Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carboxymethylglucan (CMG), a water-soluble glucan derivative, enhanced the number of granulocytes in the peripheral blood as well as other indices of haemopoietic recovery (total cellularity and the number of granulocyte-macrophage progenitor cells in femoral marrow, spleen weight) investigated after fractionated gamma-irradiation in mice (five doses of 2 Gy each, or three, four and five doses of 3 Gy each given at 24-h intervals). An increased liver weight and a more pronounced anaemia found in the CMG-treated mice suggested, however, that also inflammatory side effects were evoked by the repeated administration of CMG. On the other hand, the development of tolerance, i.e., a decreased effectiveness of the treatment with CMG upon its repeated administration, did not seem to play any major role under the experimental conditions studied, because the protective effects of CMG increased with the increasing number of CMG injections.
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PMID:Haemopoiesis-enhancing effects of repeatedly administered carboxymethylglucan in mice exposed to fractionated irradiation. 871 74

Possible influence of most frequently encountered types of pathology during pregnancy on the cell composition of umbilical cord blood was studied. These pathologies included: treated iron-deficiency anemia, essential hypertension, threatening spontaneous abortion. A number and proliferative potential of granulocyte-macrophage precursor cells of umbilical cord blood were studied by agar drop-liquid media culture method. It was found that the types of pathology studied do not influence cell composition, number and proliferative potential of granulocyte-macrophage precursor cells from umbilical cord blood. These results show that umbilical cord blood after pathological pregnancy can be considered as a source of transplantable hemopoietic cells.
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PMID:[Cell composition of umbilical cord blood in complicated and uncomplicated pregnancy]. 875 54

Patients with anorexia nervosa (AN) frequently suffer from a mild degree of anemia and from moderate leukopenia on top of their undernourished state and metabolic disarrangements. To evaluate in vitro granulopoiesis and its relationship to cytokine production and undernutrition, we have studied 10 adolescent girls with moderate AN (age range, 13.5-18.0). Study methods included assessment of peripheral blood (PB) granulocyte-macrophage colony-forming cells (GM-CFC) of the patients and age-matched controls, and determination of plasma and conditioned medium (CM) of mononuclear cells levels of IL-1, IL-3, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF), all of which may play a role in GM-CFC growth regulation. GM-CFC numbers were significantly lower in AN patients compared with the normal controls (13.09 +/- 11.15 versus 39.33 +/- 26.61 colonies/5 x 10(5) cells, p < 0.01). No inhibitory effect was found in either plasma or CM of patients with AN. However, when CM were applied to non-recombinant human GM-CSF-stimulated normal bone marrow GM-CFC targets, the number of colonies stimulated by the CM of patients with AN was significantly lower than those stimulated by the CM of the controls (73.5 +/- 20.1 versus 113.0 +/- 11.6, p < 0.025). GM-CSF concentrations in CM were significantly lower in patients with AN compared with normal controls, but no such differences were found in IL-1, IL-3, IL-6, or TNF concentrations. These results indicate defective in vitro granulopoiesis in AN patients, manifested by a reduction of both GM-CFC and GM-CSF. It has to be determined whether these changes are the result of the basic disease process or are they due to malnutrition.
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PMID:Defective in vitro granulopoiesis in patients with anorexia nervosa. 879 55

Inhibition of in vitro colony formation of human hematopoietic progenitors (CFU-granulocyte-macrophage, burst-forming unit-erythroid) by the antiviral nucleoside drugs alovudine, zalcitabine, zidovudine, ganciclovir, stavudine, didanosine, lamivudine, and acyclovir was measured. Significant correlations between in vitro 50% inhibitory concentrations and the daily human exposures (area under the concentration-time curve from 0 to 24 h; in micromolar.hour) of these chronically administered drugs in human immunodeficiency virus-positive patients that induced neutropenia or anemia were demonstrated by both linear regression and Spearman rank-order analyses. These quantitative correlations allow estimation of the exposure at which bone marrow toxicity may occur with candidate compounds.
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PMID:In vitro potency of inhibition by antiviral drugs of hematopoietic progenitor colony formation correlates with exposure at hemotoxic levels in human immunodeficiency virus-positive humans. 883 14

It has been reported that hypophysectomized rats exhibit normochromic, normocytic anaemia. Pancytopenia with impaired DNA synthesis in the bone marrow can be restored in these hypophysectomized rats by syngeneic pituitary grafts placed under the kidney capsule or treatment with growth hormone (GH). Until now, adults with hypopituitarism have received adequate replacement therapy with thyroxine, cortisol and sex steroids, but not with GH. We therefore investigated the effects of GH replacement therapy on the proliferation and differentiation of erythroid and myeloid progenitor and peripheral blood cells in 11 adult patients with growth hormone deficiency in a double-blind, placebo-controlled study for the first 6 months of therapy. The placebo group showed no changes during the first 6 months without therapy in either insulin-like growth factor I (IGF-I) levels, erythroid and myeloid progenitor precursor cells or peripheral blood cells. After commencement of GH therapy, IGF-I levels rose significantly during 24 months of therapy from 75.3 +/- 13.5 to 225 +/- 34.7 ng mL-1 (P < 0.001). Erythroid and myeloid progenitor precursor cells showed a steep and significant increase after 18 and 24 months of therapy (erythroid: from 10.7 +/- 3.5 to 261.4 +/- 79.8, P < 0.02, after 18 months and to 276.8 +/- 149.8 x 10(5) mononuclear cell colonies, P < 0.03, after 24 months; granulocyte-macrophage colony-forming units: from 39.7 +/- 9.8 to 316.9 +/- 124.6, P < 0.002, after 18 months and to 366 +/- 188.7 x 10(5) mononuclear cell colonies, P < 0.03, after 24 months), whereas the peripheral red and white blood cells exhibited only minimal non-significant changes. The principal regulators of erythropoiesis, such as erythropoietin, and parameters reflecting erythropoiesis in the peripheral blood, such as reticulocytes, remained almost unchanged throughout the whole study period. We therefore conclude that patients with GH deficiency do not have anaemia, but have haematopoietic precursor cells in the lower normal range, and that GH substitution therapy over a period of 24 months has a marked effect on erythroid and myeloid progenitor precursor cells but only negligible effects on peripheral blood cells in GH-deficient adults.
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PMID:The influence of growth hormone substitution therapy on erythroid and myeloid progenitor cells and on peripheral blood cells in adult patients with growth hormone deficiency. 901 96

Interferon-gamma (IFN-gamma) has been shown to inhibit proliferation and differentiation of erythroid progenitor cells and to produce apoptosis of erythroid cells, but IFN-gamma receptors are not present on red cells and have never been demonstrated on erythroid progenitor cells. We obtained highly purified day 6 erythroid colony-forming cells (ECFCs) from human blood in sufficient quantity and purity to measure binding of radioiodinated recombinant human IFN-gamma ([125I]rhIFN-gamma). When [125I]rhIFN-gamma was incubated with day 6 ECFC, 77% of the binding was inhibited by excess unlabeled rhIFN-gamma, but no inhibition occurred with a variety of growth factors and glycoproteins. Specific binding was directly proportional to the cell concentration with a straight line passing through the origin, and equilibrium was reached at 0 degree C by 24-48 hours. Saturation of specific binding occurred at a [125I]rhIFN-gamma concentration of 1.0 nM and internalization was demonstrated with further incubation at 37 degrees C. Scatchard analysis showed a single class of binding sites and at a high ECFC cell purity of 80-89%, 1910-2070 binding sites per ECFC were present with a Kd of 0.01-0.02 nM. As day 5 ECFC developed into more mature day 7-day 12 cells, with incubation at 37 degrees C in vitro, specific binding for [125I]IFN-gamma greatly decreased. These experiments delineate specific binding sites for IFN-gamma on human erythroid progenitor cells and indicate that the enhanced sensitivity to rhIFN-gamma inhibition of mature day 3-day 6 burst-forming units-erythroid may be a result of enhanced specific binding. Human IFN-gamma is a multifunctional lymphokine, secreted by activated T lymphocytes and NK cells, which exerts antiviral, antiproliferative, and immunomodulatory activities on a wide variety of cells [1,2]. With regard to hematopoietic cells, IFN-gamma has been reported to inhibit the growth of granulocyte-macrophage colony-forming units, burst-forming units-erythroid (BFU-E) and colony-forming units-erythroid (CFU-E) in vitro [3-7]. Most recently, mature day 3 to day 6 BFU-E have been shown to be most sensitive to the inhibitory effect of recombinant human (rh) IFN-gamma, while primitive day 1 to day 2 cells and later day 7 cells were less affected [7]. Incubation of rhIFN-gamma with mature BFU-E inhibits hemoglobin accumulation and produces apoptosis of the maturing erythroid cells [7]. Moreover, since blood IFN-gamma levels are elevated and vary directly with the degree of the anemia, in patients with hematologic malignancies [8] and HIV-seropositivity [9], IFN-gamma appears to have a prominent role in producing the anemia associated with chronic disease [10,11]. Although characterization of human IFN-gamma receptors has been extensively performed for a variety of human cells including fibroblasts, lymphocytes, monocytes, granulocytes, eosinophiles, platelets, and many tumor cells [12-17], IFN-gamma receptors have not been identified on red cells [12] and the presence plus the extent of IFN-gamma receptors on progenitor cells, including human erythroid progenitor cells, remains unknown. A method has been reported from our laboratory by which human erythroid colony-forming cells (ECFC) can be highly purified, starting with peripheral blood BFU-E, in a sufficient amount for analysis of cytokine binding [18-20]. In this paper, we report the results of [125I]rhIFN-gamma binding to day 6 ECFC in vitro and demonstrate the presence of specific binding that is saturable at 1.0 nM. Scatchard analysis reveals that there are 1910-2070 rhIFN-gamma binding sites per ECFC with a Kd of 0.01-0.02 nM and, as with erythropoietin (EP) and insulin-line growth factor I (IGF-I) receptors, specific binding is highest with the earliest BFU-E studied and declines progressively as the erythroid progenitors mature.
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PMID:Specific binding of interferon-gamma to high affinity receptors on human erythroid colony-forming cells. 909 Dec 93

Hematopoietic progenitor cells (HPC) from mice nullizygous at the Fanconi anemia (FA) group C locus (FAC -/-) are hypersensitive to the mitotic inhibitory effects of interferon (IFN-gamma). We tested the hypothesis that HPC from the bone marrow of Fanconi group C children are similarly hypersensitive and that the fas pathway is involved in affecting programmed cell death in response to low doses of IFN-gamma. In normal human and murine HPC, IFN-gamma primed the fas pathway and induced both fas and interferon response factor-1 (IRF-1) gene expression. These IFN-gamma-induced apoptotic responses in HPC from the marrow of a child with FA of the C group (FA-C) and in FAC -/- mice occurred at significantly lower IFN doses (by an order of magnitude) than did the apoptotic responses of normal HPC. Treatment of FA-C CD34+ cells with low doses of recombinant IFN-gamma, inhibited growth of colony forming unit granulocyte-macrophage and burst-forming unit erythroid, while treatment with blocking antibodies to fas augmented clonal growth and abrogated the clonal inhibitory effect of IFN-gamma. Transfer of the normal FAC gene into FA-C B-cell lines prevented mitomycin C-induced apoptosis, but did not suppress fas expression or inhibit the primed fas pathway. However, the kinetics of Stat1-phosphate decay in IFN-gamma-treated cells was prolonged in mutant cells and was normalized by transduction of the normal FAC gene. Therefore, the normal FAC protein serves, in part, to modulate IFN-gamma signals. HPC bearing inactivating mutations of FAC fail to normally modulate IFN-gamma signals and, as a result, undergo apoptosis executed through the fas pathway.
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PMID:Inactivation of the Fanconi anemia group C gene augments interferon-gamma-induced apoptotic responses in hematopoietic cells. 924 26

The effect of 406, a novel fusion protein between the N-terminal sequence of the insect insulin-like peptide, bombyxin, human insulin-like growth factor II and mouse interleukin 3 was investigated in its capacity to abrogate the toxic effects of azidothymidine (AZT) in C57BL/6 mice. Mice receiving 2.5 mg/ml AZT in their drinking water were concurrently treated with daily s.c. injections of 14, 140 or 1400 ng 406 for 4 wk. AZT-treated mice had a lower total weight, hemoglobin content and white blood cells than non treated controls. 406 significantly increased the number of circulating white blood cells at all doses, and the optimal effects were observed at a dose of 140 ng/mouse. Using this optimal dose, 406 completely abrogated the AZT-mediated weight loss. The effects on erythroid cells depended on the severity of the AZT-induced anemia. The amounts of hemoglobin were equal or slightly lower than those of controls under conditions of mild anemia, but were significantly higher than controls under conditions of severe anemia. 406 significantly increased the number of all hematopoietic colony-forming cells in bone marrow and spleen, but the effects were particularly striking in granulocyte-macrophage precursors. Blood glucose levels did not change at optimal or suboptimal 406 doses but increased at a dose of 1.4 microg/mouse. These experiments demonstrate the usefulness of these IGF-cytokine fusion proteins, whose low cost production represents a significant advantage for future in vivo studies.
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PMID:Efficacy of an insulin-like growth factor-interleukin-3 fusion protein in reversing the hematopoietic toxicity associated with azidothymidine in mice. 945 83

Erythropoietin (EPO) is a factor essential for erythroid cell proliferation, differentiation, and survival. The production of EPO by the kidneys in response to hypoxia and anemia is well documented. To determine whether EPO is also produced by hematopoietic cells, we analyzed the expression of EPO in normal human hematopoietic progenitors and in their progeny. Undifferentiated CD34(+)lin- hematopoietic progenitors do not have detectable EPO mRNA. Differentiating CD34(+) cells that are stimulated with recombinant human EPO in serum-free liquid cultures express both EPO and EPO receptor (EPOR). Because CD34(+) cells represent a heterogeneous cell population, we analyzed individual burst-forming units-erythroid (BFU-E) and nonerythroid colony-forming unit-granulocyte-macrophage colonies for EPO mRNA. Only BFU-E colonies were positive for EPO mRNA. Lysates from pooled BFU-E colonies stained positively for EPO by immunoblotting. To further confirm the intrinsic nature of erythroid EPO, we replaced extrinsic EPO in erythroid colony cultures with EPO-mimicking peptide (EMP). We show EPO expression in the EMP-stimulated BFU-Es at both mRNA and protein levels. Stimulation of bone marrow mononuclear cells (BMMCs) with EMP upregulated EPO expression. Furthermore, we found EPO and EPOR mRNAs as well as EPO protein in K562 cells, a human erythroleukemia cell line. Stimulation of K562 cells with EMP upregulated EPO expression. We suggest that EPO of erythroid origin may have a role in the regulation of erythropoiesis.
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PMID:Human hematopoietic progenitors express erythropoietin. 957 13

Prolactin (PRL) is a neuroendocrine hormone that influences immune and hematopoietic development. The mechanism of action of this hormone in vivo remains unclear; therefore, we assessed the effects of PRL on hematopoiesis in vivo and in vitro. Normal resting mice were treated with 0, 1, 10, or 100 microg of recombinant human prolactin (rhPRL) for 4 consecutive days and euthanized on the fifth day for analysis of myeloid and erythroid progenitors in the bone marrow and spleen. Both frequencies and absolute numbers of splenic colony-forming unit granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-e) were significantly increased in mice receiving rhPRL compared to the controls that had received saline only. Bone marrow cellularities were not significantly affected by any dose of rhPRL, but the absolute numbers and frequencies of bone marrow CFU-GM and BFU-e were augmented by rhPRL. These results suggest that rhPRL can promote hematopoiesis in vivo. Because rhPRL augments myeloid development in vivo, we examined the potential of the hormone to reverse the anemia and myelosuppression induced by azidothymidine (AZT). Mice were given rhPRL injections concurrent with 2.5 mg/mL AZT in drinking water. rhPRL partially restored hematocrits in the animals after 2 weeks of treatment and increased CFU-GM and BFU-e in both spleens and bone marrow. The experiments with AZT and rhPRL support the conclusion that the hormone increases myeloid and erythroid progenitor numbers in vivo, and they suggest that the hormone is clinically useful in reversing myelosuppression induced by AZT or other myeloablative therapies.
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PMID:Prolactin exerts hematopoietic growth-promoting effects in vivo and partially counteracts myelosuppression by azidothymidine. 1034 Mar 96


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