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Quesniaux VF; Wehrli S; Steiner C; Joergensen J; Schuurman HJ; Herrman P; Schreier MH; Schuler W 《Blood》1994,84(5):1543-1552
The immunosuppressive drug rapamycin suppresses T-cell activation by impairing the T-cell response to lymphokines such as interleukin-2 (IL- 2) and interleukin-4 (IL-4). In addition, rapamycin blocks the proliferative response of cell lines to a variety of hematopoietic growth factors, including interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage- colony stimulating factor (GM-CSF), and kit ligand (KL), suggesting that it should be a strong inhibitor of hematopoiesis. In this report, we studied the effects of rapamycin on different hematopoietic cell populations in vitro and in vivo. In vitro, rapamycin inhibited the proliferation of primary bone marrow cells induced by IL-3, GM-CSF, KL, or a complex mixture of factors present in cell-conditioned media. Rapamycin also inhibited the multiplication of colony-forming cells in suspension cultures containing IL-3 plus interleukin-1 (IL-1) or interleukin-11 (IL-11) plus KL. In vivo, treatment for 10 to 28 days with high doses of rapamycin (50 mg/kg/d, orally) had no effect on myelopoiesis in normal mice, as measured by bone marrow cellularity, proliferative capacity, and number of colony-forming progenitors. In contrast, the same treatment strongly suppressed the hematopoietic recovery normally seen 10 days after an injection of 5-fluorouracil (5- FU; 150 mg/kg, intravenously [i.v.]). Thus, rapamycin may be detrimental in myelocompromised individuals. In addition, the results suggest that the rapamycin-sensitive cytokine-driven pathways are essential for hematopoietic recovery after myelodepression, but not for steady-state hematopoiesis. 相似文献
43.
Antibodies to myeloid precursor cells in autoimmune neutropenia 总被引:4,自引:1,他引:4
Antibodies to mature blood neutrophils and to bone marrow myeloid cells have been described in the sera of some patients with apparent autoimmune neutropenia. To further explore the prevalence and specificities of antibodies to myeloid precursor cells, we evaluated sera from 148 patients with suspected autoimmune neutropenia for the presence of antibodies to neutrophils, to cultured myeloid cell lines, and to highly purified bone marrow myeloid progenitor cells. Using an immunofluorescence flow cytometric assay, we identified IgG antibodies in 42 (28%) of these sera that bound specifically to K562 cells, a multilineage cell line originally derived from a patient with chronic myelogenous leukemia. Twenty-two (15%) of the sera also contained IgG antibodies that bound specifically to the primitive myelomonocytic leukemia cell line KG1a. Twenty-five (17%) of the sera had IgG antibodies to myeloid cell lines in the absence of antibodies to mature neutrophils. There was a trend toward more severe neutropenia in patients with antibodies to K562 cells, without antineutrophil antibodies. In further studies, antibodies from 12 sera bound to mononuclear CD34+ cells that had been purified from normal human bone marrow by an immunomagnetic separation procedure. Moreover, two of these sera suppressed the growth of granulocyte-macrophage colony- forming units (CFU-GM) in methylcellulose cultures. The presence of antibodies to primitive hematopoietic cells in the sera of some patients with suspected immune neutropenia suggests that these antibodies may have a role in the pathogenesis of the neutropenia observed. 相似文献
44.
The current Indochinese resettlement program in the United States has resulted in an increase in the number of persons with hemoglobin E trait. American physicians should be aware of the hematologic expressions of this innocuous condition. The hematologic manifestations of 21 persons with hemoglobin E trait were evaluated. The subjects were of Tai-dam, Vietnamese, Chinese, Laotian, and European origin. These studies showed uniform hematologic manifestations in hemoglobin E trait, characterized by slight microcytosis, by morphologic features resembling those of thalassemia minor, and often by increased erythrocyte count. Hemoglobin instability also was confirmed. 相似文献
45.
Unequal crossing-over: a common basis of single alpha-globin genes in Asians and American blacks with hemoglobin-H disease 总被引:5,自引:0,他引:5
Phillips JA d; Vik TA; Scott AF; Young KE; Kazazian HH Jr; Smith KD; Fairbanks VF; Koenig HM 《Blood》1980,55(6):1066-1069
The alpha-globin genes of five black Americans, two Chinese, and five Filipinos with HbH disease (an alpha-thalassemia state in which there is a single functional alpha gene) were analyzed by restriction endonuclease techniques. All subjects were found to have one chromosome 16, lacking both alpha genes, and another containing a single alpha gene (--/-alpha). Restriction endonuclease patterns of the DNA obtained from all 12 subjects were identical and compatible with unequal crossing-over as the mechanism of origin of the single alpha gene in these individuals. 相似文献
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Eneida?A?Santos Michel?VF?Sucupira Ju?ara?Arabe Selma?A?GomesEmail author 《BMC infectious diseases》2004,4(1):29