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Biomedical subjects

S Murray

Publications and source records attributed to S Murray.

At least 217 records · Page 12Linked to original sources
PubMed1982

Restricted food intake limits brown adipose tissue hypertrophy in cold exposure.

Two factors that may determine brown adipose tissue (BAT) hypertrophy during conditions of increased metabolic heat production are increased food intake and increased sympathetic nervous system (SNS) activity. Since these two proceed pari passu during cold exposure, their independent contributions to BAT hypertrophy are unknown. To examine the role of each, we limited the food intake of a group of cold exposed rats by pair feeding them to warm exposed control rats and then compared the pair fed rats to ad lib fed cold exposed animals. Restricted food intake limited absolute BAT hypertrophy (0.226 +/- 0.01 g. vs 0.488 +/- 0.02 g, pair fed vs ad lib, P less than 0.01), BAT as per cent body weight (0.189 +/- 0.12 vs 0.252 +/- 0.012, P less than 0.01) and BAT protein content (34.4 +/- 3.8 vs 48.9 +/- 2.6 mg, P less than 0.01) despite evidence of quantitatively similar activation of the SNS in BAT in both groups. We conclude that increased food intake contributes to BAT hypertrophy in cold exposure independent of sympathetic activity.

Adipose Tissue, Brown↗
PubMed1982

Assay and characterisation of debrisoquine 4-hydroxylase activity of microsomal fractions of human liver.

1 A method for the assay of debrisoquine 4-hydroxylase activity in vitro by microsomal fractions of human liver is described. The assay utilises gas chromatography-mass spectrometry with d9-4-hydroxydebrisoquine as internal standard. 2 The limit of detection of 4-hydroxydebrisoquine was 2 ng ml -1 and the coefficient of variation was 4.4%. 3 Debrisoquine 4-hydroxylase activity was linear with protein to concentrations above 2.1 mg ml -1 and with incubation times of at least 15 min. 4 Debrisoquine 4-hydroxylase is a microsomal enzyme with a requirement for NADPH. Activity was inhibited by carbon monoxide. It is concluded that the activity is catalysed by cytochrome P-450. 5 In three samples of human liver the mean value for Vmax of debrisoquine 4-hydroxylase activity was 69.9 +/- 14.3 pmol mg -1 min -1 and for Km it was 130 +/- 24 microM. 6 The only variable from smoking status, alcohol ingestion, sex of the patients, source of liver sample and presence of liver disease that had a significant effect on 4-hydroxylation of debrisoquine was the presence of liver disease. This was associated with a decrease in enzyme activity.

Cytochrome P-450 CYP2D6↗
PubMed1982

Differential effects of 3-methylcholanthrene and phenobarbitone treatment on the oxidative metabolism of antipyrine in vitro by microsomal fractions of rat liver.

1. The effects of treating rats with the inducers phenobarbitone (4 X 80 mg/kg per day) and 3-methylcholanthrene (80 mg/kg) on the kinetics of the formation of the three major oxidative metabolites of antipyrine in vitro by hepatic microsomal fractions have been investigated. 2. Phenobarbitone treatment significantly increased the Vmax of 4-hydroxyantipyrine formation (by 2.3 fold) and of norphenazone formation (by 2.3-fold). 3-Methylcholanthrene treated caused a slight, but significant (P less than 0.05), reduction in Vmax for 3-hydroxymethylantipyrine formation. 3. Phenobarbitone markedly reduced the Km for 3-hydroxymethylantipyrine formation (from 2.2 +/- 0.5 mM to 0.65 +/- 0.09 mM), whereas 3-methylcholanthrene treatment resulted in an increase (P less than 0.05) in the Km (to 4.9 +/- 1.1 mM). The only other significant change in Km was a slight decrease in that of 4-hydroxyantipyrine formation following phenobarbitone treatment (from 4.6 +/- 1.1 mM to 2.2 +/- 0.3 mM, P less than 0.05). 4. Calculation of the ratio Vmax/Km permitted an estimate of the clearance in vivo to the metabolites. There was good agreement between predicted values and those for total body clearance of antipyrine, and four changes in clearance to individual metabolites in vivo following treatment with enzyme inducers. 5. Kinetics analysis of formation of antipyrine metabolites in vitro has enabled the enzymic basis for changes observed in their excretion to be established. Further evidence was also obtained for the involvement of multiple forms of cytochrome P-450 in antipyrine oxidation.

Animals↗
PubMed1981

The effect of limited proteolysis on rabbit muscle creatine kinase.

Creatine kinase from rabbit muscle is inactivated by limited proteolysis with proteinase K from Tritirachium album. Gel-filtration and cross-linking studies showed that the limited proteolysis did not affect the molecular weight of the enzyme under non-denaturing conditions, but did cause changes in the reactivity of the reactive thiol group on each subunit and in the ability of the enzyme to form a 'transition-state analogue' complex in the presence of magnesium acetate plus ADP plus creatinine plus NaNO3.

Adenosine Diphosphate↗
PubMed1981

Differential induction of antipyrine metabolism by rifampicin.

Antipyrine is oxidised to three main metabolites in man. There is evidence that the different metabolites are products of different forms of cytochrome P-450. The effect of rifampicin administration for two weeks on the rates of formation of these metabolites was investigated in healthy volunteers. Rifampicin increased antipyrine clearance and shortened its half-life. Two weeks after stopping rifampicin the induction had largely been reversed. Clearance to all three metabolites was increased by rifampicin. Clearance to 3-hydroxymethylantipyrine was increased from 7.8 +/- 0.9 ml/min to 13.3 +/- 1.3 ml/min, to norphenazone from 5.8 +/- 0.6 ml/min to 19.3 +/- 2.1 ml/min and to 4-hydroxyantipyrine from 14.3 +/- 2.2 ml/min to 21.9 +/- 3.9 ml/min. Thus clearance to norphenazone was increased to a much greater extent than to either of the other two metabolites. It is concluded that this provides evidence for the involvement of at least two different forms of cytochrome P-450 in antipyrine metabolism in man.

Adult↗
PubMed1981

Comparison of the in vivo and in vitro rates of formation of the three main oxidative metabolites of antipyrine in man.

1 The metabolism of antipyrine to its three main oxidative metabolites, 4-hydroxyantipyrine, 3-hydroxymethylantipyrine and norphenazone was investigated in vivo and in vitro in separate groups of subjects with normal hepatic function and in the same group of patients with suspected liver disease. 2 The rank order for the rate of formation of the three metabolites of antipyrine was similar in vivo and in vitro. 3 There was no significant correlation between the rates of formation of any pair of antipyrine metabolites either in vivo or in vitro. 4 Despite this there was a significant correlation between the in vivo and in vitro rates for formation of each of the three metabolites in the same group of patients. 5 It is concluded that determination of rates of formation of antipyrine metabolites from their excretion in urine provides an indication of the activity of the enzymes involved in their formation.

Adult↗
PubMed1980

An improved combined gas chromatographic mass spectrometric assay for the estimation of norphenazone in urine.

An improved, combined gas chromatographic mass spectrometric assay for the estimation of norphenazone in urine is described. A structural analogue of norphenazone is used as internal standard and derivatization of both norphenazone and the analogue gives these compounds better gas chromatographic properties. These modifications increase the precision and accuracy of the assay.

Antipyrine↗
PubMed1980

Stereoselective excretion of (3-methoxy-4-sulphooxyphenyl)ethylene glycol (MHPG sulphate) in the dog.

3-Methoxy-4-hydroxyphenylethylene glycol (MHPG) labelled with six deuterium atoms ([2H6]MHPG) was infused into two female greyhound dogs. Plasma and urine were analyzed for endogenous MHPG and [2H6]MHPG and their conjugates by the technique of selected ion monitoring gas chromatography-mass spectrometry. This analysis showed that the major forms of MHPG and [2H6]MHPG in the plasma and urine of the greyhounds were the sulphate conjugates. However, the plasma concentration of [2H6]MHPG sulphate increased continuously during the infusion period and the renal clearance of this compound was found to be much less than that of the endogenous sulphate. The explanation that his was due either to saturation of a renal transport mechanism or to a deuterium isotope effect was eliminated. Stereochemical analysis showed that, while the [2H6]MHPG used for infusion was a racemic mixture of two stereoisomers, much more of the nature(-)stereoisomer of [2H6]MHPG sulphate was excreted in the dog urine. It was also shown that both the (+) and (-)stereoisomers of [2H6]MHPG sulphate were sulphoconjugated at the 4-position of the aromatic ring.

Animals↗
PubMed1980

Urinary conjugates of 4-hydroxy-3-methoxyphenylethylene glycol do not provide an index of brain amine turnover in man.

1. The 24 h urinary excretion of free 4-hydroxy-3-methoxyphenylethylene glycol (HMPG), HMPG conjugated as glucuronide and HMPG conjugated as sulphate was determined in nine healthy volunteer subjects and six patients with phaeochromocytoma. In both groups of subjects most (97%) HMPG was in the conjugated form. 2. Although patients with phaeochromocytoma excreted five- to ten-fold the amounts of each of the forms of HMPG excreted by the control subjects the ratio of these different forms of HMPG to each other did not differ significantly between the groups. 3. In cerbrospinal fluid and brain about 80% of HMPG was free and of the conjugated HMPG in these two tissues most was in the glucuronide form. 4. In is concluded from these data that both HMPG sulphate and HMPG glucuronide have a substantial peripheral origin and that measurements of their urinary excretion cannot be used as an index of brain catecholamine turnover.

Adrenal Gland Neoplasms↗
PubMed1980

A new finding relating to transfusion and renal transplants.

Results in 29 recipients of second renal transplants from cadaver donors show a significantly better graft survival at 1 year of 90% in 10 recipients who had not received blood transfusion before their first transplant compared to 41% in 19 recipients who had been transfused prior to their first transplant (P = 0.025).

Blood Transfusion↗
PubMed1980

Measurement of drug dosage intensity in MVPP therapy in Hodgkin's disease.

The dose of combination chemotherapy in Hodgkin's disease is commonly calculated from a formula based on the body surface area. A method is described for measuring the intensity of combination chemotherapy actually received compared to the calculated planned dose. The technique is applied to 56 patients receiving mustine, vinblastine, procarbazine and prednisolone, but would also be suitable for other cytotoxic regimens. The planned dosage intensity had to be significantly reduced in over half of the patients because of marrow toxicity. Splenectomized patients received a higher dose intensity than those in whom the procedure was not performed.

Adult↗
PubMed1980

Dissimilar effects of ultraviolet light on HLA-D and HLA-DR antigens.

Since HLA-DR antigens are closely related to HLA-D antigens, we studied the effect of low-dose ultraviolet irradiation on the ability of human lymphocytes to induce a proliferative response in mixed lymphocyte culture (HLA-D) and on the serologic reactivity of B lymphocyte HLA-DR antigens. We found (1) no alteration in the serologic definition of DR antigens despite the abrogation of the induction of proliferative responses in mixed lymphocyte culture, (2) no evidence that ultraviolet light (UVL) stimulated suppressor cells contributed to the loss of allostimulation, and (3) no evidence that the abrogation of the induction of proliferative responses could be modified by increasing the number of UVL exposed lymphocytes in mixed lymphocyte culture. These findings suggest that HLA-D and HLA-DR antigens are different molecularly, but are also consistent with the concept that certain active metabolic processes are required of stimulator cells for allostimulation and that these processes are UVL sensitive.

B-Lymphocytes↗