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Biomedical subjects

F A Oski

Publications and source records attributed to F A Oski.

At least 109 records · Page 6Linked to original sources

Biochemical characteristics of "young" and "old" erythrocytes of the newborn infant.

Cord blood samples from ten term infants were fractionated into populations of young and old erythrocytes and compared with cells prepared in a similar fashion from eight normal adults. The old cell fraction from the newborn infants had very low phosphofructokinase activity and did not display the usual decline of activity of the enzymes phosphoglycerate kinase and enolase. In addition, the old cells from the newborn infants demonstrated impaired glucose consumption, which, upon analysis of the pattern of glycolytic intermediates, appeared to be a result of the phosphofructokinase deficiency. These findings suggest that cells produced earlier in gestation possess the developmental characteristics of fetal blood to a more significant degree and that these biochemical alterations may produce functional impairment.

Adult↗

Iron deficiency anemia and increased urinary norepinephrine excretion.

Chronic iron deficiency in rats resulted in decreased MAO activity both in vitro and in vivo. Since MAO is an important enzyme in inactivation of catecholamines, urinary excretion of DA, NE, E, MN-NMN, and VMA was measured in 24-hour samples from 11 iron-deficient children before and after treatment with intramuscular iron. Pretreatment NE excretion was abnormally high and returned to normal (P=0.001) within one week of therapy. VMA excretion also was higher before than after treatment (P greater than 0.05), but most values were within the normal range for healthy children of comparable size. There was no significant difference between DA, E, and MN-NMN excretion before and after iron therapy. Anemic, non-iron-deficient children had normal urinary NE, E, and VMA excretion before and after transfusion. These findings suggest that the irritability, lack of attentiveness, and low performance scores of iron-deficient children may be related to alterations in catecholamine metabolic pathways secondary to dependence of MAO on adequate iron stores.

Adolescent↗

Lack of relationship of red cell enzyme activity to bilirubin and carboxyhemoglobin levels in healthy term infants.

A total of 32 term infants were studied in an attempt to confirm and extend the recent observation of Petrich & associates (14) that minor degrees of transient deficiences of the red cell enzymes glucose phosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase were related to hyperbilirubinemia in otherwise healthy term infants. No relationships could be observed between the activity of these enzymes and the bilirubin level on day three. In addition, no correlation was present between bilirubin values and carboxyhemoglobin levels on day three, suggesting that in the healthy term infant excessive hemolysis is not usually responsible for the variations observed in bilirubin levels.

Bilirubin↗

Hemoglobin Syracuse (alpha2beta2-143(H21)His leads to Pro), a new high-affinity variant detected by special electrophoretic methods. Observations on the auto-oxidation of normal and variant hemoglobins.

Family members from four generations were found to have polycythemia and increased whole blood O2 affinity (P50; 11 mm Hg; normal, 27 mm Hg). No abnormal hemoglobin bands were seen after electrophoresis on starch gel at pH 8.6 or agar gel at pH 6.0. Analysis of the oxygenated hemolysate by isoelectric focusing on polyacrylamide gel revealed two closely spaced bands. When deoxygenated hemolysate was analyzed in oxygen-free gels, the two components were more widely separated. About 40% of the patient's hemoglobin focused at a more acid pH than hemoglobin A, indicating a hemoglobin variant with impaired Bohr effect. Chromatography of globin in 8 M urea revealed two beta-chain peaks, the first of which was eluted at a lower buffer molarity than normal beta chain. Fingerprints of tryptic digests of the aminoethylated chains were done on silica gel thin-layer plates. Tp 14 from the abnormal beta chain had slower electrophoretic mobility and a greater Rf value. Amino acid analyses of this peptide gave values identical with those of betaTp 14, except that it contained one proline residue and no histidine. Since the one His in betaTp 14 is in position 143, hemoglobin Syracuse in alpha2beta2-143 His leads to Pro. Native Hb Syracuse could be separated from hemoglobin A on a carboxymethylcellulose column. The inclusion of 0.1 mM EDTA in the preparative buffers proved very useful in reducing the formation of methemoglobin. Oxygen equilibria of purified hemoglobin Syracuse showed high oxygen affinity (P50 value 12% that of hemoglobin A) and lack of cooperativity between subunits (Hill's n equals 1.1). The alkaline Bohr effect was about half that of hemoglobin A. The proline substitution at betaH21 disrupts the helical configuration and probably prevents the formation of salt bonds that are important in stabilizing the deoxy structure and contribute to the alkaline Bohr effect. Since beta143 His is a binding site for 2,3-diphosphoglycerate (2,3-DPG), it is not suprising that hemoglobin Syracuse had markedly impaired reactivity with 2,3-DPG. Hemoglobin Syracuse auto-oxidized more slowly than hemoglobin A, probably reflecting a slower rate of dissociation of oxygen from fully liganded hemoglobin.

Adult↗

Syndrome of recurrent increased secretion of antidiuretic hormone following multiple doses of vincristine.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been recognized to occur following treatment with vincristine. None of the reports have provided information regarding its potential for recurrence on further challenge with vincristine (VCR), an agent generally required for repeated use in patients with malignancies. Symptomatic hyponatremia and SIADH that occurred 8 days following administration of VCR in a child with acute lymphatic leukemia was documented with specific radioimmunoassay of urinary ADH levels. The further occurrence of recurrent elevations in ADH excretion 8-10 days following repeated treatment with VCR was also observed. However, SIADH was prevented by prophylactic rigorous fluid restriction. The occurrence of SIADH following VCR therefore does not preclude the further safe usage of this drug.

Child, Preschool↗

The measurement of free erythrocyte porphyrin (FEP) as a simple means of distinguishing iron deficiency from beta-thalassemia trait in subjects with microcytosis.

Assay of free erythrocyte porphyrin (FEP) and measurement of red cell indices were obtained in a group of subjects with iron deficiency and beta-thalassemia trait to determine if these studies cound detect these disorders and discriminate bbetween them. FEP values were increased in 90.2 per cent of subjects with iron deficiency but were within the normal range in 96.6 per cent of subjects with beta-thalassemia trait. Mean FEP values increased sligtly as transferrin saturation fell but became abnormally elevated when the transferrin saturation fell but became abnormally elevated when the transferrin saturation was less than 15 per cent. Unlike subjecs with iron deficiency in whom the mean corpuscular volume varied from 46 to 84, all individuals with beta-thalassermia trait exhibited microcytosis. In most instances, determination of FEP appears to distinguish beta-thalassemia trait from iron deficiency in patients with microcytosis.

Anemia, Hypochromic↗

Abnormal erythrocyte metabolism in hepatic disease.

Erythrocyte (RBC) metabolic studies were done on 114 patients with severe hepatic disease. Heinz body formation after incubation of RBCs with acetyl phenylhydrazine was found to be significantly higher in patients than in controls. RBC-reduced glutathione levels were lower than those of controls both before and after incubation with acetyl phenylhydrazine, and patients with the highest Heinz body counts had the lowest reduced glutathione levels. RBC methylene blue-stimulated hexose monophosphate (HMP) shunt metabolism and glucose recycling through the shunt were significantly lower in patients with active hepatic disease than in controls. There was no difference in resting HMP shunt activity or in resting recycling of glucose. Despite impairment of shunt metabolism, total glucose consumption was greater in patients than in controls. The patients with the lowest stimulated HMP shunt metabolism and glucose recycling had the highest Heinz body counts, lowest reduced glutathione, and highest total glucose consumption. A continuum of abnormal shunt metabolism was seen, from a mild reduction of stimulated HMP shunt activity to a severe combined decrease in both the HMP shunt and glucose recycling. When measured, glutathione reductase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, and transketolase were normal or increased. Sequential studies were done on 11 patients who had abnormal metabolic studies. Coincident with improvement of HMP shunt metabolism, the Heinz body counts became lower, reduced glutathione higher, hematocrit higher, and liver function improved. Impaired HMP shunt metabolism appears to be a common, acquired RBC abnormality in patients with severe, active liver disease.

Erythrocytes↗