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)

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

The nature, type and mechanism of action of various colony stimulating factors (CSFs) have been described. Among these CSFs, injection of the recombinant human granulocyte CSF (rhG-CSF) caused a marked increase in neutrophils in mice as well as in monkeys. The neutrophilia of injected mice were preceded by a marked increase of hematopoietic precursors in hematopoietic organs. Injection of monkeys with rh granulocyte-macrophage CSF (rhGM-CSF) also induced a marked increase in peripheral blood neutrophils as well as eosinophilia and monocytosis. Injection of recombinant mouse interleukin 3 (rmIL-3) caused a significant increase in peripheral blood eosinophils, neutrophils and lymphocytes. With rmIL-3, however, a remarkable increase was observed in various hematopoietic precursor cells in hematopoietic organs. Both G-CSF and GM-CSF were shown to shorten significantly the period of neutropenia after irradiation and autologous bone marrow transplantation in monkeys. rhG-CSF was demonstrated to accelerate the recovery from neutropenia induced in mice and monkeys by 5-fluorouracil or cyclophosphamide. Human urinary CSF (CSF-HU), which had been reported to stimulate monocyte-macrophage to produce G-CSF, was demonstrated to be effective in accelerating the recovery from neutropenia in patients with various kinds of gynecological and urological malignancies after chemotherapy for their cancers. It also accelerated the recovery from neutropenia after allogenic as well as autologous bone marrow transplantation. These results indicate that CSFs are very effective for the treatment of neutropenia after cancer chemotherapy and bone marrow transplantation.
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PMID:[Colony-stimulating factor]. 310 75

Cephalosporins are among the safest antibiotics. Nevertheless, hematologic abnormalities ranging from mono- to pancytopenia do occur, albeit infrequently, following their therapeutic use. Similar abnormalities to those reported in people have been seen in dogs given high doses of cephalosporins. As part of a study to define the latter thoroughly, we explored the effects of long-term, high-dose cephalosporin administration on canine marrow erythroid (CFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. Cefazedone (Refosporen, E. Merck, Darmstadt) was administered intravenously at doses of 540 to 840 mg/kg daily to 14 healthy beagle dogs for up to 4 months, or less if hematologic effects were evident earlier. Within 6 to 10 weeks, treated dogs developed pancytopenia (5/14), thrombocytopenia (11/14), moderate to severe neutropenia (8/14), and/or normocytic anemia (8/14). There was evidence of immune-mediated destruction of peripheral blood cells. All treated dogs exhibited a significant reduction in marrow colony-forming capacity, irrespective of whether peripheral cytopenia was present, with 12/14 showing decreased CFU-GM and 14/14 decreased CFU-E activity. Within a week following cessation of dosing, all affected dogs achieved hematologic remission as defined by restoration of the peripheral blood counts. However, despite this apparent recovery, both CFU-E and CFU-GM activities of the bone marrow remained depressed for at least another 8 months. We conclude that in dogs prolonged administration of high doses of cefazedone induced a persistent deficit of CFU-E and CFU-GM progenitor cells. The clinical relevance of this, if any, remains to be established.
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PMID:Cephalosporin-induced alterations in erythroid (CFU-E) and granulocyte-macrophage (CFU-GM) colony-forming capacity in canine bone marrow. 322 Feb 16

Clinical effects of purified human urinary colony-stimulating factor (CSFHU) were studied in nine patients with chronic neutropenia of childhood who ranged in age from 1 to 18 years. The patients were given CSFHU at a dose of 6 x 10(6) U/m2/d for seven consecutive days, and their peripheral neutrophil counts were serially followed for 6 to 12 months. In addition, changes in bone marrow morphology and granulocyte-macrophage colony-forming cells (GM-CFUs) were studied. Transient increases in neutrophil counts occurred during the first 4 weeks in all patients except one. Repeated increases were seen in a cyclic fashion in five patients. Three of the patients recovered from the neutropenia after several cycles of fluctuation of neutrophil counts; the counts (per microliter) reached 5,880, 5,640, and 2,000 as compared with pretreatment levels (mean +/- 2 SD) of 80 +/- 164, 182 +/- 250, and 2 +/- 14, respectively. The percentage (mean +/- SE) of marrow neutrophilic cells increased from 30.4% +/- 7.0% to 34.9% +/- 6.9% (P less than .05) and the ratio of the later neutrophil precursors to the earlier ones from 1.02 +/- 0.27 to 1.42 +/- 0.36 (P less than .02) 2 weeks after CSFHU infusion. There were no changes in GM-CFU numbers. These results indicate that CSFHU can increase neutrophil counts by increasing the number and maturity of the marrow neutrophil precursors in some types of childhood chronic neutropenia.
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PMID:Increases in neutrophil counts by purified human urinary colony-stimulating factor in chronic neutropenia of childhood. 325 46

The influence of IL-1 administration on the recovery of the hemopoietic and immune systems from sublethal irradiation was assessed. Mice were irradiated (750 R) and injected twice daily with purified recombinant derived IL-1 beta (200 ng/injection). At various times after irradiation, the functional capacity of the hemopoietic and immune systems was determined. It was found that IL-1 therapy resulted in a significantly greater number of granulocyte-macrophage-CSF responsive colony-forming cells in the bone marrow of the irradiated mice on days 5 and 11 postirradiation but not at later times. In addition the radiation induced neutropenia recovered quicker in the IL-1-treated mice with significantly greater numbers of peripheral blood granulocytes being seen on days 15 and 20 after irradiation. The influence of IL-1 therapy on the recovery of the immune system was also assessed. Of note was the observation that mice receiving IL-1 therapy had chronically hypoplastic thymi. Although thymic cellularity increased with time after irradiation in the control mice, there was no such increase in the IL-1-treated mice. Similarly, the number of pre-B cells in the marrow of these mice was also diminished. Thus, in the IL-1-treated mice the regeneration of the peripheral immune function was retarded, characterized by a general lymphopenia and decreased splenic responses to mitogenic stimuli.
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PMID:The influence of IL-1 treatment on the reconstitution of the hemopoietic and immune systems after sublethal radiation. 328 69

A limited number of cases of acquired hypoplastic neutropenia or pure white blood cell aplasia (PWCA) associated with thymoma have been reported, in contrast to the well-documented association of pure red blood cell aplasia and thymoma. The mechanism of the aplasia in these disorders is unclear. The authors report a case of PWCA (with total absence of all granulopoietic elements in the bone marrow) in a patient with metastatic spindle cell thymoma, in which suppression of autologous granulocyte-macrophage colony-forming units by the patient's serum could be demonstrated. This finding suggests a humoral autoimmune mechanism for the pathogenesis of PWCA in this patient and lends support to the possibility that all hematologic phenomena associated with thymoma may have an autoimmune basis.
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PMID:White blood cell aplasia associated with thymoma. 334 Dec 86

We observed a 24-month-old infant who developed anaemia, thrombocytopenia and neutropenia while recuperating from an extensive burn. In order to determine the mechanism(s) responsible for the pancytopenia, we quantified marrow-derived haematopoietic progenitor cells, assessed the relative proliferative rate of haematopoietic progenitor cells, and sought the presence of progenitor cell inhibitors. The concentration and relative proliferative rate of pluripotent progenitors (CFU-GEMM) were elevated. No inhibitors of progenitor cells were observed; in fact, the patient's serum contained very high levels of stimulatory activity for CFU-GEMM as well as for granulocyte-macrophage progenitors (CFU-GM). However, the marrow concentration of erythroid progenitors (BFU-E and CFU-E) was diminished. We conclude that the anaemia in this patient was the result of either hypoproduction of differentiated erythroid progenitors or intramyeloid destruction of early erythroid cells. In contrast, the neutropenia was likely to be due to accelerated neutrophil consumption at a rate that exceeded the capacity for increasing neutrophil production.
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PMID:Haematopoietic progenitor cells in an infant who developed pancytopenia following an extensive burn. 339 Jul 31

An association between eosinophilia and neutropenia has been observed in a number of clinical conditions. To probe the role of eosinophils in granulopoiesis, marrow and peritoneal eosinophils, obtained from Schistosoma mansoni-infected mice, were separated and purified. Normal bone marrow cells were cultured in semi-solid culture medium in concentrations ranging from 5 X 10(4) to 5 X 10(5), with and without added eosinophils. To examine whether high prostaglandin E (PGE) content of eosinophils affects granulopoiesis, indomethacin was added to duplicate marrow cultures containing eosinophils. The addition of eosinophils to normal syngeneic marrow culture caused a significant inhibition of granulocyte-macrophage colony formation (CFU-GM) in culture. This suppressive effect was reversible upon addition of indomethacin. These findings suggest that eosinophils, in vitro, are capable of inhibition of granulopoiesis. The reversal of this effect by indomethacin indicates that this suppression may be prostaglandin mediated.
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PMID:The role of eosinophil in regulation of granulopoiesis. 347 Feb 48

Suppression of hematopoiesis is far too often the main consequence of antineoplastic therapy, such that the developing degree of myelosuppression and/or thrombocytopenia are usually the rate-limiting steps to adjuvant therapy. This communication reports the results of studies designed to investigate the capability of lithium to accelerate in vivo hematopoietic recovery following exposure to vinblastine sulfate (VB). Male mice (144 BC3F1) received VB (4 mg/kg/b.w.) i.v. Twenty-four h following VB, 72 mice received 35 micrograms m/animal, ultra-pure lithium carbonate (Li2CO3) i.p. Another 72 mice received either VB or phosphate buffered saline as controls. Beginning 24 h later and continuing on days 2, 5, 7, 9, 12, 21 and 28, three mice from each group were randomly sacrificed and their hematological parameters analyzed. Bone marrow and splenic granulocyte-macrophage progenitor cells (CFU-gm) and megakaryocyte progenitor cells (CFU-meg) content were evaluated. Lithium was unable to prevent the onset of either neutropenia or thrombocytopenia; however, lithium was successful in restoring normal white blood cell and platelet values earlier than the VB control group, thus significantly reducing the period of drug-induced neutropenia and thrombocytopenia. This lithium-enhanced hematopoiesis was measured by an accelerated recovery in both marrow and splenic CFU-gm and CFU-meg compared to controls. These data demonstrate the efficacy of lithium to accelerate hematopoietic recovery following exposure to cytotoxic antineoplastic drugs.
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PMID:Lithium and hematopoietic toxicity. II. Acceleration in vivo of murine hematopoietic progenitor cells (CFU-gm and CFU-meg) following treatment with vinblastine sulfate. 357 50

Mitoxantrone (MIT) has recently been introduced into cancer therapy as a possible substitute for the structurally related drug, adriamycin (ADR), because it causes less cardiotoxicity and fewer gastrointestinal side effects. However, the dose-limiting toxicity of MIT is pronounced neutropenia. The in vitro hematoxicity of both drugs in granulocyte-macrophage precursor cells (GM-CFCs) was analyzed using drug-exposure schedules analogous to the principles of the in vivo pharmacokinetics of MIT. Bone-marrow and peripheral-blood cells were exposed to 0.075-20 ng/ml MIT or ADR for 5, 20, 60, and 120 min, and for 14 days. The 14-day exposure resulted in Do values of 0.95 and 0.68 ng/ml for bone-marrow and peripheral-blood GM-CFCs subjected to MIT. Exposure to ADR resulted in Do values of 5.43 and 5.13 ng/ml, respectively. As was the case after 14-day exposure to MIT or ADR, short-term exposure again revealed that peripheral-blood GM-CFCs were more sensitive to both drugs. Moreover, at low concentrations, ADR was less toxic than MIT in both types of GM-CFCs, but was more toxic than MIT when a concentration of 20 ng/ml was used. The intracellular concentration of MIT, as measured by high-performance liquid chromatography, was constantly below 1 ng per 2 X 10(7) cells, even when it was applied at a concentration of 20 ng/ml for an exposure time of 2 h. The fact that such low concentrations of MIT are toxic for hemopoietic precursor cells may explain the myelotoxicity of this drug. However, the difference between the precursor-cell toxicity of MIT and that of ADR was small when their respective therapeutic doses were taken into consideration. Further analyses of their toxicity in stem cells and/or the microenvironment would appear to be needed.
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PMID:Comparative in vitro toxicity of mitoxantrone and adriamycin in human granulocyte-macrophage progenitor cells. 362 56


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