Lipopolysaccharidic materials

Arnold and Brown (1978) reported on the possibility that bacterial endotoxins, which are widespread, could result in hypersensitivity to histamine. These compounds are complex, heat-stable, lipopolysaccharide materials produced primarily by Gram-negative bacteria. They also reported that endotoxin is known to be capable of inducing histamine release in animals (sometimes called endotoxin shock) similar to that seen in anaphylaxis. Baranowski et al. (1990), however, reported extremely low levels of endotoxin in both good tuna and tuna known to have caused illness in humans. 

With regard to synthetic membrane surfaces, complement activation operates solely through the alternative pathway (40). The biological role of the alternative pathway is to act as a defense mechanism against endotoxin Introduced into the circulation. Endotoxin is a lipopolysaccharide material and has... 

The alternative pathway may become activated by lipopolysaccharides, endotoxin (sepsis), virus, fungi, immunoglobulin A-antigen (IgA-Ag) immunocom-plexes, and foreign material. These activate C3, after which the common pathway of complement activation takes place (Fig. 4). There are also a number of inhibitors that regulate and control complement activation. The most important are the Cl-esterase inhibitor (Cl-Inh) and the membrane attack complex inhibitor factor (MACIF CD59). In sepsis a relative deficiency of Cl-Inh has been reported. Administration of Cl-Inh to patients with septic shock attenuates complement acti-... 

Endotoxin. Endotoxin is the lipopolysaccharide that comprises a major portion of the cell wall of the gram-negative bacteria. The endotoxins from each species of bacteria are different but the lipid A moiety is similar for the Enterobacterlaceae, and has a similar series of biological actions regardless of its source. The lipid A material is different in some of the gram-negative rods present in cotton (i.e. in the Pseudomonas species). This variety of compounds makes quantitation of endotoxin difficult. Hence, it is usually measured by its biological activity as compared to a standard endotoxin (usually that of E. coll). (See Table VIII.)... 

Biological membranes consist primarily of proteins and lip-ids. The relative amounts of these materials vary considerably, depending on the source of the membrane. At one extreme, the inner mitochondrial membrane is about 80% protein and 20% lipid by weight at the other, the myelin sheath membrane is about 80% lipid and 20% protein. The plasma membrane of human erythrocytes contains about equal amounts of protein and lipid. Many membranes also contain small amounts of carbohydrates. These almost always are covalently attached to either proteins (as glycoproteins) or lipids (as glycolipids or lipopolysaccharides). The mitochondrial inner membrane has little or no carbohydrate, but the myelin membrane has about 3% carbohydrate by weight, and the erythrocyte plasma membrane about 8%. 

Hydrolysis by 1% acetic acid for a period of time sufficient to liberate the lipid A gave this material as 10—202 by weight of the entire lipopolysaccharide. Hydrolysis under more-vigorous conditions, followed by analysis for various constituents, as displayed in Table I, showed all of the lipopolysaccharides to... 

The lipid material precipitated upon mild acid treatment of the Boivin-extracted lipopolysaccharide is here termed a lipoidal precipitate. The fatty-acid profile (Table IV) of hydrolyzates of this material shows little variation between the seven lmmunotype strains. If the original lipopolysaccharides are first treated by phenol—water extraction, and the resultant materials then subjected to hydrolysis to release the lipid, the composition of the latter is significantly different it corresponds closely to the classic composition expected for lipid A. It is noteworthy that material extracted by the phenol—water (Westphal) method is rich in the Csaturated acid and in the hydroxy fatty acids having ten and twelve carbon atoms, whereas the and C g saturated acids present in the lipoidal precipitate, as prepared by the Boivin procedure, are absent or present at much lower levels in the lipid prepared by the Westphal procedure -9). It... 

Rheumatoid factors of the IgM and IgG classes have been shown to form immune complexes in serum or joint fluid either by self-association (K17, M4, M26, P13, Sll, W21) or by reaction with native IgG (C4, K17, M4, N5, Sll, W21, W22), and these appear to be the predominant immune complex material in rheumatoid arthritis (C4, Gl, K17, M4, M26, N5, Sll, W21, W22). The primary cause of rheumatoid factor production in rheumatoid arthritis is unknown. However, rheumatoid factors are known to be present in other diseases associated with chronic antigenic stimulation (C14, M14) and can be induced in vitro by stimulation with antigens, autologous aggregated IgG, anti-idiotype reagents, and polyclonal B cell activators such as lipopolysaccharide and Epstein-Barr virus (C4, Dll, F6, F7, Gil, 16, P10, S24). Rheumatoid factors, including IgG rheumatoid factors which form selfassociating intermediate-sized (11-19 S) complexes, play a major role in... 

Adjuvants can be classified into two main groups based on their mechanism of action. The first group are particulate materials that act as vaccine delivery systems and target associated antigens into APC. These include emulsions, microparticles, iscoms, and liposomes. The second group are immunostimula-tory and are derived mainly from pathogens. These include lipopolysaccharide... 

In a series of papers, Westphal and his collaborators have reported on many different strains, using phenol-extracted lipopolysaccharides the physical properties were fully described, the antigenic and serological properties were reported, and some of the sugar compositions were given. The product of Escherichia coli 08 was described in the most detail the material was composed of 26 % of lipide and 74% of polysaccha-... 

Adsorbents are used in medicine mainly for the treatment of acute poisoning, whereas other extracorporeal techniques based on physico-chemical principles, such as dialysis and ultrafiltration, currently have much wider clinical applications [1]. Nevertheless, there are medical conditions, such as acute inflammation, hepatic and multi-organ failure and sepsis, for which mortality rates have not improved in the last forty years. These conditions are usually associated with the presence of endotoxin - lipopolysaccharide (LPS) or inflammatory cytokines - molecules of peptide/protein nature [2]. Advantages of adsorption over other extracorporeal techniques include ability to adsorb high molecular mass (HMM) metabolites and toxins. Conventional adsorbents, however, have poor biocompatibility. They are used coated with a semipermeable membrane of a more biocompatible material to allow for a direct contact with blood. Respectively, ability of coated adsorbents to remove HMM solutes is dramatically reduced. In this paper, preliminary results on adsorption of LPS and one of the most common inflammatory cytokines, TNF-a, on uncoated porous polymers and activated carbons, are presented. The aim of this work is to estimate the potential of extracorporeal adsorption technique to remove these substances and to relate it to the porous structure of adsorbents. 

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