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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colony stimulating factors (CSFs) are glycoprotein hormones that regulate growth and differentiation of hematopoietic progenitor cells. Their use to stimulate granulocyte precursors during periods of neutropenia in patients with acute myeloid leukemia (AML) is limited by their concomitant stimulation of the proliferation of myeloblasts. The effects of these agents on leukemic lymphoblasts is not entirely known. We have investigated the in vitro effects of granulocyte-CSF (G-CSF) and granulocyte/macrophage-CSF (GM-CSF) on leukemic cells from children with acute lymphoblastic leukemia (ALL). DNA synthesis of bone marrow cells from 22 children with ALL, either at diagnosis or in relapse, was examined with and without CSFs. Proliferative potential was also tested in a clonogenic assay with 13 bone marrow specimens. These factors did not stimulate the growth of ALL cells in either assay. Our results indicate that G-CSF and GM-CSF should be able to stimulate granulocyte proliferation without enhancing leukemic proliferation during periods of neutropenia in children with ALL.
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PMID:The effect of recombinant GM-CSF and G-CSF on the bone marrow cells of children with acute lymphoblastic leukemia. 127 25

A 23-year-old woman experienced six distinct episodes of severe combined neutropenia and thrombocytopenia. At least one of the episodes was accompanied by hemodialysis-requiring acute renal failure and fragmentation hemolysis (hemolytic uremic syndrome [HUS]). In retrospect, all episodes were probably associated with the ingestion of quinine. Quinine-dependent antibodies to platelets, neutrophils, T lymphocytes, and red blood cells (RBCs) were detected in the patient's serum. By a monoclonal antibody antigen capture assay, the patient's serum contained IgG antibodies, which in the presence, but not absence, of quinine reacted with platelet glycoprotein (GP) complexes Ib/IX and IIb/IIIa, but not Ia/IIa. By immunoprecipitation assay, the serum, after addition of quinine, reacted strongly with an 85-Kd neutrophil membrane protein and weakly with 130- and 60-Kd moieties. Serum adsorbed with RBCs in the presence of quinine continued to react with platelets and neutrophils, and serum that was absorbed with platelets continued to react with neutrophils and RBCs, indicating that the antigenic targets were different on platelets, neutrophils, and RBCs. Since platelets and endothelial cells share some antigens, we tested patient serum for antibodies to human umbilical vein endothelial cells (HUVEC); no quinine-dependent antibodies to HUVEC were detected. However, her quinine-dependent antibodies not only bound to platelets and neutrophils, but also activated neutrophils. Thus, the patient's serum with quinine aggregated neutrophils, but neither agent alone caused activation. Moreover, the patient's serum with quinine (but not without) augmented the adherence of neutrophils to HUVEC. Treatment of the patient's serum with staphylococcal protein A removed the quinine neutrophil aggregation cofactor, suggesting it was due to IgG. In both neutrophil aggregation and adherence assays, decomplementation of the patient's serum markedly blunted its effect. Furthermore, the patient's serum failed to aggregate formalin-inactivated neutrophils, suggesting neutrophil activation, probably by activated complement, was necessary for aggregation and adhesivity to endothelium. We conclude that our patient's neutropenia, thrombocytopenia, lymphopenia, and anemia were due to quinine-dependent antibodies, and that these antibodies recognized epitopes that were different in the three target cell populations. We further suggest that HUS was likely secondary to the activation and adhesion of neutrophils to endothelium.
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PMID:Characterization of multiple quinine-dependent antibodies in a patient with episodic hemolytic uremic syndrome and immune agranulocytosis. 161 Oct 88

Recombinant granulocyte colony-stimulating factor (rG-CSF) is a glycoprotein hormone which has been produced in mammalian cells and, in a nonglycosylated form, in the bacterium Escherichia coli through recombinant DNA technology. It stimulates proliferation, differentiation and activation of cells of the neutrophil-granulocyte lineage and has been investigated as therapy for patients with various neutropenic conditions, both iatrogenic and disease related. rG-CSF is well tolerated, the most frequently reported adverse effect being mild to moderate bone pain. A major use for rG-CSF therapy will be in ameliorating the neutropenia which follows cytoreductive chemotherapy. rG-CSF accelerates neutrophil recovery after chemotherapy, leading to a reduction in duration of the neutropenic phase. Consequently, infection rate is diminished, as is the associated usage of antibiotics and duration of hospitalisation. The implications are that rG-CSF may allow increased dose intensity and stricter adherence to chemotherapy schedules. The increase in neutrophils produced by rG-CSF renders it a useful treatment for conditions such as congenital, acquired and cyclic neutropenias for which current therapy is not very successful. rG-CSF may be an effective therapy in myelodysplasia, although there is concern about acceleration of the possible rate of conversion of this disease to acute myelogenous leukaemia. It is also likely that rG-CSF will be useful in accelerating the recovery of transplanted bone marrow in patients with leukaemia, lymphoma and solid tumour. Furthermore, there is great potential for expansion of the role of rG-CSF as monotherapy or in combination regimens with other cell factors in various haematological disorders such as aplastic anaemia. In summary, while many aspects of its use remain to be clarified, rG-CSF must be seen as an exciting advance in therapeutics. It should rapidly find an important place as an adjunct to cancer chemotherapy, and also appears to have substantial potential in a number of other neutropenic conditions which are currently difficult to treat.
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PMID:Recombinant granulocyte colony-stimulating factor (rG-CSF). A review of its pharmacological properties and prospective role in neutropenic conditions. 171 26

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein of Mr of about 20,000, which stimulates proliferation and differentiation of progenitor cells of neutrophils. Recent clinical application of G-CSF has proven that this hormone is effective in treatment of patients suffering from neutropenia. In the last few years, the biochemical and molecular nature of the G-CSF receptor has been characterized. The G-CSF receptor is a glycoprotein of Mr 100-130,000, and is expressed on the cell surface of various myeloid cells. A homodimer of this polypeptide can bind G-CSF with a high affinity, and transduce G-CSF-triggered growth signals into cells. Its extracellular domain contains a sequence of about 200 amino acids which can be found in various cytokine receptors. In addition, it contains an immunoglobulin-like domain and three fibronectin type III domains. The overall structure of the beta-chain (gp130) of the interleukin 6 receptor was found to be very similar to that of the G-CSF receptor.
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PMID:Granulocyte colony-stimulating factor and its receptor. 172 14

Antibodies to the neutrophil-specific antigens NA1 and NA2 are associated with alloimmune neonatal neutropenia (ANN), autoimmune neutropenia of childhood, and acute pulmonary transfusion reactions. These antigens have been found to be located on the neutrophil Fc-gamma receptor III (FcRIII). The mother of a child with ANN was found to lack both NA antigens and to produce an antibody that reacted with all normal neutrophils tested. We used maternal antibody and a CD16 monoclonal antibody (MoAb) that has specificity for FcRIII to immunoblot and immunoprecipitate neutrophil membranes of various NA phenotypes. Both antibodies immunoblotted an approximately 40- to 70-Kd glycoprotein (GP) on NA1, NA2-positive membrane, an approximately 40- to 55-Kd GP on NA1-homozygous membranes, and an approximately 55- to 70-Kd GP on NA2-homozygous membranes. Both antibodies also immunoprecipitated a 50- to 80-Kd GP from NA1, NA2-positive cells, a 50- to 60-Kd GP from NA1-homozygous cells, and a 55- to 80-Kd GP from NA2-homozygous cells. To further examine the specificity of the maternal antibody, sequential immunoprecipitation studies were performed using maternal antisera and a CD16 MoAb. After extracts of 125I surface-labeled neutrophils were precleared with maternal serum, CD16 MoAbs no longer immunoprecipitated any GP. Neither the CD16 MoAb nor a rabbit polyclonal antibody specific for FcRIII detected any GP in maternal neutrophil membranes by immunoblotting. Neutrophil FcRIII is a glycosyl-phosphatidylinositol anchored membrane GP as is decay accelerating factor and both are absent from neutrophils of patients with paroxysmal nocturnal hemoglobinuria (PNH). Maternal neutrophil membranes were probed with antibody specific for DAF and an 80-Kd GP was detected. This woman also has had no clinical evidence of PNH. These studies provide further evidence that the NA1 and NA2 antigens are on FcRIII and identify a healthy person whose neutrophils lack not only the neutrophil specific antigens NA1 and NA2 but multiple other epitopes of FcRIII and, therefore, likely lack FcRIII entirely.
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PMID:Alloimmune neonatal neutropenia due to an antibody to the neutrophil Fc-gamma receptor III with maternal deficiency of CD16 antigen. 182 24

The paraneoplastic syndrome (PNS) is an association of symptoms and signs not directly related to the site or local manifestations of a malignant tumor or its metastases. Hematologic abnormalities as PNS include erythrocytosis, anemia, neutrophilia, neutropenia, eosinophilia, thrombocytosis, thrombocytopenia, venous thromboembolism and disseminated intravascular coagulation (DIC). These abnormalities are, by and large, due to the production of biologically active growth factors, hormones or as yet unidentified "humors" by the tumor. As our understanding of growth factors controlling hematopoiesis has increased in recent years, the biologic basis of hematologic PNS are better understood. For instance, tumor-associated neutrophilia is now known to be caused by the production of G-CSF by the tumor. The mechanism by which tumor causes thromboembolism have also been extensively investigated. Cancer cells induce platelet aggregation both in vitro and in vivo. Platelet aggregating material has been isolated and partially characterized from tumor cells. The involvement of platelet glycoprotein II b/IIIa in the tumor-platelet interaction has also been shown. Malignant cells contain a unique procoagulant, cancer procoagulant A, that directly activates factor X. Together with tissue factor, this procoagulant appears to have been contribute to a high incidence of thromboembolism in cancer patients. Better understanding of hematologic PNS is important for clinical care of the patients with cancer.
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PMID:[Paraneoplastic syndrome hematologic abnormalities]. 200 36

The colony-stimulating factors (CSF) are a class of glycoprotein hormones that regulate the production and function of blood cells. Human sequences encoding four of the factors active on myeloid cells--granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin-3 (IL-3)--have been molecularly cloned and the biosynthetic (recombinant) products introduced into clinical trials. Sufficient clinical data have accumulated regarding G-CSF and GM-CSF to allow insight into their potential use in clinical practice. Both molecules have shown some impact in the prevention of chemotherapy-induced neutropenia and in the treatment of cytopenias associated with myelodysplastic syndromes and aplastic anemia. G-CSF has shown promise in the treatment of congenital and idiopathic neutropenias.
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PMID:The colony-stimulating factors: biology and clinical use. 214 19

Neutrophil-specific alloantibodies and the antigens they recognize are important in clinical medicine, but little is known about the structure of these antigens. Alloimmunization to the antigen NB1 is a clinically important cause of neonatal neutropenia and febrile transfusion reactions. To study the immunochemistry of the NB1 antigen, we prepared neutrophil plasma membranes and granules by nitrogen cavitation and differential centrifugation and then analyzed them by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting with alloantibodies to several neutrophil-specific antigens. Two different antisera to the neutrophil-specific antigen NB1 identified an approximately 55-Kd protein by immunoblotting on neutrophil membranes from four NB1-positive donors but not on neutrophil membranes from five NB1-negative donors. Four anti-NB1 antisera immunoprecipitated a 58- to 64-Kd protein from extracts of NB1-positive neutrophils surface-labeled with 125I using lactoperoxidase, but not from similarly treated NB1-negative neutrophils. Normal human serum did not immunoprecipitate or immunoblot any proteins from these same neutrophil preparations. The NB1 antigen was detected by immunoblotting in secondary granules but was not found in primary granules. The electrophoretic mobility of the antigen was decreased slightly by reduction, suggesting that intrachain disulfide bonds were present. After reduction, the antigen could no longer be recognized by anti-NB1 antisera, but treatment of the antigen with periodate had no effect on the ability of anti-NB1 antisera to recognize the antigen, suggesting that it is not a carbohydrate. The data suggest that the neutrophil-specific antigen NB1 is present on a 58- to 64-Kd surface glycoprotein that is also present in secondary granules, and that the NB1 epitope is not a carbohydrate but probably resides in the tertiary structure of the protein backbone.
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PMID:Biochemical characterization of the neutrophil-specific antigen NB1. 215 25

Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered to 10 patients with refractory malignancies, 2 patients who had myelodysplastic syndromes with severe neutropenia and to a patient who had delayed marrow recovery after 3 cycles of therapy for acute leukemia. A marked neutropenia and monocytopenia was observed within 5 min after an i.v. injection of GM-CSF. This persisted for 1-2 h and seemed related to activation of an adhesive glycoprotein (MO1) on the surface of these cells. With continued daily i.v. administration of GM-CSF, all patients with refractory malignancies developed a striking leukocytosis. Total leukocyte counts reached 75,000/microliters within 2 weeks of treatment. This was due to an increase in band and segmented neutrophils, eosinophils and monocytes. Accelerated myelopoiesis required the continuous presence of GM-CSF; with pump failure for 24 h or discontinuation after 14 days, leukocyte counts returned to normal levels in 24-48 h. GM-CSF also increased myelopoiesis in the patients with myelodysplastic syndromes or following anti-leukemic treatment. These observations suggest that this growth factor should prove a useful adjunct in the treatment of patients with malignancies and bone marrow failure.
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PMID:Use of granulocyte-macrophage colony-stimulating factor in patients with malignancy and bone marrow failure. 218 42

Human monocytic colony-stimulating factor (hM-CSF) is a glycoprotein which stimulates monocyte production in the bone marrow. It enhances CSF (such as G- and GM-CSF) production of monocytes and megakaryocyte-potentiating activity (Meg-POT). It also enhances tumor-killing activity of monocytes against several leukemic cell lines such as K562, U937, HL60 and Daudi. In the clinical studies, it was shown that hM-CSF infusions accelerated the recovery from neutropenia as well as thrombopenia after anticancer chemotherapy against hematological, gynecologic and urogenital malignancies. Human M-CSF infusions were tolerable without any serious side effects. It is reported that infusions of G-CSF and GM-CSF cause the increment of leukemic cell counts in some cases, but hM-CSF infusions did not increase leukemic cell counts. These results indicate that hM-CSF may be potentially useful for the treatment of myelosuppression induced by cancer chemotherapy in cancer patients.
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PMID:[Human monocytic colony-stimulating factor]. 268 18


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