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Biomedical subjects

D G Nathan

Publications and source records attributed to D G Nathan.

At least 271 records · Page 15Linked to original sources
PubMed1970

Correction of metabolic deficiencies in the leukocytes of patients with chronic granulomatous disease.

Polymorphonuclear leukocytes from patients with chronic granulomatous disease (CGD) exhibit metabolic and bactericidal deficiencies that may be the result of inadequate production of H(2)O(2). A hydrogen peroxide-generating system was, therefore, inserted into CGD leukocytes. This was accomplished by allowing the cells to phagocytize latex spherules coated with glucose oxidase. This produced an amelioration in the known metabolic deficiencies of these cells during phagocytosis: (a) intracellular (catalatic) formate oxidation dependent upon hydrogen peroxide production was enhanced fourfold; and (b) hexose monophosphate shunt activity, which other workers have shown to be at least partially dependent upon the availability of H(2)O(2), was markedly stimulated. These data strengthen the evidence that the fundamental metabolic lesion in CGD cells during phagocytosis is indeed deficient production of hydrogen peroxide, probably, as previously shown, due to diminished oxidase for reduced nicotinamide adenine dinucleotide.

Carbon Isotopes↗
PubMed1969

Globin chain synthesis in the alpha thalassemia syndromes.

Whole blood samples of patients with various forms of alpha thalassemia including hemoglobin H disease, alpha thalassemia trait, and the "silent carrier" state were incubated with leucine-(14)C for definition of relative rates of production of alpha and beta chains in these disorders. The chains were separated by carboxymethyl cellulose chromatography in the presence of 8 M urea and dithiothreitol. Their absorptions at 280 mmu were determined and their radioactivities measured in a liquid scintillation spectrometer. After correction for differences in extinction coefficients, the specific activities of the widely separated alpha and beta peaks were determined. In 11 nonthalassemic individuals, the alpha/beta specific activity ratios were found to be 1.02+/-0.07; in nine patients with alpha thalassemia trait, 0.77+/-0.05; in six patients with hemoglobin H disease, 0.41+/-0.11; and in four "silent carriers," 0.88 with a range of 0.82-0.95. The results show that in peripheral blood, alpha chain production relative to beta chain production is indeed limited in the alpha thalassemia syndromes. Hemoglobin H disease results from doubly heterozygous inheritance of a gene resulting in moderate depression of alpha chain production (alpha thalassemia trait) and a gene resulting in very mild depression of alpha chain production (the "silent carrier" syndrome."

Anemia, Hypochromic↗
PubMed1969

Influence of hemoglobin precipitation on erythrocyte metabolism in alpha and beta thalassemia.

Certain aspects of the metabolism of centrifuged young and old erythrocytes in hemoglobin H disease have been examined and compared with similar studies of beta thalassemia and normal cells. Glycolysis, hexose monophosphate shunt activity (HMPS), potassium flux, and glutathione (GSH) content were measured. The distributions of hemoglobins H and F, as well as the activities of erythrocyte glucose-6-phosphate dehydrogenase (G6PD) and glutamic oxalacetic transaminase (GOT), were utilized for estimations of the relative ages of the cell samples. The young erythrocytes in hemoglobin H disease differed in several respects from older hemoglobin H cells. They contained more soluble hemoglobin H and GSH and, after splenectomy, fewer inclusions. HMPS activity was subnormal in hemoglobin H young cells and rose to normal activity in old cells. Potassium flux tended to increase in old cells when inclusions were present.Beta thalassemia young cells contained less hemoglobin F and, after splenectomy, more inclusions than old cells. In addition, they had markedly increased glycolysis and HMPS activity. GSH was randomly distributed. Potassium flux was increased in younger cells and particularly increased when inclusions appeared in younger cells after splenectomy. The results are interpreted to indicate that inclusion formation is associated with increased erythrocyte cation permeability in the thalassemia syndromes. This is not related to the level of intracellular GSH. The decreased HMPS activity in young hemoglobin H cells may be due to the presence of the extra thiols of soluble hemoglobin H which can act as a reducing agent. The substitution of hemoglobin H for glutathione in this capacity would then spare the NADPH-requiring glutathione reductase system. As a consequence, HMPS activity would decline. However, in older cells the oxidized hemoglobin H precipitates; these must rely upon GSH and glutathione reductase activity for thiol reduction capacity. Accordingly, HMPS activity increases to normal in the old cell population.

Carbon Isotopes↗
PubMed1969

Failure of nitro blue tetrazolium reduction in the phagocytic vacuoles of leukocytes in chronic granulomatous disease.

The leukocytes of patients with chronic granulomatous disease (CGD) may be identified by their failure to reduce Nitro Blue Tetrazolium (NBT) during phagocytosis. This reaction, normally detected in the phagocytic vacuole, is absent or delayed in CGD monocytes and eosinophils as well as in neutrophils, even though sonicates of normal and CGD leukocytes contain equal activities of a cyanide insensitive enzyme system capable of reduction of NBT in the presence of pyridine nucleotide. Enlargement of CGD phagocytic vacuoles appears to be inhibited. Histochemical estimates of the rate of release of alkaline phosphatase are normal in CGD cells. Peroxidase activity is released from CGD cells, but the rate appears to be somewhat slower than normal in some cases. The latter observation may be explained by the increased intensity of the peroxidase stain in resting and phagocytizing CGD cells. The severity of the defect in NBT reduction within the phagocytic vacuoles of the leukocytes of patients and carriers is more variable than was previously appreciated. Some female carriers have profoundly reduced dye reduction and others are nearly indistinguishable from normal. Three brothers with CGD demonstrated significant, albeit delayed, NBT reduction in phagocytic vacuoles during prolonged incubation of their leukocytes. No obvious relationship exists, however, between the rate of reduction of NBT in vacuoles and the clinical severity of the disease.

Alkaline Phosphatase↗
PubMed1968

Beta thalassemia trait: detection at birth.

The synthesis of alpha, beta, and gamma chains in samples of cord blood was measured by the incorporation of leucine labeled with carbon-14 into these chains. In a newborn affected with beta thalassemia trait, the presence of one beta thalassemia gene was revealed on the 1st day of life by the lower specific radioactivity of the beta chain.

Birth Weight↗