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A new haemoglobin with increased oxygen affinity, beta82 (EF6) lysine leads to threonine (Hb Rahere), was found during the investigation of a patient who was found to have a raised haemoglobin concentration after a routine blood count. The substitution affects one of the 2, 3-diphosphoglycerate binding sites, resulting in an increased affinity for oxygen, but both the haem-haem interaction and the alkaline Bohr effect are normal in the haemolysate. This variant had the same mobility as haemoglobin A on electrophoresis at alkaline pH but was detected by measuring the whole blood oxygen affinity; it could be separated from haemoglobin A, however, by electrophoresis in agar at acid pH. The raised haemoglobin concentration was mainly due to a reduction in plasma volume (a relative polycythaemia) and was associated with a persistently raised white blood count. This case emphasises the need to measure the oxygen affinity of haemoglobin in all patients with absolute or relative polycythaemia when some obvious cause is not evident.
Br Med J 1975 Oct 25
PMID:Haemoglobin Rahere (beta Lys-Thr): A new high affinity haemoglobin associated with decreased 2, 3-diphosphoglycerate binding and relative polycythaemia. 0 Jan 24

1. We measured the minute ventilation and arterial blood catecholamine concentrations in four normal men standing and at two levels of moderate treadmill exercise breathing 14% oxygen or air. 2. Minute ventilation was significantly higher during hypoxic exercise than during normoxic exercise at an oxygen uptake of 1500 ml/min. 3. Arterial plasma noradrenaline during hypoxic exercise at an oxygen uptake of 1500 ml/min was significantly greater than at rest. 4. Arterial plasma noradrenaline during normoxic exercise at an oxygen uptake of 1500 ml/min was not elevated above the resting concentration. 5. The results are compatible with the suggestion that increased concentrations of arterial plasma noradrenaline contribute to the hypoxic potentiation of the respiratory response to moderate exercise.
Clin Sci Mol Med 1975 Nov
PMID:Arterial catecholamines in hypoxic exercise in man. 0 Jan 71

Nine sickle cell trait and nine control subjects underwent six-hour ammonium chloride acid loading. Maximal urine osmolality and renal hemodynamics were studied separately. Base line arterial pH, carbon dioxide pressure (Pco2), and [HCO3] were normal and comparable in the two groups. After ammonium chloride loading, urine pH decreased to 5.3 or less in all, and maximal excretion of ammonium and titratable and net acid was comparable as was urine minus blood Pco2 after bicarbonate loading. The ammonium chloride acidosis caused a small decrease in red blood cell 2,3-diphosphoglycerate levels but no alteration in oxygen pressure at 50% saturation at pH 7.4, sickling, or adverse effects. Control and sickle cell trait subjects had comparable renal hemodynamics but maximal urine osmolality was lower in sickle-cell trait subjects. Adults with sickle cell trait have diminished renal concentrating ability and normal renal acidification and hemodynamics.
Arch Intern Med 1976 Jan
PMID:Renal acidification in sickle cell trait. 0 28

The effects of varying pH and of increasing intracellular hemoglobin (Hb) concentration on red cell sickling and oxygen affinity were studied in whole blood from persons with sickle cell anemia (SS) and sickle cell trait (SA). Small increases in SS blood pH inhibited sickling, and small reductions in both SS and SA blood pH promoted sickling far more than accounted for by the Bohr effect. Sickling behavior correlated with minimum gelling concentrations (MGC) of deoxygenated hemolysates without 2,3-diphosphoglycerate. MGC values fell sharply when pH was lowered from 7.25 to 7.15 for HbS and from 7.15 to 6.90 for SA hemolysates, suggesting effects on specific ionic interactions involved in Hb gelation. Possible clinical counterparts are acute metabolic acidosis and alkalosis (prior to change in red cell 2,3-diphosphoglycerate), where the Bohr effect and oxygen affinity-independent effects of pH alterations on sickling would be additive. Osmotic shrinkage of HbS-containing red cells produced a large fall in oxygen affinity and a marked increase in sickling independent of that fall. The oxygen affinity and sickling properties of SA cells whose MCHC was raised to 40 per cent resembled those of unaltered SS cells, supporting a relationship between molecular aggregation of Hb and low oxygen affinity. Sickling of aerated SS cells in hypertonic saline depended upon partial Hb desaturation due to lowered oxygen affinity. Thus osmotic shrinkage of HbS-containing cells acts synergistically with partial deoxygenation to promote sickling. These conditions are present in the renal medulla, but may occur elsewhere in severe hyperosmolar states.
J Lab Clin Med 1976 Apr
PMID:Determinants of red cell sickling. Effects of varying pH and of increasing intracellular hemoglobin concentration by osmotic shrinkage. 0 63

Static performance characteristics of current-inventory USAF oxygen regulators were evaluated with the use of a specialized regulator test stand. Outlet suction pressures, flows, positive pressures, and delivered oxygen dilutions were monitored and recorded as functions of operational altitudes. General findings indicated that: 1) excessive oxygen addition occurs in all models, especially at low cabin altitudes; 2) positive pressure schedules generally conform to specifications; 3) negative suction pressures for most regulators are less than -2.54 cm H2O. The validity of static evaluation is discussed and data interpretation is considered with respect to biomedical compatibility emphasizing maintenance of crewmember physiological sufficiency.
Aviat Space Environ Med 1976 May
PMID:Biomedical aspects of oxygen regulator performance: I. Static characteristics. 0 93

1. Oxygen-binding, plasma and intra-erythrocytic pH, and haemoglobin, 2,3-diphosphoglycerate and inorganic phosphate concentrations were measured in sixty-two healthy non-smokers aged between 18 and 89 years. 2. P50 (oxygen tension at 50% oxygen saturation) expressed at plasma pH 7-40 and PCO2 5-33 kPa showed a positive correlation with age. 3. This correlation of P50 with age was closer when P50 was expressed at a constant intra-erythrocytic pH 7-20. On average P50 at intra-erythrocytic pH 7-20 increased from 3-59 kPa at 20 years to 3-96 kPa at 90 years of age. 4. 2,3-Diphosphoglycerate, inorganic phosphate, haemoglobin and mean corpuscular haemoglobin concentrations did not correlate with P50 or with age.
Clin Sci Mol Med 1976 Aug
PMID:Effect of age on oxygen-binding in normal human subjects. 0 33

The behaviour of partial tensions of respiratory gases and pH in the arterial blood was evaluated in anoxiaemic and hypercapnic (1st group) and hypo-eucapnic (IInd group) subjects undergoing oxygen therapy. The following phenomena were observed: 1) normalization in paO2 values in both groups; 2) statistically significant diminution in paCO2, especially as regards hypercapnic subjects; 3) statistically significant diminution in blood pH; 4) statistically significant diminution in bicarbonates. In the light of these findings, it is considered that other variables, such as the electrolytes, might play an important role in pH diminution during oxygen therapy and that further research should be carried out to look into the possibility.
Minerva Med 1976 Sep 22
PMID:[Changes in partial pressures of gases and of pH in the arterial blood of hypocapnic and hypercapnic subjects subjected to oxygen therapy]. 0 99

The behaviour of the partial tensions of respiratory gases and the main parameters of acid base balance in hypoxaemic and eucapnic chronic bronchopneumopathics undergoing oxygen therapy has been assessed. The patiests were subdivided into two groups, the first consisting of subjects undergoing oxygen therapy alone, the second of subjects having oxygen and i.v. theophylline at the same time. Two subgroups were also distinguished. These consisted respectively of normochloraemic and hypochloraemic patients, the purpose being to reveal whether electrolytic changes could be attributed to the concentration of chlorine evaluated in basal conditions. The results obtained showed a disappearance of the hypoxaemic state without appreciable changes in paCO2 in all patients; in those undergoing oxygen therapy only, also observed were: 1) increase in plasmatic H+ and reduction in pH; 2) diminution in HCO3- and plasma Na+; 3) increase in plasma concentration of Cl-; 4) statistical significance of these data; 5) tendency of all values in the parameters considered to return to basal values upon suspension of oxygenation.
Minerva Med 1976 Sep 22
PMID:[Changes in acid-base equilibrium of the arterial blood in hypoxemic-eucapnic subjects subjected to oxygen therapy with and without an antiphosphodiesterase drug]. 0

Changes in partial tension of the respiratory gases and in acid-base balance were studied in venous blood subjected to oxygenation, with or without incubation with theophylline. The following modifications were noted: 1) increased pO2; 2) decreased CO2 due to true wash-out caused by tonometry in oxygen; 3)decreased hydrogen ion concentration and bicarbonates following CO2 washing in both experimental models. A smaller reduction in pH and HCO3 was statistically significant in specimens treated with theophylline. This is seen as proof of the view that theophylline inhibits red cell membrane ion exchanges, such as to oppose or at any rate limit metabolic changes in acid-base balance induced by oxygenation.
Minerva Med 1976 Sep 22
PMID:[Gasometric changes and acid-base equilibrium of venous blood oxygenated in vitro and incubated with or without a phosphodiesterase inhibitor]. 0 1

Deoxyhemoglobin (deoxyHB) and oxyhemoglobin (HbO2) were covalently fixed to BrCN-activated Sephadex G-200. At pH 6, the oxygen semi-saturation pressure for the deoxyHb coupling product was 14.1, and for the HbO2 coupling product, 7.2 mm Hg. The alkaline Bohr effect delta was calculated to be - 0.55 and - 0.4 respectively. The Hill coefficients n are for both Hb derivatives between 1.4 and 1.5, independently of pH (for free Hb the respective values are pO2 50% = 18.2 mm Hg, delta = -0.55 and n = 2.5). Non-crosslinked dextran and Sephadex G-200 have no influence upon the affinity of free Hb to oxygen and upon cooperativity. As a reason for the varying oxygen-binding properties for the two Hb derivatives it is assumed that the amino group of valin alpha 1 is involved in the HbO2 fixation. In deoxyHb, this group is not probably converted. The reduced Hill coefficients and enhanced oxygen affinity are assumed to be due to impairment of the inter-chain contacts, to restrained cooperative mobility, and heterogeneity of the coupling products.
Acta Biol Med Ger 1975
PMID:[Oxygen binding of hemoglobin following covalent fixation in the deoxy- and oxy- conformation]. 0 63


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