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)

We studied the relationship between serum antibodies to the cross-reactive endotoxin core of Escherichia coli and survival following Pseudomonas aeruginosa septicemia. Core glycolipid was purified from the outer cell membrane of a uridine diphosphate galactose 4-epimerase-deficient rough mutant E. coli (J5 strain), characterized, and used as the antigen in a quantitative enzyme-linked immunosorbent assay (ELISA) to measure core-specific IgG and IgM antibodies. 43 patients with Pseudomonas septicemia, among whom there was a mortality of 42%, were evaluated. Core-specific antibody concentrations in acute sera ranged from 1 to 49 micrograms/ml in the case of IgG and from 1 to 200 micrograms/ml for IgM. Core-specific antibodies of both isotypes were higher in patients who survived compared with those who succumbed to their septicemias (mean, microgram/ml +/- SEM, 26 +/- 3 vs. 14 +/- 4, P = 0.005 for IgG, and 55 +/- 12 vs. 18 +/- 5, P = 0.009 for IgM). Although total IgG levels were also higher in acute sera from survivors compared with nonsurvivors (mean, mg/dl +/- SEM, 1,120 +/- 99 vs. 694 +/- 119, P = 0.004), total IgM levels were virtually identical in the two groups (146 +/- 23 vs. 148 +/- 48, P = 0.52). Conversely, patients with core-specific IgG levels greater than 10 micrograms/ml at the onset of septicemia had better survival than those with levels less than 10 micrograms/ml (79 vs. 14%, P less than 0.001), and patients with core-specific IgM levels greater than 30 micrograms/ml had better survival than those with levels less than 30 micrograms/ml (81 vs. 44%, P = 0.01). In comparison, patients with total IgG levels greater than 1,000 mg/dl also had better survival than those with levels less than 1,000 mg/dl (82 vs. 42%, P = 0.01), while those with total IgM levels greater than 150 mg/dl showed somewhat less improvement in survival compared with those with levels less than 150 mg/dl (71 vs. 50%, P = 0.12). Core-specific IgM was highly correlated with core-specific IgG (r = 0.52), but not with type-specific anti-lipopolysaccharide (r = 0.13) or anti-toxin A (r = 0.12) antibodies, or with total IgG (r = 0.28) or IgM (r = 0.31). In contrast, core-specific IgG correlated somewhat more closely with type-specific antibodies (r = 0.36), and with total IgG (r = 0.51) and IgM (r = 0.52). Stepwise linear discriminant analysis indicated that type-specific antibody levels were the best predictor of outcome, among those antibodies examined, followed by anti-core IgM. Although anti-core IgG, anti-toxin A, and total IgG levels all correlated individually with survival, none augmented the prognostic power of type-specific antibodies in combination with anti-core IgM, which together predicted outcome accurately 73.5% of the time. Host factors not significantly associated with anti-core antibody levels included rapidly fatal underlying disease, age, sex, leukopenia, and prior treatment with cytotoxic drugs. In contrast, prior steroid therapy was associated with low levels of both core-specific IgG and IgM (P < 0.05). These data suggest cross-protective activity against P. aeruginosa septicemia of naturally occurring antibodies to the endotoxin core of E. coli. Anti-core antibodies, particularly of the IgM isotype appear to augment the more specific protective immunity engendered by antibodies to the O-specific side chains of Pseudomonas lipopolysaccharides. This cross-protective immunity likely applies to other Gram-negative pathogens as well.
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PMID:Enhanced survival in Pseudomonas aeruginosa septicemia associated with high levels of circulating antibody to Escherichia coli endotoxin core. 635 57

A purified fraction of the extracellular slime of Pseudomonas aeruginosa, characterized chemically as a glycolipoprotein (GLP), has been identified as responsible for a number of biologic properties of the viable cell. Mice immunized actively or passively against GLP are protected against an otherwise lethal challenge with viable bacteria. GLP is chemically, physically, and antigenically distinct from the lipopolysaccharide of the same strain. An in vivo association of GLP with blood leukocytes has been demonstrated, and the leukopenia in mice following challenge with P. aeruginosa may be accounted for by the subsequent sequestration of a neutrophil-GLP complex in the liver. Anti-GLP serum in the absence of complement mediates the phagocytosis and eventual killing of viable P. aeruginosa by mouse polymorphonuclear leukocytes and unstimulated peritoneal macrophages. A polysaccharide fraction isolated from the GLP is responsible for its protective immunogenicity. Although the lipid moiety governs the leukopenic and lethal capacities, the carbohydrate, specifically the mannose of this moiety, is required for full expression of GLP lethality. Mannose is also an immunodominant sugar.
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PMID:Determinants of the biologic activity of surface slime in experimental Pseudomonas aeruginosa infections. 641 19

Lambs received T-2 toxin at a rate of 0.6 or 0.3 mg/kg body weight per day in a protein reduced diet for 21 days to study the immunological and pathological effects of T-2 toxin in sheep. Blood was collected before T-2 treatment and on days 7, 14 and 21 of the trial for hematological and biochemical examination and for the separation of peripheral blood lymphocytes for the mitogen assay. Myeloid:erythroid ratios were determined from sternal bone marrow samples taken a day before T-2 treatment began, on day 12 and at death (day 22). Lambs treated with 0.6 mg/kg body weight of T-2 toxin daily were leukopenic on day 7 and lymphopenic on days 7 and 14. Also, on day 7, the mitogenic responses of these lambs to the B-cell mitogen, lipopolysaccharide, were significantly depressed and prothrombin times were prolonged. At necropsy, lymphoid atrophy of mesenteric lymph nodes and spleens was most marked in lambs treated with 0.6 mg/kg body weight of T-2 toxin per day. To the authors' knowledge, this is the first report of leukopenia, lymphopenia and lymphoid depletion in ruminants fed T-2 toxin.
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PMID:Experimental T-2 toxicosis in sheep. 664 Apr 13

Hirulog is a thrombin catalytic site inhibitor which exhibits specificity for the anionic binding exosite of alpha thrombin. Here, we have evaluated the effect of Hirulog (1, 5 and 10 mg/kg, 30 min pretreatment) in a rat model of endotoxemia. Intravenous injection of lipopolysaccharide from E. coli (25 mg/kg; serotype 0127:B8) caused decreases in blood pressure which were significantly reduced (about 60%) in animals pretreated with Hirulog. Rat survival to endotoxin was significantly increased in Hirulog pretreated group (5 and 10 mg/kg) up to 24 hours. Hirulog at the dose of 10 mg/kg inhibited both endotoxin-induced leukopenia at 30 and 60 minute points and thrombocytopenia at 30 minute point but not at 90 and 120 minute points. Fibrinogen levels were significantly reduced after 2 hours following endotoxin administration. Pretreatment with Hirulog (5-10 mg/kg i.v.) 30 min prior to administration of endotoxin prevented changes in fibrinogen plasma levels. These results demonstrate that Hirulog-induced inhibition of thrombin is effective in reducing toxic and lethal effects of endotoxin.
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PMID:Hirulog effect in rat endotoxin shock. 747 25

1. A neutrophil recruitment inhibitory factor (NRIF) recovered from the crude supernatant of lipopolysaccharide (LPS)-stimulated macrophages inhibited neutrophil migration following both intratracheal and intravenous administration of LPS, but did not alter the pattern of leukopenia/leucocytosis induced by intravenous LPS. 2. The correlation between airway infiltration by inflammatory cells and hyperreactivity in lungs from actively sensitized and challenged guinea-pigs was investigated by use of NRIF. 3. Increased eosinophil counts were found in the bronchoalveolar lavage fluid from guinea-pigs sensitized with 10 micrograms ovalbumin and challenged at day 14 by the intranasal administration of the antigen. The increase was evident 5 h after challenge and persisted at 24 h. Neutrophil numbers were also increased at this time. Pretreatment with NRIF suppressed the leucocyte increase in the bronchoalveolar lavage fluid. 4. Bronchoconstriction and histamine release induced by 3 ng PAF injected into the isolated lungs were increased in challenged guinea-pigs as compared to sensitized but unchallenged controls. Pretreatment of the animals with NRIF did not interfere with this response, but significantly reduced the bronchoconstriction induced by ovalbumin injection. 5. Even though the increased number of inflammatory cells in bronchoalveolar lavage and airway hyperresponsiveness were concomitant, NRIF inhibited cellular infiltration but failed to alter airway hyperreactivity to PAF, demonstrating that these events may occur independently. Conversely, the inhibition of antigen-induced bronchoconstriction by NRIF suggests that this response is dependent upon the emigration of granulocytes.
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PMID:Interference of a neutrophil recruitment inhibitory factor upon the accumulation of inflammatory cells and airway hyperreactivity in sensitized guinea-pigs after intranasal antigen challenge. 768 May 96

Some studies have suggested that the addition of ciprofloxacin to in vitro cultures of mitogen-stimulated lymphocytes exerts inhibitory effects on cell cycle progression and immunoglobulin (Ig) secretion. We tested the effects of this drug on some immunity parameters in BALB/c mice. Mice treated intraperitoneally with ciprofloxacin (10 mg/kg of body weight per day) for 3 consecutive days and immunized with sheep erythrocytes 24 h after the last injection showed significant suppression of hemolytic IgG-forming cells, whereas the response of IgM-forming cells remained unchanged. When treatment lasted 7 days the response of antibody-forming cells was not modified. When the 3-day treatment was started at 24 h after immunization with sheep erythrocytes, the response of IgM-forming cells was increased, whereas the response of IgG-forming cells was suppressed. Delayed-type hypersensitivity to sheep erythrocytes was significantly suppressed in animals that received the 3-day treatment with ciprofloxacin and were immunized subcutaneously 24 h after the last injection. In vitro proliferation of lymphocytes from ciprofloxacin-treated mice in response to either lipopolysaccharide or concanavalin A was also suppressed. Leukopenia and an increase in the level of granulocyte-macrophage colony-forming cells in bone marrow were also observed in ciprofloxacin-treated mice. These results, together with those from other reports, suggest that modification of the biological responses by ciprofloxacin is a complex phenomenon that may be influenced by several factors.
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PMID:Modification of immune response in mice by ciprofloxacin. 769 98

To examine the role of systemic plasma tumor necrosis factor (TNF) in the septic response following trauma, an endotoxin (lipopolysaccharide (LPS)) challenge was administered to anesthetized mongrel pigs 72 h following either hemorrhagic shock/resuscitation or sham shock. For TNF to be considered a mediator, at least two conditions should be satisfied: a TNF increase should precede other manifestations of the septic response and the magnitude of that increase should correlate with the symptoms. Immediately following resuscitation from shock, hemodynamics were stable, but heart rate, cardiac index (CI), and systemic oxygen delivery (DO2) were elevated 20-60%, and systemic vascular resistance (SVR) was decreased 40%, relative to the preshock baseline. After 72 h, the animals were reanesthetized, reinstrumented, and all hemodynamic values were near normal in both groups. At this point, either 1.5 (shock, n = 2; sham, n = 2), 15 (shock, n = 7; sham, n = 6) or 150 (shock, n = 11; sham, n = 4) micrograms/kg of Escherichia coli LPS was administered intravenously over 30 min. Serial hemodynamic data, complete blood counts, and TNF were recorded for 3 h post-LPS. LPS evoked profound leukopenia and pulmonary hypertension within 15 min that was followed by a hyperdynamic septic response (i.e., progressive arterial desaturation, tachypnea, tachycardia, increased CI, and decreased SVR) and rise in plasma TNF at 60-90 min. In the shock group, LPS-evoked TNF changes were less than or equal to those in the sham group, even though mortality was higher after shock.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma tumor necrosis factor and post-traumatic hyperdynamic sepsis evoked by endotoxin. 773 48

The characteristics of two types of intraperitoneal (i.p.) soilage sepsis models, autologous fecal inoculum (FEC) and a pure culture of Escherichia coli (EC), were studied in 26 male Yucatan minipigs (20-30 kg). Early (1-4 h) and late (24-72 h) changes were different between the two groups. The EC group was characterized early by hypotension, low cardiac output, and increased systemic and pulmonary vascular resistances, along with leukopenia, hypoglycemia, lactacidemia, and elevated blood urea nitrogen. Of the pigs in the EC group that survived the early effects, there were few significant differences in physiological parameters, compared to control pigs, that would indicate ongoing pathological processes. In contrast, the FEC group pigs demonstrated early hypotension, but with increased cardiac output and reduced systemic vascular resistance. Other parameter changes were similar to those seen in the EC pigs, but to a lesser degree, with the exception of elevations in serum lactate dehydrogenase. Also in contrast to the EC group, most of the changes in the FEC group persisted in later days, and FEC pigs demonstrated leukocytosis. There were also greater elevations in circulating lipopolysaccharide (LPS) concentrations in the EC group that returned later to baseline levels. In the FEC group, there were persistently elevated LPS concentrations over 72 h. These observations suggest that pigs challenged with intraperitoneal E. coli demonstrated an initial acute peritonitis and damaging physiologic effects of high levels of circulating LPS. Survivors in this group improved and were physiologically stable after 24 h. Pigs that received i.p. autologous feces developed an early acute peritonitis phase with lower levels of circulating LPS, and later developed pronounced peritoneal reaction as demonstrated by multiple abdominal abscesses, pyogenic granuloma formation, and adhesions with physiological evidence of developing sepsis over 72 h. These observations indicate that i.p. EC models evoke a systemic response not unlike intravenous administration of LPS or EC, however, the FEC model produced a systemic response akin to a slower developing septic process.
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PMID:Porcine peritoneal sepsis: modeling for clinical relevance. 773 52

Bacterial lipopolysaccharide (LPS) can elicit septic shock; however, there is growing evidence that most of its pathophysiological effects are mediated by the release of tumor necrosis factor (TNF) and other cytokines. In turn, LPS-induced TNF production is thought to implicate the activation of intracellular protein kinase C (PKC). In this study, we examined whether pH-sensitive liposomes containing staurosporine (STP), a potent inhibitor of PKC, when injected intravenously would suppress TNF production and reduce mortality in an endotoxin rat model. We found that pretreatment of rats with pH-sensitive STP-liposomes by intravenous administration 1.5 h prior to LPS injection decreased lethality from 80% to approximately 30%. Importantly, this improvement in outcome was associated with significant reductions in TNF serum levels; 1 h after LPS injection serum TNF was 73% lower than in a saline control group, and at 2 h TNF levels were 84% lower. STP-liposome pretreatment also ameliorated the severe reduction in body temperature, characteristic for a hypodynamic shock, that was observed in LPS-challenged rats, but had relatively little effect on the transient leukopenia. We conclude that STP-liposomes can suppress LPS-induced TNF production by the mononuclear phagocytic system, can reduce the symptoms of septic shock, and can increase survival.
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PMID:Staurosporine encapsulated into pH-sensitive liposomes reduces tnf production and increases survival in rat endotoxin shock. 773 68

The role of leukotriene B4 (LTB4) in the pathogenesis of acute lung injury was examined in endotoxemic pigs. In a preliminary study, the activity and specificity of an LTB4-receptor antagonist, LY-306669, were evaluated. In vitro, LY-306669 completely blocked the functional upregulation of phagocyte opsonin receptors induced by LTB4 but had a much smaller effect on opsonin receptor upregulation induced by platelet-activating factor. In pigs treatment with LY-306669 prevented leukopenia induced by injection of authentic LTB4 but had no effect on the hematologic or hemodynamic effects of PAF or U-48816, a thromboxane-A2 mimetic. In a second study, pigs received an intravenous priming dose of lipopolysaccharide (LPS) at time (t) = -18 h and were randomized to receive 1) no further treatment (n = 5), 2) LPS (250 micrograms/kg over 1 h beginning at t = 0 h) and LY-306669 (10 mg/kg bolus and 3 mg.kg-1.h-1 infusion beginning at t = -15 min) (n = 7), or 3) LPS and vehicle (n = 6). Treatment with LY-306669 significantly ameliorated LPS-induced hypoxemia, pulmonary edema, and alveolitis. These data suggest that LTB4 is an important mediator of pulmonary dysfunction and transendothelial migration of neutrophils in LPS-induced acute lung injury.
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PMID:Acute lung injury in endotoxemic pigs: role of leukotriene B4. 777 6


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