R Fernandez-Delgado | PubMed Health

PubMed1995

Factors regulating megakaryocyte progenitor commitment to polyploidization.

Recognizable megakaryocytes are polyploid cells generated by a clonogenic, diploid progenitor, termed CFU-MKC (colony forming unit, megakaryocyte). In order to quantify polyploidization, ploidy histograms of megakaryocytes determined by microphotometric or flow cytometric measurements of megakaryocyte DNA have generally been used. However these techniques provide no information on the rate of commitment of CFU-MKC to polyploidy. Using a technique of clonal analysis determining the distributions of the number of doublings (NbD) undergone by CFU-MKC before committing to polyploidization, the polyploidization probability of CFU-MKC could be derived. This probability was found to be a constant independent from CFU-MKC mitotic history, since NbD distributions are exponential functions characterized by a constant rate of decay per doubling. By studying the effects of growth factors on polyploidization probability, it was also shown that: (1) this parameter is negatively regulated by growth factors contained in poke-weed or WEHI conditioned media, as well as by erythropoietin; (2) commitment to polyploidization does not require prior CFU-MKC division; (3) bipotent erythroid-megakaryocyte progenitors have a lower polyploidization probability than CFU-MKC; (4) determination of polyploidization probability reflects the activity of growth factors with greater accuracy than megakaryocyte colony count.

Acetylcholinesterase↗

PubMed1995

Factors regulating megakaryocyte progenitor commitment to polyploidization.

Recognizable megakaryocytes are polyploid cells generated by a clonogenic, diploid progenitor, termed CFU-MKC (colony forming unit, megakaryocyte). In order to quantify polyploidization, ploidy histograms of megakaryocytes determined by microphotometric or flow cytometric measurements of megakaryocyte DNA have generally been used. However these techniques provide no information on the rate of commitment of CFU-MKC to polyploidy. Using a technique of clonal analysis determining the distributions of the number of doublings (NbD) undergone by CFU-MKC before committing to polyploidization, the polyploidization probability of CFU-MKC could be derived. This probability was found to be a constant independent from CFU-MKC mitotic history, since NbD distributions are exponential functions characterized by a constant rate of decay per doubling. By studying the effects of growth factors on polyploidization probability, it was also shown that: (1) this parameter is negatively regulated by growth factors contained in poke-weed or WEHI conditioned media, as well as by erythropoietin; (2) commitment to polyploidization does not require prior CFU-MKC division; (3) bipotent erythroid-megakaryocyte progenitors have a lower polyploidization probability than CFU-MKC; (4) determination of polyploidization probability reflects the activity of growth factors with greater accuracy than megakaryocyte colony count.

Acetylcholinesterase↗

PubMed1990

Anaemia during pregnancy as a risk factor for infant iron deficiency: report from the Valencia Infant Anaemia Cohort (VIAC) study.

A prospective cohort study with a 1-year follow-up of 156 neonates was carried out specifically designed to test the hypothesis that there is a positive relationship between iron deficiency during pregnancy and the development of the same disease in newborn infants. Exposure was defined as being born of a mother with ferropenic anaemia at delivery, and cases as the infants who developed iron deficiency during their first year of life. A statistically significant positive association was detected with an odds ratio of 6.57 (95% confidence limits 1.81-25.97). A stratified analysis was also performed to control the effect of potential confounders such as socio-economic variables, feeding practices and other factors linked with the iron status of infants. This second analytical procedure showed no alteration in the association detected in the simple analysis but that there was a statistically significant strong interaction between the quantity of cow's milk intake and the ferropenic status of the mother. These results show a relationship between iron deficiency of the mother at delivery and the development of iron deficiency in the infants. These new findings could be important in the development of new prevention programmes applied to pregnant women.

Anemia, Hypochromic↗

PubMed1987

Abnormal splenic megakaryopoiesis in MPSV-induced myeloproliferative disease.

The myeloproliferative sarcoma virus (MPSV) induces a murine myeloproliferative syndrome characterized by an erythromyelemia, an anemia, a thrombocytopenia associated with a myeloproliferation in the spleen and a splenic and medullar fibrosis. We have used the in-vitro plasma clot technique to measure megakaryocytic precursors in the spleen and bone-marrow of MPSV-infected mice. We report that megakaryocytic colonies are increased, in number (X75), in concentration (X9) and in size, in the spleen but not in the bone-marrow of neoplastic mice. Furthermore, these splenic precursors are hypersensitive to growth factors present in the anemic mouse serum used in the culture system. These data show that the thrombocytopenia observed in the MPSV-induced neoplasia does not result from a lack of megakaryocyte precursors, but rather from an excess of megakaryocyte destruction. This ineffective splenic megakaryopoiesis associated with the presence of a massive splenic fibrosis make the MPS-induced neoplasia a suitable model for studying the perturbation of megakaryopoiesis in myeloproliferative syndrome associated with fibrosis.

Animals↗

PubMedDate not supplied

Organization of haematopoietic stem cells and their relationship to mastocytopoiesis.

Haematopoiesis is a dynamic process in which differentiated blood cells are regularly replaced by the proliferation and differentiation of stem cells. Two types of haematopoietic stem cells (HSC) can be distinguished: totiopotent HSC capable of giving rise to cells of all haematopoietic lineages, and pluripotent HSC capable of giving rise only to the myeloid lineages. HSC are characterized by their capacity for self-renewal and differentiation in committed stem cells determined towards one of the haematopoietic lineages. These committed stem cells, also named progenitor cells or colony-forming units (CFU), have the capacity to give rise, in semi-solid medium, to colonies composed of differentiated cells. It has recently been shown that mast cells originate from a pluripotent HSC and that CFU Baso/Masto can be detected from murine and human bone marrow and blood cells. The in vivo regulation of the proliferation and differentiation of HSC is not well known. Several studies have emphasized the role of the haematopoietic microenvironment and of long- and short-range factors in such regulation. The in vitro growth of HSC is strictly dependent on growth factors, also named CSF (colony-stimulating factors) and interleukin (IL), in particular IL3. IL3 is a glycoprotein which induces the proliferation and differentiation of pluripotent and committed HSC and which seems to have a preferential role in mast cell regulation.

Animals↗