mainly explained by promotion of nonprotein nitrogen reutilization.

Aged↗

Anabolic role of urea in renal failure.

The amount of urea nitrogen released and the amount reincorporated into albumin has been measured in healthy and uremic individuals on both normal and low-protein diets. The albumin synthesis rate was measured simultaneously. Gut urea breakdown was only 50% higher in renal failure than in health, but the efficiency of utilization of the nitrogen thus released was increased more than 6-fold in renal failure and was higher on a low protein than on a normal protein diet. The lower the albumin synthetic rate, the greater was the efficiency of incorporation of urea nitrogen into albumin. The rate of urea nitrogen incorporation into albumin increased on average 14-fold in chronic renal failure. The absolute rate of utilization (84 mumole/hr) was, however, small and comprised on average only 2.4% of the nitrogen used in albumin synthesis. These findings suggest that although some urea derived nitrogen is incorporated into albumin, the amount is not nutritionally significant even under conditions of protein deprivation and high urea availability.

Albumins↗

Detection of intracellular immunoglobulin in nodular lymphomas.

In lymph node tissue sections, six of 11 human cases of nodular lymphoma showed immunoglobulin within malignant nodules, and seven of nine cases of benign follicular hyperplasia showed immunoglobulin within follicles. In addition, distributions of lymphocyte cell membrane markers for T cells and B cells were determined in ten of 11 cases of nodular lymphoma. Lymphocyte suspensions in five cases contained monoclonal immunoglobulins and in three cases neoplastic cells showed a lack of surface membrane immunoglobulins. In two cases, the distribution of lymphocyte surface markers could not be distinguished from cells of benign lymph nodes. Combined data from intracytoplasmic immunoglobulin studies and lymphocyte surface marker assays indicated that eight of ten cases are of B cell lineage. Thus, the detection of intracellular immunoglobulin is not helpful in differentiating benign follicular hyperplasia from nodular lymphoma, but is complementary to lymphocyte surface marker assays in the determination of the origin of neoplastic cells in lymphoreticular malignancies.

Antibodies↗

Direct evidence for synthesis of valine in man.

Plasma valine and 13C-valine concentrations were measured in 2 healthy volunteers and 2 uraemic patients during and after a 3-hour intravenous infusion of the 13-c-labelled alpha-keto-acid analogue of valine. Plasma-valine increased by 23-43%. 13C-valine accounted for most of the early increase, but for less than 30% of the increase 1 hour after infusion. It was concluded that valine had increased by 2 mechanisms with different time courses. Initially, transamination of the infused ketoacid predominated, confirming directly for the first time that the essential aminoacid valine can be synthesised in-vivo both in health and uraemia. The previously unsuspected second mechanism was quantitatively more important but slower in ooperation; it may prove to be the key to understanding the metabolic effects of essential aminoacid precursors.

Adult↗

Precise measurement of total body water using trace quantities of deuterium oxide.

This study was undertaken to investigate the possibility of measuring total body water in human subjects to better than +/-0.5%. Accurate serial estimates of total body water were required to complement densitometric and anthropometric measurements used to monitor body compositional changes in obese patients undergoing dietary or surgical weight reduction therapy. The method required the oral administration of 1-2 g of deuterium oxide and the analysis of pre-dose and respective equilibrated samples of urine, plasma or saliva. The sample size required for analysis was 5 microliter and the conversion of gaseous phase was accomplished using a uranium reduction furnace. Isotopic enrichment of samples was measured using a mass spectrometer incorporating several features designed to cope with problems inherent in H2/H2H isotopic analysis. Reproducibility of sample preparation and accuracy of the mass spectrometer were tested using international standards and shown to give an overall sensitivity of 2 parts in 10(7) for the determination of deuterium in H2O/H2HO mixtures. This precision has enabled us to demonstrate that isotopic fractionation of deuterium with respect to hydrogen occurs within the body and expands the potential use of this isotope for quantitative biochemical studies in the human subject.

Body Water↗

Reversal of ineffective erythropoiesis in pernicious anaemia following vitamin B12 therapy.

Ineffective erythropoiesis was quantitated in a series of patients with pernicious anaemia at different times in relation to vitamin B12 therapy by measuring the incorporation of [15N]delta aminolaevulinic acid and [15N]glycine into early labelled bilirubin. Prior to therapy ineffective erythropoiesis was grossly increased but this was reversed within 24 h of giving vitamin B12, suggesting that most of the existing megaloblasts are enabled to mature into circulating red cells.

Aged↗

Role of ineffective erythropoiesis in the anaemia of rheumatoid arthritis.

The importance of inadequate haemoglobin synthesis and ineffective erythropoiesis in the anaemia of rheumatoid arthritis was studied by measuring the incorporation of 15N glycine into haemoglobin haem and early labelled bilirubin in a patient with severe anaemia before and after response to gold therapy. Initially, total erythroid haem turnover was decreased but haem turnover due to ineffective erythropoiesis was markedly increased, accounting for 29% of total erythroid haem turnover. Gold therapy resulted in marked clinical improvement, accompanied by a rise in haemoglobin to normal. Total erythroid haem turnover increased and the percentage ineffective erythropoiesis fell to normal. Ineffective erythropoiesis may thus be an important reversible factor in the production of the anaemia of rheumatoid arthritis.

Anemia↗

Congenital dyserythropoietic anaemia: response to splenectomy and quantitation of ineffective erythropoiesis.

The clinical and haematological features of an unusual case of congenital dyserythropoietic anaemia are described. There was a pronounced haemolytic component to the anaemia, with a mean cell life of five days, and a remarkable response to splenectomy. Measurement of the incorporation of 15N glycine into the haem of circulating red cells and into bilirubin showed that haem turnover due to ineffective erythropoiesis was increased 45 times compared with a control group (11.63 mg/kg/day, NR = 0.26 + 0-10) and represented 51% of total erythroid haem turnover.

Anemia↗

Increased myofibrillar protein catabolism in Duchenne muscular dystrophy measured by 3-methylhistidine excretion in the urine.

Myofibrillar protein catabolic rate was calculated in seven patients with Duchenne muscular dystrophy from the amount of 3-methylhistidine excreted in the urine, and found to be over three times that found in a control series when expresses as the percentage of myofibrillar protein catabolised per day. It is suggested that measurement of myofibrillar protein catabolic rate may add a useful parameter in the study of muscle disorders.

Adolescent↗