losartan-potassium and Leukemia--Radiation-Induced

By definition, idiopathic erythrocytosis (IE) applies to a group of patients characterised by having a measured RCM above their predicted normal range (an absolute erythrocytosis) and following investigation do not have a form of primary or secondary erythrocytosis. Patients with IE are heterogenous. The possibilities include physiological variation, 'early' polycythaemia vera (10-15% develop clear features of PV over a few years), unrecognized congenital erythrocytosis, unrecognized or unrecognizable secondary acquired erythrocytosis or a currently undescribed form of primary or secondary erythrocytosis. Patients are more commonly male with a median age at presentation of 55-60 years. Approximately half of the patients present with vascular occlusive complications. Retrospective evidence indicates that vascular occlusion occurs less frequently when the PCV is controlled at normal levels. Venesection is the treatment of choice to lower the PCV. As a general approach to management, all patients with a PCV above 0.54 should be venesected to a PCV less than 0.45. This target PCV should also apply to patients with lesser degrees of raised PCV who have additional other risk factors for vascular occlusion.

Topics: Aged; Arterial Occlusive Diseases; Bone Marrow; Chlorambucil; Diagnosis, Differential; Endocrine System Diseases; Erythrocyte Volume; Erythroid Precursor Cells; Erythropoietin; Genetic Predisposition to Disease; Humans; Hypoxia; Kidney Diseases; Leukemia; Leukemia, Radiation-Induced; Middle Aged; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera; Receptors, Erythropoietin; Sequence Deletion; Smoking; Stroke

Some mouse myeloid leukemias induced by X-irradiation and serially transplanted into syngenic mice do not proliferate in vitro even in the presence of hematopoietic factors. To examine whether such leukemic cells can proliferate in response to stromal cells, we cocultured them with MC3T3-G2/PA6 (PA6) preadipocytes, cells that can support the growth of hematopoietic stem cells. All leukemias developed into in vitro cell lines, showing a dependence on contact with the PA6 cells. Two cell lines responded to none of the known hematopoietic factors including interleukin-3 (IL-3), IL-4, IL-5, IL-6, GM-CSF, G-CSF, M-CSF, and Epo. These results demonstrate that the mechanism of the action of PA6 cells is different from that of any of the known hematopoietic factors, and that, because these two leukemic cell lines retained the ability to grow in vivo, responsiveness to the known hematopoietic factors is not essential for the leukemic cell growth in vivo. Furthermore, all leukemic cell lines could respond also to the preadipocytes fixed with formalin, paraformaldehyde, or glutaraldehyde, suggesting that some molecule(s) associated with the surface of PA6 cells or with extracellular matrix secreted by the preadipocytes is responsible for the leukemic cell growth.

Topics: Adipose Tissue; Animals; Cell Communication; Cell Division; Cell Line; Erythropoietin; Female; Formaldehyde; Glutaral; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Interleukins; Leukemia, Experimental; Leukemia, Myeloid; Leukemia, Radiation-Induced; Macrophage Colony-Stimulating Factor; Male; Mice; Mice, Inbred C3H; Polymers; Recombinant Proteins

Here we describe the characterization of Epo-responsive mouse erythroleukemia cell line ELM-I-1. ELM-I-1 cells possess Epo binding sites on their membranes and differentiate into hemoglobin-positive cells when cultured in the presence of Epo. About 20% of the cells were hemoglobin-positive after a 3- to 4-day exposure to recombinant human Epo in liquid culture. Supplementation of recombinant mouse IL-3 during culture had an augmentative effect on Epo-mediated differentiation, although IL-3 alone did not induce differentiation. Both Epo and IL-3 stimulated the growth of ELM-I-1 cells, and their effects were a slightly additive. These findings indicate that ELM-I-1 cells are suitable for studying the interaction between Epo and IL-3 in erythroid differentiation at a subcellular level. ELM-I-1 may also offer a valuable bioassay system for Epo.

Topics: Animals; Cell Differentiation; Cell Division; Cell Line; Dose-Response Relationship, Drug; Erythropoietin; Interleukin-3; Kinetics; Leukemia, Erythroblastic, Acute; Leukemia, Radiation-Induced; Mice; Mice, Inbred C3H; Recombinant Proteins; Tumor Cells, Cultured