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

Strain differences in susceptibility to the development of thyroiditis following adult thymectomy and repeated sublethal X-irradiation (4 X 200 rad) were investigated in the rat. Marked strain variation was noted, with AUG and PVG/c rats having the highest incidence and severity of lesion (100 and 80% respectively) whilst CAM rats had a low incidence (9%). WAG and LIS rats occupied an intermediate position. The incidence of autoantibodies to thyroglobulin correlated closely with the strain incidence of thyroiditis (r = 0-87). Fractionation of the sera from thymectomized and irradiated rats by gel filtration chromatography indicated that the bulk of the antibodies to thyroglobulin were of the IgG class. Freund's complete adjuvant, but not lipopolysaccharide, enhanced the rate of development of thyroiditis in thymectomized rats given a shortened series of irradiations. It was not found possible to induce thyroiditis in thymectomized rats by substituting antilymphocyte serum for irradiation as a T cell-depleting agent, despite the fact that the treated rats had markedly reduced responses to phytohaemagglutinin. A combination of thymectomy, three doses of 200 rad, and a development period of 8 weeks were found to be the optimum conditions for induction of severe thyroiditis together with high antibody titres to thyroglobulin. These findings add support for the role of thymus-derived cells in the regulation of autoimmune responses and further suggest that thymectomy, combined with a series of sublethal irradiations, causes a selective depletion of those T cells specifically involved in the suppression of autoimmune reactivity to thyroid components, whilst leaving autoreactive helper T cells unimpaired.
 ...
PMID:Thyroiditis in T cell-depleted rats. Influence of strain, radiation dose, adjuvants and antilymphocyte serum. 108 32

We described previously (W.M. Shafer, L.E. Martin, and J.K. Spitznagel, Infect. Immun. 45:29-35, 1984) the presence of a 37-kilodalton cationic antimicrobial protein (37K CAP) in extracts of granules prepared from human polymorphonuclear granulocytes (PMN). In this investigation, we prepared 37K CAP from PMN granule extracts by sequential ion-exchange and molecular-sieve chromatography and examined its antimicrobial activity against a number of gram-negative and gram-positive bacteria. At concentrations of 5 micrograms/ml or lower, 37K CAP exerted selective antimicrobial activity against gram-negative bacteria. These bacteria included Acinetobacter lwoffii, Escherichia coli, Neisseria gonorrhoeae, Pseudomonas aeruginosa, Pseudomonas cepacia, Salmonella typhi, Salmonella typhimurium, and Shigella sonnei. However, at 5 micrograms of 37K CAP per ml, Proteus mirabilis, Proteus vulgaris, and Serratia marcescens resisted this antimicrobial activity. The bactericidal activity of 37K CAP was greatest in acidic (pH 5.5) as opposed to alkaline (pH 7.5) media. The level of S. typhimurium resistance to 37K CAP correlated with the presence of O antigen in the lipopolysaccharide. In the absence of O antigen repeat units, resistance was proportional to the length of the core oligosaccharide. These results suggest that 37K CAP may contribute significantly to the ability of PMN to kill gram-negative bacteria by nonoxidative means, particularly as the maturing phagolysosome becomes acidified.
 ...
PMID:Late intraphagosomal hydrogen ion concentration favors the in vitro antimicrobial capacity of a 37-kilodalton cationic granule protein of human neutrophil granulocytes. 352 87

The influence of the relA gene on lipopolysaccharide (LPS) biosynthesis and release by Escherichia coli and Salmonella typhimurium was investigated. Similar results were obtained with both species. The incorporation of [3H]galactose into LPS by galE mutants was inhibited by at least 50% (as compared with normal growing controls) during amino acid deprivation of relA+ strains. This inhibition could be prevented by the treatment of the amino acid-deprived relA+ bacteria with chloramphenicol, a known antagonist of the stringent control mechanism. Furthermore, LPS biosynthesis was not inhibited during amino acid deprivation of isogenic relA mutant strains. These results indicate that LPS synthesis is regulated by the stringent control mechanism. Normal growing cells of both relA+ and relA strains released LPS into the culture fluid at low rates. Amino acid deprivation stimulated the rate of LPS release by relA mutants but not by relA+ bacteria. Chloramphenicol treatment markedly stimulated the release of cell-bound LPS by amino acid-deprived relA+ cells. Thus, a low rate of LPS release was characteristic of normal growth and could be increased in nongrowing cells by relaxing the control of LPS synthesis.
 ...
PMID:Control of lipopolysaccharide biosynthesis and release by Escherichia coli and Salmonella typhimurium. 353 Nov 74

Endotoxin(lipopolysaccharide = LPS), cell wall component of gram-negative bacteria, activates monocytes and macrophages to release cytokines, reactive nitrogen intermediates (RNI), and to generate tissue factor(TF) which initiate coagulation. We have purified 7kDa and 18kDa cationic antibacterial proteins (CAP-7 and CAP-18) with LPS-binding and LPS-neutralizing activities from rabbit granulocytes using as an assay the agglutination of erythrocytes coated with Re-LPS. From protein sequencing, CAP-7 was identified as the C-terminal 37 amino acid fragment of CAP-18. Synthetic peptide #197 (identical sequence to CAP-7, Gly1-Try37) and #36-1 (a truncation of CAP consisting of 32 amino acid residues, Gly1-Ala32) showed LPS-binding activity. Each peptide inhibited LPS-induced tissue factor(TF) generation by murine peritoneal macrophages, even added 1-3 hours after stimulation of cells with LPS. C57BL/6 mice treated with #197 were significantly protected from lethal LPS challenge. Peptide #36 also blocked the LPS-induced lethality. These peptides had antibacterial activity to gram-negative bacteria, such as E.coli, S.typhimurium, K.pneumonia, Ps.aeruginosa and also to gram-positive S.aureus (Methicillin sensitive and resistant strains). Both peptides inhibited TF- and Xa-induced plasma clotting. Using synthetic chromotogenic substrates, both CAP7 peptides blocked the coagulation cascade at two sites, activation of factor X to Xa and conversion of Factor II (prothrombin) to factor IIa (thrombin). In vivo treatment of peptide #197 prevented acute lethality in mice injected with tissue factor (rabbit brain thromboplastin). Two other peptides, #32(Gly1-Phe9) and #50(Ile13-Typ37) failed to demonstrate LPS-binding, LPS-neutralizing, antibacterial and anticoagulant activities. The active peptides but not the inactive peptide maintain a putative heparin binding domain at their N-termini. This heparin binding domain is participate in the LPS-binding, LPS neutralizing, antibacterial and anticoagulant activities of CAP7. These active peptides may have a therapeutic potential for treatment for DIC due to sepsis and endotoxin shock.
 ...
PMID:Endotoxin-binding synthetic peptides with endotoxin-neutralizing, antibacterial and anticoagulant activities. 783 55

Inbred CE/J mice have been identified as extremely resistant to azocasein-induced amyloidosis relative to five commonly used inbred strains, A/J, CBA/J, C57BL/6J, C3H/HeN, and SJL/J. The enhanced amyloid resistance in CE/J mice seems to derive from the novel structure of the SAA gene family in CE/J mice, as determined by Southern blot hybridization analysis of SAA gene structure and isoelectric focusing analysis of acute phase SAA proteins in the six inbred strains. In CE/J mice, a single, novel SAA isoform of pI 6.15 is present, whereas in the other strains the amyloidogenic SAA2 isoform (pI 6.3) is codominantly expressed with SAA1 (pI 6.45). Two other inbred strains, PERU and IS/CAM, share common SAA specific HindIII DNA fragments with CE/J mice. Wild-derived Mus musculus mice differ from all of the inbred strains studied, both in SAA gene structure and in the pattern of SAA isoform production; two isoforms, one pI 6.15 and the other pI 6.3 (corresponding to SAA2), were codominantly expressed. Only the pI 6.15 isoform, not SAA1 and 2, was produced by CE/J mice in response to lipopolysaccharide, casein, silver nitrate, interleukin-1, or tumor necrosis factor; tumor necrosis factor was a weaker stimulus than interleukin-1 for the pI 6.15 isoform as it is for SAA1 and 2 production in the other inbred strains. This study provides a new line of evidence supporting the role of precursor structure as a determining factor in murine amyloid A amyloidosis and provides a valuable model for studies of amyloidogenesis.
 ...
PMID:Characterization of the inbred CE/J mouse strain as amyloid resistant. 790 95

The murine cell surface antigen mCD156 is a glycoprotein that is expressed in monocytic cell lines and consists of a metalloprotease domain, a disintegrin domain, a cysteine-rich domain, and an epidermal growth factor-like domain in the extracellular region. The mCD156 gene is composed of 24 exons and 23 introns and spans approximately 14 kilobases. The first exon encodes most of the signal peptide sequence, and the transmembrane region is encoded by a single exon (19). In contrast, the other regions are composed of multiple exons. Of these, exons 7-12 and 12-15 encode a metalloprotease domain and a disintegrin domain, respectively. Sequence analysis of the 5'-flanking DNA revealed many potential regulatory motifs. Chloramphenicol acetyltransferase analysis demonstrated that nucleotides at positions -183, -334, and -623 contained cis-acting enhancing elements in a mouse monocytic cell line, aHINS-B3. Nucleotides at positions -183 and -390 contained elements responsible for lipopolysaccharide (LPS) inducibility, although several other 5'-flanking regions were also involved in LPS responsiveness. Regions -202, -507, and -659 play a role in interferon-gamma inducibility. Some of the potential regulatory motifs and other unknown cis elements may be involved in the constitutive expression, and LPS and interferon-gamma inducibilities. The mCD156 gene was mapped to chromosome 7, region F3-F4.
 ...
PMID:Structure of the murine CD156 gene, characterization of its promoter, and chromosomal location. 921 57

Both nitric oxide and arachidonic acid metabolites have been implicated in pathogenesis of septic shock. We have recently described a model of endotoxin-induced acute lung injury in rats in which nitric oxide synthase is inhibited. The possible interplay between nitric oxide and eicosanoids (thromboxane A2, prostacyclin) in this model have been presently studied. Animals were randomly assigned to four experimental groups which received the following treatment. 1. Lipopolysaccharide (LPS) infusion only, 2 mg.kg-1min-1 during 10 min (LPS group). 2. N omega-Nitro-L-Arginine 10 mg.kg-1 (L-NNA, nitric oxide synthase inhibitor) pretreatment followed by LPS infusion (L-NNA + LPS group). 3. L-NNA and camonagrel 25 mg.kg-1 (CAM, thromboxane synthase inhibitor) pretreatment followed by LPS infusion (L-NNA + CAM + LPS group). 4. L-NNA and iloprost 0.3 microgram.kg-1.min-1(ILO, stable analog of prostacyclin) pretreatment followed by LPS infusion (L-NNA + ILO + LPS group). LPS infusion resulted in a biphasic response in mean arterial blood pressure. A transient but deep fall in arterial blood pressure was followed by a long-lasting hypotension that led to death after 278 +/- 49 min. L-NNA + LPS rats died within 22 +/- 5 min among the symptoms of systemic hypotension and acute lung injury. In L-NNA + CAM + LPS group a significant attenuation of early phase of hypotension occurred and survival time was comparable with that of the LPS group (298 +/- 68 min). In rats of the L-NNA + ILO + LPS group survival time increased insignificantly to 48 +/- 41 min. It is concluded that immediate deleterious effects of lipopolysaccharide in NO-deficient rats are at least partially mediated by thromboxane A2 while prostacyclin cannot replace NO in its pneumoprotective action.
 ...
PMID:Pneumotoxicity of lipopolysaccharide in nitric oxide-deficient rats is limited by a thromboxane synthase inhibitor. 944 13

The aim of the present study was to further characterize the role of alveolar macrophages (AM) in acute human lung inflammation by evaluating their capacity to produce pro-inflammatory cytokines such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8. Patients with severe community-acquired pneumonia (CAP; n=12) and healthy volunteers (n=10) underwent bronchoalveolar lavage (BAL). AM were separated to high purity (>96%) using fluorescence-activated cell sorting. We determined the TNF-alpha, IL-6 and IL-8 cytokine gene expression in AM ex vivo using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Moreover, we measured in vitro unstimulated, lipopolysaccharide (LPS)- and LPS/interferon-gamma inducible TNF-alpha, IL-6 and IL-8 cytokine release and evaluated samples of BAL fluids for the same pro-inflammatory cytokines using an enzyme-linked immunosorbent assay (ELISA). We found increased TNF-alpha, IL-6 and IL-8 messenger ribonucleic acid (mRNA) levels in AM from CAP patients that were significantly elevated only for IL-8. When challenged with endotoxin in vitro, AM obtained from CAP patients showed a strongly reduced potential to release TNF-alpha and IL-6 compared to healthy controls, whereas IL-8 secretion did not differ significantly between groups. Moreover, stimulation of AM from CAP patients with LPS plus IFN-gamma augmented TNF-alpha and IL-6 cytokine release to near normal levels. Interestingly, no TNF-alpha protein was measured in BAL samples from CAP patients, whereas IL-6 and IL-8 protein levels were found to be significantly increased. Together, highly purified alveolar macrophages from community-acquired pneumonia patients show relatively low ex vivo tumour necrosis factor-alpha and interleukin-6 but not interleukin-8 messenger ribonucleic acid levels that are associated with a decreased pro-inflammatory cytokine release in vitro which, however, can be restored by concurrent interferon-gamma stimulation.
 ...
PMID:Expression of pro-inflammatory cytokines by flow-sorted alveolar macrophages in severe pneumonia. 959 98

Chloramphenicol acetyltransferase (CAT) transgenic mice, in which the transgene is regulated by the VH promoter and heavy-chain intron enhancer (E mu), were examined to investigate the variation of activity of these cis-acting elements during the late stage of B-cell development. CAT enzyme activity decreased when resting B cells were stimulated through B-cell receptors (BCR) with goat anti-mouse IgM antibodies in vitro. On the other hand, when these B cells were stimulated by lipopolysaccharide (LPS) in vitro, they showed enhanced CAT activity, accompanied by an increase in the number of CD43+ B220+ cells (pro-plasma and plasma cells). In addition, the CAT activities in CD43+ B220+ and PNAhi B220+ cells from immunized mice were higher than those in CD43- B220+ and PNAlo B220+ cells, respectively. These results suggest that the activity of E mu in the context of VH promoter was transiently down-regulated by stimulation through the BCR but enhanced at the pro-plasma and plasma stages.
 ...
PMID:Regulation of promoter and intron enhancer activity in immunoglobulin heavy-chain genes during B-cell differentiation. 965 73

We have evaluated the use of proteinase K (PK)-treated cells isolated from Helicobacter pylori as lipopolysaccharide (LPS) antigens in an immunoblot assay and an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of H. pylori infection. The sera from patients with chronic gastritis, gastric ulcer, duodenal ulcer or gastric cancer, and from healthy adults with or without H. pylori infection were assayed with three commercial serodiagnostic kits (HM-CAP, Helico-G, and G.A.P. II) and novel methods relying on the use of PK-treated cells. The PK-treated cells used in these assays were selected on the basis of their possibility to possess a common epitope in the O-polysaccharides of H. pylori, which is known to be highly immunogenic in humans. Of the sera from these patients, 71-94% were positive with the commercial kits, 97% with immunoblot assay, and 90% with ELISA. On the other hand, of the healthy adults infected with H. pylori, 72-97% were positive with the commercial kits, 86% with immunoblot assay, and 72% with ELISA. PK-treated cells that did not contain the common epitope were unsuitable as an antigen for immunoblot assay or ELISA. Furthermore, the reactivity of these sera reacted specifically with H. pylori PK-treated cells but not with LPSs from other gram-negative bacteria, such as Campylobacter, Proteus, Bordetella, and Salmonella. These results demonstrate that the serological assays relying on the use of H. pylori PK-treated cells possessing a highly antigenic epitope are potentially useful as a serodiagnostic test for H. pylori infection.
 ...
PMID:Utilization of proteinase K-treated cells as lipopolysaccharide antigens for the serodiagnosis of Helicobacter pylori infections. 971 4


1 2 3 4 Next >>