Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone marrow transplantation using an HLA-MLC-identical sibling is the most valuable treatment of severe aplastic anemia.2,6,7 Between November 1973 and March 1977, 25 consecutive patients have been treated by marrow transplantation in our unit. Nine patients are alive with complete hematologic restoration between 3 months and 3 years. The high mortality can be largely accounted for by marrow graft rejection (14 patients). Despite the small number of patients, we have tried to identify prognostic factors associated with marrow graft rejection. They are mainly the existence of anti-HLA antibodies, the sex difference, and the normal PHA and MLC response before grafting. After the graft, the disappearance of anti-HLA antibodies has a good prognostic value. The appearance of autolymphocytotoxins seems to correlate strongly either with rejection or graft-versus-host disease.
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PMID:Allogeneic bone marrow transplantation in aplastic anemia--report of 25 cases. 34 52

In this study we have analyzed the activity of Cyclosporin A (CsA) on the "in vitro" production of TNF and IL-3/GM-CSF as a preliminary basis for explaining the successful use of CsA in aplastic patients. Thus, 73 T cell clones, obtained by a limiting dilution technique from the peripheral blood and bone marrow of 3 patients with severe aplastic anemia (SAA), were studied for TNF and IL-3/GM-CSF production as induced by stimulation with 1% PHA plus 1 ng/ml TPA. Lymphokines obtained in this manner were then tested by biological assays. Twelve out of the initial 73 T cell clones were selected for the production of a large quantity of IL-3/GM-CSF and/or TNF. With these clones we studied the ability of CsA to inhibit TNF and IL-3/GM-CSF production, which was stimulated with specific monoclonal antibodies directed against the CD2 and CD3 surface antigens. TNF and IL-3/GM-CSF production displayed a different sensitivity to CsA inhibition. In fact, at 400 ng/ml CsA a residual production of IL-3/GM-CSF was present in all clones tested (CD3: 21.8% and CD2: 14.4% of the maximal IL-3/GM-CSF activity), while secretion of TNF was virtually abrogated at 100 ng/ml. Moreover, the mean ID50 for TNF production was significantly lower than that of IL-3/GM-CSF (CD2: p = 0.028, CD3: p = 0.01). Using specific anti-IL-3 and anti-GM-CSF monoclonal antibodies, we showed that only GM-CSF, and not IL-3, was resistant to CsA inhibition. In conclusion, these results may represent a possible explanation of the successful use of CsA in the treatment of some patients with SAA.
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PMID:Effect of cyclosporin A on T cell clones from severe aplastic anemia: differential sensitivity of TNF and GM-CSF production. 142 30

The effect of recombinant alpha interferon (INF) and of antilymphocyte globulin (ALG) to the colony stimulating factor (CSF) production was examined with in vitro culture of the bone marrow of healthy and of aplastic anaemia (AA) persons. In healthy persons the supernatant of lymphocytes preincubated with PHA and ALG was found to show a stimulating effect to clonogenic properties of marrow progenitors, the mentioned effect being not in proportion to the concentration value. Similar properties are shown by interferon in these persons. In patients with aplastic anaemia, a considerable stimulating ALG effect to the granulocytic formation of colonies and a lesser stimulating effect of interferon were shown.
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PMID:Effect of recombinant human alpha interferon (INF) and antilymphocyte globulin (ALG) on normal and aplastic anaemia haematopoietic progenitor cell growth. 169 83

The activity of tumor necrosis factor-alpha (TNF-alpha) in the supernatant of cultured peripheral blood mononuclear cells (PBMC) was measured in patients with aplastic anemia. It was significantly higher in patients with aplastic anemia than in normal controls, both when PBMC were unstimulated or when they were stimulated with PHA. Results from aplastic anemia patients were also significantly higher than patients who had received allogeneic bone marrow transplants. In aplastic anemia patients, the TNF-alpha value produced by PBMC upon stimulation and the platelet count were inversely correlated, as well those patients who had high TNF-alpha values tended to have lower hemoglobin and leukocyte values although this was not significant statistically. These results suggest that the increased production of TNF-alpha by PBMC plays a role in the severe suppression of hematopoiesis in aplastic anemia.
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PMID:Increased production of tumor necrosis factor-alpha by peripheral blood mononuclear cells in the patients with aplastic anemia. 206 66

To evaluate the role of cytokines in patients with aplastic anemia, colony stimulating activities (CSA) and interferon-gamma (IFN-gamma) in cultured media of lymphocytes with phytohemagglutinin (PHA-LCM) were measured with methylcellulose culture method in 20 patients (age 3 to 69 years). The CSA for granulocyte/macrophage (GM-CSA) in patients was equivalent to that of normal donors, while low burst promoting activity (BPA) was observed in PHA-LCM from 7 adult patients (61 +/- 17%). The ability of BPA production varied widely in 13 children (97 +/- 37%). In some patients, low production of BPA improved after successful treatment of antilymphocyte globulin. The IFN-gamma in PHA-LCM disclosed no significant difference between patients and normal donors. From these results, low production of BPA may have a role in the development of AA in certain patients. It is also suggested that therapy with recombinant cytokines such as GM-CSF and IL-3, detected as BPA in our culture system, could be effective for those patients.
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PMID:[Effect of humoral factors produced by lymphocytes on hematopoietic progenitor cells--productive ability of colony stimulating activities and interferon-gamma by blood mononuclear cells in patients with aplastic anemia]. 211 75

The following immunological studies were performed in circulating mononuclear cells of 17 patients with severe aplastic anemia (SAA): a) lymphocytic phenotypes; b) proliferative response to PHA; c) determination of interleukin 2 (IL2) production and d) expression of Tac CD25. Fifteen of the seventeen patients showed altered CD4/CD8 regulatory populations, expressed as a significantly diminished CD4/CD8 ratio (0.72 +/- 0.19, NV: 1.8 +/- 0.6) (Table 1). The proliferative response to PHA was normal in 80% of the cases; only 2 of the patients showed a diminished response to the mitogen (Fig. 1). IL2 production by PHA-stimulated mononuclear cells was significantly increased (56.6 +/- 9.8; NV: 11 +/- 7.69) (Fig. 1), and a deficient expression to CD25 antigen was also recorded (Table 2). In the other two patients, we observed a normal CD4/CD8 ratio (Table 1, patients 1 and 2) with absence of proliferative response to PHA and hypo-production of IL2 (Fig. 1). These results suggest that in these two cases the hematopoietic defect could be associated to a primary deficiency of cellular immunity. Our results support the current concept of diversity of pathogenetic mechanisms implicated in SAA, and suggest that there are groups of patients with variable degrees of immunological defect that can be delineated through laboratory assays. On the other hand, the altered distribution of regulatory populations mostly due to an absolute decrease of the CD4 subpopulation, associated to the hyperproduction of IL2 and deficient expression of the Tac antigen in most of our patients, suggest the existence of functional alterations.
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PMID:[Changes in distribution of T subpopulations in the peripheral blood of patients with severe idiopathic anemia]. 213 Feb 43

We produced an antiserum by immunizing rabbits with purified human megakaryocyte colony stimulating factor (Meg-CSF). With the use of an anti-Meg-CSF IgG fraction (AM-IgG), we detected immunoreactive Meg-CSF both in human aplastic anemia serum (AAS) and normal serum. Based on our immunological and biological analyses, Meg-CSF appeared to be antigenically as well as functionally distinct from human urinary erythropoietin (EPO) and thrombopoietic stimulating factor. The AM-IgG fraction was able to suppress the ability of both aplastic anemia serum and purified Meg-CSF to promote megakaryocyte colony formation. In addition, the supernatant formed after immune precipitation of the AAS with AM-IgG no longer possessed Meg-CSF-like activity. The AM-IgG did not suppress the ability of EPO, phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM), or PHA-LCM + EPO to promote erythroid, granulocyte-macrophage, or mixed colony formation, respectively. The use of this antibody has further defined the dependency of human megakaryocytopoiesis on Meg-CSF.
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PMID:Studies of human megakaryocytopoiesis using an anti-megakaryocyte colony-stimulating factor antiserum. 308 83

Colony formation by megakaryocytic progenitors from the blood or bone marrow was studied in 22 patients with chronic myeloid leukemia (CML) and in 17 patients with idiopathic myelofibrosis (MF). Thirteen of the 22 CML patients showed megakaryocytic colony formation, when PHA-LCM and plasma of a patient with aplastic anemia were used as a source of colony stimulating activity. Twelve of these 13 patients also showed spontaneous megakaryocytic growth, i.e. colony formation when PHA-LCM was omitted and normal plasma was used instead of aplastic plasma. All the untreated CML patients exhibited both stimulated and spontaneous growth. Each patient without any megakaryocytic colony formation had recently received cytotoxic treatment. Thirteen of the 17 patients with MF grew megakaryocytic colonies and ten of these 13 patients also showed spontaneous megakaryocytic growth. The colony numbers were roughly similar in the stimulated and non-stimulated cultures. The present study shows that spontaneous megakaryocytic colony formation, previously shown to be common in PV and ET, is also seen in many patients with CML and MF.
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PMID:Megakaryocyte colony formation in chronic myeloid leukemia and myelofibrosis. 319 13

Recent studies suggest that megakaryocytopoiesis is governed by a dual-level regulatory process, with megakaryocyte colony-stimulating factor (Meg-CSF) primarily influencing proliferation of the committed precursors and thrombopoietin required for megakaryocyte ploidy amplification and for maturation. The authors have examined different sources of Meg-CSF in a microagar culture system with a view to their capacity to enhance megakaryocyte colony formation directly or via an indirect T-lymphocyte- or monocyte-mediated effect. The comparative influences of phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM), erythropoietin (Epo), sera of patients with severe aplastic anemia, and direct PHA addition to the culture were evaluated for their capacity to enhance megakaryocytic colony formation as well as for the maturation rate of megakaryocytes (Mk) grown in our microagar culture system. Each treatment by itself enhanced colony formation from unseparated low-density cells. Removal of T-lymphocytes and monocytes from the bone marrow sample caused a cessation of the enhancing effect of direct PHA addition to cultures stimulated with Epo, but did not influence the enhancing activities of severe aplastic anemia serum (SAA), PHA-LCM, and Epo. The results show that SAA serum, Epo, and PHA-LCM induced Mk colony formation directly and therefore may act via a common mechanism. Differences, however, were observed concerning their colony-stimulating potency and their influence on the Mk maturation rate.
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PMID:The role of erythropoietin, megakaryocyte colony-stimulating factor, and T-cell-derived factors on human megakaryocyte colony formation: evidence for T-cell-mediated and T-cell-independent stem cell proliferation. 349 18

We have postulated that the p-NO2 group of chloramphenicol (CAP) is the structural feature underlying aplastic anemia from this drug. In a series of studies to examine this hypothesis we have demonstrated the toxic nature of the CAP-reduction intermediate nitroso CAP (NO-CAP) and its damaging effect on isolated DNA in vitro. The present study was designed to examine the comparative effects of CAP, NO-CAP, and thiamphenicol (TAP) on the integrity of DNA in intact cells. By using the alkaline elution technique of Kohn, DNA damage in the form of single strand breaks could be readily demonstrated in cultured Raji cells and in PHA-stimulated normal human lymphocytes by small concentrations of NO-CAP (0.05-0.1 mM). A small but reproducible effect was observed from large concentrations of CAP (2 mM). In contrast, TAP, lacking the p-NO2 group, was without effect.
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PMID:DNA damage induced by chloramphenicol and its nitroso derivative: damage in intact cells. 379 96


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