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Biomedical subjects

R M Wells

Publications and source records attributed to R M Wells.

At least 55 records · Page 3Linked to original sources
PubMed1981

Hemoglobin Brisbane: beta68 Leu replaced by His. A new high oxygen affinity variant.

Hemoglobin Brisbane is a new hemoglobin variant which produces a mile erythrocytosis. It is not detectable by electrophoresis at pH 8.6 or by isoelectric focusing but it is mildly unstable and gives a positive result with standard stability tests. The new hemoglobin has increased oxygen affinity and reduced co-operativity with a normal Bohr effect and 2,3-DPG binding. Structural analysis shows that a histidine residue has replaced the leucine normally found at position beta 68 (E12).

Adult↗
PubMed1980

A new method for the detection of hydroxyl radical production by phagocytic cells.

Benzoic acid, a specific scavenger of hydroxyl radical (OH.) is known to be oxidized as the result of a reaction with OH.. We have determined that the decarboxylation of benzoic acid can be used to detect OH. generated in cell-free systems and human granulocytes. Benzoic acid is oxidized by the xanthine-xanthine oxidase enzyme system. This system is known to generate O2-, H2O2 and OH.. This oxidation is inhibited by superoxide dismutase, catalase and mannitol. Therefore, the oxidation of benzoic acid occurs by a mechanism similar to that reported for the oxidation of methional to ethylene and involves OH.. Resting granulocytes do not oxidize benzoic acid. However, marked oxidation of this substrate occurs during the phagocytosis of opsonized zymosan particles, indicating the production of OH. by these cells. The reaction can be inhibited by superoxide dismutase, catalase, azide and mannitol. Therefore, the production of OH. in the cell may be similar to that observed in the cell-free system. The granulocytes of a patient with known chronic granulomatous disease did not oxidase benzoic acid, indicating a defect in the generation of OH. by these cells.

Benzoates↗
PubMed1980

Evidence that OH. production by human PMNs is related to prostaglandin metabolism.

Recent studies indicate that human granulocytes generate OH. during the phagocytosis of zymosan particles. Several theoretical considerations suggested to us that this OH. production might be related to prostaglandin metabolism, particularly the observation that OH. is generated by the reducation of hydroperoxides in microsomal systems. In our studies, we tested the importance of prostaglandin metabolism in the production of OH. by human granulocytes (PMNs). Indomethacin and aspirin at concentrations known to impair cyclooxygenase activity decreased OH. production by PMNs during the phagocytosis of zymosan particles. Phenol, which is known to alter prostaglandin metabolism, ablated OH. completely. None of these drugs at the concentrations used impaired the generation of O-2 or H2O2 by PMNs, as indicated by their failure to diminish significantly the generation of chemiluminescence. Thus, the decrement in OH. production by these drugs could not be attributed to a nonspecific effect on the production of O-2 or H2O2. These experiments therefore, indicate that the model for OH. production observed during prostaglandin synthesis with microsomal systems applies to human granulocytes.

Aspirin↗
PubMed1980

Hemoglobin Volga, beta 27 (B9) Ala replaced by Asp: functional and clinical correlations of an unstable hemoglobin.

Hb Volga (beta 27 Ala replaced by Asp) on the basis of physical tests is only a mildly unstable hemoglobin yet it is associated with a gross reticulocytosis. This is partly explicable by an increased oxygen affinity with a compensating erythrocytosis but there is also brisk hemolysis. It is not certain that this hemolysis is due to precipitation of the hemoglobin as in vitro inclusion body formation is not remarkable and there is no evidence of preferential proteolysis of the abnormal subunits, at least in the reticulocytes. There is increased autoxidation and it may be the consequence of this that is the prime cause of hemolysis.

Alanine↗
PubMed1977

Haemoglobin Radcliffe (alpha2beta299(Gi)Ala): a high oxygen-affinity variant causing familial polycythaemia.

Three members of an Oxfordshire family have polycythaemia. In each case their whole-blood oxygen affinity is increased. This is due to a previously undescribed haemoglobin variant which has been named haemoglobin Radcliffe (alpha2beta299(Gl)Ala). In addition to having a high oxygen affinity haemoglobin Radcliffe shows virtually no haem-haem interaction and a diminished Bohr effect. It is synthesized at the same rate and is as stable as haemoglobin A. X-ray analysis indicates that crystals of deoxyhaemoglobin Radcliffe are isomorphous with those of deoxyhaemoglobin A. Solutions of haemoglobin Radcliffe were also studied by high-resolution proton nuclear magnetic resonance spectroscopy. The structure/function relationships of haemoglobin Radcliffe are discussed in the light of these studies.

Adult↗
PubMed1976

The oxygen affinity of chicken haemoglobin in whole blood and erythrocyte suspensions.

The oxygen equilibrium of whole chicken blood has a P50 of 52.3 mm Hg and a Hill coefficient of 2.6 at pH 7.4 and 37 degrees C when determined with new microtechniques which are not vitiated by cellular respiration. The apparent failure of the haemoglobin to reach full saturation at arterial PO2 IS DISCUSSED IN RELATION TO THE HAEMoglobin-oxygen equilibrium concept. The low affinity observed is due to intraerythrocytic inositol pentaphosphate (IPP), and the affinity of a haemolysate "stripped" of IPP is greatly increased (deltalog P50 =1.25). Unlike the mamalian analogue 2, 3-diphosphoglycerate, IPP concentration of whole blood does not decrease after incubation for 10 hr at 37 degreesC.

Adult↗
PubMedDate not supplied

Absence of cooperative haemoglobin-oxygen binding in Sphenodon, a reptilian relict from the Triassic.

It is generally accepted that the sigmoidal nature of the haemoglobin-oxygen dissociation curve (ODC) is necessary for efficient oxygen transport in terrestrial vertebrates because it allows large volumes of oxygen to be bound or released for relatively small changes in the partial pressure of oxygen (PO2) in the blood. Furthermore, the amount of oxygen to tissues is increased by hydrogen ions produced from the dissociation of carbon dioxide in solution. The generality of these key features of cooperative oxygen binding and the Bohr effect holds for reptiles, birds and mammals, including representatives with special respiratory requirements for diving, burrowing and living at high altitude. Sphenodon punctatus is the sole surviving representative of the ancient order of 'beakhead' reptiles (order Rhynchocephalia) which were once widely distributed during the Triassic period before the spectacular radiation of dinosaur faunas. We have now investigated the oxygen transporting properties of blood from Sphenodon and find that the ODC is hyperbolic, with a high affinity for oxygen and very small Bohr effect. This combination of characteristics is unique among terrestrial vertebrates and accords with a low demand for oxygen and limited scope for aerobic activity.

Allosteric Regulation↗
PubMedDate not supplied

Changes of blood oxygen affinity in different CPD solutions during liquid storage.

Soft and hard-packed red blood cells in four different CPD anticoagulant-preservative solutions were stored with and without added glucose, adenine, and electrolytes. The hemoglobin-oxygen affinity of the red blood cell concentrates was tested over a six-week storage period. No single solution conferred better protection than any other against an expected increase in oxygen affinity due to loss of 2,3-DPG during storage. In all solutions, P50 at pH 7.4 decreased linearly when measured in a physiological system using CO2. After six weeks' storage at 4 C, the normal oxygen-binding properties of red blood cells could be restored in all instances following incubation for one hour in a rejuvenation solution. By contrast, red blood cell ATP levels were highest when resuspending solutions contained adenine and added glucose, but did not significantly compensate the allosteric role of 2,3-DPG in regulating oxygen affinity when the latter became depleted.

2,3-Diphosphoglycerate↗