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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T-lymphocyte colonies were cultured using lymphocytes from patients with aplastic anaemia and normal donors to assess their respective proliferative activities. Colony numbers from aplastic patient's cells were lower than from normal donors', though this was not significant. When lymphocytes from patients were co-cultured with normal lymphocytes, inhibition of T-colony formation was observed in 8 out of 12 experiments. As the degree of inhibition was greater than if patient cells grew no colonies, then, clearly, normal T-colony formation was inhibited. This ability of patients' lymphocytes to suppress lymphopoiesis might account for the low levels of patient T-colony formation, as well as low in vivo numbers of lymphocytes found in patients with aplastic anaemia. The role of patients' lymphocytes in causing marrow aplasia was investigated. Although the incorporation of patients' lymphocytes in normal granulocyte-macrophage (GM) colony-forming systems inhibited colony growth, in only 1 out of 8 patients was this inhibition significantly greater than that caused by the addition of normal lymphocytes to GM colony systems. Therefore, lymphocytes may not be the primary cause of aplastic anaemia, except for a few rare cases.
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PMID:T-lymphocyte colony formation by lymphocytes from patients with aplastic anaemia. 349 9

The marrow is a tissue distributed in numerous skeletal parts and works as an organ which is composed of a haemopoietic cell parenchyma and a supporting stroma. The pathophysiological mechanisms involved in the radiation-induced late effects depend mainly on the damage produced to each of these elements. Parenchymal cell damage ends with a failure of the stem cell pool to supply an adequate number of highly differentiated functional blood cells and is clinically manifested as aplastic anaemia or leukaemia. The effects of radiation on the haemopoietic stem cell can be measured by means of spleen colony forming units (CFU-S) in rodents. The self-maintaining capacity of the CFU-S was found to be lower than normal 16 weeks after a dose of 0.64 Gy. In larger animals it is only possible to measure the activity of some of the progenitor cells, estimating the number of granulocyte-macrophage colonies in culture (CFU-GM) as an indicator of stem cell changes. Their number in the blood is about 50 per cent of normal even 160 days after about 0.78 Gy. The stromal cells are also radiosensitive if measured with respect to their capacity to support long-term cell replication in vitro. Marrow fibrosis develops after single, repeated and chronic radiation exposure, and a dose of 40 Gy impairs the capacity of the marrow to support haemopoiesis.
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PMID:The development of radiation late effects to the bone marrow after single and chronic exposure. 351 Jan 81

Lymphocyte phenotype, bone marrow cellularity, in vitro marrow growth potential, and treatment responses were examined in 22 patients with acquired aplastic anemia who were given anti-thymocyte globulin. Eleven of 22 patients (50 percent) had a significant hematologic response within three months of therapy, confirming the effectiveness of this therapy. Pretreatment fetal hemoglobin concentration, age, sex, severity of pancytopenia, degree of maximal lymphopenia, and total hemolytic complement consumption did not affect response. Patients with severe disease who were treated within 16 weeks after diagnosis had a higher response rate (55 percent) than those treated after 16 weeks (20 percent). In patients with severe disease, a higher pretherapy bone marrow cellularity (p less than 0.001) and presence of granulocyte-macrophage colony growth correlated with response. The actuarial survival of patients with response in the group with severe disease was 100 percent at 12 months as compared with 33 percent in patients without response. Following anti-thymocyte globulin therapy, a reduced number of blood lymphocyte T subpopulations was seen in all patients. At three months after therapy, the patients with response who had severe disease had increased T8-positive cells (+56 percent versus -4 percent for patients without response) and la-positive cells (+32 percent versus -62 percent).
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PMID:Predictive factors for response to anti-thymocyte globulin in acquired aplastic anemia. 387 46

Normal human peripheral blood T cells and T-cell subsets defined by monoclonal antibodies of the OKT series were pretreated with pokeweed mitogen (PWM). Their effects on the haematopoietic precursors, erythroid (BFU-E, CFU-E), granulocyte-macrophage (CFU-GM) and megakaryocyte (CFU-M) colony forming cells were evaluated by coculture. While unstimulated T cells and T-cell subsets enhanced growth of autologous blood BFU-E, PWM-stimulated T and OKT4+ cells suppressed it, also inhibiting proliferation of both autologous and allogeneic bone marrow BFU-E, CFU-E, CFU-GM and CFU-M. PWM-stimulated OKT8+ cells had little effect on the growth of any of the precursors at the cell concentration at which growth was completely inhibited by PWM-stimulated OKT4+ cells. Irradiation of T or OKT4+ cells with 3000 rad before PWM stimulation completely abrogated the inhibition. These observations might be related to the mechanism of pancytopenia in some cases of immune-mediated aplastic anaemia.
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PMID:Inhibitory effect of PWM-stimulated OKT4+ subsets on erythro-, granulo- and megakaryocytopoiesis in vitro. 387 21

Two patients with aplastic anemia evolving from cellular bone marrows with severely diminished megakaryocytes are reported. During this evolution a plasma inhibitor of in vitro granulocyte-macrophage colony formation was demonstrated associated with non-A, non-B hepatitis in one patient. The second patient had abnormal liver function that corrected after the delivery of a normal newborn but there was persistence of pancytopenia without evidence of a plasma inhibitor.
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PMID:Aplastic anemia occurring as amegakaryocytic thrombocytopenia with and without an inhibitor of granulopoiesis. 391 71

To determine whether or not abnormalities exist in the bone marrow stroma in aplastic anaemia, we analysed the ability of marrow stromal cells to support haemopoiesis using a long-term culture system. Marrow stromal cell layers from 3 of 9 patients with this disorder failed to maintain granulocyte-macrophage colony-forming cells in vitro. The stromal dysfunction was reversible in 1 patient who recovered after androgen therapy. The results of the present study add to the available evidence for a functional defect of marrow microenvironments in some cases of aplastic anaemia.
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PMID:Functional changes in marrow stromal cells in aplastic anaemia. 393 17

Chloramphenicol, an antibiotic associated with reversible bone marrow suppression and fatal aplastic anemia, was found to increase human bone marrow granulocyte-macrophage colonies (CFU-GM) in vitro. Maximal stimulation was at a concentration of 1.0 micrograms/ml (3.1 microM), with inhibition at concentrations greater than 10 micrograms/ml. This effect was noted in normal donors and in children with neutropenia of various etiologies. Stimulation was ablated by depletion of bone-marrow-adherent cells and was restored by addition of peripheral-blood-adherent mononuclear cells. The stimulatory effect appears to be specific for chloramphenicol, as numerous structural analogues of chloramphenicol, including its three stereoisomers, did not show stimulation. The stimulation was present at plateau concentrations of colony-stimulating activity, suggesting that the stimulatory effect is not due to elaboration of excess colony-stimulating activity by chloramphenicol. We hypothesize that low concentrations of chloramphenicol stimulate CFU-GM by a highly specific interaction with adherent mononuclear cells and elaboration of an undefined growth factor.
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PMID:Stimulation of human committed bone marrow stem cells (CFU-GM) by chloramphenicol. 394 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

Colony forming unit (CFU) assays were developed for feline granulocyte-macrophage (CFUGM), early erythroid (day 2 CFUE), and late erythroid (day 7 CFUE) colonies in methylcellulose medium. Feline CFUGM and both day 2 and day 7 CFUE were enhanced by feline macrophage conditioned medium and late CFUE often were intimately associated with macrophages. Kittens were inoculated with the Kawakami-Theilen (KT) strain of feline leukemia virus (FeLV) and sequential changes in marrow CFU determined. Erythroid aplasia, characterized by progressive non-regenerative anemia, lymphopenia, and a profound decrease in early and late CFUE but not CFUGM was induced by 3 to 5 weeks after FeLV-KT inoculation. The susceptibility of kittens to FeVL-induced erythroid aplasia was strongly age-related; neonatal kittens were most sensitive and substantial natural resistance developed by 4 weeks of age. The results demonstrate that FeLV-KT infection induced a rapid and selective suppression of erythroid progenitor cells and represents a suitable model of experimentally-induced acquired erythroid aplasia.
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PMID:Feline leukemia virus-induced erythroid aplasia: in vitro hemopoietic culture studies. 627

Fibroblasts grown from the bone marrow of normal individuals and incubated with colony-stimulating factor (CSF) enhance the stimulating activity of this CSF on granulocyte-macrophage colony-forming cell (GM-CFC) proliferation. For this study, the ability of fibroblast monolayers grown from the marrows of six patients with severe aplastic anaemia to increase the activity of CSF has been compared with the activity of normal fibroblasts. Tests of this function showed subnormal CSF-enhancing activity by fibroblasts grown from the marrows of three of the six aplastic patients. Since cultured bone marrow fibroblasts are thought to represent an important component of the haemopoietic microenvironment, the results suggest that some of the patients had a microenvironmental abnormality at the time of study. One of the patients whose fibroblasts were abnormal was reinvestigated after he had been given a graft of allogeneic bone marrow cells. His post-graft fibroblast function was normal, showing that the abnormality was reversible.
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PMID:Bone marrow fibroblast function in relation to granulopoiesis in aplastic anaemia. 660 Jun 20


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