G. Brecher

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.

Abstract The literature on spiculed red cells, contains a redundant nomenclature and contradictory claims on the pathogenesis of the abnormal red cells. A resolution of these difficulties requires knowledge of the many conditions that induce crenation in normal and abnormal red cells because these artifacts have frequently been confused with spiculed cells in the patient’s circulation. The biconcave red cells (disocytes) can be transformed into crenated red cells (echinocytes) (1) by extrinsic factors (plasma incubated at 37°C for 24 hr, lysolecithin, high levels of fatty acid or physiologic levels of fatty acid in the presence of lysolecithin and many others); (2) by intrinsic factors, such as aging of red cells, which are probably related to depressed ATP; and (3) by washing in saline and the "glass effect" of observing cells between slide and cover slip. The extrinsically induced discocyte-echinocyte transformation is generally reversible by washing in fresh plasma, the intrinsically induced transformation is not. The discocyte-echinocyte transformation due to glass contact is prevented by observation between plastic cover slips. Echinocytes probably occur in various diseases, but such claims must be reevaluated because examination of fresh cells between plastic cover slips is necessary to exclude artifactual crenation during preparation of smears. Sphero-echinocytes and spherocytes may develop with higher concentration of echinocytogenic agents. The relationship of these cells to echinocytes, on one hand, and prelytic spheres, on the other, needs further clarification. The spiculed cells in the circulation of certain patients with liver disease are indistinguishable from the acanthocytes of abetalipoproteinemia. Acanthocytes can develop crenation superimposed on their own spicules and become acanthoechinocytes. It is suggested that the term burr cell for echinocyte and spur cells for the acanthocytes of liver disease be abandoned because they are redundant and do not allow for designation of the mixed forms of acantho-echinocytes which are of diagnostic importance. Speculations are presented on the pathogenesis of echinocyte formation and their importance for an understanding of the structure of the red cell membrane.

Cell proliferative activity and potential in the circulating blood and in the bone marrow of individuals with normal hematopoiesis, and in patients with hematopoietic dyscrasias was studied by means of in vitro one hour incubation with tritiated thymidine (H3Th) and 6tripping film autoradiography. The labeled material is incorporated only into DNA during synthesis. In normal bone marrow, labeling was seen at 1 hour in all cell lineages, and in cells variously referred to as reticulum, stem,'' stroma,'' etc., cells. Erythropoietic cells were labeled as far as the polychromatic normoblast; the myeloid series was labeled to the myelocyte state. Leukemia cells in the bone marrow and peripheral blood of patients with acute or chronic myelocytic leukemia incorporated label avidly; the small typical leukemia cell of chronic lymphocytic leukemia did not label at all. Less than 3 per cent of the myeloma cells in patients with multiple myeloma incorporated thymidine. Most striking was the finding of small numbers of labeled large mononuclear cells of different morphological types in the peripheral blood of normal human beings, and an increase in the number of morphologically identical cells in the blood of patients with infection and infectious mononucleosis. The labeling indicates active DNA synthesismore » and thus these cells presumably are capable of division. It is suggested that these cells may represent a mobile pool of primitive progenitor cells and are multipotential in their function.« less

The widely held view that transfused bone marrow cells will not proliferate in normal mice, not exposed to irradiation or other forms of bone marrow ablation, was reinvestigated. Forty million bone marrow cells from male donors were given to female recipients on each of 5 consecutive days, 5 to 10 times the number customarily used in the past. When the recipients were examined 2-13 weeks after the last transfusion, donor cells were found to average 16-25% of total marrow cells. Similar percentages of donor cells were found when variants of the enzyme phosphoglycerate kinase determined electrophoretically were used for identification of donor and recipient cells. Evidence is presented that the proportion of donor cells is compatible with a linear dependence on the number of cells transfused over the range tested--i.e., 20-200 million bone marrow cells injected intravenously. Special proliferative sites thus do not appear to be required.