Biomedical subjects
T L Dormandy
Publications and source records attributed to T L Dormandy.
The mechanism of insulin action. The effect of insulin action. The effect of insulin on the allosteric properties on intracellular haemoglobin.
1. The results in three experimental series have suggested that a number of modifying factors must be taken into account in considering the allosteric behaviour of structurally bound intracellular, as distinct from free, haemoglobin. It seems that intracellular haemoglobin maintains its maximal internal stability during oxygen uptake and release by configurational changes which involve not only its acid-base-binding groups but also partial electron-transfer complexes with the stromal macro-molecular framework. Conversely, the affinity of intracellular haemoglobin for oxygen reflects the positive or negative electron pressures prevailing at the haemoglobin-stromal complexing sites.2. Active glucolysis in intact cells entails continuous poising of metabolic redox potential changes by the stromal material (in the same way as it entails continuous buffering of acid metabolic products). The consequent shifts in stromal redox potential and capacity are transmitted to haemoglobin and are reflected in a changing affinity for oxygen.3. The behaviour of the intracellular haemoglobin-stromal complex is further modified by extracellular electron donors and acceptors and by the capacity of the cell/extracellular interface to act as an electrochemical barrier between them. It is probably the last variable which is directly influenced by insulin.4. Two parameters have been introduced as empirical measures of the distinctive allosteric properties of cell-bound haemoglobin: (i) D-pH to represent the apparent cell/extracellular pH gradient; and (ii) D-O(2) to represent the volume of oxygen evolved when cells are lysed at a constant P(O2). Under a variety of experimental conditions insulin affected both these parameters.5. The insulin effects were consistent with a concept which rests on three main contentions. (i) Insulin has an immediate physical action on the cell/extracellular interface, altering the redox potential gradient (electron conductance) across the plasma membrane. (ii) Conversely, the formation of an insulin-membrane complex depends, among other factors, on the prevailing trans-membrane redox potential difference. (iii) The consequences of insulin-membrane interaction are both immediate and sustained, and, under appropriate conditions, they are reflected in the affinity of intracellular haemoglobin for oxygen.6. At a more general level it has been shown that in many respects haemoglobin behaves as a built-in intracellular redox indicator dye. Like most synthetic redox indicators, it is pH dependent.
Oxyhaemoglobin without oxygen.
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The mechanism of insulin action: the immediate electrochemical effects of insulin on red-cell systems.
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The mechanism of insulin action: the effect of insulin on phosphate turnover in red-cell systems.
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The experimental and clinical pathology of diene conjugation.
The simple spectroscopic measurement of diene conjugation has long been an established but somewhat problematic marker of free-radical activity in biological systems. The main diene-conjugated compounds in human tissues and tissue fluids have now been identified as esters of octadeca-9,11-dienoic acid (18:2(9,11)), a non-peroxide isomer of linoleic acid (18:2(9,12)); and a range of high-performance liquid chromatographic methods has been developed for their detection and measurement. Significant abnormalities of phospholipid-esterified 18:2(9,11) have been found in the serum of chronic alcoholics and in paraquat poisoning and of non-esterified 18:2(9,11) in lipolytic states. The phospholipid-esterified 18:2(9,11) is increased in the bile of patients with pancreatic disease. In exfoliated cells from the cervix uteri an abnormal molar ratio between phospholipid-esterified 18:2(9,11) and 18:2(9,12) may prove to be the most sensitive biochemical marker of precancerous change.
Free-radical oxidation (peroxidation) products in serum and synovial fluid in rheumatoid arthritis.
Free-radical oxidation (peroxidation) products were measured in (a) 65 synovial effusions and (b) 30 sera from normal subjects and 58 sera from patients with rheumatoid arthritis (RA). Free-radical oxidation products were detectable in 90% of synovial fluids, their concentration being higher in "inflammatory" than in "degenerative" joint disease. Free-radical oxidation products in serum were significantly elevated in patients with RA compared to normal controls; the levels declined after treatment with a variety of antiinflammatory agents.