Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sublethal doses of vincristine (VNC) and bacterial lipopolysaccharide (LPS) administered simultaneously to adult male mice resulted in markedly enhanced mortality. All of 10 strains of Pseudomonas aeruginosa tested, 4 of 7 strains of Bacteroides, and 6 of 10 strains of Listeria monocytogenes were able to substitute for purified LPS in enhancing mortality in VNC-treated mice. Inoculation of mice with each of 10 strains of Pseudomonas, each of 7 strains of Bacteroides, and about half of the 10 strains of Listeria tested elicited increased resistance to the lethal action of purified LPS. The patterns of responses of mice receiving a lethal combination of 2 mg of LPS/kg and 1 mg of VNC/kg resembled those of mice receiving a lethal dose of 10 mg of VNC/kg alone or 15 mg of LPS/kg alone with respect to (i) serum glutamic pyruvate transaminase activity, (ii) hematocrit values, and (iii) thrombocytopenia. The patterns of responses of mice receiving a lethal combination of LPS and VNC resembled those of mice receiving a lethal dose of LPS alone with respect to (i) hypothermia, (ii) retention of sulfobromophthalein, (iii) fibrinogen level, (iv) prothrombin activity, (v) blood urea nitrogen levels, and (vi) time of death. These data are consistent with the proposition that the combination of VNC and LPS produces a fatal renal failure. Histological studies confirmed that there was extensive renal damage in mice treated with lethal doses of LPS alone or a lethal combination of LPS and VNC.
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PMID:Enhanced toxicity for mice of combinations of bacterial lipopolysaccharide and vincristine. 94 80

Changes in the plasma thrombomodulin (TM) level were examined in endotoxin-infused rabbits. The plasma TM level in normal rabbits was 143.8 +/- 8.4 ng/ml (n = 67) and the molecular weight of the major TM was about 55 kd. Endotoxin (lipopolysaccharide, LPS, E. Coli B8:0127) was intravenously infused. LPS infusion increased the plasma TM level dose-dependently between 0.2 mg/kg and 5 mg/kg. When 5 mg/kg LPS was infused, the plasma TM level started to increase immediately and was 2.3 times higher than the control value within 1 hr. The molecular weight of the major TM was about 75 kd. This rapid increase in TM occurred before the decrease in fibrinogen content and the prolongation of prothrombin time. To examine the effect of circulating leukocytes on the TM increase in endotoxin-infused rabbits, 5 mg/kg LPS was infused into rabbits with leukocytopenia induced by X-ray irradiation. The maximum plasma level of TM was significantly lower than in the untreated rabbits given LPS. These data suggest that the increase in plasma TM is caused by LPS-stimulated leukocyte's prior to hemostaseological changes. It is well known that endothelial cells can be injured by stimulated leukocytes, so this increase in plasma TM probably reflects the deterioration of endothelial cells. This deterioration decreases the ability of endothelial cells to inhibit thrombosis, which would, in turn, contribute to the development of disseminated intravascular coagulation in endotoxin-infused rabbits.
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PMID:Changes in thrombomodulin level in plasma of endotoxin-infused rabbits. 131 90

An experimental model incorporating cultured endothelial cells (EC) was used to study the "factor VIII bypassing" activity of prothrombin complex concentrates (PCC), a property exploited in the treatment of hemophiliacs with alloantibodies to factor VIII. Two PCC preparations were ineffective as stimuli of tissue factor expression by EC. However, incubation with a combination of PCC plus endotoxin (lipopolysaccharide, LPS) or tumor necrosis factor (TNF) induced much greater tissue factor expression than was seen in response to either substance alone. PCC expressed an additional direct procoagulant activity at the EC surface, which could not be attributed to either thrombin or factor Xa, and which was diminished by an anti-tissue factor antibody. Therefore factor VIIa, which was detectable in both PCC preparations, likely provided this additional direct procoagulant activity at the EC surface. We also excluded the possibility that coagulation proteases contained in or generated in the presence of PCC are protected from inactivation by AT III. Therefore, PCC can indirectly bypass factor VIII by enhancing induced endothelial tissue factor expression, and also possess direct procoagulant activity, probably mediated by factor VIIa.
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PMID:The factor VIII bypassing activity of prothrombin complex concentrates: the roles of factor VIIa and of endothelial cell tissue factor. 180 20

A panel of 24 IgG2ak monoclonal antibodies was produced against murine hepatitis virus strain 3 (MHV-3)-induced procoagulant activity (PCA) from murine macrophages. The antibodies were specific and did not react in an enzyme-linked immunosorbent assay with purified MHV-3; lipopolysaccharide-induced PCA; crude mouse, human, or rabbit tissue factor, or unstimulated murine macrophages. Sixteen of 24 monoclonal antibodies inhibited functional PCA expression in a one-stage clotting assay. More detailed studies on one monoclonal antibody, 3D4.3, demonstrated that it inhibited prothrombin cleavage at concentrations of greater than or equal to 0.1 microgram/ml, and by Western blot this antibody reacted with proteins of a molecular mass of 140, 74, and 70 kDa on nonreduced gels and 74 and 70 kDa on reduced gels distinct from tissue factor known to have a molecular mass of 47 kDa. Induction of PCA was dependent on both host RNA and protein synthesis. Immunofluorescence studies showed specific binding to MHV-3-stimulated PCA-positive macrophage membranes. Both numbers of positive macrophages and intensity of staining correlated with multiplicity of infection. These monoclonal antibodies will be useful in isolation and characterization of the unique viral-induced PCA as well as in determining its biologic role in MHV infection and other diseases in which the prothrombinase has been implicated.
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PMID:Monoclonal antibody analysis of a unique macrophage procoagulant activity induced by murine hepatitis virus strain 3 infection. 184 63

To clarify whether activated platelets play an important role in the occurrence and exacerbation of disseminated intravascular coagulation (DIC), we investigated the effects of 4 anti-platelet drugs, a PGI2 analog (CS-570), a thromboxane synthetase inhibitor (dazoxiben), a thromboxane receptor antagonist (BM-13177), and ticlopidine, in an experimental DIC model in rats. Experimental DIC was induced by a continuous infusion of lipopolysaccharide (LPS derived from E. coli, 055 B5, 25 mg/kg/hr) for 4 hrs. In the time-course determination of the coagulation parameters and prostanoids, an abrupt increase in TxB2 (a stable metabolite of TxA2) and 6-keto-PGF1 alpha (a stable metabolite of PGI2) was followed by a decrease in platelet count, a prolongation of blood coagulation time, and an increase in fibrinogen/fibrin degradation products (FDP). Four hours after the start of LPS infusion, the rats were considered to be in the state of DIC. The effects of the anti-platelet drugs were investigated 4 hrs after the start of LPS infusion. CS-570 and ticlopidine ameliorated DIC in a dose-dependent manner. CS-570 (10 micrograms/kg/min) improved DIC in the platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fbg), and FDP, without affecting TxB2 and 6-keto-PGF1 alpha formation. Ticlopidine (200 mg/kg, i.p.) prevented the exacerbation of DIC in such item parameters as platelet count, APTT, and FDP. Both dazoxiben and BM-13177 (30 mg/kg, i.p.) ameliorated DIC in following parameters as platelet count, APTT and FDP. Dazoxiben, but not BM-13177, significantly inhibited the increase in TxB2 concentration at 4 hr. These observations suggest that drugs which inhibit platelet activation by a TxA2-dependent route are effective in improving DIC induced by LPS, and that drugs which inhibit multiple platelet-activating routes improve DIC in more item parameters than drugs which inhibit only the TxA2-dependent activating route. Consequently, it is concluded that activated platelets might play an important role in the occurrence and exacerbation of DIC induced by LPS, and that one of the roles of TxA2 in DIC is to activate platelets.
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PMID:Role of activated platelets in endotoxin-induced DIC in rats. 208 Apr 92

The purpose of this investigation was to determine if culture supernatants of Pasteurella haemolytica containing crude leukotoxin and lipopolysaccharide (CLCL) causes disseminated intravascular coagulopathy (DIC) when injected into calves. The effect of intraduodenal (ID) exposure followed by a subsequent subcutaneous (SC) inoculation of either heat-treated or untreated CLCL was evaluated. The relative contribution of the crude leukotoxin and lipopolysaccharide (LPS) to the virulence of P. haemolytica was evaluated. One group of calves received an ID inoculation of CLCL followed two weeks later by a SC inoculation of CLCL; one group received an ID inoculation of tissue culture medium followed two weeks later by a SC inoculation of CLCL; and a third group received an ID inoculation of CLCL followed two weeks later by a SC inoculation of heat-treated CLCL. Hematological parameters used to evaluate DIC included white cell count, platelet count, neutrophil number, fibrinogen, fibrin degradation products, one stage prothrombin time (OSPT), activated partial thromboplastin time, body temperature and clinical signs. Each parameter was measured in calves at 0, 2, 4, 6, 12 and 24 h following the SC inoculation of CLCL. Each group had significant changes over time in all parameters except body temperature. Calves that received a SC inoculation of heat-treated CLCL had smaller changes in all parameters except OSPT compared to the other groups. Results suggest that the LPS and leukotoxin of P. haemolytica exert additive effects on the coagulation cascade and number of peripheral leukocytes, and that the ID inoculation of CLCL does not affect the response of calves to a SC inoculation of toxin.
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PMID:Hematological changes in calves exposed to a mixture of lipopolysaccharide and crude leukotoxin of Pasteurella haemolytica. 224 75

The results of a study conducted to determine the clinico-pathological changes in 4 experimentally-induced cases of endotoxaemia in the horse are reported on. Endotoxaemia was induced by injecting commercially available E. coli 055:B5 lipopolysaccharide intravenously at a dose of 1 microgram kg-1. The haematocrit, red cell count, total and differential white cell counts, thrombocyte count, prothrombin time, partial thromboplastin time, fibrinogen level, level of fibrin degradation products, arterial acid-base status, serum lactate and blood glucose were determined repeatedly. Changes that occurred, include increases in the haematocrit and red cell count, a leucopaenia followed by a leucocytosis caused mainly by changes in the number of neutrophils, the development of disseminated intravascular coagulation, minor changes in the arterial acid base parameters, hyperglycaemia followed by hypoglycaemia and an increase in serum lactate.
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PMID:[Clinico-pathological changes after intravenous administration of endotoxin in the horse]. 248 30

We have studied concurrent production of macrophage agglutination factor (MAggF) and procoagulant activity by antigen-stimulated human blood mononuclear cells to gain insight into biochemical mechanisms underlying delayed hypersensitivity inflammatory reactions. After stimulation of cells from tuberculin-sensitive donors with tuberculin, MAggF was present in culture supernatants while the overwhelming majority of procoagulant activity remained cell-associated. Neither MAggF nor procoagulant activity was found in reconstituted control cultures, nor in tuberculin-stimulated cultures of non-sensitive cells. Concanavalin A and lipopolysaccharide elicited both activities from cultured mononuclear cells, regardless of donor sensitivity. Human MAggF bound to insolubilized gelatin, heparin and a monoclonal anti-fibronectin (FN) antibody, and its activity was inhibited by another monoclonal antibody directed against the gelatin-binding domain of FN. Treatment of indicator peritoneal exudate cells with monoclonal anti-FN receptor antibody inhibited their response to human MAggF. These results suggest that human MAggF, like the analogous guinea-pig activity, is FN-associated. Antigen-elicited procoagulant activity shortened the recalcification time of normal, factor VII- and factor IX-deficient plasma, partially corrected prothrombin times of factor VII-deficient plasma, had no effect on recalcification and prothrombin items of factor X- and factor V-deficient plasma, and was inhibited by specific anti-factor VII antibody. Thus, human mononuclear cell procoagulant consists of both tissue factor and factor VII, whether it is induced by antigen or mitogen. Antigen-stimulated blood mononuclear cells are able to provide a signal for local fibrin deposition and a protein mediating fibrin binding to mononuclear phagocytes and collagen at sites of delayed hypersensitivity reactions.
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PMID:Concurrent production of macrophage agglutination factor and factor VII by antigen-stimulated human peripheral blood mononuclear cells. 293 89

Experimental thrombosis which developed exclusively in glomerular capillary walls was induced in rats by the combined injection of nephrotoxic antiserum (0.2 ml of pooled material) as a preparatory agent and 20 micrograms or more of lipopolysaccharide as a provoking agent. Effects of some antiplatelet and anticoagulant drugs on the glomerular lesions were tested in this experimental glomerular thrombosis. With administration of 2000 units/kg or more of heparin at the time of provoking injection, coagulation time was prolonged for over 5 hr, and the glomerular thrombosis was adequately prevented. Prolongation of prothrombin time (PT) for over 60 sec to prevent thrombosis required warfarin, but with this drug there was only a narrow margin between an effective dose and that which produced a fatal hemorrhage. Low levels of fibrinogen (less than 50 mg/dl) induced by batroxobin seemed to protect partially and high doses of urokinase did not seem to protect from glomerular thrombosis. OP-41483, a derivative of prostacyclin which is about five times more active than PGE1 in inhibiting platelet aggregation, and other anti-platelet drugs except for ticlopidine were not effective in preventing glomerular thrombosis. These findings were in accordance with the fact that thrombocytopenia induced by antiplatelet antiserum did not prevent glomerular thrombosis. Ticlopidine may have a unique and valuable therapeutic potential for the control of this condition.
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PMID:Effect of drug administration on experimental renal glomerular thrombosis. 328 90

An equine antiserum to core lipopolysaccharide was produced by inoculation of 6 horses with a boiled cell bacterin made from the J-5 mutant of Escherichia coli O111:B4. The antiserum immunoglobulin G titer to J-5 mutant E coli, as determined by enzyme-linked immunosorbent assay, was 1:15,006. Pooled serum prepared before inoculation (preimmune serum) had a J-5 immunoglobulin G titer of 1:350. The J-5 antiserum was tested for its protective efficacy in sublethal endotoxemia in 14 horses. Four horses served as nontreated controls and were given nothing before endotoxin challenge exposure (10 micrograms/kg of body weight, IV). Pooled preimmune serum (3 ml/kg, IV) was administered to 5 horses and J-5 antiserum (3 ml/kg, IV) was administered to 5 other horses 2 to 15 hours before endotoxin challenge exposure. During the 24 hours postendotoxin challenge exposure, endotoxemia was accompanied by significant (P less than 0.05) time-related changes in temperature, heart rate, pulse character, respiratory rate and character, capillary refill time, mucous membrane color, fecal composition, attitude, PCV, total plasma protein, WBC count, platelet count, plasma fibrinogen, prothrombin time, activated partial thromboplastin time, fibrinolytic degradation products, plasma glucose, and plasma lactate in all horses. There were no apparent treatment vs time interactions (P greater than 0.05). Two horses (1 control and 1 given J-5 antiserum) died suddenly from unknown causes immediately after endotoxin challenge exposure. Seemingly, equine antiserum to core lipopolysaccharide did not provide protection from the adverse effects of experimental endotoxemia produced by bolus IV infusion of 10 micrograms of endotoxin/kg.
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PMID:Endotoxemia in horses: protection provided by antiserum to core lipopolysaccharide. 351 25


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