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Biomedical subjects

I Fabian

Publications and source records attributed to I Fabian.

At least 73 records · Page 4Linked to original sources
PubMed1986

Effect of a new retinoidal benzoic acid derivative on normal human hematopoietic progenitor cell growth in vitro.

13-cis-Retinoic acid (RA) has been demonstrated to alter hemopoiesis in vitro. We compared proliferation and differentiation effects of RA to a synthetic retinoid, (E)-4-[2-(5,6,7, 8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl-1-propenyl]benzoic acid (TTNPB), on human normal bone marrow cells. TTNPB stimulated the in vitro growth of erythroid-granulocyte-macrophage progenitors and erythroid progenitors. Dose-response curves showed that maximal increments of erythroid-granulocyte-macrophage progenitor growth [173 +/- 17% (SE)] and erythroid progenitor growth [210 +/- 40%] occurred with TTNPB at 10(-9) M. With RA, there was maximal increment (173 +/- 21%) for erythroid progenitors only, and that at 10(-8) M. Evaluating clonogenicity of marrow cells in the presence of the two retinoic acid derivatives demonstrated that TTNPB and RA enhanced myeloid colony (CFU-C) growth; maximal stimulation occurred at 10(-6) M (130 +/- 8% and 161 +/- 5% increment for TTNPB and RA, respectively). The two retinoic acid analogues did not alter the differentiation pattern of myeloid colonies (macrophage colonies, granulocytic colonies, or granulocyte-macrophage colonies). Replating studies showed that the formation of secondary hemopoietic colonies was not altered following incubation of hemopoietic progenitors with TTNPB or RA. These data demonstrate that TTNPB is more active than RA in stimulating the growth of hemopoietic progenitors from normal marrows. Such findings may have therapeutic implications for various hemopoietic disorders.

Benzoates↗
PubMed1986

In vitro hemopoiesis of marrow cells from myelodysplastic patients: effects of mitogen-stimulated spleen cell-conditioned medium and vitamin A and D derivatives.

We determined the ability of pokeweed mitogen-stimulated human spleen cells to support the growth and proliferation of hemopoietic progenitors from normal and myelodysplastic syndrome (MDS) patients, in the presence and absence of the maturation-inducing agents 13-cis-retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (vit D). The addition of various concentrations of vit D or RA to culture plates containing MDS patients' marrow cells stimulated myeloid colony growth. A higher number of myeloid colony-forming units-cell was noted in cultures containing vit D or RA in addition to pokeweed mitogen spleen-conditioned medium compared to these substances and placenta conditioned medium. When colony-forming units-cell from MDS patients was incubated with 2 X 10(-8) M vit D the percentage of monocyte-macrophage colonies was increased and the number of granulocyte colonies was decreased. Neither vit D nor RA affected the number of cells per colony. Our findings suggest that pokeweed mitogen spleen-conditioned medium provides a more potent source than placenta-conditioned medium for humoral factors that stimulate the growth of hemopoietic progenitors from MDS patients and that the use of pokeweed mitogen spleen-conditioned medium may improve studies of hemopoiesis in MDS patients.

Agar↗
PubMed1985

Human spleen cell generation of factors stimulating human pluripotent stem cell, erythroid, and myeloid progenitor cell growth.

Mitogen-stimulated murine spleen cells produce humoral substances capable of supporting murine hematopoiesis and pluripotent stem cell proliferation in vitro. Thus, we evaluated conditioned media generated by human spleen cells (SCM) in the presence or absence of mitogens for factors stimulatory for human pluripotent (CFU-GEMM), erythroid (BFU-E), and myeloid (CFU-GM) precursors. Two and one half percent to 10% SCM stimulated proliferation of all three types of precursor cells from nonadherent buoyant human marrow target cells. Mitogen-stimulated SCM augmented CFU-GM (175% to 225%), whereas CFU-GEMM and BFU-E growth was essentially unchanged. Cell separation procedures used to determine which cells provided these microenvironmental stimuli indicated that nonadherent mononuclear spleen cells provided the bulk of the CSF-GM, whereas adherent cells (95% nonspecific esterase + monocyte-macrophages) and nonadherent cells provided similar proportions of CSF-mix and erythroid burst-promoting activity (BPA). The nonadherent cells generating high levels of CSF-mix, BPA, and CSF-GM were predominantly Leu-1-negative, ie, non-T, cells. In the presence or absence of mitogens, SCM was a more potent source (1.3- to 3.8-fold) than peripheral leukocyte CM of the growth factors for the three progenitor cell types. Specific in situ cytochemical stains for analyzing morphology of myeloid colonies demonstrated that SCM stimulated the proliferation of the same types and proportions of colonies as human placental CM, suggesting that these CMs may contain similar CSF-GMs. These data show the contribution of spleen cell subsets to the generation of hematopoietic growth factors and the responsiveness of these cells to various mitogenic stimuli.

Bone Marrow Cells↗
PubMed1983

Circulating pluripotent haemopoietic cells in patients with myeloproliferative disorders.

Peripheral blood cells of 17 patients with myeloproliferative disorders were grown in vitro to form mixed colonies (CFU-mix). CFU-mix were found in four of nine patients with chronic phase chronic myelocytic leukaemia (CML) at levels 28- to 132-fold higher than the upper limits of normal subjects. These patients also had higher than normal levels of circulating granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitors. Development of blastic crisis was associated with disappearance of CFU-mix from the blood. CFU-mix was detected in the blood of three of five patients with polycythaemia vera (PV) and two patients with myelofibrosis with myeloid metaplasia (MMM) at levels slightly higher than those of normal subjects. Our results are consistent with a clonal expansion of multipotent haematopoietic precursor cells in CML and abnormal kinetics of this cell in CML, PV and MMM.

Adult↗
PubMed1982

Cryopreservation of the human multipotent stem cell.

Light density human bone marrow cells were cryopreserved, then thawed and tested for their ability to form myeloid (CFUGM), erythroid (BFUE) and mixed myeloid-erythroid colonies in vitro. Proliferation of mixed hematopoietic colonies was supported by conditioned media from a human T-lymphocyte cell line and erythropoietin. All mixed colonies contained neutrophil and erythroid precursors and approximately 25% had mononuclear phagocytes. Following cryopreservation the bone marrow retained its capacity to form mixed colonies without apparent loss. The recovery of CFUGM and BFUE was 76% and 72% respectively.

Bone Marrow↗
PubMed1981

Mode of binding and internalization into mouse macrophages of heparin complexed with polycations.

Heparin uptake by cultured macrophages was investigated from the standpoint of: (1) whether the increased uptake in the presence of polycations is due to charge neutralization, and (2) whether the heparin becomes internalized. Regarding the first point, our results are compatible with the notion that charge neutralization is mainly responsible for the enhanced uptake of heparin in the presence of protamine, histone, poly(DL-lysine) and poly(L-ornithine). As for the second point, chasing experiments at low and high temperatures strongly suggest that while heparin binds onto the cell membrane at both 4 degrees C and 37 degrees C, it undergoes internalization only at 37 degrees C.

Animals↗
PubMed1981

Chronic myelocytic leukaemia: a pluripotent haemopoietic cell is involved in the malignant clone.

Haemopoietic cells with pluripotent capabilities, were grown in soft-gel cultures from the peripheral blood of a glucose-6-phosphate dehydrogenase (G6PD) electrophoretic A,B heterozygous female with chronic myelocytic and granulocytic progeny. Only type B isoenzyme of G6PD was found in mixed colonies, in mature neutrophils, erythrocytes, and committed granulocyte and isoenzymes of G6PD. This study provides direct evidence that a pluripotent haemopoietic stem cell is involved in the malignant clone in CML.

Adult↗
PubMed1981

In vitro analysis of the contributions of adherent cell layer and recharging population to hemopoietic cell proliferation in long-term bone marrow cultures.

Cell proliferation in long-term suspension cultures of mouse bone marrow was studied. Bone marrow cells were maintained on irradiated or conventional non-irradiated semiallogeneic adherent feeder layers and the origin of the proliferating cells was investigated by using the unique T6 chromosome marker. In cultures containing irradiated feeder layers total cell numbers were less at the first week after "recharging," but the levels soon reached those of conventional non-irradiated cultures. At the first weeks after recharging, proliferating cells, maintained on conventional non-irradiated feeder layers, originated mainly from the adherent layer. The contribution of the recharging population to the proliferating cell population increased with time. In contrast, the proliferating cells grown on irradiated adherent layers originated mainly from recharging population from the first week after recharging. The origin of the nonadherent CFUs and their development in F1 hybrid mice and mice of syngeneic strains was also examined. The pluripotent stem cells grown on non-irradiated feeder layers were derived mainly from the adherent layer.

Animals↗
PubMed1979

Differential effect of polycations on uptake and desulphation of heparin.

Previous work has established that macrophages in culture release sulphate from heparin. We now report that increased uptake and desulphation of heparin occurred in the presence of polycations (poly-L-ornithine and poly-DL-lysine) and that the increase in heparin uptake was by about 30-fold. The desulphation was less related to uptake than to the nature of the bound polycation. Serum was found to have an inhibitory effect on heparin uptake while polycations inhibited heparin desulphation by macrophage extracts.

Albumins↗
PubMed1978

Increased uptake and desulphation of heparin by mouse macrophages in the presence of polycations.

Heparin uptake and desulphation by cultured macrophages were investigated. Histones, polyamino-acids, protamine and eosinophil-basic protein stimulated both heparin uptake and desulphation, processes found to be non-related. Poly-L-ornithine and poly-DL-lysine increased the heparin uptake by about 33-fold, and histone produced up to 7.5-fold increase in the desulphation. The same polycations inhibited heparin desulphation by macrophage extracts.

Animals↗
PubMed1976

Desulphation of heparin by mice and guinea pig leukocytes.

Leukocytes from mice and guinea pigs were tested for their sulphate-splitting activity on heparin. Mouse macrophages showed the highest degrading activity while mouse neutrophils and lymphocytes showed only a week degrading activity. Mouse macrophages maintained in tissue culture were also found to degrade heparin, the amount of sulphate released increasing with time up to 96 h. Spleen extracts were found to neutralize the anticoagulatory activity of heparin.

Animals↗