Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was the specific aim of this study to test the stimulatory effects of recombinant human GM-CSF (rhGM-CSF) on haemopoietic regeneration in dogs which had received total-body irradiation (TBI) with a dose of 2.4 Gy. In normal dogs rhGM-CSF given subcutaneously at 10 microgram/kg per day or 30 microgram/kg per day for 21 days caused strong but transient increases in the peripheral blood neutrophils. The monocyte counts also showed a transient rise during treatment in a dose-dependent fashion, whereas the lymphocyte counts increased only at the higher dose of rhGM-CSF and the platelet counts were transiently depressed during the course of the treatment. In the irradiated animals treatment with rhGM-CSF decreased the severity and shortened the duration of neutropenia but had no significant influence on monocyte or lymphocyte recovery. The granulocyte values showed a characteristic pattern of fluctuations with the first peak occurring at the same time (day 10 to day 13) when the abortive rise was observed in the untreated dogs. In contrast the GM-CFC in the peripheral blood remained depressed during the whole treatment course, similar to the untreated irradiated controls. These results indicate that treatment with GM-CSF can be an effective biological monotherapy for radiation-induced bone marrow failure, but that for higher radiation doses the number of GM-CSF responsive target cells will become a critical determinant of therapeutic efficacy.
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PMID:Haematological effects of rhGM-CSF in dogs exposed to total-body irradiation with a dose of 2.4 Gy. 134 34

The short biologic half-life of the peripheral neutrophil (PMN) requires an active granulopoietic response to replenish functional PMNs and to maintain a competent host defence in irradiated animals. Recombinant human G-CSF (rhG-CSF) was studied for its ability to modulate haemopoiesis in normal dogs as well as to decrease therapeutically the severity and duration of neutropenia in sublethally and lethally irradiated dogs. For the normal dog, subcutaneous administration of rhG-CSF induced neutrophilia within hours after the first injection; total PMNs continued to increase (with plateau phases) to mean peak values of 1000 per cent of baseline at the end of the treatment period (12-14 days). Bone-marrow-derived granulocyte-macrophage colony-forming cells (GM-CFC) increased significantly during treatment. For a sublethal 200 cGy dose, treatment with rhG-CSF for 14 consecutive days decreased the severity and shortened the duration of neutropenia and thrombocytopenia. The radiation-induced lethality of 60 per cent after a dose of 350 cGy was associated with marrow-derived GM-CFC survival of 1 per cent. Treatment with rhG-CSF markedly reduced the lethality associated with exposure to 350 cGy of radiation to zero. White blood cell (WBC) and platelet recovery kinetics were correlated with degree of marrow damage. The rhG-CSF reduced the severity and duration of neutropenia. Control animals required antibiotic therapy (WBC less than 1000 mm3) for a total of 16 days versus 3 days for rhG-CSF-treated dogs. The duration of thrombocytopenia was reduced, although the severity of depletion was unchanged with treatment. These data indicate that in the lethally irradiated dog, effective cytokine therapy with rhG-CSF will increase survival through the induction of earlier recovery of neutrophils and platelets.
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PMID:Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sublethal and lethal whole-body irradiation. 169 Dec 55

The content of hemopoietic and stromal precursor-cells was studied in the bone marrow of 46 children with congenital neutropenia and of 2 children with chronic benign neutropenia. It was found that the number of GM-CFC and F-CFC in the bone marrow of patients with chronic benign neutropenia did not differ from that in the control group of normal children, and the lowering of the neutrophil number in the blood was, probably, associated with their redistribution mechanism or increased destruction in the body. Multiple defects of hemopoietic and stromal tissue were detected in children with a hereditary form of congenital neutropenia when anomalous proliferation of F-CFC and disorders in GM-CFC differentiation led to hypoplasia of granulocytic growth stem and neutropenia.
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PMID:[Evaluation of hematopoietic and stromal cells-precursors in children with neutropenia]. 206 51

Colony stimulating activity (CSA) and granulocyte-macrophage progenitor cells (GM-CFC) were assayed in the bone marrow and peripheral blood of 17 patients with drug-induced chronic neutropenia. Leukocyte-derived and monocyte/macrophage-derived CSA from the neutropenic patients was found to be significantly decreased compared to normal control. However, bone marrow and peripheral blood GM-CFC were within normal limits. These data suggest that in neutropenic patients monocyte/macrophages exhibit most likely a qualitative defect in CSA production, which may account at least in part, for the impaired granulopoiesis observed in drug-induced neutropenia.
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PMID:Defective CSA-dependent granulopoiesis in patients with chronic drug-induced neutropenia. 227 34

A physiologic role for lactoferrin (Lf) has been implicated by (1) its antibacterial effect and (2) its involvement as a negative-feedback regulator for colony stimulating factor (CSF) and, therefore, granulocyte production. The isolation and purification of endotoxin-free, species-specific mouse and human Lf have enabled a study of the role of Lf both in vitro and in vivo. Injection of Salmonella typhimurium or LPS into mice resulted in a dose-dependent increase in plasma Lf. Treating normal and neutropenic mice with LPS showed that the plasma Lf level was directly related to the number of granulocytes found in the peripheral blood. The effect of neutropenia did not inhibit release of Lf. By incubating mouse bone marrow and adherent peritoneal cells with 0.1 microM mouse or human Lf in the absence or presence of the prostaglandin synthesis inhibitor, indomethacin (1.0 microM), no evidence could be obtained in support of a negative-feedback regulation of CSF. In fact, rather than an inhibition of CSF, the production of the latter was found to be stimulated from both cell types. Injection of endotoxin-free, mouse Lf (2 mg/animal) into mice at concentrations in the same order of magnitude as that found during bacterial infection, resulted in an increase in CSF production by 12 hours and prior to the increase in bone marrow granulocyte-macrophage progenitor cells (GM-CFC) at 48 hours. The results do not support a negative-feedback regulation of CSF by macrophages. Instead, they can be incorporated into a "demand signal" model for CSF production by macrophages.
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PMID:Lactoferrin stimulates colony stimulating factor production in vitro and in vivo. 267 3

Two siblings with congenital neutropenia are reported. The first patient, female, died after Pseudomonas sepsis. The second patient male, suffered from recurrent pyogenic infections, with a more benign course. Bone Marrow (BM) and Peripheral Blood (PB) analysis in the second patient revealed a reduced number of granules and myelin bodies in the PB neutrophils, suggesting a developmental defect of primary and secondary granules. BM promyelocytes were almost normal, but the myelocytes and metamyelocytes showed defective granulogenesis. The BM in vitro granulocyte-macrophage-colony-forming cell (GM-CFC) growth and the PB white blood cells (WBC) granulocyte-macrophage-colony-stimulating factor (GM-CSF) production, which were analyzed in the second patient, showed normal numbers of GM-CFC, with differentiation mostly toward monocytes and a defect in the GM-CSF production capacity. The second patient's PB mononuclear cells or serum did not inhibit normal GM-CFC when added to control BM cells. We suggest that in this specific form of congenital neutropenia, which is probably an autosomal recessive disorder, the abnormal neutrophil granule production and the defective provision of GM-CSF by PB WBC are unique pathognomonic characteristics, possibly associated with the overt neutropenia.
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PMID:Congenital dysgranulopoietic neutropenia in two siblings: clinical, ultrastructural, and in vitro bone marrow culture studies. 270 1

An infant with Down's syndrome developed severe persistent neutropenia at the age of 9 months and fluctuating anemia and thrombocytopenia at one year of age which terminated as full-blown aplastic anemia at 26 months of age. Immunological evaluation revealed increased peripheral and bone marrow lymphocytes and impaired blood OKT4: OKT8 ratio. Bone marrow granulocyte-macrophage colony forming cells (GM-CFC) were markedly increased, while peripheral blood mononuclear cells (PBMN) produced normal numbers of colonies. The patient's PBMN and serum were both somewhat inhibitory to normal bone marrow derived GM-CFC, suggesting the existence of a suppressor activity both in his serum and PBMN. This unusual course of aplastic anemia and the abnormalities in T-cells and hematopoiesis in Down's syndrome are discussed.
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PMID:Fatal aplastic anemia in a child with Down's syndrome. 295 35

We have previously shown that disulfiram (DSF) blocks the urotoxicity of cyclophosphamide (CYT) in mice and increases the oncolytic effect of CYT in the L1210 murine leukemia. However, mice treated with CYT and DSF appeared to have longer-lasting neutropenia than animals treated with CYT alone. To determine whether DSF uroprotection of CYT-treated mice was associated with increased myeloid toxicity, we examined the effects of DSF plus CYT treatment on the bone marrow granulocyte/macrophage progenitor cell (GM-CFC). Marrow cellularity and GM-CFC numbers were analyzed at 1, 2 and 3 days after injection of CYT (62.5 or 125 mg/kg) or CYT plus DSF (200 mg/kg). CYT alone caused a decrease in total marrow cellularity varying from 20% to 50% of control. Animals given CYT plus DSF had a somewhat greater decrease in total marrow cellularity than those treated with CYT alone. However, in mice treated with CYT plus DSF, the GM-CFC were relatively well preserved and the recovery of the GM-CFC was not prolonged by DSF. It appears from these studies that the acute toxic effect of CYT on the granulocyte/macrophage progenitor cells is not enhanced by DSF.
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PMID:The effect of disulfiram on cyclophosphamide-mediated myeloid toxicity. 394 1

A child treated for NHL developed acute non-lymphoblastic leukaemia 27 months after stopping treatment. Serial in vitro bone marrow studies showed a normal incidence of GM-CFC following treatment. However, GM-CFC incidence dropped at least 15 months prior to the development of leukaemia. This was associated with an asymptomatic neutropenia but no disturbance of bone marrow morphology. It is concluded that sub-clinical disturbances of bone marrow function may play an important part in leukaemogenesis.
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PMID:Serial incidence of bone marrow GM-CFC prior to the development of acute non-lymphoblastic leukaemia in a child treated for non-Hodgkin's lymphoma. 397 Aug 53

An assessment of the numbers of myeloid precursor cells in human bone marrow, obtainable earlier than with conventional colony assays, would be useful for many reasons. Recently an isotopic assay for murine-colony-stimulating activity has been devised and we have modified this technique for use in man. Bone marrow mononuclear cells are incubated in microtitre plates in the presence of optimal amounts of placental-conditioned medium, pulsed with 3H-galactose for 24 h and the isotope incorporation measured. Isotope uptake by normal bone marrow was found to be proportional to both the number of cells cultured and the amount of conditioned medium added. The cells responsible for isotope incorporation have been characterized partially and found to be nonadherent immature myeloid cells and have a density of less than 1.077. This short-term isotopic assay was also compared to the GM-CFC assay in ten normals and in 24 patients with either neutropenia (of different etiology), myeloid leukemias, or neutrophil leukocytosis. There was good correlation between the two assays in all the patients studied. Thus, our observations suggest that the cell incorporating 3H-galactose in response to conditioned medium has many of the properties of the GM-CFC and its immediate progeny. Although assay specificity has yet to be proven, our early results indicate that it may have use as a rapid, but indirect, assessment of human myeloid precursor cells and thus prove to be a useful adjunct to the standard hematological methods of assessment of certain patients.
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PMID:A short-term assay of myeloid precursor cells in man. 674 32


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