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)

Major outer membrane antigens, proteins, and lipopolysaccharides (LPSs), from nontypable Haemophilus influenzae were characterized and examined as targets for complement-dependent human bactericidal antibodies. Outer membranes from two nontypable H. influenzae isolates that caused otitis media and pneumonia (middle ear and transtracheal aspirates) were prepared by shearing organisms in EDTA. These membranes were compared with membranes prepared independently by spheroplasting and lysozyme treatment of whole cells and found to have: similar sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns of the proteins; identical densities (rho = 1.22 g/cm3); and minimal d-lactose dehydrogenase activity indicating purity from cytoplasmic membranes. Outer membranes were solubilized in an LPS-disaggregating buffer and proteins were separated from LPS by molecular sieve chromatography. The SDS-PAGE patterns of outer membrane proteins (OMPs) from the two strains differed in the major band although other prominent bands appeared similar in molecular weight. LPS prepared by hot phenol water extraction of each of the strains contained 45% (pneumonia isolate) and 60% (otitis isolate) lipid (wt/wt), 49% and 50% carbohydrate (wt/wt), respectively, and less than 1%, 3-deoxy-manno octulosonic acid. Immunoglobulin M (IgM) purified from normal human serum (NHS) plus complement was bactericidal for both strains. Purified immunoglobulin G (IgG) from NHS killed the middle ear isolate and immune convalescent IgM from the serum of the patient with pneumonia killed his isolate. NHS or convalescent serum were absorbed with OMPs and LPS (0.6-110 micrograms) from each of the strains and immune specific inhibition of bactericidal antibody activity by each antigen was determined. OMPs from the pulmonary isolate inhibited bactericidal antibody activity directed against the isolate in both NHS (1.5 microgram of antigen) and immune serum (0.75 microgram of antigen). OMPs (60 micrograms) from the ear isolate also inhibited bactericidal activity in the respective immune serum. LPSs exhibited minimal inhibition (greater than 110 micrograms). Three human sera (two normal, one immune) were selectively depleted of 80% of antibody activity against OMPs (measured by enzyme-linked immunosorbent assay) by affinity chromatography using OMPs from the pulmonary isolate coupled to a solid phase. These OMP antibody-depleted sera also showed an 88% reduction of bactericidal activity against this strain. Immunopurified antibody against OMPs eluted from the solid phase was bactericidal.
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PMID:Characterization of antigens from nontypable Haemophilus influenzae recognized by human bactericidal antibodies. Role of Haemophilus outer membrane proteins. 387 75

A total of 120 Hartley strain guinea pigs were used to investigate the possible role of influenza A in endotoxin-induced otitis media with effusion. Intratympanic inoculation of 0.2 ml physiologic saline solution containing 10(4) plaque-forming units (PFU)/ml of influenza A suspension or 100 ng/ml lipopolysaccharide failed to induce either middle ear effusions or mucociliary pathologies in the tubotympanum. In contrast, intratympanic inoculation 100 ng/ml endotoxin resulted in prolonged mucociliary dysfunction and middle ear effusions when 0.2 ml 10(4) PFU/ml of influenza A was inoculated in the tympanic cavity. The inference is drawn that an influenza A infection might predispose the middle ear to endotoxin-induced otitis media with effusion.
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PMID:Influenza A modification of endotoxin-induced otitis media with effusion in the guinea pig. 846 47

Using a rat model, the authors investigated the role of nitric oxide (NO) in endotoxin-induced middle ear effusion (MEE). After the eustachian tube was obstructed, the middle ear was transtympanically injected with 35 microL of either 1 mg/mL lipopolysaccharide (LPS) or LPS and 1 mmol/L N-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase. Over the next 6 hours, the fluid within the middle ear was collected every 2 hours, and the quantity of albumin in the fluid, an index of vascular leakage, was determined using enzyme-linked immunosorbent assay. L-NAME significantly reduced LPS-induced vascular extravasation into the middle ear. Inoculation of the ear with L-arginine, the substrate for NO synthase, reversed the effects of L-NAME. These results indicate that NO is a mediator of LPS-induced MEE. Therefore, inhibition of NO synthase may represent a novel approach to the treatment of otitis media with effusion.
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PMID:Nitric oxide: a mediator of endotoxin-induced middle ear effusions. 869 94

The clinical efficacy of erythromycin (EM) therapy has been demonstrated in otitis media with effusion (OME). However, the mechanism of action of this drug is not clear. In this study, to elucidate the possible mechanism of action of EM, we examined the effect of the drug on the expression of neutrophil adhesion molecules such as L-selectin and Mac-1. Furthermore, we examined production of leukotrienes B4, C4 (LTB4, C4) and prostaglandin E2 (PGE2) in rat OME induced by injection of a lipopolysaccharide. EM down-regulated L-selectin expression, and inhibited up regulation of Mac-1 expression on peripheral blood neutrophils. Also it inhibited the accumulation of inflammatory cells such as neutrophils and macrophages in middle ear effusion (MEE). Furthermore, EM suppressed the exudation of plasma protein and the production of LTB4, C4 and PGE2, in OME. These results suggest that EM may exert the antiinflammatory effect on MEE through suppression of leukocyte accumulation the middle ear by affecting the expression of adhesion molecules on leukocytes and inhibiting the production of arachidonic acid metabolitis.
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PMID:[Evaluation of the effect of erythromycin on otitis media with effusion in experimental rat models]. 883 Dec 36

The presence of growth factors in the middle ear fluid was examined during lipopolysaccharide-induced otitis media (OM) in the chinchilla. There was a progressive significant increase in the proliferative activity detected in the LPS-free MEF by five days in culture. We conclude that lps indirectly mediates hyperproliferative changes in the middle ear during OM by inducing growth factors.
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PMID:Growth factors during endotoxin-induced otitis media. 897 21

Studies in our laboratory and others have indicated that endotoxin is present in a high percentage of human middle ear effusions, including those that are culture negative. Endotoxin has been identified as one of the most potent inducers of tumor necrosis factor (TNF), but this relationship has not been investigated in regard to the pathogenesis of otitis media. The purpose of this study was to determine whether endotoxin induces the production of TNF in the middle ear. Otitis media was induced in chinchillas by the injection of isolated lipopolysaccharide and middle ear fluids (MEFs) and serum harvested and assayed for TNF content by means of a cytolytic assay using L-929 cells and the Cell Titer 96 assay (Promega, Madison, WI). The MEF pools' TNF concentration ranged from 200 to 1,100 pg/mL MEF. Serum pools did not contain any detectable TNF. The results of the present study suggest that endotoxin induces TNF production locally in the middle ear cleft, which may contribute to the pathogenesis of otitis media via any number of established inflammatory pathways.
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PMID:Tumor necrosis factor during experimental lipopolysaccharide-induced otitis media. 912 15

The mechanisms that regulate mucin release in chronic otitis media with effusion, a leading cause of hearing loss in children, remain largely unknown. We developed an animal model using Sprague-Dawley rats to determine the factors responsible for mucin production in chronic otitis media with effusion. N-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of nitric oxide synthase, was used to investigate the role of nitric oxide in mucin secretion by the middle ear epithelium. All rats underwent eustachian tube obstruction. In the first set of rats, the middle ear was then injected transtympanically with 35 microl of either 300 mOsm Krebs-Ringer bicarbonate buffer (control group) or 1 mg/ml lipopolysaccharide in Krebs-Ringer (experimental group 1). In a second set of rats, the middle ear space was injected with lipopolysaccharide and then infused at a continuous rate for 7 days with either Krebs-Ringer (experimental group 2) or 1 mmol/L L-NAME in Krebs-Ringer (experimental group 3) through an osmotic infusion pump. After 7 days the volume of effusion and the quantity of mucin collected were significantly greater in lipopolysaccharide-exposed ears than in controls. In addition, antimucin immunostaining demonstrated mucous cell hyperplasia in response to lipopolysaccharide. The lipopolysaccharide-induced production of mucin and mucous cell hyperplasia was inhibited in ears treated with lipopolysaccharide and L-NAME. These results suggest that nitric oxide is a mediator in the pathway of mucin secretion in chronic otitis media with effusion.
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PMID:Nitric oxide mediates mucin secretion in endotoxin-induced otitis media with effusion. 912 82

In a rat model, we investigated the role of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in endotoxin-induced middle ear effusions (MEEs). After the eustachian tube was obstructed, the middle ear was transtympanically injected with 35 microL of either 1) 1 mg/ mL lipopolysaccharide (LPS); 2) LPS and 100 micrograms TNF binding protein (TNFbp); 3) LPS and 1 microgram IL-1 receptor antagonist (IL-1ra); or 4) LPS, TNFbp, and IL-1ra. Every 2 hours, the fluid within the middle ear was collected, and the quantity of albumin in the fluid, an index of vascular leakage, was determined by enzyme-linked immunosorbent assay. After 6 hours, the middle ear was fixed for histologic analysis. The TNFbp significantly attenuated vascular extravasation into the middle ear. The IL-1ra did not significantly alter effusion development. These results indicate that TNF, but not IL-1, is a mediator of LPS-induced MEE. Therefore, TNFbp may represent a novel approach to the treatment of otitis media with effusion.
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PMID:Role of tumor necrosis factor and interleukin-1 in endotoxin-induced middle ear effusions. 927 Apr 24

Interleukin-8 possesses chemotactic-activating properties toward neutrophils, and may contribute to the pathogenesis of middle ear inflammation. GRO/CINC-1 is a rat chemokine with structural and functional homology to human interleukin-8, the induction and regulation of which in the middle ear cavity in vivo remains to be established. The production of GRO/CINC-1 in middle ear lavage and gene expression in the middle mucosa was investigated using topical inoculation with lipopolysaccharide (LPS) in the rat in vivo model. GRO/CINC-1 in middle ear lavage showed time- and dose-dependent production under LPS stimulation. The peak of the GRO/CINC-1 production was reached by 4 h after LPS 1 h exposure, whereas the level of production subsequently returned to the level without LPS stimulation at 8 h after LPS stimulation. The topical corticosteroid perfusion in the middle ear after LPS stimulation significantly reduced the production of GRO/CINC-1 in the middle ear cavity compared with that without corticosteroid. At the time of peak production, the expression of GRO/CINC-1 mRNA, evaluated using the polymerase chain reaction, was considerable in the middle ear mucosa. This investigation of the characteristics of interleukin-8-like cytokine in the middle ear cavity using a rat in vivo model has extended the functional concept of chemokines at the initial stage in otitis media.
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PMID:In vivo induction and regulation of interleukin-8-like chemokine GRO/CINC-1 in rat middle ear. 934 69

With current pharmacotherapy, otitis media with effusion (OME) is often recurrent and even develops to become chronic. There is now considerable experimental and clinical evidence that the cilia in the tubotympanum play an important part in the prevention of OME. A herbal medicine, sairei-to, has been shown to stimulate the ciliary activity in vitro, and oral administration of the medicine also stimulated the ciliary activity in the tubotympanum rather than physiological states. This study was designed to investigate whether oral administration of sairei-to could prevent experimental OME in the guinea pig. A total of 120 guinea pigs were used. The control group was treated with intratympanic injection of 0.1 ml of physiologic saline solution. The saline-control group was treated with oral administration of physiologic saline solution for 14 successive days. The low-dosage group and the high-dosage group were treated with oral administration of 120 and 600 mg/kg of sairei-to for 14 successive days, respectively. The saline-control group, the low-dosage group and the high-dosage group were then treated with intratympanic injection of 0.1 ml of lipopolysaccharide solution (100 micrograms/ml) derived from Klebsiella pneumoniae. All 10 animals from the 4 groups were sacrificed 1, 3, and 7 days after the intratympanic injection, to examine ciliary activity, mucociliary clearance time, and mucosal pathology of the tubotympanum. The saline-control group exhibited middle ear effusions and pathologies similar to human OME. The incidence of middle ear effusions in the low-dosage and the high-dosage groups was somewhat reduced compared with the saline-control group. The ciliary activity in the tubotympanum was significantly reduced in the saline-control and low-dosage groups compared with the normal-control group. By contrast, the magnitude of reduction in ciliary activity was much smaller in the high-dosage group. The ciliary activity especially in the Eustachian tube and the middle ear close to the tympanic orifice at 3 and 7 days in the high-dosage group was not significantly different from that in the normal-control group. Mucociliary clearance time in the high-dosage group was not different from that in the normal-control group throughout the observation period. The groups treated with sairei-to, especially the high-dosage group, exhibited much milder pathological changes in the tubotympanum than did the saline-control group. In conclusion, clinical application of sairei-to could be an effective measure to prevent the occurrence of OME and also the recurrence of the disease, especially OME-prone individuals.
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PMID:The herbal medicine, sairei-to, prevents endotoxin-induced otitis media with effusion in the guinea pig. 934 84


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