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)

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

Nine anesthetized pigs were subjected to short (90 min) sham dialysis with blood membrane contact with the aim to select effects of the artificial surface during dialysis. The importance of the neutrophil (PMN) was investigated by the selective isotope labelling, dynamically followed by gamma-camera imaging and biochemical assays specifically oriented for PMN function. These assays included cell count, PMN aggregation, PMN luminescence, fibronectin and catalase activity. Additionally, pulmonary and systemic hemodynamics and acid base balance were monitored. Sham dialysis induced an accumulation of labelled PMN attaining a maximum between 15 and 17 min. This was coupled with a time-related neutropenia, pulmonary vasoconstriction, increased in vitro PMN aggregation and luminescence response. The neutrophil response abated by the end of dialysis. Cardiac output and arterial blood pressure declined to a steady level after 30 min of sham dialysis. There was an insignificant decrease in catalase activity. All other parameters remained unaltered. The results indicate that PMN accumulates in the pulmonary vessels, in association with neutropenia and activation. The transience of the event points to a protective mechanisms of humoral and/or cellular character.
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PMID:Dynamic pulmonary accumulation of labelled neutrophils by blood membrane contact in the pig. 223 54

Interleukin 1 (IL-1) is an important regulator of immune system function. IL 1 also affects haematopoiesis in vitro: it causes release of colony stimulating factors from fibroblasts and endothelial cells and can directly act on primitive haematopoietic stem cells. We investigated IL 1 production in vitro by stimulated peripheral blood mononuclear cells of patients with aplastic anaemia (N = 17), patients with other haematologic diseases (N = 27), and normal individuals (N = 22) using a bioassay for IL 1 activity. Ten aplastic patients showed markedly decreased IL 1 production. IL 1 production by fibronectin-affinity purified monocytes was decreased in six of seven of these patients; in three other cases, in which IL 1 mononuclear cell production was undetectable, sufficient monocytes could not be isolated. IL 1 alpha and IL 1 beta precursor molecules were also absent or much decreased when mononuclear cell lysates from these patients were analysed by immunoblot using specific polyclonal sera. Aplastic patients with low IL 1 production were distinguished by the severity of their disease and the degree of neutropenia. Patients with myelodysplasia with comparable degrees of pancytopenia had normal IL 1 production. This is the first example of deficient haematopoietic growth factor production in a bone marrow failure syndrome. Decreased IL 1 production may contribute to the pathogenesis of some cases of aplastic anaemia and to susceptibility to infection.
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PMID:Decreased interleukin 1 production in aplastic anaemia. 278 89

This chapter has reviewed the deficiencies in immune defense that place the neonate, particularly the premature infant, at increased risk of invasive bacterial disease. We also have reviewed the literature on the rationale for exchange transfusion, granulocyte transfusion, intravenous immunoglobulin, and fibronectin administration as immunotherapeutic agents in infected infants. There have been no randomized controlled trials of exchange transfusion, immunoglobulin, or fibronectin administration in human infants with infection. Granulocyte transfusion in the infected newborn infant has been studied in a controlled fashion, but the results of clinical trials are conflicting. Thus, all of these interventions appear to need further evaluation. We therefore recommend that in the septic newborn infant with neutropenia and an I/T ratio greater than or equal to 0.8, who fails to demonstrate a favorable response to conventional antibacterial chemotherapy and cardiopulmonary support, the administration of approximately 1 X 10(9) irradiated granulocytes per kg may be beneficial. In the absence of equipment to isolate the granulocytes, a double-volume exchange transfusion with fresh heparinized whole blood will provide a similar quantity of functional phagocytes.
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PMID:Immunotherapy of neonatal septicemia. 352 Apr 60

Plasma fibronectin is regarded to play an important part in a decrease of the resistance to infections. To specify the role of fibronectin in the pathogenesis of infectious complications in patients with depressions of hemopoiesis, the content of this opsonin was measured by ELISA in 113 patients with different patterns of hemoblastoses, lymphoproliferative diseases and with an aplastic syndrome. In 42 patients, the concentration of opsonin was measured in the presence of the superimposed infection of varying gravity. The fibronectin content was examined in 39 patients before, during and after completion of the cytostatic polychemotherapy. It turned out that in patients with paraproteinemic hemoblastoses, lymphogranulomatosis, aplastic anemia, chronic lympholeukemia, acute lympho- and myelo(mono)blastic leukemias, cyclic neutropenia, chronic myelosis and hematosarcomas, the concentration of fibronectin remained normal in the absence of infections. The computation of the linear correlation ratio did not reveal any association between the opsonin level and the concentration of neoplastic elements in the peripheral blood. Repeated measurements of the fibronectin level in patients whose underlying disease ran its course in association with marked neoplastic fever failed to detect any deficiency of the glycoprotein. The lowering of the fibronectin level was recorded in patients with a grave concomitant infection of the type of sepsis, necrotic enteropathy and lobar pneumonia. The degree of opsonin deficiency correlated with the patients' disease gravity. Prolonged reduction in the blood fibronectin level was of unfavourable prognostic importance. Cytostatic polychemotherapy, myelotoxic agranulocytosis as well as infectious complications of low gravity did not influence the concentration of fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Plasma fibronectin level in patients with depression of hematopoiesis]. 404 64

The reticuloendothelial system (RES) is thought to ensure organ integrity following trauma, burn, and sepsis by removing potentially embolic particulate matter and blood-borne bacteria from the circulation. Blockade of the RES with foreign colloids is known to result in a consumptive depletion of opsonic fibronectin, which modulates reticuloendothelial function, and an increase in lung localization of test particles. We investigated the role of neutrophils as a contributing factor in the increased localization of blood-borne bacteria in the lung after blockade. RE blockade induced by gelatin-coated colloid particle injection resulted in an acute (15-minute) increase in the number of 51Cr-labeled neutrophils localized in the lung, with return to control levels at 60 minutes after blockade. Fibronectin administration following blockade resulted in a significant (P less than 0.05) prolonged retention of neutrophils in the lung up to 2 hours after blockade. A parallel increase (P less than 0.05) in lung localization of heat-killed 14C-labeled Pseudomonas aeruginosa following colloid-induced RE blockade was observed, and fibronectin further increased the number of bacteria localized in the lung. Experimentally induced neutropenia abrogated the effect of colloid injection on lung localization of bacteria. It is concluded that a particulate load results in simultaneous RE blockade and neutrophil margination in the lung, both of which contribute to the increase in lung localization of bacteria. A mechanism for neutrophil-mediated pulmonary injury related to RE dysfunction following trauma is proposed.
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PMID:Neutrophil-mediated lung localization of bacteria: a mechanism for pulmonary injury. 679 Dec 89

In acute leukaemia, low plasma fibronectin was seen at diagnosis and when the disease relapsed. This was not directly related to tumour load, chemotherapy or neutropenia, but correlated well with episodes of intercurrent infection. In severe infections, fibronectin fell rapidly to very low levels, and was sometimes not restored to normal up to 2 weeks later. Preliminary attempts at replacement therapy were successful and the possible importance of this is discussed.
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PMID:Plasma fibronectin in acute leukaemia. 695 72

The cellular and molecular mechanisms responsible for hematopoietic progenitor cell (HPC) mobilization from bone marrow (BM) into peripheral blood after administration of cytokines such as granulocyte colony-stimulating factor (G-CSF) are still unknown. In this study we show that high concentrations of soluble calcium induce the detachment of BM CD34(+) HPC adherent on fibronectin, a major component of BM extracellular matrix. Because G-CSF has been shown to induce osteoporosis in patients with congenital neutropenia and in G-CSF-overexpressing transgenic mice, we hypothesized that short-term G-CSF administration may be sufficient to induce bone resorption, resulting in the release of soluble calcium in the endosteum leading in turn to the inhibition of attachment to fibronectin and the egress of HPC from the BM. We show herein that in humans, serum osteocalcin concentration, a specific marker of bone formation, is strongly reduced after 3 days of G-CSF administration. Furthermore, in patients mobilized with G-CSF either alone or in association with stem cell factor or interleukin-3, the reduction of serum osteocalcin is significantly correlated with the number of HPC mobilized in peripheral blood. Urine levels of deoxypyridinoline (DPyr), a specific marker of bone resorption, gradually elevated during the time course of G-CSF administration until day 7 after cessation of G-CSF, showing a simultaneous stimulation of bone degradation during G-CSF-induced HPC mobilization. In an in vivo murine model, we found that the number of osteoclasts was dramatically increased paralleling the elevation of DPyr after G-CSF administration. When pamidronate, an inhibitor of osteoclast-mediated bone resorption, was administered together with G-CSF in mice, the G-CSF-induced increase of DPyr levels was completely abolished whereas the numbers of colony-forming cells mobilized in peripheral blood were not decreased, but unexpectedly increased relative to the numbers elicited by G-CSF alone. Collectively, our data therefore show that short-term administration of G-CSF induces bone degradation by a simultaneous inhibition of bone formation and an enhanced osteoclast-mediated bone resorption. This increased bone resorption is inhibited by pamidronate without reducing G-CSF-induced HPC mobilization, suggesting that the activation of bone resorption after G-CSF administration is not the direct cause of HPC mobilization as initially hypothesized, but a parallel event.
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PMID:Osteoclast-mediated bone resorption is stimulated during short-term administration of granulocyte colony-stimulating factor but is not responsible for hematopoietic progenitor cell mobilization. 978 89

Effects of lisofylline (1-(5-R-hydroxyhexyl)-3,7-dimethylxanthine), a functional inhibitor of phosphatidic acid (PA) generation derived from de novo synthesis, on neutrophil function were examined in a porcine sepsis model. Hanford minipigs (18-25 kg) were randomly separated into six groups of six animals each: (1) saline control group; (2) sepsis control group, infused with Pseudomonas aeruginosa (1 x 10(6) colony-forming units/kg/min) for 2 h; (3) lisofylline control group, given a 25 mg/kg bolus of lisofylline 30 min prior to time zero, followed by a continuous infusion of 10 mg/kg/h throughout the study; (4) lisofylline pretreatment sepsis group, given lisofylline 30 min prior to sepsis, (5) lisofylline 1-h post-treatment sepsis group, and (6) lisofylline 2-h post-treatment sepsis group. All animals were studied for 6 h. Neutrophils were isolated at -0.5, 2, and 6 h. In the pretreatment and 1-h post-treatment groups, sepsis-induced neutrophil attachment to fibronectin was significantly attenuated. Sepsis-enhanced phagocytic activity was significantly reduced in the lisofylline pretreatment sepsis group, but not in the post-treatment groups. No treatment affected phorbol 12-myristate 13-acetate-induced chemiluminescence and basal filamentous actin content, which increased in sepsis, and cap formation, which declined in sepsis. Sepsis caused neutropenia, pretreatment produced neutrophilia, and 1-h post-treatment caused the neutropenia to recover to control levels. Interestingly, toward the end of the 6-h period, the neutrophil count was higher in the lisofylline control group than in the saline control groups. Thus, the inhibition of PA generation from de novo synthesis during sepsis not only can selectively downregulate some neutrophil functions but can also reverse neutropenia.
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PMID:Selective downregulation of neutrophils by a phosphatidic acid generation inhibitor in a porcine sepsis model. 992 33

The etiology of drug-induced agranulocytosis is poorly understood. Many drugs that induce neutropenia or agranulocytosis can be metabolized to reactive intermediates that covalently bind to macromolecules. Until now, the myeloid precursor cell or an earlier committed progenitor cell has been favoured as the target for toxicity, due to evidence in some cases of cytotoxic action or antibodies against neutrophils. In the bone marrow, where neutrophils mature, certain components of the stromal microenvironment, e.g. intracellular adhesion molecule 1, vascular cell adhesion molecule 1, CD11b/CD18, heparan sulfate proteoglycans, fibronectin and hemonectin are essential for normal myeloid maturation. This article proposes that drugs implicated in agranulocytosis, or more likely their reactive metabolites, interact with specific components of the extracellular matrix and interfere with the normal regulation of granulopoiesis.
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PMID:Drugs that induce neutropenia/agranulocytosis may target specific components of the stromal cell extracellular matrix. 1053 10


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