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)

The lack of a simple, rapid, and quantitative test of the functional activity of the monocyte has hampered studies of the contribution of this cell type to host defense and human disease. This report describes an assay of antibody-dependent cellular cytotoxicity, which depends exclusively upon the monocyte as the effector cell and therefore provides a convenient test of monocyte function. In this system, mononuclear leukocytes (MNL) obtained by Ficoll-Hypaque separation of whole blood are cytotoxic for 51Cr-labeled human erythrocyte targets coated with anti-blood group antibody. Removal of phagocytic monocytes from the MNL by iron ingestion, followed by exposure to a magnetic field, completely abolishes all cytotoxic activity from the remaining MNL population. Similarly, in severely mono-cytopenic patients with aplastic anemia, cytotoxic effector activity is absent. In normals and less severely monocytopenic aplastic anemia patients, cytotoxicity correlates significantly (p less than 0.001) with monocyte number. Application of this monocyte-mediated antibody-dependent cellular cytotoxicity assay to the study of patients with the Wiskott-Aldrich syndrome has revealed defective monocyte cytotoxic activity in spite of normal monocyte numbers, suggesting that this test may be useful for the assessment of monocyte function in a variety of clinical situations.
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PMID:Monocyte-mediated antibody-dependent cellular cytotoxicity: a clinical test of monocyte function. 100 82

Twelve patients with aplastic anaemia were studied with regard to the frequency of NK progenitors in the bone marrow (BM) to investigate the mechanism of depressed NK activity and low NK cell count in the peripheral blood. NK cell (CD16+ cell) count and NK (K562) activity were significantly decreased (P less than 0.02 and P less than 0.001, respectively) in the patients as compared to eight healthy control subjects. Nylon wool non-adherent (NW-NA) BM mononuclear cells (MNC) of each patient and control were prepared. Mature T and NK cells were extensively depleted by sheep red cell rosette formation followed by a centrifugation on Ficoll-Hypaque and monoclonal antibody mediated complement dependent cytolysis. Those selected BM cells were cultured in the presence of recombinant interleukin 2 (rIL2). Generation of NK activity was significantly decreased (P less than 0.01) in the patients with aplastic anaemia. Frequency of NK progenitors in the selected BM cells assayed by the limiting dilution method was significantly decreased in those patients (P less than 0.05). The frequency of BM NK progenitors relative to NW-NA BM cells were related to NK cell count (P less than 0.01). Those results indicate that depressed NK activity in aplastic anaemia is closely related to decreased NK cell count which is probably due to decreased production of NK cells in the BM.
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PMID:Decreased frequency of bone marrow NK progenitors in aplastic anaemia. 271 73

The effect of acute graft-versus host disease (GVHD) on T4 and T8 lymphocyte regulation of in vitro immunoglobulin production was explored. The peripheral blood lymphocytes from 20 patients were studied sequentially in the first 100 days after sibling bone marrow grafting for hematologic malignancy or aplastic anemia. T and non-T lymphocytes were prepared from peripheral blood by Ficoll-Hypaque density gradient centrifugation and sheep erythrocyte rosetting. T cells were enriched for T4 or T8 cells and cocultured for six days with pokeweed mitogen and autologous non-T or T and non-T cells from unrelated normal individuals. Immunoglobulin production was assessed using a reverse hemolytic plaque assay. All three patients without acute GVHD had failure of non-T cells to secrete immunoglobulin, one had failure of helper T cell activity, and 2 developed suppressor T cells. Similarly, all six patients studied sequentially after the development of GVHD had non-T-cell failure, five developed helper T cell failure, and five had suppressor T cells. These data suggest no difference in lymphocyte function before or after the development of acute GVHD. When the T cells of these patients were split into T4 and T8 subpopulations and studied for immunoglobulin production there was helper T cell failure in 4 of 9 tests with enriched T4 populations. Five of 9 tests with T8 enriched populations showed suppressor activity. Suppressor T cell function was also seen in 4 of 9 tests with with T4-enriched populations. These data show that T cell function does not necessarily correlate with the surface phenotype during the first 100 days after grafting. A role for cytomegalovirus (CMV) infection in bringing out suppressor activity is suggested, because among patients without GVHD, 6 of 8 tests in CMV-positive patients showed suppressor cells compared with none of 4 tests in patients without CMV infection.
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PMID:Regulation of immunoglobulin production after human marrow grafting. The role of helper and suppressor T cells in acute graft-versus-host disease. 293 88