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Biomedical subjects

I Ofek

Publications and source records attributed to I Ofek.

At least 109 records · Page 6Linked to original sources
PubMed1979

Interaction of group A streptococcal lipoteichoic acid with bovine myelin basic protein.

Group A streptococcal lipoteichoic acid (LTA), a polyglycerol phosphate ester linked with fatty acids, formed precipitin lines in agar gels with the positively charged myelin basic protein (MBP) isolated from bovine brain. The LTA-MBP complexes were formed with deacylated teichoic acid and were not inhibited by monomeric glycerol phosphate, a finding indicating the participation of the polyglycerol phosphate (PGP) backbone of LTA in the reaction. Following interaction with PGP, MBP inhibited the agglutination of LTA-sensitized erythrocytes by induction of antibodies to LTA, directed against the PGP antigenic determinant. The amplification of the humoral immune response to the insoluble complex of LTA and MBP was of particular interest in view of the lack of immunogenicity of either LTA or MBP alone.

Antibody Formation↗
PubMed1979

Prevention of colonization of the urinary tract of mice with Escherichia coli by blocking of bacterial adherence with methyl alpha-D-mannopyranoside.

Methyl alpha-D-mannopyranoside (alpha MM), a competitor inhibitor of the binding of mannose by Escherichia coli, was tested for its ability to prevent infection of the urinary tract of mice with infective strains of the organisms. Injection of the bacteria in the presence of the drug resulted in a considerable reduction in the number of bacteriuric mice. In this system alpha MM was inactive against Proteus mirabilis in accordance with its inability to inhibit the adherence of this organism to epithelial cells in vitro, and methyl alpha-D-glucopyranoside proved inactive against both E. coli and P. mirabilis.

Adhesiveness↗
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

Interference with the mannose binding and epithelial cell adherence of Escherichia coli by sublethal concentrations of streptomycin.

When Escherichia coli was grown in sublethal concentrations of streptomycin, mannose binding activity and epithelial cell adherence of the E. coli cultures at stationary phase were significantly reduced in the drug-grown organisms. In a strain whose minimal inhibitory concentrations was 30 mug/ml, the percentage of reduction in mannose binding activity was dose related over a range of concentrations between 0.5 and 10 mug/ml streptomycin. Concomitant with the drug-induced suppression of mannose binding activity, antigenic and ultrastructural alterations on the surface of the drug-grown organisms were observed by agglutination tests and electron microscopy, respectively. The streptomycin effect was reversible, required actively growing organisms, and was most apparent in the early log-phase of growth. High doses of antibiotic were ineffective when added to cultures which had acquired mannose binding activity. An isogenic derivative with high-level resistance to streptomycin was obtained as a single-step mutation from the test E. coli strain. Whereas the isogenic mutant possessed mannose binding activity and adhering ability similar to the parent strain, it was resistant to the streptomycin-induced suppression of the two activities at enormous concentrations (up to 10,000 mug/ml) of streptomycin. Taken together the results suggest that the suppression of epithelial cell adherence and mannose binding activity of E. coli grown in sublethal concentrations of streptomycin is a result of classic mechanisms of drug action upon the bacterial ribosome. The results support the possibility that antibiotics may act through mechanisms other than inhibition of growth and bacterial killing to eradicate bacteria from mucosal surfaces.

Antigens, Bacterial↗
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↗
PubMed1978

Influence of pili on the virulence of Proteus mirabilis in experimental hematogenous pyelonephritis.

The ability of heavily and lightly piliated Proteus mirabilis to infect the renal parenchyma was compared in a model of hematogenous pyelonephritis. Cortical abscesses occurred in 13 of 24 rats injected with lightly piliated P. mirabilis but in none of 24 rats challenged with heavily piliated organisms (P less than 0.001). Lightly and heavily piliated organisms were cleared from the vasculature equally rapidly and were also delivered to the kidney in equal numbers. During the first 24 hr, however, titers of the lightly piliated organisms in the kidney increased by 4 logs, whereas the heavily piliated P. mirabilis were virtually all eliminated. Pili are believed to mediate attachment to cell surfaces, and heavy piliation has been correlated with enhanced virulence when P. mirabilis invades the kidney across the pelvic mucosa. The results in this study suggest, however, that pili may adversely affect bacterial survival within the renal parenchyma.

Animals↗
PubMed1978

Mannose binding and epithelial cell adherence of Escherichia coli.

The mannose-binding activity of several isolates of Escherichia coli was monitored by aggregometry with mannan-containing yeast cells. The velocity of yeast cell aggregation was found to correlate with the ability of the organisms to adhere to human epithelial cells. Mannose or its derivatives specifically inhibited or reversed epithelial cell adherence and yeast cell aggregation. Most of the adherent bacteria could be displaced within 30 min from the epithelial cells with methyl alpha-d-mannopyranoside, but not with other sugars tested. Cultures of E. coli were fractionated into nonadherent and adherent populations by adsorption with epithelial cells followed by elution of the adherent bacteria with methyl alpha-d-mannopyranoside. When the methyl alpha-d-mannopyranoside-displaced organisms were washed free of the sugar, they exhibited a high degree of mannose-binding activity and were heavily piliated. In contrast, the nonadherent fraction of organisms lacked detectable mannose-binding activity and were devoid of pili. Our results suggest that the binding activity of a mannose-specific lectin on the surface of E. coli can be quantitated directly on intact organisms, and the observed variations in the amount of mannose-binding activity among human isolates accounts for the variation in adherence of the organisms to mannose residues on epithelial cells.

Antigens, Bacterial↗
PubMed1977

Postnatal development of binding of streptococci and lipoteichoic acid by oral mucosal cells of humans.

The colonization of mucosal cells in the oral cavity of newborn infants was studied at various intervals after birth in an attempt to define the nature of the epithelial binding sites for group A streptococci and their lipoteichoic acid (LTA). Stained smears of buccal mucosal cells showed that the average number of naturally acquired bacteria/cell was zero to one in infants less than one day old, one to four in infants one day old, and 11-19 in infants two days old. Samples of the same mucosal cells were incubated with group A streptococci, and the average number of streptococci bound per cell was 10-31 in infants less than one day old, 33-62 in one-day-old infants, and 75-100 in two-day-old infants. Experiments that were repeated with group B streptococci type III produced similar results. LTA, the substance that mediates the binding of streptococci to epithelial cells, was similarly bound by fewer buccal mucosal cells obtained within 6 hr of birth than cells obtained during the next 48 hr. Streptococcal and LTA binding reached adult levels between 48 and 72 hr after birth. No difference was shown in the streptococcal binding capacity of oral epithelial cell obtained from mothers at term and cells obtained from other normal adults. Preincubation of adult buccal cells with amniotic fluid did not decrease streptococcal binding. These studies demonstrated a scant capacity of the oral mucosal cells of neonates to bind LTA and streptococci and suggest that LTA-binding sites are developed or unmasked during the first few days after birth.

Adult↗
PubMed1977

Interaction of lipoteichoic acid of group A streptococci with human platelets.

The interaction of group A streptococcal lipoteichoic acid (LTA) with mammalian cell membranes was studied in human platelets. The binding of LTA to platelets was platelet concentration and time dependent. Binding approached a maximum within 10 min of incubation. The bound LTA could be displaced by adding a 50-fold excess of unlabeled LTA. An association constant of 1.9 X 10(-7) M was calculated, and only one population of binding sites was detected. Immuno-ferritin labeling of LTA-treated platelets demonstrated a patchy distribution of LTA binding sites on the platelet surface. LTA inhibited collagen- and alpha1 chain-induced platelet aggregation, but not the platelet release reaction, suggesting that the LTA and collagen binding sites on human platelets are distinct. Apparently, LTA binds to platelets and interferes with collagen-induced aggregation although collagen is still able to attach to binding sites to trigger the release reaction.

Binding Sites↗
PubMed1977

Adherence pharyngeal and skin strains of group A streptococci to human skin and oral epithelial cells.

Group A streptococci isolated from skin adhere in greater numbers to human skin epithelial cells than to cells obtained from buccal mucosa whereas streptococci isolated from a throat tend to adhere in greater numbers to buccal epithelial cells than to skin epithelial cells in vitro. M protein-producing strains of group A streptococci did not adhere in significantly greater numbers than M-negative strains. Lipoteichoic acid inhibited binding of streptococci to skin epithelial cells as well as was previously shown for oral epithelial cells. Our results suggest that lipoteichoic acid is more centrally involved than M protein in binding streptococci to skin and mucosal surfaces.

Adhesiveness↗
PubMed1976

Epithelial cell binding of group A streptococci by lipoteichoic acid on fimbriae denuded of M protein.

Group A streptococci were treated with various enzymatic and chemical agents in an attempt to dissociate the type-specific M protein from intact surface "fimbriae." Mild peptic digestion at pH 5.8, which was previously shown to extract serologically active M antigen from intact streptococci had little visible effect on the fimbriae even though virtually all of the M protein was removed as demonstrated by (a) increased susceptibility to phagocytosis, (b) lack of opsonic effect of homologous M antibody on the treated streptococci, and (c) loss of HCl-extractable M protein. These fimbriated streptococci which lacked M protein adhered to human oral mucosal cells equally as well as untreated, fimbriated organisms which retained their M protein. Removal of both fimbriae and M protein by digesting organisms with HCL at pH 2.0 at 94 degrees C. or with trypsin abolished their ability to bind mucosal cells. Electron microscopy of streptococci bound to epithelial cells demonstrated fimbriae radiating from the surface of the organisms to the membrane of the epithelial cells. It is apparent, therefore, that the determinants of streptococcal fimbriae involved in resistance to phagocytosis can be dissociated from those involved in epithelial cell binding. These results are consistent with our previous studies which suggested that fatty acids ester linked with glycerol teichoic acid rather than M protein of streptococci binds the organisms to epithelial cells.

Antigen-Antibody Reactions↗
PubMed1976

Studies on opacity factor production by pharyngeal isolates of group A streptococci.

Production of opacity factor (OF) by 841 pharyngeal isolates of group A streptococci from schoolchildren in Casper, Wyoming was studied along with T- and M-typing of the streptococcal strains. The majority (89%) of M-typable strains were OF-negative in contrast to M-nontypable isolates, 45% of which were OF-positive. There was no apparent relation between the production of OF by the M-nontypable isolates and the type of infection (symptomatic vs. asymptomatic), degree of positivity of initial culture, antistreptolysin O response, and failure to eradicate the organisms by treatment with antibiotics. However, seasonal shifts in the prevalence of M-nontypable OF-positive strains provided evidence of change in streptococcal ecology, such a shift would not have been detected by T-typing alone. Thus, OF production is an additional epidemiologic marker that is helpful in differentiating M-nontypable group A strains that bear common T-antigens.

Child↗
PubMed1976

Chemotactic response of leukocytes to cord factor (trehalose-6,6'-dimycolate).

Cord factor (trehalose-6,6'-dimycolate), a glycolipid extractable from myocobacteria, was chemotactic for peritoneal cells of mice at concentrations from 5 to 25 mug/ml medium, as well as for peripheral white blood cells of mice and humans. At higher concentrations, presumably only macrophages were attracted.

Animals↗