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Biomedical subjects

D M Boyle

Publications and source records attributed to D M Boyle.

At least 37 records · Page 2Linked to original sources
PubMed1986

Estrogen receptor is associated with protein and phospholipid kinase activities.

The ability of immunopurified estrogen receptor from MCF-7 cells, incubated with [Y-32P]-ATP, to conduct its own phosphorylation and to phosphorylate phosphatidylinositol and 1,2-diacylglycerol was investigated. SDS gel electrophoresis analysis of the phosphorylated products revealed three major labeled phosphopeptides with molecular weights of 57, 47 and 43 kilodaltons. Other polypeptides were detected although in much smaller amounts. When the phosphorylation system was supplemented in vitro with phosphatidylinositol, phosphatidylinositol-4-P, or 1,2-diacylglycerol and the 32P-lipids were analyzed by thin layer chromatography, PI, but not 1,2-diacylglycerol, was converted in part to 32P-phosphatidic acid and phosphatidylinositol-4-32P. Phosphatidylinositol-4-P was also phosphorylated to phosphatidylinositol-4,5-32P. An estrogen receptor-negative cell line (MDA) produced negligible 32P-polypeptides and 32P-lipids under identical conditions used for MCF-7 cells.

Breast Neoplasms↗
PubMed1986

Natural history of diabetes presenting age 40-69 years: a prospective study of the influence of intensive dietary therapy.

Two hundred and twenty-three newly-diagnosed symptomatic diabetic patients with onset age 40-69 years enrolled in a prospective study of intensive dietary management of diabetes were observed for a period of six years and the data obtained is analysed. The variables studied were weight and fasting levels of plasma glucose and insulin, and of serum total cholesterol and triglyceride. These tests were monitored throughout the study and in addition the oral glucose tolerance test was analysed at entry to the study, after six months intensive dietary management and again after 72 months. Blood pressure, electrocardiogram and the presence of posterior tibial artery pulsation were recorded at entry to the study and at 36 months and 72 months. Approximately 80 per cent of the patients were managed solely by dietary restriction for the entire six years, but 25 patients received oral hypoglycaemic drugs and 26 required insulin treatment. Weight, and fasting glucose and triglyceride values fell in the first few months of intensive dietary management. Analysis of possible risk factors in survivors and patients dead at six years showed no significant differences, apart from a higher mean age at diagnosis in those who died. During the six years of intensive dietary management the mortality from all causes in these diabetic patients was no greater than that for the general population of Northern Ireland.

Adult↗
PubMed1985

Rapid, high-resolution procedure for assessment of estrogen receptor heterogeneity in clinical samples.

Approximately two-third of the women with breast cancer may benefit from hormone therapies if the lesion contains estrogen receptor in reasonable levels (greater than 10 fmol/mg cytosol protein). Our lab and others have suggested that not only the concentration, but the various molecular form(s) of the receptor may be an important factor in predicting patient responsiveness. Until now, this heterogeneity has been determined by analysis on sucrose density gradients requiring 16 h of centrifugation. Other methodologies which can disclose the profile of receptor isoforms are compromised by irreproducibility, poor recovery, or the length of time required to perform the analysis. We believe that high-performance liquid chromatography (HPLC) in the anion-exchange and chromatofocusing modes may be able to supply more insight into receptor structure than currently available by any other method. Utilizing the high activity ligand [16 alpha-125I]iodoestradiol-17 beta (2200 Ci/mmol) and flow-through equipment to monitor conductivity, pH, and radioactivity, we are able to describe the distribution of ionic isoforms in crude cytosolic preparations of breast cancer and uterus. This "on-line" technology is rapid (chromatogram is complete within 120 min), sensitive (receptor isoforms equivalent to 1 fmol are apparent), efficient (columns typically return greater than 90% of applied radio-labeled receptor) and reproducible (due to the sophistication of modern HPLC equipment). It is clear these techniques may be used in the clinical setting to better describe the profile of estrogen receptor isoforms and should be explored as a method of correlating receptor structure with hormone function in responsive tissues.

Breast Neoplasms↗
PubMed1985

Very early intervention with metoprolol in suspected acute myocardial infarction.

A double blind randomized study of 800 patients was carried out to determine if very early intervention with metoprolol (15 mg I.V. followed by oral administration) in suspected acute myocardial infarction affected overall mortality in selected subgroups, (age, site of infarct, delay to intervention). Sudden death occurred less frequently in patients allocated to metoprolol but there was no significant difference in total mortality on discharge, at three months and at twelve months. Ventricular fibrillation after intervention was not significantly reduced. Adverse reactions did not occur significantly more frequently in patients assigned to metoprolol.

Aged↗
PubMed1984

Effect of in vivo changes in phospholipid composition on liver microsomal calcium transport.

We recently reported that the phospholipid composition of mouse liver microsomes could be altered in vivo by a combination of dietary choline deprivation and administration of the methylation inhibitors periodate-oxidized adenosine and cycloleucine (D.M. Boyle & W.L. Dean (1982) Biochim. Biophys. Acta 688, 667-670). We have now determined the effect of this in vivo change in phospholipid composition on 7 microsomal enzyme activities and 2 cytochromes. The specific contents of cytochromes b5 and P-450 were unaffected by the treatment. Similarly, NADH-cytochrome c reductase, cytochrome P-450 reductase, cyclohexane hydroxylase and Mg2+-ATPase were not significantly altered. In addition, the phospholipid/protein ratio was not changed. In contrast, Ca2+-ATPase and Ca2+ transport rates were reduced by more than 60%. This result suggests that the mouse liver microsomal Ca2+-ATPase is extremely sensitive to the phospholipid composition of the membrane in which it is embedded and that one mode of control of calcium metabolism in liver cells could be at the level of membrane phospholipid composition.

Animals↗
PubMed1984

Diagnosis of myocardial infarction from serum creatine kinase MB isoenzyme (CKMB) measurement.

The cardiospecific isoenzyme MB of creatine kinase (CKMB) has previously been shown to be of value in the diagnosis of myocardial infarction (MI). We studied 418 admissions to a coronary care unit (CCU) with suspected MI and calculated the sensitivity, specificity and positive and negative predictive values for several CKMB test functions. Several functions performed better than any combination of the other enzymes in common use. 97% of patients achieving a CKMB activity of at least 15 U/l did so between 6 and 30 h following the onset of symptoms. The present study confirms that the use of the CKMB isoenzyme leads to an earlier and more accurate diagnosis or exclusion of MI compared to the "cardiac enzyme series". The timing of blood sampling for CKMB estimation is also discussed.

Aged↗
PubMed1983

Effect of very early intervention with metoprolol on myocardial infarct size.

All patients with a presumptive diagnosis of myocardial infarction, who were seen within six hours of the onset of symptoms and had no reason for exclusion, were considered for entry into a trial to compare the effects of metoprolol and placebo on creatine kinase MB isoenzyme release. The trial was randomised and double blind. The median time from onset of symptoms to receiving trial drug was just under two hours. Two hundred and four patients (of whom 120 had myocardial infarction) received metoprolol and 187 (of whom 105 had myocardial infarction) received placebo. Infarct size was estimated semiquantitatively using cumulative release of the cardiospecific isoenzyme, creatine kinase MB. Mean creatine kinase MB isoenzyme was less in patients who received metoprolol, but the reduction did not achieve statistical significance. Clinical problems related to early intravenous metoprolol were uncommon.

Aged↗
PubMed1982

Alteration of phospholipid composition of mouse liver microsomes in vivo and the effect on membrane properties.

Administration of the methylation inhibitor periodate-oxidized adenosine to male Swiss-Webster mice on a choline-deficient diet produced a decrease (17%) in phosphatidylcholine to phosphatidylethanolamine ratios compared to saline-injected controls in liver, and also in kidney (11%), but not in muscle microsome preparations. Both intact liver microsomes and reconstituted membranes from lipid extracts showed a higher fluorescence anisotropy of the hydrophobic probe 1,6-diphenyl-1,3,5-hexatriene than control samples in the temperature range of 20-31 degrees C.

Adenosine↗
PubMed1980

Mexiletine in clinical practice.

Mexilitine is an antiarrhythmic drug with pharmacological properties similar to lignocaine. It is effective against ventricular arrhythmias, both parenterally and orally, and has been used in acute myocardial infarction, in the convalescence following myocardial infarction and in ventricular arrhythmias of different aetiology. The incidence of serious side-effects is sufficiently low to warrant its use.

Acute Disease↗
PubMed1977

Simple lignocaine regimen for transit to hospital after myocardial infarction.

A simple combined intravenous/intramuscular regimen is described for lignocaine administration in the early vulnerable stage of myocardial infarction. Plasma levels in the therapeutic range are attained. This allows adequate drug protection during transport to hospital when an intravenous regimen may be impractical or impossible.

Adult↗