Leucostasis, an underestimated cause of death in leukaemia

Massive sludging of leukaemic cells in blood vessels is a frequent and often lethal complication of leukaemia. In a retrospective clinicopathological study on the causes of death in 52 patients with acute myeloid leukaemia and myeloproliferative disease, pulmonary leucostasis was found in 40% of the patients. In many of these patients the vessels of the heart, brain and testes were also involved. In search for signs and symptoms specific for leucostasis, the clinical records of the 21 patients with leucostasis (the study group) were compared to those of 20 patients without leucostasis (the control group). Dysfunction of the organs most affected by leucostasis, namely lungs, heart and brain, was found more often in the study group than in the controls, but the combination of unexplained fever with cardiopulmonary and/or central nervous system failure occurred almost exclusively and in half of the patients with leucostasis. Leucostasis occurs predominantly, but not exclusively, in patients with high leucocyte counts, and especially, but again not exclusively, when the leucocyte counts rise sharply.     

Roles of surface electrochemistry and macromolecular adsorption in heparin-induced red blood cell aggregation

Red blood cell (RBC) aggregation in heparin-saline solution was quantified by microscopic observation. The adsorption isotherms of heparin onto normal and neuraminidase-treated RBC surfaces were determined by radioactive heparin labeled with 125I-Bolton-Hunter Reagent. RBC aggregation by heparin requires the presence of sialic acids at cell surface and was enhanced by reduction of ionic strength of the suspending medium. Adsorption of heparin onto RBC surface was increased by removal of sialic acids. These findings not only serve to elucidate the basic mechanism of cell-cell interaction mediated by negatively charged macromolecules, but also provide experimental evidence for the possible conformational change of macromolecules at the charged surface.     

Parathyrin and calcitonin stimulate cyclic AMP accumulation in cultured murine brain cells.

Despite the key role Ca2+ plays in the nervous system, biochemical actions on neural tissue of the Ca2+-regulating peptide hormones parathyrin and calcitonin were unknown. Until a few years ago only neurons, but not glial cells, were considered as targets for peptide hormones. Our recent observation that peptide hormones do indeed act on glial cells is extended by the present report that these cells respond to the calcaemic peptide hormones parathyrin and calcitonin. In cultured murine brain cells mainly consisting of glioblasts, parathyrin stimulates the accumulation of cyclic AMP. The half-maximal effect is elicited at 30 nM parathyrin. With rat brain cells the effects are three times those observed with mouse brain cells. Calcitonin, which is less potent than parathyrin, elevates the concentration of cyclic AMP only in rat brain cells. If properly occupied, the inhibitory receptors present on the cells lower the increase in the level of cyclic AMP evoked by parathyrin and, to some extent, that elicited by calcitonin. The results suggest that: (i) these or closely related hormones might exert regulatory functions in brain; and (ii) glial cells must be considered in discussions of the targets of the calcaemic and other peptide hormones.