Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Actively phagocytizing polymorphonuclear leukocytes (PMN) emit light or chemiluminescence (CL) which has been shown to be linked to the oxidative activity of the PMN. The measurement of CL has been demonstrated to be a useful tool for the in vitro assessment of intracellular and opsonophagocytic function of PMN. We have increased the sensitivity of the CL measurement by the addition of luminol to the in vitro reaction of PMN, bacteria, and serum. The presence of luminol, which can be oxidized to emit light, amplifies the detection of CL and PMN cellular activity. This amplification effectively reduces the number of PMN that are necessary for assessment of PMN function from 1 x 10(7) to as low as 2 x 10(4) PMN/assay and permits the evaluation of PMN function in severely neutropenic patients (100 PMN/mm3) in whom cellular PMN function has been heretofore extremely difficult to assess by other methodology. When this luminol-dependent CL method was used, three of eight neutropenic leukemic patients with gram-negative septicemia were found to have deficient opsonic activity and/or increased or depressed cellular oxidative activity. Because the initial slope of CL is dependent on the amount of serum and heat-labile factors, this method can also be used effectively as a simple technique for the analysis of specific rates of opsonophagocytosis of various microorganisms. Additionally, this method can detect the cellular PMN abnormalities of chronic granulomatous disease and myeloperoxidase deficiency. The luminol-dependent CL method is a simple, sensitive, reproducible technique that provides useful information about PMN metabolic activity, particularly in studies in which the number of PMN is limited.
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PMID:In vitro evaluation of opsonic and cellular granulocyte function by luminol-dependent chemiluminescence: utility in patients with severe neutropenia and cellular deficiency states. 21 46

Ketorolac tromethamine, a new nonsteroidal anti-inflammatory agent of the pyrrolo-pyrrole group, was assayed for inhibitory effects on polymorphonuclear leukocytes (PMN) in a variety of systems. Ketorolac inhibited PMN superoxide anion generation, lysozyme release, myeloperoxidase release, adherence to plastic surfaces, and chemotaxis in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) in a dose-dependent manner. Ketorolac also inhibited phorbol myristate acetate-stimulated adherence of PMN to bovine pulmonary artery endothelial cells. The drug inhibited lysozyme and myeloperoxidase release by PMN in response to C5a but failed to inhibit C5a stimulation of PMN in any of the other assays. Levels of ketorolac required to inhibit PMN function in most systems were in the range of 0.2 to 1.0 mg/ml, but chemotaxis to fMLP was inhibited by concentrations of ketorolac as low as 1 microgram/ml. Ketorolac, currently the only nonsteroidal anti-inflammatory drug available in a parenteral form may have therapeutic usefulness in a variety of conditions thought to be mediated in part by PMN, including sepsis.
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PMID:Inhibition of some human neutrophil functions by the cyclooxygenase inhibitor ketorolac tromethamine. 131 50

The purpose of this study was to examine how intra-abdominal sepsis and extracellular matrix proteins (fibronectin, laminin) affect adherent polymorphonuclear leukocyte (PMN) function. Two groups of swine were studied: Group I (n = 5) underwent sham laparotomy; Group II (n = 8) underwent cecal ligation and incision. PMN adherent to either fibronectin (F) or laminin (L) had increased candicidal activity over buffer (B) by Group I but not by post-operative day 8 Group II PMN. (Percent specific release 51Cr-Group I--35.00, 68.25, 64.75% for B, F, and L; P less than 0.001 comparing B vs. F or L; Group II--14.25, 12.50, 12.75% for B, F, and L; P = NS comparing B vs. F or L.) To determine the mechanism for this finding, PMN priming was then assessed by evaluating both PMN adherence to extracellular matrix proteins and the cell surface expression of CR1/CR3 by using sheep RBC opsonized with C3b or C3bi. PMN activation was assayed by using MTT-Formazan, myeloperoxidase, and hypochlorous acid (HOCl) production. Fibronectin and laminin increased PMN adherence and CR1/CR3 expression over buffer by Group I and Group II animals. Fibronectin and laminin increased MTT-Formazan, myeloperoxidase, and HOCl production over buffer by Group I PMN but not POD 8 Group II PMN. These results suggest that untreated intra-abdominal sepsis partially abrogates the effect of extracellular matrix proteins on PMN function; in particular, the activation but not priming of adherent PMN by extracellular matrix proteins is reduced in this clinical situation.
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PMID:Polymicrobial sepsis disrupts normal neutrophil extracellular matrix protein interactions. 132 74

Both gram-negative infection and bacterial endotoxin (lipopolysaccharide, LPS) produce a marked neutropenia and increase glucose disposal by peripheral tissues. The purpose of the present study was to determine whether leukocyte depletion before these insults would diminish the commonly observed increases in tissue glucose uptake. Rats were depleted of circulating and marginated leukocytes with cyclophosphamide (CPA). Under basal postabsorptive conditions the subcutaneous injection of live Escherichia coli into control animals enhanced whole body glucose disposal that resulted in part from a stimulation of glucose uptake by the liver, spleen, intestine, and lung. These increases in tissue glucose uptake were not associated with an increase in neutrophil number, as assessed by myeloperoxidase (MPO) activity. CPA-induced leukopenia did not alter the sepsis-induced increase in glucose uptake by these tissues and whole body glucose use remained elevated. In contrast, skin and muscle proximal to the site of infection showed an increase in both glucose uptake and MPO activity. Furthermore, leukocyte depletion attenuated the elevated glucose uptake by skin and muscle near the inflammatory focus. The intravenous injection of LPS also increased whole body glucose disposal and enhanced glucose uptake by the lung, liver, spleen, intestine, and skin in saline-treated rats. Of these tissues the lung, liver, and spleen had a corresponding increase in neutrophil number. The LPS-induced increases in tissue glucose uptake in leukopenic rats were comparable, with the exception of liver and lung. In these tissues the incremental increase in glucose uptake after LPS was reduced 40-50% in leukopenic animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sepsis- and endotoxin-induced increase in organ glucose uptake in leukocyte-depleted rats. 133 18

Neutropenia was seen in rats made septic by subcutaneous (sc) injection of Escherichia coli. The sepsis-induced increase in glucose uptake by tissues distant from the site of infection was not associated with increased myeloperoxidase (MPO) activity. Only the skin and muscle at the site of infection demonstrated an increase in both glucose uptake and MPO activity. Granulocyte colony-stimulating factor (G-CSF) attenuated the sepsis-induced decrease in circulating neutrophils. Both glucose uptake and MPO activity of skin and muscle adjacent to the infection site showed a smaller increase in G-CSF treated rats. In contrast, septic rats injected with G-CSF exhibited a greater number of leukocytes and a larger reduction in the number of bacteria in the sc lavage fluid. These results demonstrate that G-CSF is a potent immunomodulator that stimulates neutrophil function and also increases their recruitment to the site of infection, resulting in improved bacterial killing and host defense.
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PMID:Effect of granulocyte colony-stimulating factor on sepsis-induced changes in neutrophil accumulation and organ glucose uptake. 137 72

We report a case of idiopathic crescentic glomerulonephritis with pulmonary hemorrhage associated with anti-myeloperoxidase antibodies (anti-MPO ab). A 74 year-old female was admitted to our hospital because of rapidly progressive glomerulonephritic syndrome and dyspnea with bloody sputum. On admission anti-MPO ab, one of anti-neutrophil cytoplasmic antibodies, were detected but anti-GBM antibodies and immune complexes were not detected. Renal biopsy showed crescentic glomerulonephritis and lung biopsy showed massive alveolar hemorrhage. Both tissue had pauci-immune deposit by immunofluorescence microscopy. Hemodialysis and steroid administration were started. Pulmonary hemorrhage was improved remarkably, but renal failure progressed rapidly to end stage kidney, then hemodialysis was continued. Although subsequent 3 years uneventful maintenance hemodialysis had been performed, she admitted to our hospital again because of progressive dyspnea with hemoptysis after upper respiratory tract infection. On admission anti-MPO ab were detected again and steroid administration was started. Pulmonary hemorrhage was improved with decreased anti-MPO ab titer. While tapering the dosis of steroid, anti-MPO ab again increased and pulmonary hemorrhage recurred. Although pulse methylprednisolone therapy and plasma exchange were performed, respiratory failure progressed rapidly and she died of sepsis. Postmortem examination showed no evidence of systemic vasculitis. In this case, titer of anti-MPO ab was associated with not only idiopathic crescentic glomerulonephritis but also with pulmonary hemorrhage. We tried to detect enzymatically active MPO in serum. Titer of serum MPO was also associated with disease activity and anti-MPO ab. It is suggested that both anti-MPO ab and serum MPO are closely related to the pathogenesis of idiopathic crescentic glomerulonephritis and pulmonary hemorrhage.
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PMID:[A case of anti-myeloperoxidase antibodies-associated idiopathic crescentic glomerulonephritis with pulmonary hemorrhage]. 166 75

The haem enzyme myeloperoxidase (MPO) (EC 1.11.1.7) with a spectral A430/A280 ratio greater than 0.7 and a specific activity of 125 U/mg was purified from isolated human neutrophils. To obtain a radioimmunoassay (RIA) for this enzyme, a specific antiserum against human neutrophil MPO was raised in rabbits and used at an initial dilution of 1/10,000. MPO labelled with 125iodine by a technique of self-labelling in the presence of H2O2, had a specific activity of 24 mCi/mg. After incubation at room temperature (2 h) and separation by double antibody precipitation in the presence of polyethylene glycol, the sensitivity of the RIA was 21 ng/ml. The RIA showed good precision and accuracy with intra- and interassay coefficients of variation of less than 7% for MPO concentrations ranging from 100 to 800 ng/ml, and satisfactory recoveries of known amounts of exogenous MPO in plasma. For the measurement of MPO in blood, the best sampling technique was to collect blood into EDTA. Rapid centrifugation (within 20 min) was necessary for blood collected into heparin. Mean MPO values in normal individuals were 340 +/- 98 ng/ml in EDTA plasma (n = 152) and 332 +/- 82 ng/ml in heparinized plasma (n = 34). When MPO was measured 12-6 h after injury in critically ill patients high values (above 1000 ng/ml) were found in 6/15 patients with multiple injuries. In patients with sepsis (n = 22), MPO values were always above 1000 ng/ml.
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PMID:Fast double antibody radioimmunoassay of human granulocyte myeloperoxidase and its application to plasma. 184 40

In vitro studies have shown that phagocytic cells are capable of undergoing activation in response to inflammatory signals and that the activation process is quite complex. A relationship between polymorphonuclear leukocyte (PMN) Fc receptor-mediated phagocytosis and oxidative metabolism has been seen in humans. We have sequentially examined circulating polymorphonuclear leukocytes (PMNs) from a total of 13 postoperative swine with either no sepsis, untreated intraabdominal sepsis, or treated intraabdominal sepsis to determine phagocytic activity over 8 postoperative days (POD). Products of the oxidative burst (i.e., myeloperoxidase) reduced the phagocytic activity of nonseptic swine PMN. Phagocytic activity was augmented by inhibiting the nonseptic swine oxidative burst with 10 mM sodium azide (an inhibitor of myeloperoxidase). In swine with untreated intraabdominal sepsis, PMN Fc receptor-mediated phagocytosis exhibited a biphasic response. An initial (between POD1 and POD4) increase in PMN function was followed by a subsequent (between POD4 and POD8) decrease in PMN function. Partial preservation of phagocytic capability was seen when swine were reexplored on POD4 and had their intraabdominal sepsis treated. These results indicate that (1) as in humans, nonseptic swine PMN Fc receptor-mediated phagocytosis is augmented by inhibition of the PMN respiratory burst; (2) untreated intraabdominal sepsis produces an initial increase and subsequent decrease in PMN Fc receptor-mediated phagocytosis; (3) early treatment of intraabdominal sepsis results in partial restoration of PMN Fc receptor-mediated phagocytosis.
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PMID:Intraabdominal sepsis: effects on polymorphonuclear leukocyte Fc receptor-mediated phagocytosis. 235 94

Polymorphonuclear leukocytes (PMN) and monocytes from 20 patients with acute bacterial infections were examined for phagocytic function. PMN of patients expressed markedly enhanced phagocytosis as measured by the ingestion of erythrocyte (E)IgG and IgG/C3b-coated E. Phagocytosis of E coated with C3b alone was not seen, while low levels of ingestion of iC3b-E by patients' PMNs was noted. Monocytes from patients and controls expressed similar phagocytic activity in a fixed endpoint assay; however, the kinetics of phagocytosis by patients' monocytes was strikingly faster. Superoxide anion (O2.) and myeloperoxidase activities were similar to controls in PMN of four patients studied on day 1 of admission. PMN from two of three patients studied longitudinally showed an initial elevation in EIgG phagocytosis, which fell to normal levels by day 4, concomitantly with increased O2. generation and clinical improvement. Phagocytosis remained elevated in the third patient who did not clear his septicemia. Surface membrane FcRII, FcRIII, CR1, and CR3 were similar on patient and control PMN. In contrast, FcRI was increased on PMN of five of seven patients by monomeric IgG binding, and on two of two patients by monoclonal anti-FcRI binding. Thus, PMN and monocytes of patients with acute bacterial infections are either upregulated with regard to phagocytic function or are less susceptible to downregulation than are normal cells. This presumably would have a beneficial effect on host defenses during infection.
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PMID:Studies on phagocytosis in patients with acute bacterial infections. 253 44

The myeloperoxidase-hydrogen peroxide-chloride (MPO-H2O2-Cl) system is an antimicrobial system of polymorphonuclear leukocytes. We demonstrated that the MPO-H2O2-Cl system is fungicidal for Trichophyton rubrum. Fungal growth of a synchronous cell culture of T. rubrum germlings was assayed by measuring the uptake of tritiated N-acetyl-D-glucosamine, and the viability of the fungi was assayed by counting colony-forming units. Cytotoxins produced by the interaction of myeloperoxidase with hydrogen peroxide and chloride ion were fungicidal for T. rubrum. Growth inhibition was abolished in the presence of catalase or L-methionine. Polymorphonuclear leukocytes through the MPO-H2O2-Cl system may prevent invasion and sepsis by dermatophytes even in the absence of specific immunity.
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PMID:Inhibition of growth of Trichophyton rubrum by the myeloperoxidase-hydrogen peroxide-chloride system. 253 15


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