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Biomedical subjects

C R Lowe

Publications and source records attributed to C R Lowe.

At least 109 records · Page 6Linked to original sources

The synthesis of several 8-substituted derivatives of adenosine 5'-monophosphate to study the effect of the nature of the spacer arm in affinity chromatography.

Reaction of adenosine 5'-monophosphate (Ado-5'-P) with bromine at pH 4.0 yielded 8-bromo-adenosine 5'-monophosphate and following reaction with several alpha,omega-diaminoalkanes gave the corresponding 8-(omega-aminoalkyl)-Ado-5'-P derivatives. Condensation of these analogues with N-trifluoroacetyl-glycine or beta-alanine in the presence of a water-soluble carbodiimide generated several 8-substituted derivatives. These analogues: (see article) comprised an 8-substituted Ado-5'-P ligand to which a spacer molecule of similar length but differing hydrophobicity was attached. The derivatives were purified, characterised and attached to CNBr-activated Sepharose. The chromatographic behaviour of the resulting absorbents was investigated in terms of their ability to bind both lactate and alanine dehydrogenase. The enzymes bound tighter to the more hydrophobic derivatives with the strength of the interaction decreasing with increasing hydropholicity. The effect of the introduction of a single hydroxyl group in the spacer arm was also studied with several enzymes known to exhibit anomalous behavior on affinity chromatography. In free solution, (Ado-5'-P)-8-NH CH2CH2CH2CH2CH2CH2NH2 and (Ado-5'-P)-8-NH CH2-CH CH2NH CO CH2NH2 were competitive with NADH for rabbit muscle lactate dehydrogenase, (see article) with Ki values of 2.0 and 1.8 mM respectively. These data suggest a difference in accessibility of the hydrophobic and hydrophilic derivatives when attached to Sepharose rather than a fundamental difference in affinity. This suggestion is supported by the fact that there is no obvious correlation between the Ki values in free solution of a series of 8-(omega-aminoalkyl)-Ado-5'-P derivatives of increasing chain length, and hence hydrophobicity, and their chromatographic behaviour when immobilised. The data suggest that the hydrophobicity/hydrophilicity of the spacer arm determined the accessibility of the immobilised ligand to interaction with the complementary enzyme.

Adenosine Monophosphate↗

Regional variations in need for and provision and use of child health services in England and Wales.

An analysis of indicators of the need for and provision and use of child health services in the 15 pre- 1974 hospital board regions in England and Wales showed that need and provisions were badly matched. There was a high degree of correlation between the indices within each of the three groups, indicating that a region with a small provision in one area of child health services would tend to have few resources in other areas also. Statistics on the use of services relate more to the provision of those services than to the need for them. Regions with large resources will justify these resources by claiming that their use statistics indicate needs, whereas they really indicate met demands. It is more important to identify demands and needs that are not being met.

Birth Rate↗

Some international differences in treatment and survival in breast cancer.

In a recent study, 5-year survival rates for breast cancer patients in Boston (Massachusetts), Glamorgan (Wales), Slovenia (Yugoslavia) and Tokyo (Japan) were 57.3%, 49.5%, 41.9% and 74.9%, respectively. In this report, data are presented on the types of treatment used in the four areas and on the relationship of differences in treatment practices to the differences in survival rates. Generally, surgically treated patients who also had radiotherapy had lower survival rates than patients in the same area who had similar operations without radiotherapy. In each area, the survival rate was higher for patients who had radical mastectomy than for those who had simple mastectomy. The Japanese patients had the highest survival rate within nearly every treatment and extent-treatment category. Thus, the high survival rate of these patients was not explained by the variables considered. Survival differences between Boston, Glamorgan and Slovenia were largely explained by differences in extent of disease and type of treatment. As the nature of the treatment--survival trends was consistent with the interpretation that treatment tended to be selected according to apparent prognosis, the degree to which treatment customs were determinants of the differences in survival rate among the three areas is uncertain.

Boston↗

Mortality from ischaemic heart disease--inter-town variation and its association with climate in England and Wales.

In both seasonal and inter-town variation, the mortality from ischaemic heart disease in England and Wales in 1969-71 is very highly correlated with temperature. Also in the inter-town variation, IHD mortality is highly correlated with rainfall and with socio-economic index. It is postulated that the same mechanism of body cooling underlies seasonal, inter-town and socio-economic variations in IHD mortality. The first law of thermodynamics states the heat and energy are equivalent. Therefore to maintain body temperature against an increased thermal gradient (caused by a lower environmental temperature as in seasonal variation, or a temperature-rainfall interaction as in inter-town variation) more energy must be expended by the body or, alternatively, the body must reduce heat loss by increasing thermal insulation. It is to be expected that there will be many accompanying changes in physiological parameters and several of these are discussed.

Age Factors↗

Biospecific affinity chromatography in aqueous-organic cosolvent mixtures. The effect of ethylene glycol on the binding of lactate dehydrogenase to an immobilised-AMP analogue.

The effect of the weak polarity-reducing agent, ethylene glycol, on the binding of pig heart lactate dehydrogenase to N6-(6-aminohexyl)-AMP-Sepharose has been investigated. In the absence of the reagent and under the conditions used, a non-specific interaction of the enzyme with the adsorbent led to recoveries of enzyme activity as low as 60% when the enzyme was eluted from the columns with a linear NADH gradient. The inclusion of low concentrations of ethylene glycol in column irrigants considerably improved the recovery of enzyme activity with quantitative recoveries being obtained in the presence of 20-30%. Concentrations of ethylene glycol about 35% altered the native conformation of lactate dehydrogenase and led to a decreased affinity for the immobilised ligand. Under these conditions, the altered protein fluorescence and decreased ability to bind NADH could be correlated with the chromatographic behaviour of the enzyme on columns of N6-(6-aminohexyl)-AMP-Sepharose. These effects were exploited to elute the enzyme from a column of immobilised-AMP with a linear gradient of ethylene glycol.

Adenosine Monophosphate↗