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)

The effects of lisofylline [(R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine] (LSF), an inhibitor of de novo phosphatidic acid (PA) generation, on sepsis-induced acute lung injury was studied using Hanford minipigs weighing 18 to 25 kg. Sepsis was induced by an intravenous infusion of Pseudomonas aeruginosa (1 x 10(6)/colony-forming units/kg/min over 2 h). Saline was used as the control vehicle. Six groups were studied: saline control group (SALINE: n = 5); sepsis control group (SEPSIS: n = 5); LSF control group (LSF: n = 5), which received a 25-mg/kgbolus of LSF 30 min before time zero followed by continuous infusion of 10 mg/kg/h throughout the study; LSF-treated septic groups, which were treated with LSF 30 min prior to sepsis (Pre: n = 5), 1 h postonset (Post-1 h: n = 8) or h postonset (Post-2 h: n = 8) of the bacterial infusion. Hemodynamics PaO2, neutrophil counts, and plasma porcine tumor necrosis factor-alpha concentrations were monitored for 6 h. After the minipigs were killed, lung tissue was sampled to measured wet-to-dry weight ratio (W/D), tissue albumin index (TAI), thiobarbituric acid-reactive material content (TBARM), and myeloperoxidase (MPO) activity. Compared with the SALINE group, the SEPSIS group showed significant systemic hypotension, pulmonary hypertension, arterial hypoxemia, neutropenia, and increase in TNF-alpha, MPO activity, W/D, TBARM, and TAI. LSF treatment attenuated sepsis-induced pulmonary hypertension, neutropenia, and hypoxemia, and increased MPO activity and lung injury measurements in the Pre and Post-1 h groups, but its efficacy was blunted in the Post-2 h group. Plasma TNF-alpha was decreased only in the Pre group. Thus, inhibition of intracellular PA generation through de novo pathways attenuates sepsis-induced acute lung injury.
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PMID:The effects of post-treatment with lisofylline, a phosphatidic acid generation inhibitor, on sepsis-induced acute lung injury in pigs. 911 28

The influence of the primary antibody, the fixative, and the antigen unmasking technique on the method sensitivity of immunohistochemistry as a method for the identification of viral hemorrhagic septicemia (VHS) virus in paraffin-embedded specimens of naturally infected rainbow trout (Oncorhynchus mykiss) was examined. Fish (200-300 g) were collected during an outbreak of VHS. Parallel specimens from liver, spleen, kidney, and brain were fixed by immersion in 10% phosphate-buffered formalin, periodate-lysine-paraformaldehyde (PLP), Bouin's fluid, or absolute ethanol. Virus cultivation was also performed on parallel specimens, and the virus titer (TCID50/ml) was determined. Purified nucleocapsid protein (N-protein) of the virus was incorporated in an artificial antigen substrate polymerized bovine serum albumin), fixed as described above, and embedded in paraffin wax. Microwave unmasking was performed on formalin-, PLP-, and Bouin's fluid-fixed specimens. The presence of virus peptides in situ or N-protein in the artificial antigen substrates was visualized using an immunohistochemical method based on alkaline phosphatase or peroxidase and one polyclonal and five monoclonal polypeptide-specific antibodies. VHS virus was identified in situ in specimens with high virus titers (10(7-8) TCID50/ml) regardless of the fixative and without the need of an unmasking procedure. A pronounced masking effect was observed for the cross-linking formalin and PLP fixatives. Regardless of the primary antibodies used, there was a significantly higher epidemiologic sensitivity (the proportion of virus positive samples that tested positive by immunohistochemistry) using ethanol and Bouin's fluid compared with formalin and PLP (P < 0.05). At 10(5) TCID50/ml, the average sensitivity reached 0.5, and at > or = 10(6) TCID50/ml, sensitivity was 0.9. Unmasking procedures showed a moderate effect and did not result in significantly higher epidemiologic sensitivity (P = 0.17), There was great variation for the different monoclonal antibodies/antigens and fixatives. Sensitivity studies on antigen substrates were in accordance with results of in situ studies that showed the highest sensitivity for ethanol and Bouin's fluid. Virus cultivation was more sensitive than immunohistochemistry. This study showed that the fixative and the primary antibody both influence method sensitivity and that VHS virus antigens concealed during fixation are difficult to reexpose. Immunostaining for VHS virus should be performed with monoclonal antibodies specific for the N-protein, and tissue samples should be fixed in either ethanol or Bouin's fluid. Immunohistochemistry is specific but is less sensitive than virus cultivation. Immunostaining for VHS virus can be a valuable supplement to virus cultivation during acute outbreaks of disease.
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PMID:Immunohistochemical detection of VHS virus in paraffin-embedded specimens of rainbow trout (Oncorhynchus mykiss): the influence of primary antibody, fixative, and antigen unmasking on method sensitivity. 916 87

The level of different immunoglobulins (IgA, IgG, IgM) in the tissues of 28 late fetuses and newborns was studied with peroxidase-labeled monoclonal antibodies. IgA+ and IgM+ lymphocytes were found in the spleen, lymph nodes and sometimes in the liver. IgG+ lymphocytes were not found. A high level of IgA+ material was found in the epithelium of the trachea, the epithelium and submucosal glands of the bronchi, but not the bronchioles, and in the epithelium of hepatic bile ducts and in their lumina. Such IgA is considered to be secretory--sIgA. Secretory IgA-containing epithelial cells appeared at 20 to 21 weeks of gestation; their number increased from 2.5 cells/10,000 microns2 in 23- to 26-week-old fetuses, to 8 cells/10,000 microns2 in 36- to 40-week-old fetuses. Secretory IgG and IgM were not detected. In fetuses with pneumonia or sepsis, the number of IgM+ and IgA+ lymphocytes increased significantly. IgM+ lymphocytes appeared not only in the spleen and lymph nodes, but also in the lungs. In such cases, the number of sIgA-containing epithelial cells in the trachea, bronchi and intrahepatic bile ducts decreased, sometimes completely disappearing. The amount of IgA+ material in the lumina of these organs increased, reflecting an intensification of sIgA secretion during infections. The presence of a marked amount of sIgA in fetuses from week 20 of gestation is considered to reflect the high importance of this immunoglobulin against normal contamination by microbes after birth, and to evidence the early maturation of the immune system.
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PMID:Immunoglobulin A in the epithelium of the respiratory tract and intrahepatic bile ducts of fetuses and newborns with pneumonia and sepsis. 932 81

Eleven patients, 13 to 76 (mean, 40) years of age, had granulocytic sarcoma of the female genital tract (FGT) (ovary, seven cases; vagina, three cases; cervix, one case). In nine cases, the FGT involvement was the initial clinical presentation of the disease, and in the other two cases, the FGT involvement was discovered during a relapse of acute myeloid leukemia. The tumors ranged from 0.5 to 14 (mean, 7.5) cm in greatest dimension. Two ovarian tumors were bilateral, and three were green. Microscopic examination revealed a predominantly diffuse pattern of growth, but cords and pseudoacinar spaces were also present focally in several cases. Sclerosis was seen in five tumors and was prominent in one. Prominent myeloid differentiation was readily recognizable on routinely stained sections in three cases, whereas the neoplastic cells in the other cases were primitive with only rare eosinophilic myelocytes. All 11 tumors were positive for chloroacetate esterase, nine of nine were strongly and diffusely positive for lysozyme, eight of eight for myeloperoxidase, seven of seven for CD68, and six of six for CD43. Examination of bone marrow or peripheral blood performed after the diagnosis of FGT involvement revealed acute myeloid leukemia in three of five cases. Two of these patients died of disease, 1 and 16 months after the initial diagnosis, and the third, who received chemotherapy, is alive and free of disease 8 months after the initial diagnosis. One of the two patients with negative bone marrow had recurrent granulocytic sarcoma 30 months after diagnosis and died of sepsis 1 month later; no residual disease was noted at autopsy. The other patient is alive and free of disease 18 months after the diagnosis. One of the four remaining patients with primary FGT involvement who did not have a bone marrow biopsy died of leukemia 24 months later; no follow-up information is available for the other three patients. One of the two patients with a prior diagnosis of acute myeloid leukemia was alive with disease 26 months later; follow-up is not available for the second patient. The diagnosis was often difficult in these cases, the most common problem being distinction from malignant lymphoma, but carcinoma, granulosa cell tumor, and, rarely, other tumors were considered. Immunohistochemical and enzyme histochemical staining were useful in establishing the diagnosis, although suspicion of the diagnosis on examination of routinely stained sections was of paramount importance.
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PMID:Granulocytic sarcoma of the female genital tract: a clinicopathologic study of 11 cases. 933 Dec 87

A large body of evidence has demonstrated that inhibition of the neutrophil's oxidant burst attenuates sepsis-induced acute lung injury. The present study sought to evaluate the ability of OPC-6535, a superoxide anion production inhibitor, to attenuate sepsis-induced acute lung injury. Four groups of swine were anesthetized, ventilated, and studied for 5 hr. Following surgical preparation, control (n = 10) and OPC-control (n = 2) animals received a 1-hr infusion of sterile saline. Sepsis was induced with a 1-hr intravenous infusion of live Pseudomonas aeruginosa. Untreated septic animals (n = 10) received no treatment. Animals treated with OPC-6535 (n = 6) received a 1 mg/kg bolus of OPC-6535 15 min prior to initiation of the bacterial infusion. Changes in systemic and pulmonary hemodynamics, arterial oxygen tension, bronchoalveolar lavage protein and neutrophil content, neutrophil integrin expression, neutrophil oxidant burst, and lung myeloperoxidase content were used as outcome measures. Treatment with OPC-6535 significantly reduced acute lung injury, as indicated by improved bronchoalveolar lavage protein and neutrophil content, resulting in a significant improvement in arterial oxygenation. Treatment with OPC-6535 failed to prevent the development of pulmonary hypertension and systemic hypotension. Neutrophils from animals with both treated and untreated sepsis exhibited significant up-regulation of CD18 and production of increased levels of oxidants, indicating significant activation when compared to neutrophils from control animals. Although animals treated with OPC-6535 produced 25% less superoxide anion than untreated septic animals, this decrease was not statistically significant. Treatment of animals with OPC-6535 prior to the onset of sepsis produced significant protection against acute lung injury but failed to attenuate hemodynamic derangements associated with sepsis.
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PMID:OPC-6535, a superoxide anion production inhibitor, attenuates acute lung injury. 934 16

Up-regulation of the leukocyte beta 2 integrin, CD18, is a key event in neutrophil-endothelial adhesion and neutrophil-mediated organ injury. Inhibition of CD18 with monoclonal antibodies reduces lung and liver neutrophil sequestration in animal models of Gram-negative bacteremia or endotoxemia. However, with a persistent septic challenge, interference with host leukocyte phagocytic defense could adversely affect outcome. To assess the effects of inhibiting CD18 on organ neutrophil responses, bacteremia, and organ injury after fecal peritonitis, mice underwent cecal ligation and puncture (CLP). At the time of CLP and 12 h later, mice received intravenous anti-CD18 antibody or control IgG. At 3, 6, and 18 h after CLP, lung and liver tissue neutrophil content were measured by myeloperoxidase (MPO) assay, peritoneal cells and blood leukocytes were differentially counted, blood was cultured, and serum aspartate aminotransferase was measured. There was a significant reduction in peritoneal neutrophil migration and an increase in blood neutrophils after anti-CD18 treatment compared with results from treatment with the control antibody. In the anti-CD18-treated group, liver MPO was increased fivefold at 6 and 18 h, while lung MPO was increased two-fold at 18 h when compared with the control antibody-treated group. The anti-CD18-treated group also had an increase in bacteria cultured from the blood at 6 and 18 h and an increase in serum aminotransferase at 18 h. Our data demonstrate that peritoneal neutrophil migration in response to an endogenous fecal challenge is CD18-dependent, and that this mechanism forms a vital part of host defense. Inhibition of CD18 increased neutrophil sequestration in the liver and lung and increased liver injury. This study demonstrates a paradoxical increase in organ neutrophil sequestration using a leukocyte anti-adhesion therapy during sepsis and suggests that anti-adhesion therapies targeted towards neutrophil may worsen outcome if given during an ongoing, localized infection.
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PMID:Inhibition of neutrophil migration at the site of infection increases remote organ neutrophil sequestration and injury. 937 66

To investigate interactions between the endothelium and leukocytes in patients with sepsis, we measured soluble adhesion molecules (sE-selectin and sICAM-1), von Willebrand factor antigen (vWf:Ag), myeloperoxidase (MPO), and lactoferrin (Lacto-f) as plasma markers of endothelial and neutrophil activation. We tested whether the five proteins were predictors of clinical severity, which was evaluated by simplified acute physiological score (SAPS), number of organ failures (MOF), acute lung injury (ALI), and subsequent final outcome. Levels of the five plasma markers were higher in patients with severe infection (n = 25) than in patients without sepsis (n = 7) and healthy volunteers (n = 9). In the study population, levels of sE-selectin, sICAM-1, and vWf:Ag were higher for nonsurvivors as well as for patients with septic shock or with bacteremia, and they were correlated with SAPS and MOF. Survival outcome was predicted with high sensitivity and specificity by initial plasma levels of sICAM-1 and vWf:Ag. The initial sICAM-1 level appeared to be an independent prognostic variable, based on a logistic regression analysis. Unlike sE-selectin, sICAM-1 remained at high levels indefinitely in nonsurvivors. We conclude that, unlike neutrophil activation markers, levels of endothelium-derived soluble adhesion molecules and vWf:Ag in severe sepsis syndrome are correlated with the severity of illness and may be considered as predictors of survival outcome.
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PMID:Elevated circulating E-selectin, intercellular adhesion molecule 1, and von Willebrand factor in patients with severe infection. 951 90

Increases of plasma concentrations of neutrophil myeloperoxidase (MPO) can be used as markers of polymorphonuclear leucocytes (PMN) activation in pathological situations (sepsis, acute lung injury, acute inflammation). To develop an assay for measurement of plasma MPO in horses during the above-mentioned infectious and inflammatory conditions, MPO was purified from equine PMN isolated from blood anticoagulated with citrate. PMN were extracted in a saline milieu (0.2 M Na acetate, 1 M NaCl, pH 4.7) to eliminate most of cellular proteins. Pellets were then extracted in the same buffer containing cationic detergent (1% cetyltrimethyl ammonium bromide). The supernatant was further purified by ion exchange chromatography (Hiload S Sepharose HP column 0.5 x 26 cm, equilibrated with 25 mM Na acetate, 0.2 M NaCl, pH 4.7) with a NaCl gradient (until 1 M). Most of the peroxidase activity of MPO (spectrophotometrically measured by the oxidation of orthodianisidine by hydrogen peroxide) was eluted at 0.65 M NaCl. MPO was further purified by gel filtration chromatography (Sephacryl S 200 column 2.6 x 42 cm with 25 mM Na acetate, 0.2 M NaCl, pH 4.7). MPO (specific activity: 74.3 U/mg) was obtained with a yield of 30% from the detergent extraction supernatant. Electrophoresis (non-reducing conditions) showed 3 bands identified, by comparison with human MPO, (i) the mature tetrameric enzyme (150 kDa) with 2 light and 2 heavy subunits, (ii) the precursor form (88 kDa) and (iii) a form of the heavy subunit without the prosthetic heme group (40 kDa). The mature enzyme and its precursor were glycosylated and possessed peroxidase activity. Equine MPO showed strong similarities with human and bovine MPO, with an absorption peak at 430 nm (Soret peak) characteristic of ferrimyeloperoxidase. Enzymatic activity was pH dependent (optimal value at pH 5.5).
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PMID:Purification of myeloperoxidase from equine polymorphonuclear leucocytes. 955 12

The intercellular adhesion molecule (ICAM)-1 is expressed constitutively in normal lungs and increased in pulmonary inflammation. Whether increased ICAM-1 expression in the lung contributes to neutrophil sequestration during lung inflammation in sepsis is unclear. We tested this hypothesis in mice after systemic sepsis from cecal ligation and puncture (CLP). ICAM-1 expression in mouse CLP lung tissue was found to increase with time. The time course of lung ICAM-1 up-regulation correlated with increases in lung myeloperoxidase (MPO) activity and neutrophil sequestration by light microscopy. The monoclonal IgG2b rat anti-mouse antibody, an anti-ICAM-1 antibody (YN1/1.7), administered intravenously at doses of 3, 10, or 30 mg/kg, however, did not decrease the lung MPO levels compared with nonimmune rat IgG. In support of these findings, lung MPO content in ICAM-1-deficient mice that underwent CLP was significantly higher than similarly treated ICAM-1-sufficient mice. Our results suggest that neutrophil sequestration in the mouse lung after CLP is not dependent on ICAM-1.
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PMID:Anti-intercellular adhesion molecule-1 antibody and intercellular adhesion molecule-1 gene deficiency do not prevent pulmonary neutrophil recruitment in polymicrobial sepsis. 956 60

The primary metabolic fates of L-arginine are conversion to L-citrulline by nitric oxide synthase (NOS) and to L-ornithine by arginase. In the lung, arginine utilization is increased after the inducible form of NOS (iNOS) is expressed during inflammation. The expression of arginase in normal lung and after sepsis, and its potential relationships with iNOS, however, are not known. Since arginase and iNOS share the substrate L-arginine, we tested the hypothesis that lung arginase would be co-induced with iNOS in sepsis and its cellular distribution would be related to that of iNOS in the lung. Lungs from cecal ligation and puncture (CLP) and sham-operated (S) rats were harvested 6 or 16 hours after the procedures. Lung wet-to-dry weight ratio, myeloperoxidase content, and lipid peroxidation products were measured as indices of lung injury. Western blot analyses were performed with polyclonal antibodies against two isoforms of rat arginase (I and II) and iNOS. Additional lungs from CLP and S animals were inflation-fixed for immunohistochemistry using the same antibodies. We found by Western blot that arginase II at 39 kDa was the main isoform present in normal rat lung. The enzyme was distributed diffusely in alveolar and bronchial epithelial cells, endothelial cells, and alveolar macrophages. After CLP, arginase II was almost undetectable in rat lungs at 16 hours. In contrast, in normal lung, the iNOS was not detectable by Western blot or immunohistochemistry. After CLP, strong expression of iNOS was found in similar cell types to arginase II. These data demonstrate loss of constitutive expression of arginase II in rat lung as iNOS is upregulated by the response to sepsis.
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PMID:Differential expression of arginase and iNOS in the lung in sepsis. 963 49


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