Edward R. Burka

Clinical Spectrum of Hemolytic Anemia Associated with Glucose-6-Phosphate Dehydrogenase Deficiency

Excerpt The susceptibility of certain subjects to primaquine-induced hemolytic anemia was first associated with an intrinsic abnormality of the erythrocytes by Dern and coworkers (1). Subsequent in...

PROTEIN SYNTHESIS IN ERYTHROID CELLS. II. POLYRIBOSOME FUNCTION IN INTACT RETICULOCYTES.

In the present study, the function of polyribosomes in intact reticulocytes has been investigated. The pattern of increase in the specific activity of ribosomes of cells incubated with [ 14 C]leucine indicates that the initiation and growth of polypeptide chains occurs predominantly on polyribosomes. The relative rates of incorporation of leucine and tryptophan on polyribosomes of various sizes were determined. The results suggest that reticulocyte polyribosomes corresponding to sedimentation coefficients of 110 s to 240 s are involved in globin synthesis. Inhibition of protein synthesis with puromycin is associated with a release of nascent peptide chains from ribosomes and a rapid breakdown of polyribosomes to 78 s ribosomes and smaller units. On the other hand, inhibition of protein synthesis by amino acid starvation, which is not associated with a release of nascent protein from ribosomes, does not alter the rate of polyribosome breakdown. These results support the concept that S-RNA with the attached peptide chain is important to the stability of polyribosomes in the intact cell. In reticulocytes there appear to be at least two processes involved in polyribosome breakdown. One of these mechanisms is associated with completion of peptide chains; the other accompanies cell maturation and does not require protein synthesis.

The diagnosis of pulmonary thromboembolism in sickle cell disease

The symptoms of thromboembolism in sickle cell anemia patients with acute chest syndromes are difficult to differentiate from the similar symptoms of painful thoracic crises and infectious pulmonary episodes. Furthermore, the chronic pulmonary abnormalities in sickle cell disease frequently contribute to the confusing results of noninvasive diagnostic procedures usually employed in evaluating pulmonary thromboembolism. In this study the chronic pulmonary status of asymptomatic sickle cell patients was defined, and this information was used in the evaluation of patients with acute chest syndromes suggestive of pulmonary thromembolism. Sixteen asymptomatic sickle cell patients were prospectively studied by chest roentgenography, spirometry, arterial gas analyses, and radioisotopic lung scans. There was an appreciable degree of preexisting chronic restrictive lung disease with mild to moderate arterial hypoxemia and abnormal lung scans in more than half of the patients. These prospective baseline data were incorporated into the diagnostic evaluation of four of these patients who later developed an acute chest syndrome suggestive of pulmonary thromboembolism. Determination of the cause of the chest pain was greatly facilitated by the existence of the baseline pulmonary data. In another patient persistence of abnormal studies following a presumed thromboembolic episode aided diagnostic evaluation when another episode of chest pain occurred. The findings indicate that comprehensive pulmonary studies in sickle cell patients while in an asymptomatic state will provide baseline data which aid the evaluation of possible pulmonary thromboembolism in acute chest syndromes without resorting to high‐risk invasive studies.

Hemoglobins A and F: Formation in Thalassemia and other Hemolytic Anemias.

Rates of synthesis of hemoglobin A by erythroid cells from thalassemic subjects are markedly decreased. Formation of hemoglobin F, however, proceeds at similar rates in cells from subjects with thalassemia and other types of hemolytic anemias. A mechanism is suggested regarding the altered patterns of hemoglobin synthesis under conditions of erythropoietic stimulation in subjects with and without thalassemia.

Factor V Antibody and Disseminated Intravascular Coagulation

A factor V inhibitor arose in a 79-year-old man within 1 month of an operation for a fractured leg. Absorption studies with solid-phase antibodies to human immunoglobulins showed the inhibitory activity to be primarily in the IgG class, but also in the IgA class, of immunoglobulins. This is the first report of an IgA immunoglobulin with factor V inhibitory activity. While the inhibitor was present, and at a time when no circulating Factor V activity was detectable, the patient developed septicemia and disseminated intravascular coagulation. The mechanism sustaining disseminated intravascular coagulation despite the absence of circulation factor V activity remains unexplained. The factor V inhibitor disappeared within 5 months of its initial detection. Possible origins of factor V inhibitors are discussed.

Anti-Cephalothin Antibody and Coombs'-Positive Hemolytic Anemia

Excerpt Cephalothin therapy is associated with a positive direct antiglobulin test in 3% to 65% of patients receiving this drug (1, 2). Most often the responsible mechanism is nonimmune adsorption ...

Control of Hæmoglobin A and F Synthesis: Hæmoglobin Formation in Fœtal and Adult Erythroid Cells

Control of Haemoglobin A and F Synthesis: Haemoglobin Formation in Fœtal and Adult Erythroid Cells

Infectious Disease: A Cause of Hemolytic Anemia in Glucose-6 Phosphate Dehydrogenase Deficiency

Excerpt The role played by a congenital deficiency of the erythrocyte enzyme glucose-6 phosphate dehydrogenase (G6PD) in drug-induced hemolytic anemias has received increasing attention in both the...

Hemoglobin Potomac: Clinical Picture, Biosynths and Stability

The occurrence of hemoglobin Potomac (8101 Glu→Asp), an abnormal hemoglobin with increased oxygen affinity, has been previously reported in nine members of one kindred (1). We now present the second occurrence of this hemoglobin, in a 26 year old white female of mixed northern European extraction, and report the clinical picture and studies of the stability and biosynthesis of the abnormal hemoglobin.

Disappearance of polyribosomes during in vivo erythroid maturation and nuclease activity.

DEBELLIS and I have compared the disappearance of ribosomes and polyribosomes during the maturation in vivo of erythroid cells in the rabbit1. This involved injecting twice labelled cells, obtained from a donor animal, into a recipient animal in which the bone marrow was repressed by continuing injections of colchi-cine. The events which occurred, including disappearance of total erythroid cell RNA, of reticulocytes, and of ribosomes and polyribosomes, were the result of maturation of the donor cells in the recipient circulation, for evidence was presented to show that the donor cells were not removed from the circulation during the time of the study. In contrast to previous work2–4 there was no disproportionate loss of polyribosomes during erythroid cell maturation. Rowley5 criticized these studies because the initial and subsequent sucrose density gradient centrifugation patterns of ribosomes (Fig. 1, upper) resembled those obtained by other workers6,7 with polyribosomes treated with small amounts of ribonuclease. He concluded that “the similarity in (sucrose density gradient) patterns (as a) function of age simply represents degradation to a uniform state”. No experimental evidence is offered to support this conclusion.