Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:030790 (erythroid)
 21,398 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lewis lung carcinoma (LLC) of C57BL/6 mice, a transplantable tumor widely metastatic by 6-7 days post implant (PI), caused hematopoietic alterations such as progressive anemia (hemoglobin: day 1 PI, 11.0 g/dl; day 19 PI, 7.8 g/dl), neutrophilia (neutrophils: day 1 PI, 2 X 10(3)/microliter; day 19 PI, 22 X 10(3)/microliter), and marrow and splenic myeloid hyperplasia (marrow myeloid-to-erythroid ratio: day 1 PI, 1:1; day 7 PI, 3:1). Accompanying these changes were an increased concentration of marrow granulocyte-macrophage colony-forming units (culture) (GM-CFUC) (day 3 PI, LLC 185 +/- 27% of control; day 19 PI, LLC 265 +/- 10% of control) and accelerated cycling of these myeloid progenitors [day 3 PI, LLC 45.3 +/- 6.5% GM-CFUC in cycle vs. sham (media) injected 17.5 +/- 10.5%; day 7 PI, LLC 52.2 +/- 2.5% vs. sham (media) injected 29.8 +/- 9.8%; day 11 PI, LLC 56.2 +/- 4.4% vs. sham (media) injected 22.2 +/- 14%]. This study questioned whether enhanced hematopoiesis was a result of progressive tumor growth or whether the injection of tumor cells could evoke the response. By use of groups of C57BL/6 mice given an injection of live LLC cells, x-irradiated killed LLC cells, or media, the hematopoietic response to live LLC cells versus dead LLC cells could be dissected. A biphasic colony-stimulating activity (CSA) response in the sera of tumor bearers was found to account for the myelopoietic changes. The first wave of CSA from days 1 to 3 PI stimulated 168 +/- 3.7% more GM-CFUC than control sera and was likely released by dead cells of the tumor inoculum; the second wave from day 7 onward stimulated 220 +/- 7.6% more colonies and was a result of the enlarging tumor mass. Tumor growth was necessary for GM-CFUC proliferation, and the declining growth fraction at day 19 in LLC-bearing mice suggested that hematopoietic exhaustion was a consequence of tumor growth.
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PMID:Early hematopoietic events during tumor growth in mice. 348 12

In this paper we attempt to improve upon the methods of hematopoietic stem cell expansion. We evaluate the effects of recombinant human stem cell factor (SCF or c-kit ligand) alone and also in combination with recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 3 (IL-3), on cell proliferation and differentiation in human long term bone marrow cultures (LTBMC). Weekly addition of 5 ng/ml of SCF with 25% serum containing media resulted in increased recovery of total nonadherent cells, granulocyte-macrophage colony forming units (CFU-GM), and burst-forming units erythroid (BFU-E) at week 1, but the number of bone marrow (BM) progenitor cells fell below the level of untreated control cultures at weeks 3 (BFU-E) and 4 (CFU-GM). At week 8, when the cultures were terminated, the CFU-GM recovery was markedly reduced in flasks supplemented with SCF compared with the controls (p < 0.002). Moreover, SCF treatment induced the early disappearance of BFU-E. When LTBMC were supplemented with the combination of SCF plus GM-CSF (100 U/ml) and IL-3 (5 ng/ml), synergistic activity of the CSFs was observed at week 1. The number of BM colony forming cells (CFC) rapidly declined below the level of growth factor-free controls, leading to the early exhaustion of the culture when SCF was combined with GM-CSF. By comparison, GM-CSF and IL-3 alone induced a statistically significant increase above the controls (no growth factor) in the number of nonadherent cell colonies of CFU-GM and BFU-E. Analysis of adherent layer cells from cultures supplemented with SCF showed increased cellularity, no adipogenesis, and early disappearance of myeloid progenitors while the percentage of CFU-GM in S phase, assessed by cytosine arabinoside (Ara-C) suicide assay, was 9.2 +/- 5% SD versus 27.7 +/- 10% SD in control (no growth factor) samples (p < 0.01). SCF increased the number of fibroblast colony forming units (CFU-F) and also showed a synergistic activity (9.6-fold increase) when combined with IL-3. These findings suggest that SCF, GM-CSF and IL-3 exert their activity on different cell populations within the hematopoietic system. Further investigations are needed to optimize the use of SCF in supporting hematopoiesis.
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PMID:Effect of stem cell factor (c-kit ligand), granulocyte-macrophage colony stimulating factor and interleukin 3 on hematopoietic progenitors in human long-term bone marrow cultures. 769 21

The possible interaction between intense exercise, known to suppress the immune response, and nutritive factors, such as polyunsaturated fatty acids (PUFA), was examined in inbred female C57Bl/6 mice. The animals received for 8 wk either a natural ingredient diet or a diet supplemented with 10 g/100 g linseed oil containing over 50% of 18:3 (n-3) alpha-linoleic acid. Other groups received PUFA containing only traces of 18:3 (n-3) fatty acid; beef tallow, containing mostly 18:1 (n-9) saturated fat, safflower oil, an 18:2 (n-6) PUFA, and fish oil, containing longer chain (n-3) PUFA. Each dietary group was divided into two subgroups: sedentary diet controls and exercised animals. Exercise consisted of continuous swimming at high intensity until exhaustion. It was shown in three separate experiments that (1) the primary humoral response to sheep red blood cells, determined by the plaque-forming cell (PFC) assay, was affected by PUFA diet in sedentary animals in the order beef tallow > control diet > safflower oil > fish oil > linseed oil, and (2) the PFC response was suppressed by the exhaustive exercise, as compared to sedentary controls, except for animals fed 18:3 (n-3) linseed oil, where the normal response was noted. Phagocytosis of fluorescent microspheres by peritoneal macrophages, determined by flow cytometry, was significantly lower in exercised animals receiving the linseed oil diet, whereas other diets either increased or did not significantly change the macrophage phagocytic activity, compared to the sedentary diet controls. Spleen lymphocyte subsets were unchanged in exercised animals except for a marked shift from the lymphoid peak toward the erythroid peak. Generally, our data showed a marked immunomodulatory effect of 18-3 (n-3) alpha-linoleic acid on the exhaustive exercise-related immunosuppression, as compared to the effects of other selected PUFA.
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PMID:Modulation of exercise-induced immunosuppression by dietary polyunsaturated fatty acids in mice. 793 51

The effect of aging on hematopoiesis and bone marrow exhaustion have long been debated. Unexplained anemia and impaired in vitro proliferation of erythroid precursors is frequently observed in the elderly. As hydrocortisone is known to increase the BFU-E in vitro growth, we have studied the response of BFU-E to hydrocortisone in a group of nonanemic elderly subjects. The BFU-E growth in methylcellulose from blood mononuclear cells (MNC), stimulated by lymphocyte-conditioned medium (LCM), either with or without hydrocortisone, of 10 subjects aged 76-91 years was compared with the BFU-E growth from MNC of a group of ten young subjects. While LCM induced a significant increase of BFU-E growth, both in young and old subjects, hydrocortisone induced a significant increase of BFU-E growth only in young subjects. This study shows that in the elderly, there is a latent defect of erythropoiesis, possibly consisting of a defective ability to modulate the receptors for erythropoietin on BFU-E, and that hydrocortisone offers a useful tool to identify it.
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PMID:Defective in vitro growth of BFU-E of elderly subjects revealed by hydrocortisone. 801 29

Terminally differentiated cells usually do not divide and are, thus, reproductively dead. To elucidate the significance of radiation-enhanced differentiation to reproductive cell death, murine erythroid progenitor cells were gamma-irradiated in plasma clot cultures and the development of haemoglobinized clones was studied thereafter. If irradiation occurred when the cells had resumed proliferation, the total numbers of haemoglobinized clones and, in parallel, the numbers of newly haemoglobinized clones were elevated above control levels 6-24 h after 10-30 Gy and 24-48 h after 1 Gy respectively. Thereafter, clone numbers decreased below controls. This decrease was faster with the newly haemoglobinized clones, indicating that both the accumulation of haemoglobinized clones and fast exhaustion of the pool of more primitive precursors in the cultures are due to accelerated differentiation. The haemoglobinized clones appearing after irradiation were reduced in size without indication of direct cell death. We conclude that the reproductive cell death occurring in our system is due to enhancement of differentiation. Enhancement of differentiation is expressed by omission of cell cycles normally passed through by the cell progeny before terminal differentiation is reached. Dependence of differentiation enhancement on the presence of cycling cells at the time of irradiation indicates involvement of growth of essential cytoplasmic constituents during mitotic delay as observed in other cell systems.
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PMID:Radiation-enhanced differentiation of erythroid progenitor cells and its relation to reproductive cell death. 861 80

A combination of erythropoietin (EPO) plus stem cell factor (SCF) drove purified unfractionated granulocyte colony stimulating factor (G-CSF)/chemotherapy mobilized peripheral blood CD34+ cells to selective erythroid differentiation in liquid culture with an average 28-fold increase in the total cell number after 21 d. From day 6 of culture cytologic and cytofluorimetric characterization revealed that cultured cells belonged to the erythroid lineage with a gradual wave of maturation along the erythroid pathway to terminal cells. A similar pattern of erythroid differentiation was observed when the same peripheral blood CD34+ cells were culture with EPO plus SCF in serum-free medium. This cytokine combination produced selective erythroid differentiation with the complete exhaustion of the clonogenic potential on day 21. In parallel experiments the same circulating CD34+ cells underwent granulocytic/ monocytic differentiation in liquid culture in response to granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-3 (IL-3) and SCF, demonstrating that these CD34+ progenitors had intact pluripotent differentiating potential. Conversely, bone marrow CD34+ cells isolated from bone marrow allografts were unable to selectively differentiate along the erythroid pathway when they were exposed to EPO plus SCF combination. However, these cells maintained a greater number of colony forming cells on day 21 of culture compared to mobilized peripheral blood CD34+ cells. This model is a simple and reliable way to obtain selective erythroid differentiation of peripheral blood G-CSF/ chemotherapy mobilized CD34+ progenitor cells in liquid culture. The absence of cytokines such as GM-CSF and IL-3 in the culture medium permits studies on in vitro erythropoiesis without disturbance of prevalent myelopoiesis.
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PMID:Purified unfractionated G-CSF/chemotherapy mobilized CD34+ peripheral blood progenitors and not bone marrow CD34+ progenitors undergo selective erythroid differentiation in liquid culture in the presence of erythropoietin and stem cell factor. 901 87

The presence of Yersinia ruckeri, the causal agent of enteric redmouth disease (ERM) in salmonids and a few other freshwater fish, has so far been reported from a variety of sources including the intestine of healthy carp. Since there are no data on the pathogenicity of this bacterium for carp, 15 fingerlings were experimentally infected by intraperitoneal injection of about 5 x 10(5) cells. Thirteen injected fish were moribund or died within 4 days with septicaemic lesions. Two survivors were sampled on Day 28 after infection. Yersinia ruckeri was reisolated from the internal organs of all experimental fish. By histopathological examination moribund fish had generalised bacteriaemia with inflammation, degeneration and necrotic foci in kidney, liver and spleen, corresponding to findings described previously in ERM of rainbow trout. Survivors of challenge on Day 28 had a chronic disease characterised by prominent peritonitis and enteritis, exhaustion of the erythroid, granuloid and lymphoid components in haematopoietic kidney tissue as well as focal degeneration and necrosis in organs. These data indicate a high sensitivity of carp to intraperitoneal infection with a relatively low dose of Y. ruckeri.
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PMID:Yersinia ruckeri septicaemia in experimentally infected carp (Cyprinus carpio L.) fingerlings. 1034 77

The hematopoietic system in patients with aplastic anemia (AA) shows both quantitative and qualitative deficiencies, i.e., reduced numbers of hematopoietic progenitor cells (HPC) and impaired HPC proliferation in long-term marrow cultures (LTMC). Since recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) has been shown to be a potent stimulator of normal hematopoiesis, both in vivo and in vitro, in the present study we wanted to assess the possibility of stimulating hematopoiesis in LTMC from 17 patients with AA, by weekly addition of rhGM-CSF (10 ng/ml). In LTMC from 11 patients (group of responders), rhGM-CSF induced a significant increase (4.8-fold, compared with untreated cultures) in the levels of myeloid progenitor cells; in contrast, in six patients (group of nonresponders), myeloid progenitors were refractory to this cytokine. In the group of responders, rhGM-CSF also induced a pronounced increment in the levels of nonadherent and adherent cells (5.99- and 5.18-fold, respectively, compared with untreated cultures). Among the different myelopoietic lineages, rhGM-CSF preferentially stimulated the macrophagic lineage; this was evident both at the progenitor and mature cell levels. Interestingly, the effect of rhGM-CSF in LTMC from AA patients was only transient. Indeed, the effects mentioned above were observed only during the first three weeks of culture; afterwards, myeloid progenitor and nonadherent cell levels in treated cultures declined, practically reaching the levels observed in untreated cultures. At the moment, we do not know whether this transient stimulatory effect is due to the production of inhibitory cytokines, by macrophages generated in response to rhGM-CSF, or to the exhaustion of the HPC pool in AA cultures. In all 17 patients, rhGM-CSF had no effect on the kinetics of erythroid or multipotent progenitor cells. These results are in keeping with clinical studies in which it has been observed that most AA patients treated with rhGM-CSF show increments in circulating monocytes and granulocytes, as well as in bone marrow cellularity. However, little or no effect is observed on erythropoiesis. The actual mechanisms involved in the in vitro effects of rhGM-CSF on myeloid progenitor cells from AA bone marrow are still not completely understood. Future studies on this issue should be encouraged, since they may help to understand the in vivo (clinical) effects of this cytokine.
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PMID:Effect of recombinant human granulocyte macrophage-colony stimulating factor in long-term marrow cultures from patients with aplastic anemia. 1036 89

Fetal clonogenic erythroid cells may be present in maternal blood and serve as a source of fetal DNA for prenatal genetic diagnosis. Proliferating nucleated red cells in cultures from first and second trimester fetal blood contain only fetal haemoglobin (HbF; F+A- cells), whereas nucleated red cells from adult blood contain also adult haemoglobin (HbA; F+A+ or F-A+ cells). Thus, fetal red cells can be identified and flow sorted. However, a few adult cells are also F+A-, which reduces the purity of fetal cell isolation. Culture media optimized for erythropoiesis contain interleukin-3 (IL3). We show here that IL3 strongly stimulates the growth of F+ cells (both F+A- and F+A+) in cultures from adult blood but has only a comparatively small effect on F+A- cells in cultures from fetal blood. This difference is maintained in the unified conditions of co-cultures of adult and fetal cells, so that the purity of fetal cell sorts can be increased by omitting IL3 from the culture medium. We further show that IL3 accelerates the exhaustion of the long-term division potential of adult cells, allowing fetal secondary colonies to be identified by their size following a two-stage culture scheme. Thus, the choice to omit or include IL3 in the growth medium of maternal blood cultures should depend on whether fetal nucleated red cells are to be isolated by flow sorting after one week, or by picking secondary colonies after a later secondary culture stage.
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PMID:Differential effects of interleukin-3 on fetal and adult erythroid cells in culture: implications for the isolation of fetal cells from maternal blood. 1095 74

The purpose of this study was to evaluate the efficacy and toxicity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy in patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease (GSD) type 1b. Thirteen patients with neutropenia and/or neutrophil dysfunction secondary to GSD type 1b were treated with rhG-CSF. The effects of therapy on neutrophil numbers and in vitro neutrophil function and on bone marrow cellularity and morphology were studied. The clinical status of the patients and the occurrence of adverse events associated with rhG-CSF use were monitored. Use of rhG-CSF therapy was associated with a significant increase in circulating neutrophil numbers (P <. 01) and an improvement in neutrophil function as assessed in vitro. In addition, rhG-CSF therapy produced a significant increase in marrow cellularity and an increase in myeloid:erythroid (M:E) ratio, indicating stimulation of granulopoeisis. No adverse effects on marrow function were noted; in particular, no myelodysplasia or marrow exhaustion was seen. Use of rhG-CSF therapy was associated with objective and subjective improvements in infection-related morbidity. The therapy was well tolerated, although all patients developed splenomegaly, and 5 patients developed mild hypersplenism that did not require any specific treatment. rhG-CSF therapy is efficacious in the management of neutropenia and neutrophil dysfunction associated with GSD type 1b. Patients on this therapy need to be monitored for hypersplenism. Continued follow-up will be necessary to confirm long-term safety; however, no significant short-term toxicity was noted.
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PMID:Recombinant human granulocyte colony-stimulating factor therapy for patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease type 1b. 1115 11


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