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Biomedical subjects

R Macleod

Publications and source records attributed to R Macleod.

13 recordsLinked to original sources
PubMed1999

A G1 cell cycle arrest induced by ligands of the reovirus type 3 receptor is secondary to inactivation of p21ras and mitogen-activated protein kinase.

The reovirus type 3 S1 gene product (type 3 hemagglutinin; HA3) is the viral protein responsible for binding to a mammalian cell-surface receptor. It has been shown that HA3 binding to its receptor inhibits cell growth, even in the continuous presence of serum mitogens. Here, receptor-mediated signal transduction leading to growth arrest was studied after binding with synthetic or recombinant ligands in the absence of viral infection. Receptor ligation caused rapid inactivation of p21(ras), a decrease in Raf phosphorylation and in mitogen-activated protein kinase (MAPK) enzymatic activity, and G1 cell cycle arrest. Transfection and expression of constitutively active v-Has-ras prevented the G1 arrest, indicating that inactivation of p21(ras) is causative. Interestingly, v-Has-ras expression also decreased the efficiency of reoviridae replication, suggesting that inactivation of p21(ras) signals is required at some step of the viral cycle. This study may define new mechanisms regulating cell growth and support the approach of using viral proteins to identify and study cellular receptors. Synthetic receptor ligands with antiproliferative properties may be useful in drug development with the aim of blocking mitosis.

Animals↗
PubMed1997

Uptake of genetic testing for cancer predisposition.

Although there has been much debate about the uptake and effects of predictive testing for common cancers, such as breast and colon cancer, little has been published on the more classical tumour predisposing conditions, such as von Hippel-Lindau disease and familial adenomatous polyposis. Since 1990 the genetics departments in Manchester and Cambridge have had a genetic register for cancer predisposing syndromes and presymptomatic testing for these conditions has been offered once this has become possible. To investigate the factors that might influence uptake of genetic testing in familial cancer syndromes we have reviewed our experience. Demand for predictive testing has generally been high, but men had a lower uptake (77%) than a comparable group of women (93%) (p < 0.01).

Adenomatous Polyposis Coli↗
PubMed1996

Root and shoot growth, assimilate partitioning and cell proliferation in roots of Sitka spruce (Picea sitchensis) grown in filtered and unfiltered chambers.

Rooted cuttings of clonal Sitka spruce (Picea sitchensis (Bong.) Carr.) were grown from April to October in 1 m long tubes sunk into the ground inside open top chambers. The same experiment was repeated in each of two consecutive years using a different clone of Sitka spruce each year. Air was either passed directly into the chambers (ambient air) or passed over charcoal filters which removed the majority of gaseous pollutants before entering the chambers (filtered air). Ambient pollution did not appear to influence the growth of Sitka spruce at least over the experimental period used. No significant differences were found between plants exposed to ambient or filtered air in terms of shoot and root dry mass, needle dry mass, root length, carbohydrate content of roots and needles, and in the percentage of meristematic cells close to the apex in each phase or interphase or undergoing mitosis.

Journal Article↗
PubMed1992

Metabolism of 2',3'-dideoxyinosine (ddI) in human blood.

1. 2',3'-Dideoxyinosine (ddI) has potent activity against human immunodeficiency virus (HIV). It is converted within target cells to its active form dideoxyadenosine triphosphate(ddA-TP). 2. In addition to the intracellular formation of ddA-TP, ddI can be broken down to hypoxanthine, by purine nucleoside phosphorylase (PNP) and to uric acid, by xanthine oxidase. Since PNP is present in red blood cells we have examined the metabolism of [14C]-ddI by human blood. 3. When incubated with whole blood at 37 degrees C, ddI was extensively metabolised, principally to hypoxanthine (50.4 +/- 12.5% formed at 6 h; mean +/- s.d.; n = 16). Small amounts of uric acid were formed (3.8 +/- 2.4%). 4. ddI breakdown was temperature dependent, being virtually negligible at 4 degrees C. Metabolism to hypoxanthine occurred within red blood cells. 5. The short half-life of ddI in patients is probably the result of both hepatic and erythrocytic metabolism.

Chromatography, High Pressure Liquid↗
PubMed1991

Actions of intravenous magnesium on ventricular arrhythmias caused by acute myocardial infarction.

Although the antiarrhythmic properties of magnesium are well recognized, its mechanisms of antiarrhythmic action are poorly understood. This study was designed to characterize the effects of magnesium on ventricular tachyarrhythmias related to acute myocardial infarction (MI) in dogs. When the circumflex coronary artery was occluded repeatedly for 10 min at 30-min intervals, ventricular fibrillation (VF) occurred in 30, 35 and 33% of dogs during occlusions 1, 2 and 3, respectively. Magnesium pretreatment reduced the incidence of VF to 14% during occlusion 3 (P less than .05 compared to occlusions without magnesium pretreatment). Neither the prevalence of ventricular ectopic complexes 24 h after MI nor arrhythmia inducibility 4 days after infarction were significantly altered by i.v. magnesium. Magnesium significantly attenuated the ST segment elevation (an index of ischemic injury) and ventricular conduction slowing caused by MI. Because magnesium has been reported to reverse the effects of hyperkalemia, we evaluated the role of this action by infusing potassium directly into a coronary artery (to mimic ischemia-induced hyperkalemia) and administered i.v. magnesium. Potassium infusion markedly slowed intraventricular conduction, an effect fully reversed by discontinuing potassium administration but unaffected by i.v. magnesium. We conclude that magnesium has antiarrhythmic actions only during the early phases of an experimental MI, and that these actions are associated with attenuation of indices of ischemic injury and conduction slowing. These properties of magnesium are similar to those of calcium antagonists, and suggest that magnesium's calcium antagonist properties may be important in its antiarrhythmic actions.

Animals↗