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  • American Society of Hematology  (19)
  • 1
    Online Resource
    Online Resource
    Recombinant human interleukin-3 expands the pool of circulating hematopoietic progenitor cells in primates--synergism with recombinant human granulocyte/macrophage colony-stimulating factor
    American Society of Hematology ; 1990
    In:  Blood Vol. 75, No. 12 ( 1990-06-15), p. 2305-2310
    Details
    In: Blood, American Society of Hematology, Vol. 75, No. 12 ( 1990-06-15), p. 2305-2310
    Abstract: The in vivo effect of recombinant human interleukin-3 (rhIL-3) on peripheral blood (PB) levels of hematopoietic progenitor cells was studied in nonhuman primates. Subcutaneous administration of 33 micrograms/kg/d of rhIL-3 for 11 to 14 days to rhesus monkeys slightly raised leukocyte counts (twofold) and substantially expanded the pool of circulating stem cells in the second week of treatment. At the end of rhIL-3 administration, PB levels of granulocyte/macrophage colony- forming units (CFU-GM) increased by a mean of 12-fold; burst-forming units-erythroid (BFU-E) by ninefold; CFU-mix, by 12-fold; and CFU- megakaryocyte (Mk), by 13-fold as compared with their respective pretreatment values. Subsequent administration of recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF; 5.5 micrograms/kg/d for 5 days) to rhIL-3-pretreated animals further expanded the PB stem cell compartment leading to maximum levels of CFU- GM that were in average much more increased (63-fold) than CFU-GM levels under rhIL-3 (14-fold) or rhGM-CSF (12-fold) alone. This hitherto unknown effect of rhIL-3 on the pool of circulating progenitors, particularly in synergy with rhGM-CSF, may facilitate harvest of hematopoietic progenitor cells from PB for stem cell transplantation.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V75.12.2305.2305
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1990
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    Online Resource
    Online Resource
    Recombinant human interleukin-3 expands the pool of circulating hematopoietic progenitor cells in primates--synergism with recombinant human granulocyte/macrophage colony-stimulating factor
    American Society of Hematology ; 1990
    In:  Blood Vol. 75, No. 12 ( 1990-06-15), p. 2305-2310
    Details
    In: Blood, American Society of Hematology, Vol. 75, No. 12 ( 1990-06-15), p. 2305-2310
    Abstract: The in vivo effect of recombinant human interleukin-3 (rhIL-3) on peripheral blood (PB) levels of hematopoietic progenitor cells was studied in nonhuman primates. Subcutaneous administration of 33 micrograms/kg/d of rhIL-3 for 11 to 14 days to rhesus monkeys slightly raised leukocyte counts (twofold) and substantially expanded the pool of circulating stem cells in the second week of treatment. At the end of rhIL-3 administration, PB levels of granulocyte/macrophage colony- forming units (CFU-GM) increased by a mean of 12-fold; burst-forming units-erythroid (BFU-E) by ninefold; CFU-mix, by 12-fold; and CFU- megakaryocyte (Mk), by 13-fold as compared with their respective pretreatment values. Subsequent administration of recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF; 5.5 micrograms/kg/d for 5 days) to rhIL-3-pretreated animals further expanded the PB stem cell compartment leading to maximum levels of CFU- GM that were in average much more increased (63-fold) than CFU-GM levels under rhIL-3 (14-fold) or rhGM-CSF (12-fold) alone. This hitherto unknown effect of rhIL-3 on the pool of circulating progenitors, particularly in synergy with rhGM-CSF, may facilitate harvest of hematopoietic progenitor cells from PB for stem cell transplantation.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V75.12.2305.bloodjournal75122305
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1990
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    Online Resource
    Online Resource
    Recombinant human erythropoietin and hematopoietic progenitor cells in vivo [letter]
    American Society of Hematology ; 1989
    In:  Blood Vol. 73, No. 8 ( 1989-06-01), p. 2229-2229
    Details
    In: Blood, American Society of Hematology, Vol. 73, No. 8 ( 1989-06-01), p. 2229-2229
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V73.8.2229.2229
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1989
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    Online Resource
    Online Resource
    Induction of differentiation of human mast cells from bone marrow and peripheral blood mononuclear cells by recombinant human stem cell factor/kit-ligand in long-term culture
    American Society of Hematology ; 1992
    In:  Blood Vol. 80, No. 9 ( 1992-11-01), p. 2237-2245
    Details
    In: Blood, American Society of Hematology, Vol. 80, No. 9 ( 1992-11-01), p. 2237-2245
    Abstract: In the murine system, a number of cytokines (including interleukin-3 [IL-3], IL-4, and stem cell factor [SCF] ) promote the growth of mast cells (MCs). However, so far little is known about factors controlling differentiation of human MCs. Recent data suggest that human MCs express receptors (R) for SCF. The aim of the present study was to investigate whether recombinant human (rh) SCF induces differentiation of human MCs from their precursor cells. For this purpose, bone marrow (BM; normal donors, n = 6) and peripheral blood (PB; normal donors, n = 11) mononuclear cells (MNC) were cultured in the presence of rhSCF, rhIL-3, rhIL-4, rhIL-9, recombinant human macrophage colony-stimulating factor (rhM-CSF), or control medium in long-term (8 weeks) suspension cultures. After 4 weeks, up to 5% of the MNC (BM and PB) cultured in the presence of rhSCF, but not in the presence of other cytokines, were found to exhibit the characteristics of MCs. These MCs expressed the YB5.B8-reactive domain of the SCF R as well as IgE R, as determined by combined toluidine blue/immunofluorescence staining. Myeloid antigens, likewise expressed on human basophils (ie, CD11b, CDw65, and Bsp-1), could not be detected on these cells. Furthermore, rhSCF, but not rhIL- 3, rhIL-4, rhIL-9, or rhM-CSF, induced dose- and time-dependent increases in the formation of cellular tryptase (an MC-specific enzyme) (rhSCF [100 ng/mL], 1,308 +/- 679 ng/mL v control medium, 18 +/- 6 ng/mL tryptase on day 35 of PB cell cultures), as well as an increase in cellular histamine. After 6 to 8 weeks, when other mature hematopoietic cells decreased, MCs still could be detected in culture, with up to 40% of all cells being MCs. To test whether rhSCF also activates tissue MCs, we performed histamine release experiments (dis persed tissue; lung, n = 3; uterus, n = 3). SCF was found to enhance (by up to 3.4-fold) the capacity of the MCs to release histamine upon cross-linkage of IgE R with anti-IgE. Together, these observations suggest that rhSCF induces in vitro differentiation of human MCs from their BM and PB precursor cells in long-term culture and upregulates MC releasability.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V80.9.2237.2237
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1992
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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    Online Resource
  • 5
    Online Resource
    Online Resource
    Induction of differentiation of human mast cells from bone marrow and peripheral blood mononuclear cells by recombinant human stem cell factor/kit-ligand in long-term culture
    American Society of Hematology ; 1992
    In:  Blood Vol. 80, No. 9 ( 1992-11-01), p. 2237-2245
    Details
    In: Blood, American Society of Hematology, Vol. 80, No. 9 ( 1992-11-01), p. 2237-2245
    Abstract: In the murine system, a number of cytokines (including interleukin-3 [IL-3], IL-4, and stem cell factor [SCF] ) promote the growth of mast cells (MCs). However, so far little is known about factors controlling differentiation of human MCs. Recent data suggest that human MCs express receptors (R) for SCF. The aim of the present study was to investigate whether recombinant human (rh) SCF induces differentiation of human MCs from their precursor cells. For this purpose, bone marrow (BM; normal donors, n = 6) and peripheral blood (PB; normal donors, n = 11) mononuclear cells (MNC) were cultured in the presence of rhSCF, rhIL-3, rhIL-4, rhIL-9, recombinant human macrophage colony-stimulating factor (rhM-CSF), or control medium in long-term (8 weeks) suspension cultures. After 4 weeks, up to 5% of the MNC (BM and PB) cultured in the presence of rhSCF, but not in the presence of other cytokines, were found to exhibit the characteristics of MCs. These MCs expressed the YB5.B8-reactive domain of the SCF R as well as IgE R, as determined by combined toluidine blue/immunofluorescence staining. Myeloid antigens, likewise expressed on human basophils (ie, CD11b, CDw65, and Bsp-1), could not be detected on these cells. Furthermore, rhSCF, but not rhIL- 3, rhIL-4, rhIL-9, or rhM-CSF, induced dose- and time-dependent increases in the formation of cellular tryptase (an MC-specific enzyme) (rhSCF [100 ng/mL], 1,308 +/- 679 ng/mL v control medium, 18 +/- 6 ng/mL tryptase on day 35 of PB cell cultures), as well as an increase in cellular histamine. After 6 to 8 weeks, when other mature hematopoietic cells decreased, MCs still could be detected in culture, with up to 40% of all cells being MCs. To test whether rhSCF also activates tissue MCs, we performed histamine release experiments (dispersed tissue; lung, n = 3; uterus, n = 3). SCF was found to enhance (by up to 3.4-fold) the capacity of the MCs to release histamine upon cross-linkage of IgE R with anti-IgE. Together, these observations suggest that rhSCF induces in vitro differentiation of human MCs from their BM and PB precursor cells in long-term culture and upregulates MC releasability.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V80.9.2237.bloodjournal8092237
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1992
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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    Online Resource
  • 6
    Online Resource
    Online Resource
    In vivo synergism of recombinant human interleukin-3 and recombinant human interleukin-6 on thrombopoiesis in primates
    American Society of Hematology ; 1992
    In:  Blood Vol. 79, No. 5 ( 1992-03-01), p. 1155-1160
    Details
    In: Blood, American Society of Hematology, Vol. 79, No. 5 ( 1992-03-01), p. 1155-1160
    Abstract: Using a primate model, we examined the effect of recombinant human interleukin-3 (rhIL-3) and rhIL-6 on thrombopoiesis in vivo. Administration of 33 micrograms/kg/d of rhIL-3 for 11 to 14 days increased levels of circulating colony-forming units megakaryocyte (CFU- Mk) by approximately 15-fold in five rhesus monkeys without raising their platelet counts. In contrast, administration of 30 micrograms/kg/d of rhIL-6 for 10 days in four animals did not increase CFU-Mk levels but significantly raised platelet counts from a mean pretreatment value of 460 x 10(3)/microL (range 360 to 610) to a mean maximum of 746 x 10(3)/microL (665 to 790) on day 8. If monkeys were pretreated with rhIL-3 (33 or 100 micrograms/kg/d for 11 days) to expand their CFU-Mk compartment, the thrombopoietic effect of rhIL-6 was synergistically enhanced leading to platelet counts above 1,000 x 10(3)/microL (mean maximum value 1,247) in all three primates studied. The sequential administration of rhIL-3 and rhIL-6 might represent a powerful strategy to stimulate thrombopoiesis in vivo.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V79.5.1155.1155
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1992
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    Online Resource
    Online Resource
    Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia
    American Society of Hematology ; 2007
    In:  Blood Vol. 109, No. 11 ( 2007-06-01), p. 4686-4692
    Details
    In: Blood, American Society of Hematology, Vol. 109, No. 11 ( 2007-06-01), p. 4686-4692
    Abstract: Early allogeneic hematopoietic stem cell transplantation (HSCT) has been proposed as primary treatment modality for patients with chronic myeloid leukemia (CML). This concept has been challenged by transplantation mortality and improved drug therapy. In a randomized study, primary HSCT and best available drug treatment (IFN based) were compared in newly diagnosed chronic phase CML patients. Assignment to treatment strategy was by genetic randomization according to availability of a matched related donor. Evaluation followed the intention-to-treat principle. Six hundred and twenty one patients with chronic phase CML were stratified for eligibility for HSCT. Three hundred and fifty four patients (62% male; median age, 40 years; range, 11-59 years) were eligible and randomized. One hundred and thirty five patients (38%) had a matched related donor, of whom 123 (91%) received a transplant within a median of 10 months (range, 2-106 months) from diagnosis. Two hundred and nineteen patients (62%) had no related donor and received best available drug treatment. With an observation time up to 11.2 years (median, 8.9 years), survival was superior for patients with drug treatment (P = .049), superiority being most pronounced in low-risk patients (P = .032). The general recommendation of HSCT as first-line treatment option in chronic phase CML can no longer be maintained. It should be replaced by a trial with modern drug treatment first.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2006-11-055186
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    Online Resource
    Online Resource
    Interleukin-3 is a differentiation factor for human basophils
    American Society of Hematology ; 1989
    In:  Blood Vol. 73, No. 7 ( 1989-05-15), p. 1763-1769
    Details
    In: Blood, American Society of Hematology, Vol. 73, No. 7 ( 1989-05-15), p. 1763-1769
    Abstract: The effect of recombinant human (rh) cytokines, interleukin-1 alpha (IL- 1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL- 4), granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), monocyte/macrophage colony stimulating factor (M-CSF), interferon-alpha (IF-alpha), interferon-gamma (IF-gamma), and the tumor necrosis factor-alpha (TNF- alpha) on differentiation and function of metachromatic cells (MCS) was studied. Among all cytokines tested, rh interleukin-3 (rhIL-3) selectively induced a significant formation of MCS (IL-3: 1.1 +/- 0.6 x 10(5) v control: 0.02 +/- 0.15 x 10(5) MCS/mL suspension) and dose dependent increase in formation of intracellular histamine (IL-3, 100 U/mL: 95 +/- 23 ng/mL v control: 1.8 +/- 0.8 ng/mL) in a bone marrow suspension culture system (analyzed on day 14 of culture). Besides MCS, formation of eosinophils was observed in this culture system in the continuous presence of rhIL-3, whereas IL-3 pulse-stimulation for three hours and subsequent exposure to control medium induced growth of MCS but not of eosinophils. By combined immunofluorescence/toluidine blue staining, MCS were found to express a cell surface marker profile that corresponds to the immunological phenotype of peripheral blood basophils (MY-7(CD13)+, VIM12(CD11b)+, VIM2+, MAX1-, MAX24- and YB5B8- ). Furthermore, cultured MCS expressed surface membrane receptors for IgE and could be triggered for nontoxic histamine release by a monoclonal anti-IgE antibody. To evaluate a possible influence of IL-3 on basophil function, studies were extended to freshly obtained blood basophils (healthy volunteers, n = 3). However, like all other cytokines tested, rhIL-3 failed to induce basophil histamine release. Taken together, our studies demonstrate that IL-3 is a differentiation factor for human basophils.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V73.7.1763.1763
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1989
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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    Online Resource
  • 9
    Online Resource
    Online Resource
    Recombinant human erythropoietin and hematopoietic progenitor cells in vivo [letter]
    American Society of Hematology ; 1989
    In:  Blood Vol. 73, No. 8 ( 1989-06-01), p. 2229-2229
    Details
    In: Blood, American Society of Hematology, Vol. 73, No. 8 ( 1989-06-01), p. 2229-2229
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V73.8.2229.bloodjournal7382229
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1989
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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    Online Resource
  • 10
    Online Resource
    Online Resource
    Lymphokine overproduction in severe aplastic anemia is not related to blood transfusions
    American Society of Hematology ; 1989
    In:  Blood Vol. 74, No. 8 ( 1989-12-01), p. 2713-2717
    Details
    In: Blood, American Society of Hematology, Vol. 74, No. 8 ( 1989-12-01), p. 2713-2717
    Abstract: The production of interferons (IFNs), IFN-gamma, tumor necrosis factors (TNFs) and TNF-alpha (TNF-alpha) by peripheral blood mononuclear cells (PBMNCs) of untransfused and transfused, but otherwise untreated patients with severe aplastic anemia (SAA) was determined using bioassays and immunoassays. In untransfused and pretransfused SAA patients, spontaneous and lectin-induced production of these cytokines by PBMNCs was strongly enhanced. Cytokine production in untransfused SAA patients did not differ from that in pretransfused patients. Similar relative frequencies of activated (HLA-DR+) lymphocyte subpopulations present in the PBMNCs demonstrated cytokine overproduction per cells. Cytokine production was studied in three SAA patients before and after blood cell transfusions. Spontaneous and lectin-induced production of these cytokines was abnormally high and unaffected by blood transfusions. In another patient exhibiting abnormal cytokine production, the hematopoietic response to cyclosporin- A in vivo was accompanied by normalization of cytokine production in vitro. We conclude that overproduction of IFN-gamma and TNF-alpha by lectin-stimulated PBMNCs is an intrinsic abnormality of SAA unrelated to blood transfusions. Normalization of production of IFN-gamma and TNF- alpha accompanying a clinical response to cyclosporin-A may cautiously be taken as further evidence suggesting a pathogenetic role of cytokine overproduction in SAA.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V74.8.2713.2713
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1989
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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