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Biomedical subjects

J W Eaton

Publications and source records attributed to J W Eaton.

At least 163 records · Page 9Linked to original sources
PubMed1978

Skin color and nutrient photolysis: an evolutionary hypothesis.

Human populations native to areas of intense sunlight tend to be heavily melanized. Previous explanations for this relationship have invoked only weak selective pressures. To test the hypothesis that dark pigmentation may protect against photolysis of crucial light-sensitive vitamins and metabolites by ultraviolet light, folate was used as a model. It was found that exposure of human plasma in vitro to simulated strong sunlight causes 30 to 50 percent loss of folate within 60 minutes. Furthermore, light-skinned patients exposed to ultraviolet light for dermatologic disorders have abnormally low serum folate concentrations, suggesting that photolysis may also occur in vivo. Deficiency of folate, which occurs in many marginally nourished populations, causes severe anemia, fetal wastage, frank infertility, and maternal mortality. Prevention of ultraviolet photolysis of folate and other light sensitive nutrients by dark skin may be sufficient explanation for the maintenance of this characteristic in human groups indigenous to regions of intense solar radiation.

Biological Evolution↗
PubMed1978

Extreme but asymptomatic carboxyhemoglobinemia and chronic lung disease.

Carboxyhemoglobinemia is a well-known consequence of carbon monoxide exposure from smoking. However, only moderately elevated levels have been reported. We report the case of an asymptomatic man with severe chronic obstructive lung disease and carboxyhemoglobin levels repeatedly in excess of 30% (maximum, 38.0%) due to smoking. The mechanism by which such high levels were attained was primrily a combination of arterial hypoxia and a high carbon monoxide yield from tobacco. For a given level of carbon monoxide exposure, the hypoxic person will attain a higher carboxyhemoglobin level than will a person without hypoxia.

Aged↗
PubMed1978

The role of iron in prostaglandin synthesis: ferrous iron mediated oxidation of arachidonic acid.

Arachidonic acid (AA) is the essential substrate for production of platelet endoperoxides and thromboxanes. Iron or heme is an essential cofactor for the peroxidase, lipoxygenase and cyclo-oxygenase enzymes involved in formation of these products. The present study has examined the direct interactions between iron and arachidonic acid. Iron caused the oxidation of AA into more polar products which could be detected by UV absorbtion at 232 nM or the thiobarbituric acid (TBA) reaction. High pressure liquid chromatography, chem-ionization and electron-impact mass spectrometry and nuclear magnetic resonance spectroscopy suggest that the major product was a hydroperoxide of AA. Ferrous iron (Fe++) and oxygen were absolute requirements. Fe++ was converted to the ferric iron (Fe+++) state during oxidation of AA, but Fe+++ could not substitute for Fe++. No other enzymes, cofactors or ions were involved. Conversion of AA to a hydroperoxide by Fe++ was inhibited by the antioxidant, 2, (3)-Tert-butyl-4-hydroxyanisole, the radical scavenger, nitroblue tetrazolium, and iron chelating agents, including EDTA, imidazole and dihydroxybenzoic acid. The reaction was not affected by superoxide dismutase, catalase or aspirin. These findings and preliminary studies of the Fe++ induced oxidation product of AA as a substrate for prostaglandin synthesis and inhibitor of prostacyclin production indicate the critical role of Fe++ in AA activation.

Antimetabolites↗
PubMed1978

Erythrocyte calcium abnormalities and the clinical severity of sickling disorders.

We studied erythrocyte calcium levels and uptake in a group of patients with sickle haemoglobinopathies of different clinical severity in an attempt to relate these measurements to the production of irreversibly sickled cells and disease severity. Erythrocyte calcium levels were measured by atomic absorption spectroscopy and calcium uptake by isotopic means. In sickle cell anaemia, erythrocyte calcium content was elevated and the uptake of isotopic calcium increased under both oxygenated and deoxygenated conditions. There was a direct correlation between the numbers of irreversibly sickled cells and calcium uptake and an inverse relationship between calcium uptake and red cell potassium level. The clinical course of disease was milder in patients with high fetal haemoglobin levels, but there was no relationship between clinical course and calcium levels, calcium flux or irreversibly sickled cells. Our observations suggest that calcium accumulation and irreversibly sickled cell formation are related processes. The absence of good correlation between various biochemical and clinical parameters emphasizes the complexity of factors which modify the clinical course of this disorder.

Adolescent↗
PubMed1978

Calcium-induced damage of haemoglobin SS and normal erythrocytes.

An ionophore specific for divalent cations has been used to load normal erythrocytes and erythrocytes from patients with sickle cell anaemia (Hb SS disease), with small amounts of calcium. Such calcium accumulation leads to decreased cellular water, potassium, adenosine triphosphate (ATP), and osmotic fragility, all characteristics of irreversibly sickled cells (ISCs). In addition, calcium loading of Hb SS, but not normal, erythrocytes causes a marked decrease of haemoglobin oxygen affinity; another, and specific, hallmark of ISCs. Ionophore-induced accumulation of calcium by deoxygenated Hb SS erythrocytes also leads to temporary retention of sickled shape following reoxygenation, despite the absence of detectable intracellular haemoglobin S fibres. All these effects require calcium in the incubation medium and support the idea that increased intracellular calcium is important in the formation of ISCs in patients with Hb SS disease.

Anemia, Sickle Cell↗
PubMed1978

Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity.

To assess the adaptive value of the right-shift of the oxyhemoglobin dissociation curve (decreased affinity for oxygen) observed in humans upon altitude exposure, the short-term physiologic responses to altitude-induced hypoxia were evaluated in two subjects with a high oxygen affinity hemoglobin (Hb Andrew-Minneapolis) and in two of their normal siblings. In striking contrast to normal subjects, at moderately high altitude (3,100 m) the high affinity subjects manifested: (a) lesser increments in resting heart rate; (b) minimal increases in plasma and urinary erythropoietin; (c) no decrement in maximal oxygen consumption; and (d) no thrombocytopenia. There was no difference between subject pairs in 2,3-diphosphoglycerate response to altitude exposure. These results tend to contradict the belief that a decrease in hemoglobin oxygen affinity is of adaptive value to humans at moderate altitudes. Rather, they support the hypothesis that, despite disadvantages at low altitude, a left-shifted oxyhemoglobin dissociation curve may confer a degree of preadaptation to altitude.

Adaptation, Physiological↗
PubMed1978

Retention of water and potassium by erythrocytes prevents calcium-induced membrane rigidity.

Modest increases in intracellular calcium concentrations, in association with ATP depletion, cause the appearance of pathologic changes in erthrocyte shape and deformability. The loss of erythrocyte ATP and simultaneous increase in cellular calcium have previously been considered the sole requisites for the appearance of erythrocyte membrane rigidity. We report that red cells suspended in high-potassium buffers may be simultaneously loaded with calcium (through exposure to the divalent cation ionophore A23187) and depleted of ATP without incurring drastic changes in shape or in membrane stiffness. Incubation of erythrocytes under these conditions effectively blocks both water and potassium loss normally caused by calcium accumulation. However, the high external potassium has no influence on either the ionophore-induced accumulation of calcium or on the the concomitant hydrolysis of cellular ATP. These results suggest the involvement of at least one further parameter, ie, changes in cell water and cation content, in the development of calcium-induced erythrocyte rigidity.

Calcimycin↗
PubMed1978

Prevention of chloramine-induced hemolysis in dialyzed patients.

Chloramines, compounds made up of chlorine and ammonia, when present in tap water used for dialysis cause methemoglobinemia and hemolysis. Ascorbic acid addition has been reported to effectively neutralize chloramines in vitro and in patients dialyzed with the single batch dialysis delivery system. We extended these observations to patients dialyzed with the proportioning dialysis delivery system where exposure time of ascorbic acid to chloramines is shorter. This may be important since we found that the half time of the reaction between ascorbic acid and chloramines is 4 minutes. Red cell oxidant sensitivity in 15 patients was assessed by incubating red cells with ascorbate-cyanide and measuring methemoglobin which averaged 2.17 +/- 0.42 g/100 ml (SEM) before dialysis and 2.87 +/- 0.52 g/100 ml after dialysis (NS). Reduced glutathione (GSH) levels were also measured as an index of red cell oxidant damage. GSH decreased from a mean of 7.40 +/- 0.59 micromoles/g Hb before dialysis to 6.98 +/- 0.52 micronmoles/g Hb after dialysis (P less than 0.01). In 2 patients there was no change in 51Cr red cell survival when dialyzed on either the proportioning system or other chloramine free systems. We conclude that addition of ascorbic acid to neutralize chloramines in tap water is also effective when using the proportioning dialysis delivery system.

Adult↗
PubMed1977

Hypoxic ventilatory response in subjects with normal and high oxygen affinity hemoglobins.

It has still not been shown unequivocally whether a decrement of arterial oxygen content or tension governs the ventilatory response to hypoxia. In an attempt to discriminate between the two possibilities, we have measured the ventilatory response to isocapnic progressive hypoxia in two healthy children with a high oxygen affinity hemoglobin (Hb Andrew-Minneapolis) and in their age- and sex-matched normal siblings. Hypoxic ventilatory response was identical in all subjects, there being no difference in minute ventilation at PAo2 = 40 mm Hg or in k (decrement of PO2 required to increase ventilation by a factor of 2.718). In contrast, at PAo2 = 40 mm Hg, hemoglobin oxygen saturation decreased markedly in controls but only slightly in high affinity subjects. Furthermore the increase in heart rate at PAo2 = 40 mm Hg was significantly less in high affinity subjects, suggesting a concomitant difference in oxygen delivery. Thus, with identical decrements in PAo2 but widely divergent changes in arterial oxygen content and oxygen delivery, controls and high affinity subjects showed virtually identical ventilatory response to hypoxia. We conclude that decrements of oxygen tension are the major stimulus for hypoxic ventilatory response.

Adolescent↗
PubMed1977

Influence of the ionophore A23187 on the plastic behavior of normal erythrocytes.

Previous studies have demonstrated that A23187, an ionophore which selectively transports divalent cations across cell membranes, has profound effects on human erythrocytes: it causes red cells to take up calcium; lose potassium, water, and ATP; convert from biconcave discs to echinocytes and spheroechinocytes; and become more rigid. The present study has explored the influence of calcium uptake induced by the ionophore on the behavior of individual erythrocyte membranes by the micropipette aspiration technique. Exposure of erythrocytes to calcium and A23187 for intervals of up to 30 minutes resulted in marked changes in membrane viscoelastic properties, including the development of increased resistance to aspiration. The most striking manifestation of altered membrane mechanics was apparent after 10 minutes on incubation. Cells pulled into the pipette for a few seconds and the extruded back into the medium retained the deformity imposed by the pipette for several seconds to a few minutes before regaining the form they manifested prior to initial aspiration. The calcium-induced changes in erythrocyte behavior observed in this study strongly support the concept that extrinsic proteins located inside the membrane provide mechanical support to the cell wall, and that increased levels of calcium cause precipitation or cross-linking of the proteins responsible for the increased resistence to deformation and recoil observed after aspiration into micropipettes.

Anti-Bacterial Agents↗
PubMed1977

Host heme catabolism in drug-sensitive and drug-resistant malaria.

Chloroquine resistance has arisen in both human and murine forms of malaria. CR Plasmodium berghei in mice does not produce the malaria pigment which is characteristic of the CS form. Determinations of carbon monoxide production (i.e., host heme catabolism) by individual mice revealed that those infected with CS P. berghei produce only one fourth as much carbon monoxide as do CR infected mice at all levels of infection. These observations confirm the idea that malaria pigment is composed of precipitated host cell hemoglobin and suggest that drug resistance is accompanied by a basic alteration in parasite-mediated hemoglobin catabolism.

Animals↗