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)

This study was undertaken to examine, electrophysiologically and immunohistochemically, the effect of endotoxin on the guinea pig cochlea. A bacterial endotoxin (lipopolysaccharide, LPS, 5 mg/ml, 0.2 ml) was injected into the middle ear trans-tympanically. The electrocochleograms were continuously recorded from before to 48 h after the injection with an electrode inserted into the facial canal. Then, the animals were sacrificed by intracardiac perfusion of a fixative, temporal bones were removed and immunohistochemically stained for single-stranded DNA (ssDNA) and caspase 3 (CPP32). ssDNA was detected at 48 h in the stria vascularis and spiral ligament. CPP32 was observed in the stria vascularis, the spiral ligament and the organ of Corti. The threshold of the compound action potential increased significantly at 48 h in the LPS group. These results suggest that the activation of CPP32 and fragmentation of DNA are involved in the dysfunction of the cochlea observed under inflammatory conditions.
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PMID:Detection of apoptotic change in the lipopolysaccharide (LPS)-treated cochlea of guinea pigs. 1150 43

Tumor necrosis factor (TNF)-alpha is important in the pathogenesis of otitis media with effusion (OME). The purpose of this study was to determine the effect of TNF-alpha antagonist on the outcome of lipopolysaccharide (LPS)-induced OME in rats. Otitis media was induced by injecting Pseudomonas aeruginosa LPS transtympanically. Another (combination) group was pretreated with TNF-alpha antagonist, soluble TNF receptor type I (sTNF RI), before transtympanic injection of LPS. Saline and phosphate-buffered saline solutions were used as controls. Twelve hours after the transtympanic injection, otoscopic examination and aspiration of middle ear effusion (MEE) were done. The temporal bones in each group were examined histopathologically, and the vascular permeability of the middle ear mucosa was measured by the Evans blue vital dye technique. In the LPS and combination groups, MEE developed in 90% and 0% of ears, respectively. The combination group showed less inflammation, less mucosal thickening, and significantly decreased vascular permeability as compared to the LPS group. Transtympanic administration of sTNF RI appears to suppress the development of LPS-induced OME. This study suggests that TNF-alpha antagonist, along with antibiotics, may have an adjunctive role in the future treatment of MEE.
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PMID:Effect of inhibitor of tumor necrosis factor-alpha on experimental otitis media with effusion. 1164 23

OBJECTIVE: To investigate the frequency of expression and stability of saccharide epitopes in 178 Haemophilus influenzae (39 type b and 138 non-typable) isolates from blood, cerebrospinal fluid, nasopharynx, pharynx, middle ear, conjunctiva, and pleural and bronchial fluid from symptomatic and asymptomatic children using five murine monoclonal antibodies (MAbs, MAHI 3, 4, 6, 8, 10) specific for the oligosaccharide moiety of the lipopolysaccharide (LPS) of H. influenzae, which recognize defined saccharide structures. METHODS: A whole bacteria enzyme immunoassay (EIA) and colony dot immunoblotting were used to determine the frequency of expression and stability of saccharide epitopes in the 178 H. influenzae isolates. RESULTS: Six main groups of strains were differentiated based on the EIA binding pattern with the MAbs: group A, reactive with all five MAbs (MAHI 3, 4, 6, 8 and 10); group B, reactive with four MAbs (MAHI 3, 6, 8 and 10); group C, reactive with three MAbs (MAHI 3, 6 and 8); group D, reactive with three MAbs (MAHI 3, 6 and 10); group E, reactive with two MAbs (MAHI 3 and 10); group F, reactive with MAb MAHI 3. Group B was the most common classification overall. None of the strains remained non-reactive. The frequencies of the binding patterns among the isolates obtained from different sources appeared to be statistically similar in most of the cases. Indications of phase variation of the LPS epitopes were observed with all the MAbs for strains obtained from all clinical sources as evaluated by colony dot immunoblotting. One of the epitopes displayed 22% phase variation, while four other epitopes were variably expressed, with about 50% on-off expression. CONCLUSIONS: This set of MAbs showed 100% reactivity among the isolates, in both EIA and colony dot immunoblotting, and allowed us to differentiate strains based on the LPS phenotype by whole bacteria EIA. Phase variation was indicated among all the isolates, independent of the source of isolation, and for all five MAbs. The LPS of isolates from different clinical sources often expressed some of the epitopes recognized by the MAbs, and most of the LPS phenotypes appeared at similar frequencies among isolates.
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PMID:Frequencies of lipopolysaccharide-defined epitopes in Haemophilus influenzae type b and non-typable isolates determined with monoclonal antibodies. 1185 81

beta-defensin 2 is produced by a variety of epithelial cell types in the body and exhibits potent antimicrobial activity against a variety of pathogens, including the bacteria that are most commonly associated with otitis media (OM). The human beta-defensin 2 (hBD-2) gene is an NF-kappa B regulated gene and a variety of proinflammatory stimuli can induce its expression. Although the presence of molecules of innate immunity such as lysozyme and lactoferrin has been demonstrated in the middle ear, to date there have been no reports on the expression of beta-defensin 2. In the present study, we demonstrate that beta-defensin 2 is expressed in the middle ear mucosa of humans and rats. We also show that it is expressed in a human middle ear epithelial cell line and that its expression is induced by proinflammatory stimuli such as interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF-alpha), and lipopolysaccharide (LPS). Moreover, we demonstrate that the transcriptional activation of hBD-2 gene by IL-1 alpha is mediated through an Src-dependent Raf-MEK1/2-ERK signaling pathway.
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PMID:Activation of a Src-dependent Raf-MEK1/2-ERK signaling pathway is required for IL-1alpha-induced upregulation of beta-defensin 2 in human middle ear epithelial cells. 1206 67

Growth/differentiation factors 5, 6, and 7 (GDF5/6/7) represent a distinct subgroup within the bone morphogenetic protein (BMP) family of secreted signaling molecules. Previous studies have shown that the Gdf5 gene is expressed in transverse stripes across developing skeletal elements and is one of the earliest known markers of joint formation during embryonic development. Although null mutations in this gene disrupt formation of some bones and joints in the skeleton, many sites are unaffected. Here, we show that the closely related family members Gdf6 and Gdf7 are expressed in different subsets of developing joints. Inactivation of the Gdf6 gene causes defects in joint, ligament, and cartilage formation at sites distinct from those seen in Gdf5 mutants, including the wrist and ankle, the middle ear, and the coronal suture between bones in the skull. Mice lacking both Gdf5 and Gdf6 show additional defects, including severe reduction or loss of some skeletal elements in the limb, additional fusions between skeletal structures, scoliosis, and altered cartilage in the intervertebral joints of the spinal column. These results show that members of the GDF5/6/7 subgroup are required for normal formation of bones and joints in the limbs, skull, and axial skeleton. The diverse effects on joint development and the different types of joints affected in the mutants suggest that members of the GDF family play a key role in establishing boundaries between many different skeletal elements during normal development. Some of the skeletal defects seen in single or double mutant mice resemble defects seen in human skeletal diseases, which suggests that these genes may be candidates that underlie some forms of carpal/tarsal coalition, conductive deafness, scoliosis, and craniosynostosis.
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PMID:Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes. 1260 86

Using immunohistochemistry and Western blot, the expression of inducible nitric oxide synthase (iNOS) in the lateral wall and organ of Corti was examined in normal (unstimulated) and stimulated mice and guinea pigs. The stimuli were: (1). injection of bacterial lipopolysaccharide (LPS, 5 mg/ml) into the middle ear through the tympanic membrane and (2). exposure to a 110 dB SPL (A-weighted) broadband noise, 3 h/day, for three consecutive days. For the unstimulated condition, weak iNOS expression was found in the vascular endothelium, marginal cells, nerve fibers, stereocilia of hair cells and Hensen's cells of the organ of Corti. More intense iNOS fluorescence signals were observed in cochlear tissues (particularly in hair cells and stria vascularis marginal cells) in animals exposed to loud sound or treated with LPS. Although the precise roles of iNOS expression in normal cochlear function have yet to be determined, enhanced iNOS expression following noise exposure and LPS suggests its participation in cochlear pathophysiology, including noise- and inflammatory factor-induced hearing loss.
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PMID:Altered expression of inducible nitric oxide synthase (iNOS) in the cochlea. 1261 16

Otitis media, a common and often recurrent bacterial infection of childhood, is a major reason for physician visits and the prescription of antimicrobials. Haemophilus influenzae is the cause of approximately 20% of episodes of bacterial otitis media, but most strains lack the capsule, a factor known to play a critical role in the virulence of strains causing invasive H. influenzae disease. Here we show that in capsule-deficient (nontypeable) strains, sialic acid, a terminal residue of the core sugars of H. influenzae lipopolysaccharide (LPS), is a critical virulence factor in the pathogenesis of experimental otitis media in chinchillas. We used five epidemiologically distinct H. influenzae isolates, representative of the genetic diversity of strains causing otitis media, to inoculate the middle ear of chinchillas. All animals developed acute bacterial otitis media that persisted for up to 3 wk, whereas isogenic sialic acid-deficient mutants (disrupted sialyltransferase or CMP-acetylneuraminic acid synthetase genes) were profoundly attenuated. MS analysis indicated that WT bacteria used to inoculate animals lacked any sialylated LPS glycoforms. In contrast, LPS of ex vivo organisms recovered from chinchilla middle ear exudates was sialylated. We conclude that sialylated LPS glycoforms play a key role in pathogenicity of nontypeable H. influenzae and depend on scavenging the essential precursors from the host during the infection.
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PMID:Host-derived sialic acid is incorporated into Haemophilus influenzae lipopolysaccharide and is a major virulence factor in experimental otitis media. 1285 65

We studied the damage to the cochlear lateral wall induced by otitis media and the therapeutic effects of intratympanic administration of steroid and nitric oxide (NO) synthase inhibitor. In Sprague-Dawley rats, right middle ear cavities were inoculated with lipopolysaccharide, followed after 30 min by intratympanic administration of dexamethasone, NOS-inhibitor or PBS. Twenty-four hours after lipopolysaccharide inoculation, cochlear blood flow was measured by laser-Doppler flowmetry. Prostaglandin E(1) was topically applied to the round window membrane of the right ear and changes in cochlear blood flow were calculated. Changes of cochlear blood flow were significantly different among the three groups. Increases in cochlear blood flow following PGE(1) application were higher in the group that received NOS-inhibitor. Electron microscopic examination revealed that changes in the stria vascularis were less severe in rats treated with dexamethasone or NOS-inhibitor. Our results show the effectiveness of intratympanic dexamethasone or NOS-inhibitor in treating cochlear lateral wall damage caused by otitis media.
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PMID:A comparative study of intratympanic steroid and NO synthase inhibitor for treatment of cochlear lateral wall damage due to acute otitis media. 1466 37

The middle ear apparatus is composed of three endochondrial ossicles (the stapes, incus and malleus) and two membranous bones, the tympanic ring and the gonium, which act as structural components to anchor the ossicles to the skull. Except for the stapes, these skeletal elements are unique to mammals and are derived from the first and second branchial arches. We show that, in combination with goosecoid (Gsc), the Bapx1 gene defines the structural components of the murine middle ear. During embryogenesis, Bapx1 is expressed in a discrete domain within the mandibular component of the first branchial arch and later in the primordia of middle ear-associated bones, the gonium and tympanic ring. Consistent with the expression pattern of Bapx1, mouse embryos deficient for Bapx1 lack a gonium and display hypoplasia of the anterior end of the tympanic ring. At E10.5, expression of Bapx1 partially overlaps that of Gsc and although Gsc is required for development of the entire tympanic ring, the role of Bapx1 is restricted to the specification of the gonium and the anterior tympanic ring. Thus, simple overlapping expression of these two genes appears to account for the patterning of the elements that compose the structural components of the middle ear and suggests that they act in concert. In addition, Bapx1 is expressed both within and surrounding the incus and the malleus. Examination of the malleus shows that the width, but not the length, of this ossicle is decreased in the mutant mice. In non-mammalian jawed vertebrates, the bones homologous to the mammalian middle ear ossicles compose the proximal jaw bones that form the jaw articulation (primary jaw joint). In fish, Bapx1 is responsible for the formation of the joint between the quadrate and articular (homologues of the malleus and incus, respectively) enabling an evolutionary comparison of the role of a regulatory gene in the transition of the proximal jawbones to middle ear ossicles. Contrary to expectations, murine Bapx1 does not affect the articulation of the malleus and incus. We show that this change in role of Bapx1 following the transition to the mammalian ossicle configuration is not due to a change in expression pattern but results from an inability to regulate Gdf5 and Gdf6, two genes predicted to be essential in joint formation.
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PMID:Bapx1 regulates patterning in the middle ear: altered regulatory role in the transition from the proximal jaw during vertebrate evolution. 1497 94

The purpose of this study was to elucidate the influence of otitis media on blood flow in the lateral wall of the cochlea by means of a model of endotoxin-induced otitis media. The cochlear blood flow (CBF) following lipopolysaccharide inoculation into the middle ear cavities of rats was measured by laser-Doppler flowmetry and compared with that of untreated ears. After this evaluation, the influence on CBF of concomitant use of a nitric oxide synthase inhibitor was also investigated. The first day after inoculation, the CBF of treated ears decreased significantly. This decrease recovered gradually between the 7th and 14th days. With concomitant use of a nitric oxide synthase inhibitor, the decrease in CBF was prevented to some extent. The results showed a functional influence upon CBF by endotoxin-induced otitis media. The significance of prophylactic use of the drug is also discussed in regard to the effect on CBF following otitis media.
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PMID:Changes in cochlear blood flow due to endotoxin-induced otitis media. 1522 27


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