Robert H. Bigley

Hemoglobin casper: β 106 (G8) Leu→Pro: A contemporary mutation

Abstract Two unrelated sporadic patients with hemolytic anemia were found to have the same previously undescribed abnormal hemoglobin (β106 Leu → Pro), named for Casper, Wyoming, where the first proband was born. Both were detected because of anemia and splenomegaly associated with intercurrent infections during the first 2 years of life. Progressive anemia and splenomegaly ensued; and both have showed improvement after splenectomy. No abnormal hemoglobin was detected by electrophoresis at pH 8.6 or 6.9. Freshly drawn blood contained slightly increased amounts of methemoglobin and had no gross alteration in heme to globin ratios. Heinz body generation and heat stability tests for an unstable hemoglobin were positive. Oxygen affinity of their whole blood was greater than normal. Acute hemolytic episodes with increased reticulocytosis have occurred both before and after splenectomy as accompaniments of intercurrent infections. The data reported on unstable hemoglobin variants permit a tentative classification according to clinical severity. Contemporary mutations account for the majority of the reported cases with clinical disease.

Determinants of resistance to radiation injury in blood granulocytes from normal donors and from patients with myeloproliferative disorders

Dose-dependent injury to human blood granulocytes was measured within 2 hr of x irradiation, as changes in net /sup 22/Na influx and phagocytosing O/sub 2/ consumption. Among samples from normal donors and patients with chronic myeloproliferative diseases, samples from 10 to 12 patients with chronic granulocytic leukemia exhibited increased sensitivity to injury by radiation. Selected granulocyte constituents which may contribute to inactivation of oxidant and free-radical products of radiation-activated H/sub 2/O were also measured. These included glutathione and ascorbate contents; superoxide dismutase, catalase, glutathione proxidase, and glutathione reductase activities; and capacity to take up and reduce dehydroascorbate. Catalase activity was irregularly higher in radiation-sensitive than in radiation-resistant granulocytes (P = < 0.05). Dehydroascorbate uptake and reduction was consistently low in radiation-sensitive cells (P = < 0.001). We propose that cell capacity to maintain ascorbate in reduced form against oxidant and free-radical stress is a part of mechanisms which determine resistance to injury by ionizing radiation in human granulocytes.

The effect of cyanide on vitamin C uptake by human polymorphonuclear leukocytes

1. Cyanide inhibited the uptake of vitamin C by human polymorphonuclear leukocytes (PMNs). 2. Preincubation of PMNs with cyanide had no effect on cytochalasin B-inhibitable uptake of dehydroascorbic acid (DHA) (the reversibly oxidized and transportable form of vitamin C). 3. Preincubation of DHA with cyanide resulted in inhibition of DHA uptake. 4. Vitamin C uptake was decreased by cyanide to the same degree as it was by glutathione (GSH), which effectively reduces DHA to ascorbic acid. The effects of cyanide and GSH were not additive. 5. The data are consistent with the hypothesis that cyanide inhibition of vitamin C uptake represents the chemical elimination of extracellular DHA rather than the inhibition of active transport in these cells.