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Biomedical subjects

J M Dawson

Publications and source records attributed to J M Dawson.

At least 55 records · Page 3Linked to original sources
PubMed1991

Nutritional and endocrinological manipulation of lean deposition in forage-fed steers.

The effect of supplementing grass silage with fishmeal on growth, muscle composition and the rate of muscle protein synthesis was investigated in young Friesian steers with and without oestradiol implants. The effect of the beta-adrenergic agonist cimaterol was simultaneously investigated in animals fed on silage alone. Treatments lasted for 9 or 10 weeks. Fishmeal supplementation significantly increased animal growth rates (P less than 0.001) and the weights of three dissected muscles (P less than 0.001) compared with the silage-fed controls. These effects were further enhanced in animals also implanted with oestradiol. Muscle weights expressed as a proportion of body-weight were increased by fishmeal, suggesting that protein deposition had been enhanced. No further increase in the proportional muscle weights was obtained with oestradiol. Muscle dry matter content tended to be increased in both implanted and non-implanted animals receiving fishmeal compared with controls, but the proportions of protein, fat and ash were relatively constant. The intramuscular lipid composition was slightly altered by fishmeal. Muscle protein fractional synthetic rates (FSR), measured by continuous infusion of [3H]tyrosine, were increased by fishmeal in all three muscles of both implanted and non-implanted animals. There were no differences, however, due to oestradiol, over non-implanted fishmeal animals. This suggests that oestradiol may increase muscle accretion by reducing protein degradation rate. Cimaterol significantly increased longissimus dorsi (P less than 0.05) and vastus lateralis (P less than 0.01) muscle weights but had no effect on semitendinosus muscle weight or live-weight gain. The proportion of protein was increased (P less than 0.001) and the fat content reduced (P less than 0.05) in all three muscles but intramuscular lipid composition was not markedly affected. Whilst methylhistidine: creatinine excretion was reduced by cimaterol, FSR were increased in the l. dorsi and v. lateralis muscles suggesting beta-agonists have effects on both protein synthesis and protein degradation.

Adrenergic beta-Agonists↗
PubMed1991

Endocrine function, psychiatric and clinical consequences in patients with macroprolactinomas after long-term treatment with the new non-ergot dopamine agonist CV205-502.

Although bromocriptine is the mainstay of treatment of macroprolactinomas, its therapeutic usefulness may be limited by poor tolerance, lack of consistent reduction in serum prolactin levels and tumour size, and the necessity for multiple dosing. Consequently new dopamine agonists have been developed, including the long acting non-ergot agonist CV205-502 which has been shown to date to be consistently effective in reducing serum PRL levels and causing tumour shrinkage. Twelve patients were treated for periods of up to 24 months with CV205-502 in doses ranging from 0.075 mg to 1.65 mg once daily. Clinical and psychiatric assessments, biochemical parameters, tumour size determination, and anterior pituitary function tests were performed regularly. Tumour shrinkage was noted in all patients, and varied from 11 per cent reduction to complete disappearance of tumour. Prolactin levels became normal in seven patients and were reduced by more than 90 per cent in the remaining five. Normal menstruation resumed in six of the eight women, one of whom conceived after one year of therapy; libido returned in all patients. Psychiatric complications occurred in three patients necessitating withdrawal of therapy in one. Significant weight loss was noted in 11 of 12 patients. Triglyceride concentrations fell from 1.5 +/- 0.1 to 1.0 +/- 0.1 mmol/l at 12 months (p = 0.006), and cholesterol fell from 6.3 +/- 0.4 to 5.3 +/- 0.3 mmol/l (p = 0.04). The mean TSH response 20 min following TRH injection fell from 14.3 +/- 2.9 to 8.7 +/- 1.3 mU/l at 2 months (p = 0.027). There was a significant increase in the peak growth hormone response to the insulin stress test from basal median (25th-75th centiles) values of 15 (4.4-25.5) mU/l to 24.5 (9-37) mU/l at 2 months (p less than 0.01) and 31 (19.3-63.5) at 12 months (p less than 0.005). CV205-502 is highly effective in the medical management of patients with macroprolactinomas, reducing prolactin levels and tumour size and restoring normal anterior pituitary function. It is, however, associated with the important side effects of weight loss and psychiatric complications which should be drawn to the attention of clinicians.

Adult↗
PubMed1990

The effect of fishmeal on the digestion of grass silage by growing cattle.

The effect of two levels of fishmeal substitution (50 (FM1) and 150 (FM2) g/kg) of a grass silage control diet (C) on the rumen digestion of organic matter and nitrogen, and the small intestinal disappearance of amino acids was examined in young growing cattle each equipped with simple PVC cannulas in the dorsal sac of the reticulo-rumen, the proximal duodenum and the terminal ileum. The silage was a primary growth of perennial ryegrass (Lolium perenne) (+formic acid) with a total N content of 22 g/kg dry matter (DM) (diet C). Fishmeal substitution increased this to 26 (diet FM1) and 34 (diet FM2) g/kg DM. On diets C and FM1, approximately 0.71 of digestible organic matter intake was apparently digested in the rumen, but this was significantly (P less than 0.05) reduced on diet FM2 (0.60). Whilst duodenal flows of non-ammonia N and total amino acids were significantly (P less than 0.01) increased at the highest level of fishmeal inclusion only, the synthesis of microbial N was significantly (P less than 0.001) reduced by fishmeal inclusion, and feed N degradability declined progressively in response to increased fishmeal. Both levels of fishmeal addition caused a significant (P less than 0.05) reduction in the fractional outflow rate of water from the rumen, and on the highest level of fishmeal significant (P less than 0.05) increases in rumen ammonia concentration and rumen propionate molar proportions were observed. The net effect of the highest level of fishmeal substitution was to increase amino acid absorption from the small intestine by 0.47 compared with the control diet (P less than 0.05), but due to an elevated ileal flow of amino acid no such effect was detected at the lowest level of fishmeal substitution. Composition of the absorbed amino acid fraction was relatively unaffected by the treatments imposed, despite large changes in the composition of the duodenal protein. The apparent non-linearity of response to fishmeal substitution is discussed and the amino acid supply findings are compared with the protein retention findings obtained in an earlier study by Gill et al. (1987). By two methods of calculation it was estimated that the amino acid N fraction disappearing from the small intestine was utilized with an efficiency of between 0.51 and 0.53 and no apparent effects due to diet or level of amino acid supply were detected.

Amino Acids↗
PubMed1990

Changes in the microcirculation in slow and fast skeletal muscles with long term limitations of blood supply.

STUDY OBJECTIVE: Long term limitation of blood flow leads to decreased muscle performance and to damage, particularly in predominantly oxidative muscles. This study was performed to assess to what extent such damage can be explained by changes in microcirculation in capillaries supplying glycolytic or oxidative muscle fibres. DESIGN: Velocity and intermittency of flow, capillary diameters and proportion of adhering leucocytes were measured in capillaries in the epi-illuminated superficial glycolytic layer of rat tibialis anterior and in oxidative soleus muscles five weeks after ligation of the common iliac artery. EXPERIMENTAL MATERIAL: Male Sprague Dawley rats (approximately 350 g) were used, under sodium pentobarbitone anaesthesia. MEASUREMENTS AND RESULTS: Pressure in the saphenous artery, distal to the ligation site, recovered to 61% of carotid mean pressure. In tibialis anterior with limited blood supply, capillary diameters were narrower, red blood cell velocity was greater and intermittency of flow was reduced, resulting in a calculated volume flow per capillary which was only marginally reduced compared with controls. In soleus with limited blood supply, the time spent stationary by red blood cells was increased and there was a greater adhesion of white blood cells to venular walls. In neither muscle did limitation of blood supply result in a change in capillarity. CONCLUSIONS: Long term limitation of blood supply does not diminish the capillary density or capillary to fibre ratio of anatomically present capillaries in oxidative or glycolytic muscles and does not affect blood flow in capillaries supplying glycolytic fibres appreciably; circulation in capillaries supplying oxidative fibres is impaired.

Animals↗
PubMed1990

CV205-502, a new non-ergot dopamine agonist, reduces prolactinoma size in man.

Seven patients with large prolactin-secreting pituitary adenomas were treated for 8 weeks with once-daily doses of the new, potent, non-ergot, long-acting dopamine agonist CV205-502. In five patients previous treatment with bromocriptine had failed to control their disease or been poorly tolerated and had therefore ceased. In all seven patients serum prolactin levels fell over the 8-week period of CV205-502 treatment with the decrease ranging from 33 to 99%. Associated with this decline in prolactin all patients showed symptomatic improvement with two of the five women beginning to menstruate and the two patients with visual field impairment showing marked improvement. Tolerance of the drug, with doses at 8 weeks ranging from 0.075 to 0.3 mg, was excellent with only minimal and transient side-effects being noted in three patients in none of whom was discontinuation of therapy necessary. In one patient noncompliance after 6 weeks of therapy was associated with a rapid return of her serum prolactin towards pretreatment levels. In all seven patients the clinical and biochemical improvement was accompanied by a marked reduction in tumour size.

Adult↗
PubMed1990

Skeletal muscle microcirculation: the effects of limited blood supply and treatment with torbafylline.

The effects of one and two week arterial occlusion on the microcirculation of fast glycolytic skeletal muscle (rat tibialis anterior) were assessed by direct observation. Ligation of the right common iliac artery resulted in a greater proportion of the capillary population exhibiting intermittent flow, and reduction of capillary diameters. Terminal arterioles showed a lack of responsiveness to acute contractions of the muscle, while those in control muscles dilated. Acute infusion of torbafylline reduced the heterogeneity of flow by reducing the population of capillaries with intermittent flow and the time spent stationary by red cells. It also improved the pO2 at the muscle surface. Chronic oral administration of torbafylline for one week, started one week post-ligation, resulted in a similar response of the arterioles to muscle contractions as in control muscles and marginally improved the heterogeneity of flow.

Animals↗
PubMed1989

The effects of long term administration of prazosin on the microcirculation in skeletal muscles.

The effect on the microcirculation of long term administration of the alpha 1 blocker prazosin, which increases peripheral blood flow, was studied in skeletal muscles with differing metabolic profiles. Prazosin (50 mg.litre-1), given ad libitum for 5 weeks in the drinking water, resulted in an increase in capillarity in both fast glycolytic tibialis anterior cortex and slow oxidative soleus muscles of the rat. In tibialis anterior, the velocity of red blood cells through capillaries was increased, a smaller proportion of capillaries had intermittent flow, less time was spent stationary by red blood cells, and hence the calculated volume flow per capillary was increased. In soleus, capillary diameters were larger, but velocity, intermittency and calculated volume flow were unchanged. Therefore, suggested mechanisms for capillary growth induced by prazosin are different for the two muscles studied: increased shear stress and blood/endothelial cell interaction in the case of tibialis anterior, and increased capillary wall tension in the soleus.

Animals↗
PubMed1989

The effect of long-term activity on the microvasculature of rat glycolytic skeletal muscle.

Long-term electrical stimulation of a fast skeletal muscle (rat tibialis anterior, TA), at 10 Hz, 8 hours/day for 7 days, caused an increase in capillarity, determined both as capillary density/mm2 and as capillary to muscle fibre ratio (C/F), and an increase in the weight of corrosion cast of the entire vascular bed. Chronic muscle activity caused a greater linear velocity of RBCs (Vrbc) in the capillaries supplying predominantly glycolytic fibres of the resting TA. During contractions imposed acutely, the absolute value attained was greater than in control TA, but the increase over resting Vrbc was not as great. Factors which did not change with long-term electrical stimulation were the individual capillary dimensions and the intermittency of flow; those remained similar to control values. It was calculated from capillary dimensions and density, and from the increase in corrosion cast/muscle wet weight ratios, that capillary neoformation alone could account for the growth of the microvasculature in the predominantly glycolytic surface layers of TA, but not necessarily in the oxidative core or in other mixed skeletal muscles.

Animals↗
PubMed1988

Protein metabolism in the rumen of silage-fed steers: effect of fishmeal supplementation.

1. Ryegrass (Lolium perenne cv. Cropper) silage was given to four Friesian steers (initial live weight (LW) 172 kg) alone or with a fishmeal supplement (150 g fresh weight/kg silage dry matter (DM)) in a balanced two-period change-over design. The dietary components were the same as those used in a recent experiment by Gill et al. (1987). All diets were offered hourly at 24 g DM/kg LW. 2. Fishmeal supplementation increased dietary nitrogen intake (P less than 0.01) and significantly increased the flow of total N (P less than 0.01), non-ammonia N (NAN) (P less than 0.01) and amino acids (P less than 0.05) at the duodenum. The increased supply of NAN to the duodenum was due largely (67%) to increased flow of undergraded dietary protein. 3. Microbial protein production was estimated simultaneously with 15N, diaminopimelic acid (DAPA) and a novel technique using L-[4,5-3H]leucine. Estimates varied with the marker and source of microbial isolate but mean values indicated that microbial N flow was significantly increased by fishmeal supplementation (P less than 0.05). The use of L-[4,5-3H]leucine as a microbial marker is justified and its possible advantages over other markers are discussed. 4. The efficiency of microbial protein synthesis was significantly increased from 30.8 g N/kg organic matter apparently digested in the rumen (OMADR) to 54.3 g N/kg OMADR by fishmeal supplementation (P less than 0.01). However, this indicates that relatively high efficiencies can be achieved with unsupplemented high quality silage supplied continuously. Rumen degradable N (RDN) supply was significantly increased by fishmeal supplementation (P less than 0.05) but apparent efficiency of capture of RDN by rumen microbes was not significantly increased. 5. Attempts were made to investigate the source of N utilized by the microbes on the two diets by intrarumen infusions of (15NH4)2SO4 and L-[4,5-3H]leucine but these were confounded by rumen-mixing problems. Findings obtained suggest that a lower proportion of microbial N may have been derived from rumen ammonia when the silage was supplemented with fishmeal but no differences in the extent of direct incorporation of leucine into microbial protein were observed. This could indicate an increase in microbial peptide uptake on the fishmeal-supplemented diet. However, evidence was also obtained suggesting that the improvement in microbial protein synthetic efficiency with supplementary fishmeal was also due to the provision of a more continuous supply of nitrogenous substrates for microbial growth, as a result of hourly feeding.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Feed↗
PubMed1987

A comparison of the microcirculation in rat fast glycolytic and slow oxidative muscles at rest and during contractions.

We compared the microcirculation of the predominantly glycolytic (cortex of tibialis anterior, TA) and purely oxidative (soleus) muscles of the rat. The TA has wider (3.4 +/- 0.1 microns diameter compared to 2.7 +/- 0.05 microns), longer (405 +/- 29 and 205 +/- 17 microns), and straighter capillaries. Velocity of RBCs at rest is higher in TA (0.30 +/- 0.02 mm/sec) and reaches a higher value during contractions at 1 Hz (0.38 +/- 0.04 mm/sec) more quickly than in soleus (0.21 +/- 0.02-0.28 +/- 0.03 mm/sec). The number of continuously perfused capillaries in TA increased during contractions, but there was little change in soleus. A computer program was devised to estimate the proportion of time spent stationary by RBCs in the capillaries. This was greater in soleus than in TA at rest and was reduced in TA only during contractions. The transit time (TT) through capillaries was much reduced in TA during contractions (from 1.69 +/- 0.17 to 0.78 +/- 0.13 sec) but remained unchanged in soleus (1.17 +/- 0.21 and 0.97 +/- 0.13 sec). The lack of functional hyperemia in soleus may be a direct consequence of this invariability in the TT.

Animals↗
PubMed1986

Demonstration of plasma-membrane adenosine diphosphatase activity in rat lung.

The adenosine diphosphatase (ADPase) activity of rat lung has been investigated. Subcellular fractionation of lung tissue homogenates by sucrose density gradient centrifugation has shown the ADPase activity to be associated with the plasma membrane. ADPase was solubilised from the membranes and fractionated by ammonium sulphate precipitation to separate a specific, low-Km ADPase from non-specific alkaline phosphatase activity. The solubilised ADPase has a Km of 50 microM at pH 7.5 and appears to be distinct from ATPase.

Adenosine Diphosphate↗
PubMed1986

Subcellular pathology of human neurodegenerative disorders: Alzheimer-type dementia and Huntington's disease.

Activities of enzyme markers of subcellular organelles have been measured in brain tissue from subjects with Alzheimer-type dementia (ATD) and Huntington's disease (HD). Significant increases in the activity of the lysosomal enzyme beta-glucuronidase were observed in both ATD temporal cortex and HD putamen. It is suggested that beta-glucuronidase activity may be a useful biochemical indicator of cellular damage in the CNS. A significant reduction in neutral alpha-glucosidase activity was observed in ATD temporal cortex and HD putamen. This change may reflect an alteration in glycoconjugate processing and may relate to the susceptibility of neurones to the degenerative processes of ATD and HD.

Aged↗
PubMed1985

Enzymatic synthesis of [beta-32P]ADP using adenylate kinase and [gamma-32P]ATP.

An enzymatic method for the synthesis of [beta-32P]ADP from [gamma-32P]ATP is described. This substrate is required for the assay of ADPase and is not commercially available. The method described results in a preparation of [beta-32P]ADP of high purity with a yield of approximately 40% the theoretical obtainable.

Adenosine Diphosphate↗
PubMed1985

Loss of endoplasmic reticulum-associated enzymes in affected brain regions in Huntington's disease and Alzheimer-type dementia.

Post-mortem brain samples from patients with either Huntington's disease, Alzheimer-type dementia or appropriate controls were assayed for endoplasmic reticulum enzymes, NADPH-cytochrome c reductase, neutral alpha-glucosidase, inosine diphosphatase, alpha-mannosidase and glucose-6-phosphatase and for Golgi enzymes, fucosyl- and galactosyl-transferases. In Alzheimer-type dementia there was a selective decrease in alpha-glucosidase activity in the temporal cortex. In Huntington's disease there was a selective decrease of putamen alpha-glucosidase and fucosyl-transferase activities. It is suggested that these changes reflect highly specific alterations in glycoprotein synthesis and processing and may contribute to the underlying pathology of these disorders.

Adult↗
PubMed1984

Lowry method of protein quantification: evidence for photosensitivity.

Despite reports of its susceptibility to various interfering factors, the Folin Phenol protein quantification method of O. H. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall (1951, J. Biol. Chem. 193, 265-275) remains the most convenient and accurate method for routine protein determinations. Our findings indicate that the Lowry assay is also photosensitive which can result in a discrepancy of up to 10% in estimated protein concentrations, unless appropriate precautions are taken.

Chromogenic Compounds↗
PubMed1981

Fucose incorporation and identification of fucosylglycoproteins in synaptosomes.

A synaptosome-enriched fraction from sheep cortex was incubated with L-fucose. The uptake of the sugar into this preparation was dependent on time, temperature, and concentration. A Kmapp of 0.94 mM-L-fucose and a Vmaxapp value of 0.24 nM-L-fucose/mg synaptosomal soluble protein/20 min was determined. After incubation for 10 min at 25 degrees C with L-[3H]fucose, 70% of the radioactive label was found in the soluble fraction. DEAE-cellulose chromatography resulted in the elution of three fucosylprotein peaks which were then characterised by gel filtration and sodium dodecyl sulfate-polyacrylamide electrophoresis (SDS-PAGE). At least eleven 3H protein-staining bands were identified with M. W. 13,000--115,000. Control experiments involving the incubation of the hexose with heat-treated synaptosomes and myelin, mitochondria, and microsomes indicted that the tritiated material associated with the synaptosomal soluble fraction was not due to nonspecific binding or to the presence of contaminating subcellular material. A 3H glycopeptide was identified, and on analysis the carbohydrate moiety was found to be rich in sialic acid, fucose, galactose, mannose, and N-acetylglucosamine. Mild acid treatment of the glycopeptide released fucose, which implies that this carbohydrate occupies a terminal position in the oligosaccharide chain. From these results it is proposed that synthesis or the modification of soluble fucosylglycoproteins is possible in synaptosomes.

Amino Acids↗
PubMed1980

Computed tomography in the elderly: I. The normal population.

Computed tomographic (CT) and brief psychometric findings on 50 psychiatrically and neurologically healthy community residents over 60 years old are presented. The need for normative CT data is emphasized, and the methodological problems in obtaining them are discussed. Measures of ventricular size were generally found to be greater than those reported by other workers, and variation with age was also found to be less marked than hitherto reported. A reciprocal relationship was found between a global rating of cortical atrophy and a test of memory and orientation. This communication forms the basis for comparison with groups of psychiatric patients to be presented in subsequent articles.

Age Factors↗