Hematopoiesis, characterization

SCF is encoded by the mouse Steel (SI) loci (Zsebo et al, 1990). The Sl-Dickie allele of mutant mice (Sf ) encodes a smaller protein due to deletions of the transmembrane and intracellular domains. SI cells exclusively express a secreted form of SCF (Flanagan et al, 1991). Another mutation of the Steel locus, Sl/Sl, results in complete loss of SCF production (Zsebo et al, 1990). Mutations of both the Steel and SI loci result in similar phenotypic disorders of hematopoiesis characterized by reduction in stem cell numbers, anemia, mast cell- and repair deficiencies (Nocka et al., 1989 McCulloch et al., 1965). Phenotypes of Sf mice show that the membrane inserted SCF must have an... 

Deficiency. Macrocytic anemia, megaloblastic anemia, and neurological symptoms characterize vitamin B 2 deficiency. Alterations in hematopoiesis occur because of the high requirement for vitamin B 2 for normal DNA repHcation necessary to sustain the rapid turnover of the erythrocytes. Abnormal DNA repHcation secondary to vitamin B 2 deficiency produces a defect in the nuclear maturational process of committed hematopoietic stem cells. As a result, the erythrocytes are either morphologically abnormal or die during development. 

O The acute leukemias are hematologic malignancies of bone marrow precursors characterized by excessive production of immature hematopoietic cells. This proliferation results in a large number of immature cells (blasts) appearing in the peripheral blood and bone marrow causing failure of normal hematopoiesis. 

Flow cytometric evaluation of bone marrow and peripheral blood to characterize the type of leukemia, as well as to detect specific chromosomal rearrangements. The bone marrow at diagnosis usually is hypercellular, with normal hematopoiesis being replaced by leukemic blasts. The presence of greater than 20% blasts in the bone marrow is diagnostic for AML. 

Bmmmendorf TH, Balabanov S. Telomere length d3mamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover. Leukemia 2006 20 1706-1716. 

We currently established cultural system (amphycultural diffusion capsules) that allowed for conditions favorable for stem cell expansion in vitro. Many cell types and culture protocols and their combination with cytokines, growth factors, feeder layers can be implemented with ADC. Capsules are characterized by high perfusion rates that ensure that allow dilution of inhibitory autocrine factors and support long-term cell expansion. We have shown that ADC in vitro provides optimal cellular microenvironment that supports long term hematopoiesis (Bilko et al. 2005). 

Numerous case reports and epidemiological studies suggest a leukemogenic action of benzene in humans—the leukemia tending to be acute and myeloblastic in type, often following aplastic changes in the bone marrow. Acute myelocytic leukemia may be preceded by myelodysplastic syndrome, a preleukemic state characterized by abnormal marrow architecture, inadequate hematopoiesis, and many cells with chromosome damage." Benzene may also induce chronic types of leukemia. ... 

I., Antigenic analysis of hematopoiesis. V. Characterization of My-10 antigen expression by normal lymphohematopoietic progenitor cells. Exp. Hematol. 14, 878—886 (1986). 

Numerous and diverse biological functions are regulated by chemokines. In addition to the well characterized proinflammatory activities such as integrin activation, chemotaxis, lipid mediator biosynthesis, superoxide radical production, and granule enzyme release (reviewed in refs. 1-4), chemokines have been shown to suppress and stimulate angiogenesis (5-7), suppress hematopoiesis (8-10), suppress apoptosis (11), control viral infection (12,13), and effect leukocyte differentiation (14). Among the proinflammatory activities, chemotaxis in particular has received considerable attention as a target for novel antiinflammatory therapeutics (reviewed in ref. 15). 

As the number of chemokines and receptors continue to expand so too does the list of ascribed biological functions. Beyond their characterized roles in leukocyte trafficking and inflammation, chemokines have been shown to effect angiogenesis (24-26), hematopoiesis (27-29), T-cell differentiation (30), apoptosis (31), and viral infection (32,33), although the biological significance of these effects as well as the mechanism of action remain to be determined in many cases. Furthermore, chemokine receptor expression has been reported on nonlymphoid cell types in brain and vasculature (34,35). Antibodies will no doubt prove to be useful in determining the function of these receptors in other systems. 

The biological activities of IL-11 are not fully characterized, but they are similar to those of IL-6, LIF, and OSM. For example, IL-11 (1) stimulates the development of diverse hematopoietic cell lineages from bone marrow precursors (especially of early hematopoiesis), including monocytes and/or macrophages and megakaryocytes (2) is a groivth factor for plasmacytes, hematopoietic multipotential cells. 

Benzene is the only BTEX that has well characterized hematological, immunological, and lymphoreticular effects in humans and animals at low levels of inhalation exposure. Immunological and lymphoreticular effects are the basis for the derivation of the acute inhalation MRL for benzene. Benzene affects hematopoiesis, decreasing the production of all major types of blood cells, and can also cause hyperplasia. 

The hematopoietic bone marrow is located primarily in the central portion of the pelvis, ribs, vertebrae, skuU, and femoral and humeral epiphyses. The anatomic structure of the bone marrow is characterized by the central venous marrow sinus, which is linked by coarse vascular sinusoids that intertwine a reticulin mesh where the cells are suspended. Thus hematopoiesis occurs in the extravascu-lar marrow spaces, which also contain endothelial cells, fibroblasts, macrophages, and adipocytes, collectively termed bone marrow stroma. Stromal cells are thought to be important hematopoietic components, providing growth factors, collagen, and cell adhesion proteins.When these cells are combined with accessory cells (lym-phocytes/monocytes) and cytokines, the mixture is referred to as the hematopoietic microenvironment. 

Sutherland H J, Eaves C J, Eaves A C, et al. (1989). Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro. Blood. 74 1563-1570. 

The hepatosplenic period starts 3 months after the beginning of pregnancy and is characterized by an intensive hematopoiesis in spleen, thymus, and liver, leading to the formation of white cells and red cells identical to those found in adult blood. Before this... 

Givin, G. I., Banquerigo, M. L., Strauss, L. C., and Loken, M. R. 1987. Antigenic analysis of hematopoiesis. VI. Flow cytometric characterization of My- 10-positive progenitor cells in normal human bone marrow. 

In its natural environment, hematopoiesis resides in a well-defined microenvironment characterized by local geometry (structure and vasculature), by stromal cells (accessory cells of mixed origin), and by an extracellular matrix composed of coUagen-like molecules and proteoglycans, produced by stromal cells (Nielsen, 1999). Thus, it is bkely that hematopoietic stem and progenitor cells (HSPCs) are influenced by accessory cells and the microenvironment they create in several ways. 

HSIAO c Y and song y l (2010), A long form of shrimp astakine transcript molecular cloning, characterization and functional elucidation in promoting hematopoiesis . Fish Shellfish Immunol, 28,77-86. 

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