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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When murine (C57BL/6) bone marrow cells are cultivated with WEHI-3 conditioned media, a source of megakaryocyte-colony-stimulating activity (Mk-CSA), and phorbol myristate acetate (PMA), a previously undetected population of megakaryocyte (Mk) progenitor cells is observed. These new Mk colonies are reminiscent of erythroid bursts, in that they contain large numbers (40-500) of Mk and multiple foci (2-7) of development. These burst-forming units, Mk (BFU-Mk), are defined as having greater than or equal to 42 cells/colony and, at least, three foci of Mk development (colonies grown in soft agar cultures, all studies done at limiting dilutions; colonies detected by acetylcholinesterase [ACh-E] staining). CFU-Mk and BFU-Mk require two activities for optimal growth: Mk-CSA and PMA. However, the BFU-Mk require a tenfold greater concentration of PMA for optimal development (10(-6) vs. 10(-7) M). BFU-Mk detection is linear (over a range of 25-100 X 10(3) cells/ml), with the regression line passing through the origin. Bone marrow frequencies of these two progenitor cells are CFU-Mk, 36.7 +/- 2.5, and BFU-Mk, 7.3 +/- 0.7 per 10(5) total nucleated cells (mean +/- SEM; n = 28). The BFU-Mk have a restricted velocity sedimentation range (3.3-4.5 mmh-1 vs. 3.3-6.8 mmh-1 for CFU-Mk). Modal buoyant densities are 1.068 +/- 0.0002 and 1.070 +/- 0.002 for BFU-Mk and CFU-Mk, respectively. Thus, these cells are found among the smallest and less dense of the Mk progenitors, and are not clumps or clusters of CFU-Mk. Kinetic analysis indicates that CFU-Mk require 5-7 d for optimal growth, whereas BFU-Mk require 10-12 d. Examination of the proliferative potential (cells per colony) shows 19.3 +/- 1.5 cells per colony (n = 246 colonies) for day 10 CFU-Mk, vs. 118 +/- 6.0 for day 10 BFU-Mk (n = 163). Analysis of the cellularity/subcolony within each burst indicates 37.0 +/- 2.1 (n = 146) Mk/colony and 3.9 +/- 0.1 subcolonies/burst (n = 100). Finally, greater than 90% of the BFU-Mk contain only ACh-E positive cells, indicating that these are not mixed colonies. These results indicate that the BFU-Mk, compared with the CFU-Mk, require an increased amount of stimulation in order to differentiate, show delayed in vitro development, and have a higher proliferative potential. These data are consistent with the hypothesis that these cells are early progenitor cells in the Mk lineage that antedate the CFU-Mk.
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PMID:Phorbol diesters stimulate the development of an early murine progenitor cell. The burst-forming unit-megakaryocyte. 387 29

Patients with type I diabetes mellitus treated with continuous sc insulin infusion (CSII) have improved glucose homeostasis, metabolic control, and linear growth. To determine the influence of CSII on cellular growth in vitro, we used a clonal stem cell assay for proliferation of erythroid progenitors, [burstforming units-erythroid (BFU-E)] in peripheral blood. Eight patients were studied before and after 1 week of CSII. Improvement in metabolic control was demonstrated by a decrease in mean 24-h plasma glucose from 232 +/- 29 (+/- SEM) mg/dl before treatment to 112 +/- 3 mg/dl after treatment (P = 0.01). Somatomedin-C levels increased from 1.1 +/- 0.4 to 1.4 +/- 0.4 U/ml (P less than 0.001). Numbers of BFU-E-derived colonies were not different from normal during conventional treatment, but increased 300% after 1 week of CSII. Our findings indicate that the acute metabolic and hormonal improvements that accompany short term CSII therapy in vivo are associated with a striking increase in the proliferation of erythroid committed stem cells in vitro.
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PMID:Improved diabetic control enhances erythroid stem cell proliferation in vitro. 399 70

The activity capable of promoting the growth of human erythroid burst-forming cells (BFU-E) in culture was measured in the sera from 39 patients with aplastic anemia (AA) and compared with similar activity in patients with various other hematologic disorders and 31 normal subjects. Burst-promoting activity (BPA) was determined by its ability to support erythroid burst growth from adherent cell-depleted normal human marrow cells. The results were expressed as the percentage of burst growth supported by test serum compared with cultures established in the presence of 20% test serum and 2.5% phytohemagglutinin-stimulated lymphocyte conditioned medium. The mean BPA level in normal serum was 18.5% (1.5 +/- SEM) and was not significantly different from BPA levels in patients with various forms of nonhypoplastic anemia or polycythemia (10.2% +/- 1.2%). In contrast, 15 of the 39 patients with AA had elevated BPA levels, ranging from 40.0% to 106.0%. These elevated levels did not correlate with serum erythropoietin or hematocrit values, white blood cell count, platelet count, time from diagnosis, or the presence or numbers of BFU-E in circulation. The BPA was shown not to be T cell growth factor (interleukin-2), and the effect was not blocked by the addition of cyclosporine to culture, consistent with a direct effect of this activity on BFU-E. When the 39 patients with AA were treated with antithymocyte globulin, 20 obtained a complete or partial remission. BPA levels determined from sera obtained before treatment did not correlate with response or duration of survival but did correlate with granulocyte-macrophage colony-stimulating activity (GM-CSA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hematopoietic growth factors in human serum. erythroid burst-promoting activity in normal subjects and in patients with severe aplastic anemia. 404 96

Peripheral blood burst forming units-erythroid (BFU-E) were measured by the plasma clot cell culture technique in patients with the various subtypes of polycythaemia and compared to normal. 10 patients with active polycythaemia rubra vera (PRV) were found to have a mean BFU-E level of 48 +/- 15.8 (SEM) per 5 X 10(5) cultured cells which was significantly different from normals (4 +/- 1.1, P less than 0.02), patients with controlled PRV (7 +/- 1.6, P less than 0.025), secondary polycythaemia (1 +/- 0.3, P less than 0.015) and relative polycythaemia (0, P less than 0.015). Burst forming units were found to fall to normal levels in patients with PRV with appropriate disease control and then to rise again in patients untreated for more than 18 months. Clinical aspects. Measurement of BFU-E levels from the peripheral blood could provide a useful adjunct from an accessible source in the differential diagnosis of polycythaemia as well as being of use in serial monitoring of patients with PRV.
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PMID:An analysis of peripheral blood burst forming units-erythroid in the polycythaemic states. 662 75

This report documents the results of therapy in 23 patients treated for malignant thymoma between 1944 and 1979. Of the group, 22 patients had neoplasms which invaded mediastinal structures; six had distant metastases. Four patients had myasthenia gravis and one had erythroid hypoplasia associated with collagen vascular disease. No deaths were associated with primary therapy, which included an operative procedure in all cases. Follow-up ranged from 4 months to 18 years (mean 5.63 +/- 1.03 years, SEM). Fifteen patients died, with postoperative survival times ranging from 4 months to 18 years (mean 3.8 +/- 1.27 years). Five patients were alive without recurrence from 3 to 11 years postoperatively (mean 6.8 +/- 1.36 years), and three patients were alive with recurrence or distant metastases from 4 to 17 years postoperatively (mean 10.75 +/- 2.66 years). Differences in survival on the basis of tumor cell type were not statistically significant. Therapeutic groups were analyzed for 5 year survivors, tumor deaths within 5 years of therapy, deaths due to other causes, deaths due to tumor after 5 years, those presently alive, and longest known survivor. The data suggest that complete surgical excision offers the best chance of long-term survival when compared to partial resection plus irradiation (p less than 0.05). No statistical significance could be demonstrated between the groups who had complete resection with versus without postoperative irradiation. There also was no statistically significant difference between the group of patients receiving irradiation following partial excision of most of their tumor and the group receiving irradiation following only biopsy of the lesion. This observation suggests there is no value in so-called "debulking procedures" and suggests that irradiation may be of value in local control of thymoma. Perpetual surveillance is necessary since late recurrence is common.
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PMID:Management of patients with malignant thymoma. 669 21

Acromegaloidism is a syndrome characterized by features of acromegaly without biochemical evidence of excessive GH or somatomedin production. We searched for a growth factor in the serum of patients with this syndrome. Growth-promoting activity was measured by determining the stimulatory effect of whole and fractionated serum on colony formation by human erythroid progenitors in vitro. Sera from five subjects with acromegaloidism gave a mean (+/- SEM) stimulated colony growth of 211 +/- 4.0 colonies, in contrast to normal sera which yielded a mean colony growth of 100 +/- 11.0 (n = 9; P less than 0.001). When serum was chromatographed on a Sephadex G-200 column, the maximal stimulation of colony growth was found in the fractions coinciding with the descending slope of the second protein peak. Based on gel filtration chromatography, the estimated molecular weight was 70,000 daltons. Epidermal growth factor, nerve growth factor, fibroblast growth factor, and platelet-derived growth factor resulted in no substantial stimulation of colony growth under the conditions used. Although the erythroid progenitor cells of a Laron dwarf were unresponsive to 200 ng/ml human GH, they were clearly stimulated by serum from a patient with acromegaloidism. The present study describes the presence of a heretofore unidentified growth factor in the serum of subjects with acromegaloidism. This factor also stimulated the erythroid precursor cells of a Laron dwarf whose cells were unresponsive to GH. The physiological role of this growth factor in normal man as well as its pathogenic role in subjects with acromegaloidism remain to be established.
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PMID:A unique growth factor in patients with acromegaloidism. 686 75

In order to quantitate early erythroid progenitor cells in paroxysmal nocturnal hemoglobinuria (PNH), we have cultured peripheral blood mononuclear cells from 7 PNH patients in a 0.8% methylcellulose medium containing erythropoietin, 2 U/ml. In our experimental conditions, the number of erythroid colonies obtained per 5 X 10(5) mononuclear cells plated was 20.1 +/- 1.9 (SEM) in normal subjects and 2.8 +/- 0.56 (SEM) in PNH patients. In plates from PNH subjects, 38 of 117 showed no growth of erythroid colonies, whereas plates from normal subjects always had colonies. Our findings suggest that PNH patients, despite their hemolytic condition, have a depleted erythroid precursor compartment, and this may play a major role in the pathogenesis of their anemia.
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PMID:Decreased number of circulating BFU-Es in paroxysmal nocturnal hemoglobinuria. 708 35

We have developed techniques by which normal functional elements of human bone marrow can be implanted into immunodeficient C.B-17 scid/scid (SCID) mice. Afterward, long-term multilineage human hematopoiesis is sustained in vivo. We evaluated the effect of irradiation on the function of human bone marrow with this in vivo model. After whole-body X irradiation of the engrafted animals, it was determined that the D0 value of human committed progenitor cells within the human marrow was 1.00 +/- 0.09 (SEM) Gy for granulocyte-macrophage colony-forming units (CFU-GM) and 0.74 +/- 0.12 Gy for erythroid burst-forming units (BFU-E). The effects of irradiation on the hematopoietic elements were reduced when the radioprotective agent WR-2721 was administered prior to irradiation. After low-dose irradiation, recovery of human myelopoiesis was accelerated by treatment with human granulocyte colony-stimulating factor (G-CSF). This small animal model may prove amenable for the analysis of the risk of the exposure of humans to radiation as well as for the development of new modalities for the prevention and treatment of radiation-induced hematopoietic damage.
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PMID:Direct evaluation of radiation damage in human hematopoietic progenitor cells in vivo. 750 56

This report presents results concerning the potential role of negative regulators in hematopoietic suppression observed in human immunodeficiency virus (HIV)-infected long-term cultures (LTC) of human bone marrow cells. Confluent stromal cell layers established from human bone marrow cells were exposed to HIV-1ADA, a monocytotropic strain of HIV-1. A progressive increase in the concentration of HIV-1 p24 antigen in cultures exposed to HIV-1ADA demonstrated that there was a productive infection. Cells from both noninfected and HIV-infected stromal cell layers produced factors that stimulated the proliferation of colony-forming units for granulocytes and macrophages (CFU-GM) from non-infected CD34+ cells. In contrast, when noninfected CD34+ cells were directly cocultured on intact stromal cell layers fewer CFU-GM and burst-forming units for erythroid cells (BFU-E) were detected in HIV-infected LTC than in noninfected LTC. One week after the addition of CD34+ cells, the number of CFU-GM in HIV-infected LTC in six of nine experiments was reduced compared to noninfected control LTC. In those six experiments, the number of CFU-GM was only 53 +/- 5% (SEM) of the number in noninfected LTC. The number of BFU-E in HIV-1-infected LTC was only 46 +/- 5% of the number in noninfected LTC (n = 5). There were fewer BFU-E in HIV-1-infected LTC, whether or not there was a reduced number of CFU-GM. Neutralizing antibody to tumor necrosis factor alpha (TNF-alpha) had no effect on the number of BFU-E in HIV-infected LTC. The number of BFU-E, however, was 2.1 +/- 0.2-fold greater (n = 3) in HIV-infected LTC incubated with neutralizing antibody to interferon-alpha. In HIV-infected LTC with decreased numbers of CFU-GM, the number of CFU-GM was approximately 2-fold greater after incubation of HIV-infected LTC with anti-interleukin-4 (IL-4). The effect of anti-TNF-alpha was variable, and anti-transforming growth factor-beta had no effect on the number of CFU-GM in HIV-infected LTC. After 2 weeks, the number of CFU-GM in HIV-infected LTC incubated with anti-IL-4 and anti-TNF-alpha was 2- to 4-fold greater than in untreated HIV-infected LTC. Antibody treatment did not promote an increase in the number of CFU-GM in noninfected LTC or in LTC in which CFU-GM numbers were not reduced after HIV infection.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Negative regulators may mediate some of the inhibitory effects of HIV-1 infected stromal cell layers on erythropoiesis and myelopoiesis in human bone marrow long term cultures. 754 Jun 43

Occupational exposure to benzene is known to cause leukemia, but the mechanism remains unclear. Unlike most other carcinogens, benzene and its metabolites are weakly or nonmutagenic in most simple gene mutation assays. Benzene and its metabolites do, however, produce chromosomal damage in a variety of systems. Here, we have used the glycophorin A (GPA) gene loss mutation assay to evaluate the nature of DNA damage produced by benzene in 24 workers heavily exposed to benzene and 23 matched control individuals in Shanghai, China. The GPA assay identifies stem cell or precursor erythroid cell mutations expressed in peripheral erythrocytes of MN-heterozygous subjects, distinguishing the NN and N phi mutant variants. A significant increase in the NN GPA variant cell frequency (Vf) was found in benzene-exposed workers as compared with unexposed control individuals (mean +/- SEM, 13.9 +/- 1.7 per million cells vs. 7.4 +/- 1.1 per million cells in control individuals; P = 0.0002). In contrast, no significant difference existed between the two groups for the N phi Vf (9.1 +/- 0.9 vs. 8.8 +/- 1.8 per million cells; P = 0.21). Further, lifetime cumulative occupational exposure to benzene was associated with the NN Vf (P = 0.005) but not with the N phi Vf (P = 0.31), suggesting that NN mutations occur in longer-lived bone marrow stem cells. NN variants result from loss of the GPA M allele and duplication of the N allele, presumably through recombination mechanisms, whereas NO variants arise from gene inactivation, presumably due to point mutations and deletions. Thus, these results suggest that benzene produces gene-duplicating mutations but does not produce gene-inactivating mutations at the GPA locus in bone marrow cells of humans exposed to high benzene levels. This finding is consistent with data on the genetic toxicology of benzene and its metabolites and adds further weight to the hypothesis that chromosome damage and mitotic recombination are important in benzene-induced leukemia.
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PMID:Benzene induces gene-duplicating but not gene-inactivating mutations at the glycophorin A locus in exposed humans. 773 33


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