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)

To evaluate the clinical effect by administration of recombinant human granulocyte-stimulating factor (rhG-CSF) post chemotherapy in non-Hodgkin malignant lymphoma (NHL), 17 patients with NHL were subjected to this study. Administration of rhG-CSF ameliorated the decrease in absolute neutrophil counts after the cytotoxic chemotherapies and activated neutrophil functions in active oxygen product and expressions of adhesion proteins. To consistent with these results, rhG-CSF administrations post cytotoxic chemotherapy were effective for reducing infection complications associated with neutropenia. Furthermore, administration of rhG-CSF increased peripheral hematopoietic progenitor cells, thus suggesting promising therapeutic potential for autografting. Recently, it has been reported that blood neutrophils may synthesize mRNA and proteins important in inflammation including various cytokines such as IL-1, IL-6, TNF-alpha and IFN-alpha, but, administration of rhG-CSF showed no obvious effect on the level of either IL-1, IL-6, TNF-alpha or IFN-alpha in sera, and furthermore, the in vitro stimulation by rhG-CSF induced no significant production of these cytokines and expressions of TNF-alpha and IFN-alpha mRNAs. Finally, we studied on anti-tumor effect of administration of rhG-CSF in CDF1 mice inoculated with syngeneic lymphoma cells. rhG-CSF infusion suppressed the liver metastasis and prolonged the overall survival, thus suggesting the hypothesis that use of rhG-CSF in some patients with NHL might control the disease through stimulating both production and functional activation of neutrophils.
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PMID:[In vivo effects on human neutrophils by administration of rhG-CSF and clinical significance]. 137 67

Acid aspiration leads to increased neutrophil (PMN) oxidative metabolism, an event associated with lung leukosequestration and permeability increase. Neutropenia protected the vascular barrier function against acid injury. This study tests whether active oxygen species and elastase (which are presumably released by adherent PMNs) affect the microvascular barrier. Anesthetized rats underwent tracheostomy and insertion of a cannula into a lung segment. This was followed by localized instillation of 0.1 N HCl (n = 18) or saline (n = 18). Sequestration of PMNs in acid-aspirated and nonaspirated segments was 77 and 46 PMNs/high-power field (HPF), respectively, which was higher than control values of 11 and 8 PMNs/10 HPF in saline-aspirated and nonaspirated regions (P less than 0.05). Acid aspiration was associated with increased protein concentration in bronchoalveolar lavage (BAL) fluid to 3,550 and 2,900 micrograms/ml in the aspirated and nonaspirated lungs, respectively, which were higher than control values of 420 and 400 micrograms/ml (P less than 0.05). Acid aspiration also led to increased lung wet-to-dry weight ratios (W/D) of 6.6 and 5.4, which were higher than control values of 3.4 and 3.3 (P less than 0.05). Intravenous treatment of rats (n = 18) 90 min after aspiration with scavengers of reactive oxygen species, superoxide dismutase (1,500 U/kg), and catalase (5,000 U/kg), both conjugated to polyethylene glycol, did not reduce PMN sequestration but attenuated acid aspiration-induced increase in protein accumulation in BAL fluid in the aspirated and nonaspirated segments (990 and 610 micrograms/ml) as well as the increased lung W/D (4.6 and 4.0; all P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reactive oxygen species and elastase mediate lung permeability after acid aspiration. 139 82

The role of platelet-activating factor as a potential mediator of hepatic inflammatory injury associated with liver ischemia/reperfusion was investigated using a partial no-flow model in rats in vivo. Platelet-activating factor levels of livers from sham-operated rats and from animals experiencing hepatic reperfusion for less than 6 hr were very low. They were observed to increase significantly after 12 hr of reperfusion and reached peak levels after a 24-hr reperfusion period, a time when maximal hepatic injury and inflammation occurred. Treatment of experimental rats with WEB2170, a platelet-activating factor receptor antagonist, attenuated the hepatic injury and inflammation, as evidenced by decreases in plasma ALT and in hepatocyte necrosis and neutrophil infiltration. Both inactivation of Kupffer cells with gadolinium chloride and inhibition of the formation of reactive oxygen species with allopurinol reduced platelet-activating factor production in the liver, whereas induction of neutropenia had no effect, suggesting that interaction of Kupffer cells with oxygen-derived free radicals may be a plausible mechanism for hepatic platelet-activating factor accumulation. It is concluded that platelet-activating factor contributes to the inflammatory consequences of ischemia/reperfusion underlying late-phase hepatic injury.
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PMID:Inflammation and platelet-activating factor production during hepatic ischemia/reperfusion. 142 62

During contact between blood and dialysis membrane after the first 20-30 minutes of haemodialysis there occur the complement activation, ++intra-dialysis thrombocytopenia and leucopenia, especially neutropenia following their degranulation, which results in liberation of a number of proteases and inflammatory reaction mediators and an increased production of active oxygen compounds and peroxide radicals. This is followed by the appearance of thrombocyte-leucocyte aggregates and a decrease of ++intra-dialysis lung diffusion capacity. The clinical consequences of the blood-dialysis membrane interaction exhibit an increased permeability of pulmonic capillaries, pulmonic hypertension and hypoxemia, which might bring about vasogenic respiratory distress syndrome. The remote consequence is dialytic amyloidosis that follows increased generation and accumulation of beta 2-microglobulin. All of the above disturbances occur with cuprophan membranes more significantly that with other dialysis membranes. The blood--dialysis membrane interaction also incorporates the anaphylactic reactions, in some cases occurring when the new dialyzers are used, due to hypersensitivity to ethylene oxide used in sterilisation and the changes due to tissular accumulation of plastieizers rinsed out of the biomaterials during haemodialysis.
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PMID:[Interaction between blood and dialysis membrane]. 182 94

This study was designed to test the hypothesis that administration of immune globulin to human neonates with early-onset bacterial sepsis would (1) facilitate neutrophil egress from the marrow, (2) improve serum opsonic capacity, and (3) facilitate recovery from the infectious illness. Twenty-two newborn infants with clinical signs of early-onset sepsis were given an intravenous infusion of either 750 mg of immune globulin (IVIG) per kilogram of body weight or the same volume of a vehicle control (albumin). All 22 infants survived, but significant hematologic, immunologic, and respiratory differences were observed after the IVIG and not after the control infusion. Eleven of the patients had neutropenia; 24 hours after the infusions, the neutropenia had resolved in all six IVIG recipients but persisted in all five control recipients (p less than 0.001). Ten patients had I/T neutrophil ratios (a measure of immature neutrophils to total neutrophils on the leukocyte differential count) of less than 0.2. One hour after completion of the infusions, all five IVIG recipients had elevated I/T ratios (mean +/- SEM:0.10 +/- 0.05 before vs 0.43 +/- 0.03 after infusion; p less than 0.001), suggesting a prompt release of neutrophils from the marrow neutrophil storage pool into the circulation; no increase in the I/T ratio was observed in the control recipients. Six hours after the IVIG infusions, the ratio of arterial oxygen tension to fraction of inspired oxygen increased; no increase was observed after control infusions. Serum concentrations of IgG, IgG1, IgG2, IgG3, IgG4, and total hemolytic complement and the capacity of serum to support opsonophagocytosis of type II and type III group B streptococci increased markedly in the IVIG recipients but not in the control subjects. We conclude that administration of 750 mg IVIG per kilogram to neonates with clinical signs of early-onset sepsis was associated with immunologic, hematologic, and physiologic improvement.
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PMID:Effect on neutrophil kinetics and serum opsonic capacity of intravenous administration of immune globulin to neonates with clinical signs of early-onset sepsis. 190 Oct 82

Polymorphonuclear neutrophils (PMNs) play an important role in inflammation. Activated PMNs adhere to the vascular wall and release reactive oxygen radicals and enzymes, producing vascular injury. In the present study, we investigated whether PMNs play an important role in the pathogenesis of experimental necrotizing enterocolitis (NEC). NEC was induced in rats using platelet activating factor (PAF, 1 microgram/kg) and bacterial endotoxin (LPS, 1 mg/kg) intravenously. Neutropenia was accomplished by parenteral injection of Vinblastine (VB, 0.75 mg/kg) 4 days before the experiment to deplete the total white blood cell (WBC) and neutrophil counts. The animals were divided into 4 groups: (1) 1 microgram/kg PAF; (2) 1 mg/kg LPS; (3) 1 microgram/kg PAF + 1 mg/kg LPS; and (4) PMN depleted, 1 microgram/kg PAF + 1 mg/kg LPS. Combined administration of PAF and LPS produced prolonged hypotension (blood pressure 53.5 +/- 13.8 mm Hg at 2 hours), leukopenia (4,062 +/- 497.4), hemoconcentration (hematocrit 44.5% +/- 1.1%), reduced intestinal perfusion (74% +/- 13.3%), and segmental bowel necrosis. However, in VB-treated animals combined PAF + LPS induced only mild hypotension (84.3 +/- 9.2 mm Hg at 2 hours) and no hemoconcentration. In these animals the intestinal perfusion was normal, no bowel necrosis was observed, and the intestinal myeloperoxidase activity (.0034 +/- .0017 U/g tissue) was significantly lower than that of the nondepleted group (.0075 +/- .0012 U/g tissue). We conclude that the presence of neutrophils and/or neutrophil products play a major role in the pathogenesis of NEC.
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PMID:Experimental necrotizing enterocolitis: the role of polymorphonuclear neutrophils. 194 82

1. Oleic acid was used to produce adult respiratory distress syndrome-like pulmonary microvascular injuries. The resulting injuries have previously indicated involvement of accumulating neutrophils (Hultkvist et al. 1988). Activated neutrophils release oxygen free radicals that may be possible to detect in the plasma. 2. The dynamics of neutrophils and platelets were studied in the guinea-pig after oleic acid-induced injury (0.03 ml/kg per 10 min). 3. As an indication of oxygen free radical activity, plasma levels of uric acid and red blood cell (RBC)-catalase, were analysed. 4. Allopurinol (10 mg/kg, i.p.) was given prior to oleic acid infusion to block the production of uric acid. 5. The neutropenia, in contrast to the thrombocytopenia seen at 15 min, was significantly inhibited in the allopurinol pretreated group compared with oleic acid and vehicle alone. 6. The blood plasma concentration of uric acid was significantly elevated after 15 min from start of experiment. Allopurinol pretreatment significantly reduced the uric acid plasma level. 7. The RBC catalase activity did not change with time within or between any groups. 8. The results indicate that sequestration of activated neutrophils in the microvasculature are to some extent oxygen free radical dependent.
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PMID:Oleic acid-induced injuries in the guinea-pig. Effects of allopurinol on cell dynamics, erythrocyte-catalase and uric acid plasma levels. 205 54

Vascular pathways are major transit routes for the dissemination of malignant neoplasms and are also regulators of cancer metastasis, in part because the endothelium and vascular basement membrane are barriers to the entry and exit of tumor cells. In this study, we have examined the hypothesis that host cell-mediated damage to the pulmonary microvasculature facilitates the experimental metastasis of a syngeneic fibrosarcoma in the C57BL/6J mouse. Intravenous injection of purified cobra venom factor was followed in 30 minutes by complement activation, neutropenia with sequestration of neutrophils in the lung, and increased pulmonary vasopermeability. When syngeneic fibrosarcoma cells were injected simultaneously with cobra venom factor, there was a 3 fold increase in cancer cell retention in the lungs after 24 hours and a 3- to 20-fold increase in metastatic tumor burden after 14 days. Enhanced cancer cell retention after cobra venom factor was not seen in mice deficient in complement component C5 and was diminished by pretreatment of animals with antineutrophil antibodies, catalase, inhibitors of lipoxygenase, thromboxane synthetase, and lipid peroxidation (oxygen radical scavenger). We conclude that neutrophil-mediated microvascular injury can promote the organ localization and metastasis of circulating cancer cells.
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PMID:Effects of systemic complement activation and neutrophil-mediated pulmonary injury on the retention and metastasis of circulating cancer cells in mouse lungs. 231 52

In the present investigation, the involvement of PMNLs and oxygen free radicals was explored in rats with postischemic perfusion disturbances of the brain. Reversible forebrain ischemia was induced by bilateral clamping of both carotid arteries in combination with hemorrhagic hypotension. This procedure resulted in a reproducible DPH 1 hr after start of recirculation. Neutropenia was induced by sheep ANS. One group received ANS before and a second group immediately after termination of ischemia. Two additional groups received SOD before or immediately after ischemia. Regional postischemic CBF was determined by [14C]iodoantipyrine autoradiography. It was found that CBF significantly improved in cortical structures of animals treated with ANS before ischemia. Treatment with ANS at the end of ischemia had no effect on the postischemic CBF depression. Neither was injection of SOD effective to influence DPH, irrespective whether given before or after ischemia. It is concluded that PMNLs play a role in the development of DPH of the brain, whereas free radical mechanisms seem to be less relevant.
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PMID:Effects of neutrophil depletion and superoxide dismutase on postischemic hypoperfusion of rat brain. 239 65

Neutrophilic leukocytes have been implicated as important mediators of ischemic myocardial injury. We investigated the role of neutrophils in skeletal muscle ischemia/reperfusion injury by using the rat hindlimb ischemia model. We rendered Wistar rats neutropenic by administering 750 rad of whole-body radiation (mean white blood cell count, 300 +/- 50/mm3; 3 days after radiation). In anesthetized rats (10 neutropenic and 10 control), 3 hours of ischemia were induced in one hindlimb by application of a tourniquet to the proximal thigh; the contralateral limb served as an internal, nonischemic control. After 1 hour of reperfusion the gastrocnemius and soleus muscles were excised bilaterally and evaluated for ischemic injury by means of a quantitative spectrophotometric assay of triphenyltetrazolium chloride (TTC) reduction. In control rats the reduction of TTC by ischemic muscle averaged 27.0% +/- 7.3% of that by nonischemic muscle; whereas in neutropenic rats the value for ischemic muscle was 65.4 +/- 11.6% (p less than 0.05). To determine if the contribution of the neutrophils to ischemic injury is due to oxygen-derived free radical formation, an additional 10 animals were infused with 5000 units of super-oxide dismutase and 10,000 units of catalase at the time reperfusion was restored. After treatment with free radical scavengers, TTC reduction by ischemic limbs was 25.5% +/- 7.0% of that by nonischemic limbs and did not differ from that in control animals (p greater than 0.05). The results show a protective effect of neutropenia and suggest a significant role of the white cell in the pathophysiology of ischemic skeletal muscle injury.
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PMID:The role of leukocytes in the pathophysiology of skeletal muscle ischemic injury. 247 24


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