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W A Simpson

Publications and source records attributed to W A Simpson.

85 records · Page 5Linked to original sources
PubMed1980

Fatty acid binding sites of serum albumin as membrane receptor analogs for streptococcal lipoteichoic acid.

The ability of bovine serum albumin to inhibit the binding of group A streptococcal lipoteichoic acid (LTA) to human cells was investigated. Albumin blocked the ability of LTA to sensitize erythrocytes to agglutinate in the presence of anti-LTA in a dose-dependent manner. The inhibition of LTA binding to erythrocytes was demonstrated directly with radiolabeled LTA. At an albumin/LTA molar ratio of 1.5:1, albumin binding of the radiolabeled LTA at erythrocytes was inhibited by 45%. Analysis of the binding of radiolabeled LTA to erythrocytes in the presence of albumin indicated that albumin competitively inhibited the binding of LTA to putative cell membrane receptors, indicating that albumin and erythrocytes both bind to the same moiety on the LTA molecule.

Binding Sites↗
PubMed1980

Lipoteichoic acid-binding and biological properties of T protein of group A streptococcus.

T protein was extracted with trypsin from an avirulent, M protein-deficient, type 1 group A Streptococcus and purified by ammonium sulfate precipitation and anion-exchange chromatography. The latter procedure removed contaminating lipoteichoic acid (LTA) from the T protein, which consisted of a heterogeneous mixture of polypeptides resistant to digestion by trypsin and ranged in molecular size from 160,000 to 200,000 daltons. Threonine, aspartic acid, glutamic acid, lysine, and valine were the most predominant amino acids. The binding of LTA to an affinity column of T protein was reversible with increasing concentrations of ethanol but not with increasing ionic strength. T protein bound less palmitic acid and LTA than did fatty acid-free bovine albumin and did not stimulate human peripheral lymphocytes. Because the surface and cell wall distribution of the T proteins and LTA appear similar, the possibility exists that T proteins and LTA may interact in situ by weakly hydrophobic bonds. Such ligand-ligand interaction may be indirectly involved in the adherence of group A streptococci to host cell membranes that is known to be mediated by LTA.

Amino Acids↗
PubMed1979

Erythrocyte binding properties of streptococcal lipoteichoic acids.

The lipoteichoic acids (LTA) of gram-positive bacteria are known to bind spontaneously to a variety of animal cell membranes. We investigated the biological and biochemical characteristics of the binding of LTA of Streptococcus pyogenes and S. faecalis to human and sheep erythrocytes. The kinetics of the binding of the radiolabeled LTA ([(3)H]LTA) from each of these organisms to erythrocytes was similar. The dissociation constants for sheep and adult human erythrocytes were 1.6 muM and 4.5 muM, respectively, whereas that of human cord blood erythrocytes was approximately 10-fold higher, 31 muM. The number of binding sites for sheep erythrocytes was calculated to be 7.2 x x 10(6) per cell, and that of human erythrocytes, 29 x 10(6) per cell. Binding was reversible. More than 50% of bound [(3)H]LTA was displaced from erythrocytes by a 50-fold excess of unlabeled LTA. LTA prepared from heterologous species of gram-positive bacteria were all inhibitory to the binding of [(3)H]LTA whether derived from S. pyogenes or from S. faecalis. Among a number of potential receptor analogues and other inhibitors tested, including serum albumin, gangliosides Gm(2) and Gm(3), lipopolysaccharide of gram-negative bacteria, and various sugars, only albumin and the gangliosides significantly inhibited LTA binding. Trypsin or neuraminidase treatment of erythrocytes had no effect on LTA binding. Deacylation of [(3)H]LTA abolished binding ability and binding was restored by esterification of the deacylated material with stearoyl chloride, indicating that ester-linked lipids are necessary for membrane binding.

ABO Blood-Group System↗
PubMed1979

Lymphocytes binding and T cell mitogenic properties of group A streptococcal lipoteichoic acid.

We previously reported that lipoteichoic acid (LTA) of group A streptococci binds spontaneously to mammaliam cell membranes via lipid moieties ester-linked to the LTA molecule. We now describe biochemical and immunologic evidence that LTA binds to human and murine lymphocytes as an early event in the induction of mitogenesis in T lymphocytes. The biochemical studies showed that binding of radiolabeled LTA to lymphocytes was lymphocyte-concentration, and temperature dependent, and it reached a maximum in 15 min. Binding was reversible and specific with a dissociation constant of 89 micrometer for adult lymphocytes and 57 micrometer for cord blood lymphocytes. Immunologic studies showed that the LTA was mitogenic only for T lymphocytes. Dose response curves of lymphocyte mitogenesis induced by LTA and the binding of LTA to intact lymphocytes were shown to be related. The results suggest that LTA binds to specific receptor sites on T lymphocytes to trigger the mitogenic response.

Animals↗
PubMed1977

Concanavalin A induced inhibition of cell migration in African green monkey kidney cell cultures.

The effect of concanavalin A (con A) on the mobility of Vero cells into cell free gaps is examined. The movement of cells into these wounds is inhibited by a 30 minute exposure of con A at a concentration of 12.5 ug/ml. The effects of con A on the mobility are dependent on the concentration of the lectin used for treatment as well as the total amount of time the cells are exposed to a given concentration. The con A inhibition is abrogated by alpha-methyl-mannose. The competitive effects of con A inhibition and serum migration stimulation factors are examined. Treatment of the monolayer prior to wounding inhibits as effectively as treatment after wounding, indicating that residual con A on the bed of the wound which the cells cross is not responsible for the demonstrated inhibition.

Cell Line↗
PubMedDate not supplied

Pathogenesis of experimental endocarditis.

Numerous important observations concerning the pathogenesis of infective endocarditis have been made over the past 18 years. Many of these observations have been obtained with animal models of endocarditis in which an indwelling catheter has been used to produce predisposing endocardial lesions for subsequent infection. Unlike several previously used animal models, the catheter-induced endocarditis models have many characteristics similar to infective endocarditis in humans. Key findings regarding microbial adherence and persistence and the host response to endocardial infection have led to a better appreciation of the complex issues operative in the pathogenesis of endocarditis.

Animals↗
PubMedDate not supplied

Attachment of Streptococcus pyogenes to mammalian cells.

Accumulated evidence indicates that lipoteichoic acid (LTA) is centrally involved in the attachment of group A streptococci to epithelial cells of the host. The binding of LTA to a variety of host cells is mediated by the glycolipid end of the LTA molecule, which can form ionic complexes with streptococcal surface proteins, permitting the reorientation of the LTA to expose some of its lipid ends toward the surface of the organism. The ability of albumin to block the adherence of streptococci to epithelial cells and to bind to LTA-M protein but not deacylated LTA-M protein complexes supports the idea that the lipid ends remain free to interact with cell membrane receptors. The cell membrane receptors appear to consist of a lipid-binding region(s) on fibronectin molecules on the surfaces of oropharyngeal epithelial cells. Although streptococci exhibit LTA-sensitive binding to phagocytic cells in a serum-free system, in the presence of serum, they do not; rather, complement bound to the streptococcal cell surface is required for recognition by phagocytes. The binding of fibrinogen to the M protein on the surface of M-rich streptococci specifically blocks the recognition of the organisms by opsonic complement components. The attachment of M-rich streptococci to phagocytic cells requires the development of antibodies directed specifically toward regions of M protein not blocked by fibrinogen.

Adhesiveness↗
PubMedDate not supplied

Interactions of fibronectin with streptococci: the role of fibronectin as a receptor for Streptococcus pyogenes.

Current evidence suggests that lipoteichoic acid (LTA) on the surface of Streptococcus pyogenes is centrally involved in the adherence of these bacteria to the oral mucosa. The major receptor on the surface of buccal mucosal cells for S. pyogenes is fibronectin. Fibronectin is a complex glycoprotein found in blood, extracellular matrices, and saliva. Many species of streptococci bind to fibronectin, although the characteristics of these interactions are different. Furthermore, whereas LTA is an efficient inhibitor of the binding of fibronectin to group A streptococci, it has little ability to inhibit the binding of fibronectin to Streptococcus pneumoniae or Staphylococcus aureus. Studies conducted with fibronectin show that different bacteria bind to different sites. The ability of various bacteria to interact with different domains on the fibronectin molecule may play an important role in bacterial adherence and tissue tropism.

Animals↗
PubMedDate not supplied

Benzalkonium chloride: a potential disinfecting irrigation solution.

OBJECTIVE: To determine the disinfecting properties of benzalkonium chloride as an irrigation agent. DESIGN: Comparison was made between irrigation of contaminated muscle strips with benzalkonium chloride and normal saline (control). SUMMARY OF BACKGROUND DATA: Benzalkonium chloride is a cationic disinfectant, which has questionable efficacy in an organic environment. However, no previous study has attempted to use high volumes of this cationic solution to overcome the neutralizing effect of organic tissue and thus maintain this detergent's germicidal properties. METHODS: 2.5 cm x 0.5 cm x 0.5 cm pieces of bovine muscle were aseptically cut from the center of freshly harvested beef muscle and incubated with 1.0 x 10(7) colony forming units of bacteria for 15 minutes. The muscle strips were then irrigated with either 100 mL, 1 L, or 10 L of benzalkonium chloride at a 1:2000 concentration in normal saline. Normal saline was used as the control. The muscle strips were sonicated to remove adherent bacteria; the number of living organisms was determined by quantitatively culturing the sonicate. RESULTS: In vitro, benzalkonium chloride was superior to normal saline at disinfecting bovine muscle (p < or = 0.001). When 10 L of benzalkonium chloride irrigation was used, no living bacteria could be recovered (p < or = 0.012). CONCLUSION: In this experimental setting benzalkonium chloride was an effective disinfection agent, with enhanced activity at large volumes.

Animals↗
PubMedDate not supplied

Comparison of castile soap, benzalkonium chloride, and bacitracin as irrigation solutions for complex contaminated orthopaedic wounds.

OBJECTIVE: The purpose of the present study was to determine the effects of cleaning a contaminated orthopaedic wound with different classes of wound irrigation solutions. STUDY DESIGN: Rats with a contaminated orthopaedic wound were randomized into treatment groups: normal saline (NS), castile soap (CS), benzalkonium chloride (BzC), bacitracin (Abx), or sequential irrigation with BzC, CS, and NS. INTERVENTION: Pseudomonas aeruginosa [P. aeruginosa; 1 x 10(6) colony-forming units (CFU)], or Staphylococcus aureus (S. aureus; 1 x 10(6) CFU) were placed into a paravertebral wound (containing a wire implant placed through a spinous process) and allowed to incubate for fifteen minutes. The wound was then irrigated with three liters of either NS, 0.05 percent CS, 0.03 percent BzC, Abx (33,000 units per liter) or underwent a sequential irrigation treatment (one liter each of BzC, CS, NS). MAIN OUTCOME MEASUREMENTS: The animals were observed daily for wound complications for fourteen days and then killed, and cultures of the wound were obtained. RESULTS: Pseudomonas aeruginosa: Both CS and the sequential irrigation treatment significantly lowered the rate of positive wound cultures when compared with NS (p < 0.05). Irrigation with BzC resulted in a higher rate of positive wound cultures and complications. The sequential irrigation treatment prevented the wound complications associated with irrigation with BzC alone. Staphylococcus aureus: Only BzC irrigation significantly lowered the rate of positive wound cultures when compared with NS (p < 0.05). CONCLUSION: The rate of positive wound cultures due to P. aeruginosa is effectively reduced by irrigation with CS alone or by the sequential irrigation treatment. When used alone, the antiseptic BzC results in a higher rate of positive wound cultures and wound complications. The wound complications seen with irrigation with BzC alone are prevented by the sequential irrigation treatment (BzC followed by CS and NS). The rate of positive wound cultures in this model due to S. aureus is not decreased by irrigation with CS; however, the rate of positive wound cultures is safely and effectively decreased with the use of BzC.

Animals↗