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)

Serum antibody against polyribosylribitol phosphate, the capsular antigen of Haemophilus influenzae type b, confers protection against experimental Haemophilus infection. Antibodies against noncapsular antigens are also protective, but the antigenic specificity of the protective antibodies remains unknown. Antilipopolysaccharide antibody was prepared by immunization of rabbits with boiled H. influenzae type b cells. Antilipopolysaccharide antibodies present in these sera did not protect against experimental Haemophilus bacteremia in infant rats. Antisera were also prepared by immunization of rabbits with live H. influenzae type b bacteria. After absorption of anticapsular and antilipopolysaccharide antibodies, these sera contained antibody to several outer membrane proteins which were accessible on the intact bacterial surface as detected by radioimmune precipitation. These absorbed sera prevented experimental Haemophilus bacteremia in infant rats. Thus, antibodies against noncapsular, non-lipopolysaccharide determinants, possibly against one or more outer membrane proteins, confer protection against experimental H. influenzae type b disease. In contrast, antibodies against lipopolysaccharide are ineffective.
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PMID:Further studies of the role of noncapsular antibody in protection against experimental Haemophilus influenzae type b bacteremia. 660 98

A murine burn wound model was employed to evaluate the relative efficacy of purified Pseudomonas aeruginosa lipopolysaccharide (LPS) and high-molecular-weight polysaccharide as protective immunogens. LPS was found to be both highly immunogenic and protective. As little as three 0.001-microgram doses elicited good immunoglobulin M and G titers and increased the mean lethal dose more than 1,000-fold. The level of protection against a live challenge correlated with antibody titers and was found to be serotype specific. An immunizing regimen which evoked only an immunoglobulin M response was still found to offer substantial protection. Immunization with a high-molecular-weight polysaccharide was also found to be protective. However, approximately 1,000-fold more high-molecular-weight polysaccharide, as compared with LPS, was needed to protect mice to an equivalent degree. Immunization with LPS was found to promote bacterial clearance and prevent establishment of bacteremia. A multivalent LPS vaccine conferred high levels of protection (110- to 53,000-fold) against eight different challenge strains of various serotypes.
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PMID:Protection against fatal Pseudomonas aeruginosa burn wound sepsis by immunization with lipopolysaccharide and high-molecular-weight polysaccharide. 669 8

In an effort to decrease deaths from gram-negative bacteremia and endotoxin shock, we treated bacteremic patients with human antiserum to endotoxin (lipopolysaccharide) core. Antiserum was prepared by vaccinating healthy men with heat-killed Escherichia coli J5; this mutant lacks lipopolysaccharide oligosaccharide side chains, so that the core, which is nearly identical to that of most other gram-negative bacteria, is exposed for antibody formation. In a randomized controlled trial, patients were given either J5 antiserum or preimmune control serum intravenously, near the onset of illness. The number of deaths in the bacteremic patients was 42 of 109 (39 per cent) in controls and 23 of 103 (22 per cent) in recipients of J5 antiserum (P = 0.011). In those with profound shock, mortality was 30 of 39 (77 per cent) in controls and 18 of 41 (44 per cent) in recipients of J5 antiserum (P = 0.003). We conclude that human antiserum to the lipopolysaccharide core can substantially reduce deaths from gram-negative bacteremia.
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PMID:Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli. 675 8

We assessed the ability of a solid-phase radioimmunoassay, modified to allow antigen detection in serum, to detect circulating antigens in granulocytopenic rabbits with Pseudomonas aeruginosa bacteremia. In vitro experiments with Pseudomonas lipopolysaccharide indicated that treatment of serum-lipopolysaccharide mixtures with heat, chloroform, or heparin improved the sensitivity for detecting lipopolysaccharide 8- to 16-fold. Chloroform treatment permitted antigen detection in serum or plasma of bacteremic rabbits in which antigen could be detected poorly or not at all in untreated specimens. However, chloroform-treated specimens occasionally caused dissolution of plastic tubes, resulting in nonspecific binding of 125I-labeled anti-Pseudomonas immunoglobulin G. Heating sera at 56 degree C for 30 min improved antigen detection both in both in lipopolysaccharide-serum mixtures and in bacteremic rabbits. Antigen was detected in the heated serum or plasma of 20% of 20 culture-positive granulocytopenic rabbits, none of 15 culture-negative granulocytopenic rabbits, and none of 38 normal rabbits. Antigen was detected in none of 15 rabbits with 2 to 300 colony-forming units of P. aeruginosa per ml of blood and in 4 of 5 rabbits with > 10(3) colony-forming units per ml. We conclude that circulating antigens are present in the blood of rabbits with high-level P. aeruginosa bacteremia and that these antigens can be detected by solid-phase radioimmunoassay. Further improvements in assay sensitivity will be required to detect antigens, if present, in animals with lower levels of P. aeruginosa bacteremia.
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PMID:Detection of Pseudomonas aeruginosa antigenemia in granulocytopenic rabbits by radiommunoassay. 677 8

The inability to prepare an effective polysaccharide vaccine against group B Neisseria meningitidis was the impetus for these studies. Outer membrane protein vaccines used in our initial studies failed to induce bactericidal antibodies in humans. The particulate nature of these vaccines may have led to their clearance before effective immune stimulation. Less denaturing procedures, therefore, were developed for preparation of serotype 2 protein-containing vaccines. These procedures included isolation of naturally released outer membrane vesicles and selective removal of lipopolysaccharide from the vesicles by the nonionic detergent Brij-96. The resultant protein vaccines were evaluated with and without noncovalently complexed group B meningococcal polysaccharide or polymyxin B sulfate or both. The new vaccines were at least 10-fold more immunogenic in mice and guinea pigs than the previous vaccines when assayed for bactericidal and enzyme-linked immunosorbent assay antibodies. The protein vaccines alone protected guinea pigs from intrachamber infection, and a single 0.1-microgram injection prevented meningococcal bacteremia in mice. Addition of group B polysaccharide to the protein significantly improved the immunogenicity of the protein, and this combined vaccine showed a greater protective effect. Polymyxin B generally reduced the immunogenicity of the vaccines in both mice and guinea pigs.
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PMID:Protection against group B Neisseria meningitidis disease: effect of serogroup B polysaccharide and polymyxin B on immunogenicity of serotype protein preparations. 680 28

Overwhelming infection with gram-negative bacteremia has become the most serious nosocomial infection in compromised patients. Because gram-negative bacteria share a common core lipopolysaccharide, we tried to develop a single vaccine or antiserum that might control these infections regardless of species. We used a mutant of Escherichia coli 0111 (J5) deficient in uridine diphosphate-galactose (UDP-GAL) epimerase and thus unable to attach "0" side chains, so that core lipopolysaccharide was exposed. A vaccine composed of this mutant produced antibody that gave broad protection against lethal infections by different gram-negative bacteria in immunosuppressed animals. The J5 vaccine protected against 98 percent lethal doses of Pseudomonas aeruginosa, and J5 antiserum improved survival tenfold in animals dying of Esch. coli, Klebsiella and Pseudomonas bacteremia. The protection with vaccine or prophylactic antiserum was undiminished in animals challenged six weeks after immunization. Encouraged by these results, we conducted a double-blind trial in patients with gram-negative bacteremia. In those given J5 antiserum, the mortality rate was cut in half and survival from deep shock increased from 28 percent to 82 percent. Because of these preliminary results in 136 patients, the study has been extended to 300 patients and the double blind code will be examined again to see if the early favorable results are confirmed and extended.
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PMID:Immunization against nosocomial infection. 700 92

Reconstituted high-density lipoproteins (rHDLs) have the ability to bind bacterial lipopolysaccharide and to reduce its endotoxin activity in vitro and in vivo. The aim of the present studies was to investigate the therapeutic potential of rHDL in bacteremia models. Gram-negative sepsis was induced in anesthetized rabbits by intravenous infusion of Escherichia coli organisms (4 x 10(9) CFU/kg infused over 2 hours) and treated with appropriate antibiotics. rHDL or placebo was infused either before (prophylaxis) or 1 hour after (therapy) the beginning of the bacterial challenge. In the control groups, the bacterial challenge resulted in transient bacteremia, high plasma levels of lipopolysaccharide, secretion of TNF, and symptoms of sepsis, including hypotension and acidosis. rHDL had no influence on blood bacterial counts; however, plasma lipopolysaccharide levels were significantly reduced. Peak plasma TNF concentrations were reduced after prophylactic but not after therapeutic rHDL administration. Both prophylactic and therapeutic rHDL improved clinical outcome: acidosis was significantly attenuated and blood pressure tended to be higher in the rHDL groups. No effects of rHDL were seen in a similar model of gram-positive sepsis induced by the infusion of Staphylococcus aureus.
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PMID:Protective effects of reconstituted high-density lipoprotein in rabbit gram-negative bacteremia models. 749 May 14

Monoclonal antibodies (MAbs) specific for O polysaccharide or core oligosaccharide/lipid A of Escherichia coli O111:B4 lipopolysaccharide (LPS) were compared in canine septic shock. Animals received O-specific, core-specific, or control murine IgG2a MAbs (or saline) before intraperitoneal implantation of an E. coli O111:B4-infected clot. Animals were further randomized to ceftriaxone or saline. O-specific MAb significantly reduced bacteremia and endotoxemia but not serum tumor necrosis factor. Core-specific MAb significantly increased mean arterial pressure from day 4 to 28 (P = .02). In dogs not receiving ceftriaxone, survival was enhanced by O-specific MAb (4/5) compared with core-specific MAb (0/5) and control (1/8) (P = .03). Survival rates were similar (P = .22) but survival was prolonged in antibiotic-treated animals also receiving O-specific MAb (P = .02 vs. core-specific MAb and controls) or core-specific MAb (P = .08 vs. controls). These data support the complex role of LPS in sepsis and the discrete functional effects of MAbs specific for different elements of LPS.
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PMID:Distinct functional activities in canine septic shock of monoclonal antibodies specific for the O polysaccharide and core regions of Escherichia coli lipopolysaccharide. 751 9

The toxicity of lipopolysaccharide (LPS) is modified by several proteins, such as bactericidal/permeability-increasing protein (BPI) and LPS-binding protein (LBP). BPI and LBP plasma levels were measured in patients with gram-negative (n = 36) or gram-positive (n = 28) bacteremia. Levels of BPI and LBP, which are proteins that neutralize and enhance LPS effects, respectively, were increased before bacteremia was first detected. The BPI/neutrophil ratio, reflecting neutrophil activation, was significantly associated with the presence of sepsis syndrome and death in bacteremic patients: 1.06 (0.11-6.49) versus 0.57 (0.06-3.82) in patients with and without sepsis syndrome (P < .01), respectively, and 0.64 (0.06-3.82) versus 1.02 (0.12-6.49) in survivors and nonsurvivors (P < .05), respectively (ratio in nanograms of BPI per 10(6) neutrophils). High LBP peak levels were significantly associated with the presence of sepsis syndrome (P < .01). No differences in BPI and LBP levels were observed in patients with gram-negative versus gram-positive bacteremia. BPI/neutrophil ratio, as a parameter of neutrophil activation, may be useful in monitoring infectious disease.
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PMID:Lipopolysaccharide toxicity-regulating proteins in bacteremia. 753 50

In this study, we sought to determine the mechanism(s) by which a type-specific anti-lipopolysaccharide monoclonal antibody (an IgG directed against the O-antigen polysaccharide region of Salmonella minnesota lipopolysaccharide) and its F(ab')2 fragments protect during gram-negative bacterial peritonitis and endotoxemia in mice. During peritoneal infection, (1) IgG significantly decreased mortality, bacteremia, and endotoxemia at all time points compared with saline solution pretreatment and (2) F(ab')2 fragments reduced mortality at 24 hours but not thereafter, and had no effect on bacteremia but reduced endotoxemia compared with saline solution pretreatment. In the endotoxin model, IgG pretreatment significantly reduced mortality compared with saline solution pretreatment, while F(ab')2 fragments had no significant effect on mortality. No difference in endotoxemia was observed in mice that received IgG, F(ab')2 fragments, or saline solution pretreatment during endotoxemia. These results suggest that type-specific anti-lipopolysaccharide monoclonal antibodies protect by Fc-mediated clearance of both bacteria and endotoxin.
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PMID:Anti-endotoxin monoclonal antibodies protect by enhancing bacterial and endotoxin clearance. 767 67


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