Hemopoiesis

MetaHoelement complexes may be useful for the post-irradiation treatment of radiation injury, based on the observation that several of these compounds accelerate recovery of, among other things, lympho/hemopoiesis. Preirradiation Mn2(0)(DIPS)g increases the survival of y-irradiated mice (103). Treatment of mice that have been exposed to an LD q q dose of y-rays plus Mn2(0)(DIPS)g either 1 or 3 h after irradiation also increases survival, which supports the hypothesis that this compound is an effective radiorecovery agent (105). Again, this increase in survival may result from the resynthesis of radiation-depleted Mn-dependent enzymes that facHitate the recovery of immunocompetence and tissue repair, as reported for Cu(II)2(DIPS)4. 

Interleukin-1 OC and (3. IL-1 has radioprotective activity toward BM and other tissues (151,164). IL-1 is produced in response to endotoxin, other cytokines, and microbial and viral agents, primarily by monocytes and macrophages. Other nucleated cells can also produce it. IL-1 appears to play an important role in the regulation of normal hemopoiesis directly by stimulating the most primitive stem cells and indirectly by stimulating other hemopoietic factors, including G-CSF, GM-CSF, M-CSF, and IL-6. 

The effects of lL-1 ki accelerating recovery of BM hemopoiesis ki mice have been characterized (172). Injection of lL-1 20 h prior to sublethal kradiation promotes an eadier CEU-S/CEU-GM recovery ki the BM and spleen, and markedly affects BM ceUularity and mobilization of progenitor cells (172). Differences have been found between strains and administration protocols, especially with respect to BM CEU-GM numbers. 

G-CSFPlus WR-2721. Because glucan is a potent inducer of several hemopoietic cytokines, it has been suggested that specific hemopoietic cytokines may also stimulate hemopoiesis and synergize with WR-2721 (252). Based on values, combining WR-2721 (4 mg/mouse ip 30-min... 

A vast cascade of cytokines appear to be induced by the presence of this polysaccharide, and immunopoiesis- and hemopoiesis-inhibition are probably the most prevalent during the first two weeks of daily exposure [61]. Studies relating structure to the biological activity have not been performed. 

Migliaccio, G., et al. Human embryonic hemopoiesis, kinetics of progenitors and precursors underlying the yolk sac-liver transition, J. Clin. Invest., 78, 51, 1986. 

Dorshkind K, 1990. Regulation of hemopoiesis by bone marrow stromal cells and their products. Ann Rev Immnnol 8 111... 

The HSC of peripheral blood were the source of hemopoiesis renewal for all the transplantations. 423 collections of peripheral blood HSC were carried out... 

In radiation protection studies, it was found that orotic acid does not offer a protective effect in mice against the whole-body X-irradiation of 700 y or 550 7 [189]. On the other hand, orotic acid, alone or with folic acid, definitely increased the survival rate of irradiated rats and guinea-pigs by 20—30 per cent, while hemopoiesis was not affected [190]. 

Tavassoli, M., Embryonic and fetal hemopoiesis an overview. Blood Cells, 1991. 17(2) 269-81 discussion 282-6. 

Copper is an essential component of numerous key metalloenzymes which are critical in melanin formation, myelin formation and crosslinking of collagen and elastin. Copper plays a vital role in hemopoiesis, maintenance of vascular and skeletal integrity, and structure and function of the nervous system. Thus a deficiency of copper can lead to a variety of adverse effects such as increased fragility in bones, aneurysm formation in arteries and a loss of lysyl oxidase activity in cartilage.54 57 Articles on copper also appear in Siget1, volumes 3 and 5, all of volumes 12 and 13, and volume 14,... 

Protected mice against hemopoiesis induced by mitomycin C 403... 

Examination of the bone marrow, although important, will only confirm that the hemopoiesis is megaloblastic. A deficiency of folic acid will also cause a megaloblastic anemia and it is not possible to identify the cause on the basis of morphology. A serum assay of both vitamins will usually indicate which is responsible. If the patient is vitamin B12 deficient, the next step is to carry out a vitamin B12 absorption test to confirm that the deficiency is due to a lack of intrinsic factor. Preferably this should not be done until the patient s vitamin B12 and hemoglobin levels have returned to normal, since the gastric and intestinal cells are also affected by a lack of vitamin B12 aborption may be less than optimal if it is attempted too early. Patients with pernicious anemia also have a histamine-fast achlorhydria and gastric atrophy. The disease appears to have an autoimmune basis and antibodies to intrinsic factor can be demonstrated in the serum of more than half of affected patients. 

G7. Green, C. D., and Eastwood, W., Effects of nitrous oxide inhalation on hemopoiesis in rats. Anesthesiology, 24, 341-345 (1963). 

Figure 11.4 The organization of normal hemopoiesis. Symbols are defined in the text.

Current analytic and numerical work determine the time-dependent changes in blood cell number as certain quantities, referred to as control parameters, are varied. Examples of control parameters in the regulation of hemopoiesis are the dimensionless maturation time r° and the peripheral destruction rates 7 and A. 

Recently, Bernard et al. [499] studied oscillations in cyclical neutropenia, a rare disorder characterized by oscillatory production of blood cells. As above, they developed a physiologically realistic model including a second homeostatic control on the production of the committed stem cells that undergo apoptosis at their proliferative phase. By using the same approach, they found a local supercritical Hopf bifurcation and a saddle-node bifurcation of limit cycles as critical parameters (i.e., the amplification parameter) are varied. Numerical simulations are consistent with experimental data and they indicate that regulated apoptosis may be a powerful control mechanism for the production of blood cells. The loss of control over apoptosis can have significant negative effects on the dynamic properties of hemopoiesis. 

SparwasserT, Hultner L,Koch ES, Luz A, Lipford GB, Wagner H.Immunostimula-tory CpG-oligodeoxynucleotides cause extramedullary murine hemopoiesis. J Immunol 1999 162 2368-74. 

The effects of lithium on hemopoiesis have been studied in 100 patients who had developed chronic granulocytopenia after cancer chemotherapy or radiotherapy (240). The mean leukocyte count rose by 46%, but there were no changes in platelet or erythrocyte counts. However, there was a significant increase in platelet count in those whose baseline values were below 150 x 109/1. Lithium was well tolerated (mean serum concentration 0.59 mmol/1). 

Hematological adverse effects of aldesleukin typically included transient anemia, thrombocytopenia, eosinophi-lia, neutropenia, extreme lymphopenia, and rebound lymphocytosis (4,59). Transient suppression of hemopoiesis by secondary cytokines, peripheral platelet destruction, and increased endothelium margination of lymphocytes are possible mechanisms. 

Compared with stem cells purified from bone marrow, there is no risk to donors in giving cord blood. The risk of graft-versus-host disease in recipients is lower, and the ability to reconstitute hemopoiesis and immunity after transplant is improved (35,134). 

Deferoxamine has a strong depressant effect on proliferation of bone marrow cultures in vitro (72). On the other hand, deferoxamine improves hemopoiesis in patients with anemia, for example in rheumatoid arthritis, hemolysis, or myelodysplastic sjmdromes, and reduces transfusion dependency (73-78). The mechanism is unknown, but increased erythropoietin responsiveness secondary to iron chelation may play a role (77). 

When used in patients without iron overload, deferoxamine can cause iron deficiency (12). In 20 patients, there were falls in ferritin concentrations in six, requiring withdrawal of deferoxamine and parenteral administration of iron dextran (12). Monitoring ferritin concentrations is therefore recommended in patients receiving deferoxamine for aluminium overload. On the other hand, the administration of deferoxamine (500mg/day by subcutaneous infusion) improves chronic anemia in patients with rheumatoid arthritis (77). This effect is thought to be achieved through increased erythropoietin responsiveness, secondary to iron chelation. Iron chelation with deferoxamine also improves hemopoiesis in patients with myelodysplastic syndromes and can reduce transfusion dependency (78). Exactly how deferoxamine works in these patients remains to be explained. 

The most significant adverse effect of glycosylated mammalian-derived rhM-CSF is a transient, dose- and schedule-related severe thrombocytopenia, which correlates with monocytosis and tjrpicaUy occurs after 7-10 days of treatment (7). Thrombocytopenia sometimes resolves despite continued administration of rhM-CSF and has usually not been sufficiently severe to cause bleeding. In other cases, a 50% reduction in the dose of rhM-CSF should be considered to allow treatment to be continued. The mechanism of rhM-CSF-induced thrombocytopenia does not involve suppression of hemopoiesis, but rather increased activity of the monocjTe/macrophage system in the liver and spleen (8). 

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