Heinz Body Anemia: An Ultrastructural Study. II. Red Cell Sequestration and Destruction

This study reports electron microscope observations on the process of redcell sequestration and destruction in the spleen and liver of the phenylhydrazine-treated rabbit. Damaged red cells are recognized by virtue oftheir Heinz bodies, a morphologic manifestation of the oxidative injury whichthey have sustained. Sequestration, in the spleen, involves the selective accumulation of damaged cells within the vascular spaces of the Billroth cords.Erythrophagocytosis and the intracellular digestion of red cells followssequestration. More severely injured cells may undergo intravascular hemolysiswithin the splenic red pulp. In the liver, however, no evidence for the intravascular sequestration of injured red cells is observed. Damaged cells areremoved directly from the sinusoidal blood by erythrophagocytosis. Theselectivity of spleen and liver for red cells subjected to different degrees ofinjury is discussed in terms of the observed differences in the vasculararchitecture of the two organs.

Submitted on November 15, 1964 Accepted on November 22, 1964     

ANTIPYRINE CLEARANCE IN CONGENITAL ADRENAL HYPERPLASIA

Antipyrine (AP) metabolism was studied in four adult patients with congenital adrenal hyperplasia (CAH) due to classical 21-hydroxylase deficiency and in four (adult) patients with CAH due to non-classical 21-hydroxylase deficiency. This investigation was prompted by the known biochemical and functional similarities between drug- and steroid-metabolizing enzymes. We hypothesized that a common genetic mechanism may regulate the expression and activity of both the adrenal and hepatic cytochrome P450 enzymes. AP half-lives (T1/2, mean +/- SD) were 10.7 +/- 2.1 h in classical CAH patients, 10.1 +/- 0.4 h in the nonclassical CAH patients and 10.9 +/- 2.2 h in the control group, suggesting that there was no significant difference in AP metabolism among the three groups. Similarly, no significant differences were found in the AP apparent volume of distribution (aVd) and metabolic clearance rate (MCR) among the three groups. These results indicate that despite the deficiency of adrenal cytochrome P450 in patients with 21-hydroxylase deficiency CAH, these individuals have normal hepatic drug metabolizing activity for the biotransformation of AP.     

Heinz Body Anemia--An Ultrastructural Study. I. Heinz Body Formation

The ultrastructural changes in red blood cells exposed to phenylhydrazine,either in vivo or in vitro, are described. There is an age-dependent gradientof red cell sensitivity to this drug which includes the more mature reticulocytes as well as the population of circulating erythrocytes. Oxidative denaturation of hemoglobin and the formation of Heinz bodies, which constitute themajor drug-induced lesion, are accompanied by a regular sequence of structural changes commencing in the central cytoplasm of erythrocytes and thedrug-sensitive reticulocytes. These early changes often appear in close associaion with clusters of mitochondria. The initial morphologic lesion has anapparently crystalline structure and the significance of this stage is discussed.Heinz bodies grow by coalescence and condensation and finally come tolie just beneath the cell surface. Here they result in considerable distortionof cell shape and deformation of the plasma membrane. Thus, phenylhydrazine administration produces in red blood cells extensive ultrastructural alterations both in hemoglobin and in the cell membrane which may have considerable bearing on the fate of these cells in the circulation.

Submitted on September 29, 1964 Accepted on October 9, 1964     

Cholesterol and coronary heart disease prevention--A transatlantic consensus

Recent research findings have enhanced interest in coronaryheart disease prevention. Three expert panels, one in the UnitedStates and two in Europe, have addressed the subject and recommendedappropriate action. The report of the United States ConsensusConference on Lowering Blood Cholesterol appeared in 1985, andthe reports of the European Atherosclerosis Society and BritishCardiac Society appeared in 1987. We discuss these reports andemphasize the proposals concerning cholesterol. We review thescientific background to the decisions of the expert panels,high-risk and population-based strategies, cholesterol screeningand cholesterol reference levels for the initiation of treatmentand therapeutic goals. Dietary recommendations are highlightedand the attention given to special groups such as women, theelderly and children is appraised. Finally, the recommendationsof the reports regarding the other risk factors are discussed.We note the general consensus among them and outline the strategiesand guidelines which advocate concerted effort to reduce theburden of coronary heart disease.     

Phase contrast and interferometric microscopy of the L. E. cell phenomenon

Alterations in the cellular morphology of polymorphonuclear leukocytes and lymphocytes under the influence of serum from patients having disseminated lupus erythematosus were observed under the phase contrast microscope. These changes appear to involve the cell nucleus without significant visible incorporation of cytoplasm. In the formation of the L.E. body, there is a loss of internal nuclear structure and a subsequent nuclear swelling and extrusion of the nuclear contents from the cell to form the free L.E. body. The possible incorporation of cytoplasmic substance cannot alone account for the large mass of the L.E. body as contrasted with the parent nucleus or nuclear lobe. Measurements of dry mass by means of the interference microscope show a two and one-half-fold increment in dry mass in L.E. bodies compared to parent lymphocyte nuclei. This confirms previous cytochemical studies, and establishes that an influx of protein into the leukocyte nucleus is an integral part of the L.E. phenomenon. That the accumulation of extraneous protein within the L.E. body is simultaneous with or subsequent to a disruption of the normal structure of the leukocyte nucleus is apparent from these studies, but the pathogenesis of this alteration is as yet unknown.