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Biomedical subjects

R L Gregory

Publications and source records attributed to R L Gregory.

At least 109 records · Page 6Linked to original sources

Protective secretory immunoglobulin A antibodies in humans following oral immunization with Streptococcus mutans.

Ingestion of a vaccine containing killed Streptococcus mutans, originally isolated from each volunteer, daily for 10 consecutive days induced increased levels of specific secretory immunoglobulin A (sIgA) antibodies to S. mutans cells and two cell surface proteins, glucosyltransferase and surface antigen I/II, in parotid saliva and tears of four healthy males and in parotid saliva, tears, colostrum, and milk of a pregnant woman. In addition, these antibodies inhibited glucosyltransferase activity. Both IgA1 and IgA2 antibodies were induced. The levels of IgA antibodies in all secretions remained significantly above preimmunization levels for more than 50 days after oral administration of antigen. A second series of immunizations for 7 consecutive days resulted in even higher levels of sIgA antibodies, which peaked earlier and persisted longer than those observed after the primary immunizations. No increase in levels of antibodies in serum were detected in any subject. Antibodies reactive with human heart and kidney antigens could not be detected in saliva, tears, colostrum, milk, or serum samples collected at any time during the immunization regimen. The numbers of viable S. mutans organisms in dental plaque and whole saliva decreased after each series of immunizations, which correlated with increased levels of IgA antibodies in saliva, suggesting that IgA antibodies in saliva were responsible for the reduced adherence of this bacterium. These results indicate that ingested S. mutans antigen induces secretion of specific IgA1 and IgA2 antibodies in saliva, tears, colostrum, and milk, providing further evidence for the existence of a common mucosal immune system.

Administration, Oral↗

Characterization of the serotype e polysaccharide antigen of Streptococcus mutans.

The structure of the Streptococcus mutans serotype e polysaccharide was studied in order to determine the chemical basis of the immunological cross-reactions observed between it and the streptococcal group E polysaccharide. The chemical structure was established using methylation analysis, periodate oxidation, partial methanolysis and 13C NMR spectroscopy. The polysaccharide was found to consist of a polyrhamnose backbone of alternating 2- and 3-linked alpha-L-rhamnose units and sidechain beta-D-glucosyl units linked to the 2-position of rhamnose units in the backbone. This structure of the oligosaccharide repeating unit of the S. mutans serotype e polysaccharide was identical to that of the group-specific polysaccharide of group E Streptococcus. Possible explanations for the previously reported differences in these two polysaccharides are discussed.

Chemical Phenomena↗

Naturally occurring IgA antibodies to ocular and oral microorganisms in tears saliva and colostrum: evidence for a common mucosal immune system and local immune response.

In this study, levels of naturally occurring secretory IgA (sIgA) antibodies to bacterial isolates representative of the microflora of the human eye (Staphylococcus epidermidis and a Corynebacterium species) and the oral cavity (Streptococcus mutans serotypes c and d) were assessed in three different human external secretions. Tears and parotid saliva samples collected at the same time from 22 healthy subjects and colostrum from 11 healthy women (1-14 days post partum) were assessed for sIgA anti-bacterial antibody levels by an enzyme-linked immunosorbent assay. Significantly higher levels (P less than 0.001) of IgA antibodies to Staphylococcus epidermidis and the Corynebacterium sp. were found in tears than in parotid saliva. Furthermore, higher levels of sIgA antibodies to Streptococcus mutans serotype d occurred in parotid saliva than in tears of these subjects. Although levels of salivary sIgA antibodies to S. mutans serotype c were lower than those seen to serotype d, they were not significantly different from those in tears. However, absolute sIgA anti-serotype c antibodies per mg IgA were higher in saliva than in tears. When sIgA antibody levels to the four bacterial strains were assessed in colostrum, the proportion of sIgA antibodies per mg IgA were much lower than seen in tears or saliva. These results suggest that natural sIgA antibodies which occur in human external secretions are induced by antigen ingestion and stimulation of the common mucosal immune system. However, the local presence of antigen at a mucosal site induces greater clonal expression and results in higher levels of sIgA antibodies than at mucosal sites not exposed to local antigenic stimulation.

Adolescent↗

Salivary immunoglobulin A and serum antibodies to Streptococcus mutans ribosomal preparations in dental caries-free and caries-susceptible human subjects.

Caries-free subjects or individuals with low caries susceptibility exhibited significantly higher (P less than 0.001) levels of naturally occurring salivary immunoglobulin A (IgA) and serum IgG, IgA, and IgM antibodies to a Streptococcus mutans ribosomal preparation than subjects with high caries susceptibility. Absorption of saliva and serum samples with S. mutans ribosomal preparations, but not with other S. mutans antigens or with Escherichia coli and Neisseria gonorrhoeae ribosomal preparations, removed the antibody activity. Absorption with Streptococcus sanguis ribosomes and NH4Cl-washed S. mutans ribosomes partially removed the anti-S. mutans ribosome antibody activity. These results provide evidence that naturally occurring salivary and serum antibodies to the S. mutans ribosomal preparation correlate with susceptibility to dental caries.

Antibodies, Bacterial↗

Characterization of immune response to oral administration of Streptococcus sobrinus ribosomal preparations in liposomes.

Gnotobiotic rats gastrically intubated with a total of 12.5 micrograms of Streptococcus sobrinus ribosomal protein incorporated into cholesterol-based liposomes had significantly (P less than or equal to 0.01) fewer carious lesions on their molar surfaces than did nonimmunized infected controls after challenge with a virulent organism. The immunized animals had significantly (P less than or equal to 0.01) lower numbers of molar-adherent S. sobrinus cells and higher levels of salivary immunoglobulin A antibodies to S. sobrinus whole cells and ribosomes than did the control group. Dose-response studies indicated that 12.5 micrograms of S. sobrinus ribosomal protein in liposomes induced slightly higher immune responses than did 62.5, 125.0, and 250.0 micrograms of ribosomal protein incorporated into liposomes. Intubation of rats with up to 250.0 micrograms of S. sobrinus ribosomal protein alone was no more effective in reducing the numbers of molar-adherent S. sobrinus cells than were nonimmunized infected controls, establishing that insertion of ribosomes into liposomes was required for inducing an effective immune response. These results indicate that oral administration of as little as 12.5 micrograms of S. sobrinus ribosomal protein incorporated into liposomes can protect rats from caries formation after challenge with the virulent organism by inducing specific salivary immunoglobulin A antibodies which can inhibit colonization by the challenged S. sobrinus.

Administration, Oral↗

Streptococcus mutans ribosomal preparations: purification and properties.

Ribosomal preparations were obtained from Streptococcus mutans. Sucrose density gradient analyses showed the ribosomes to be 70S and dissociated subunits to be 56S and 34S. The ribosomal preparation contained 57.4% RNA and 42.6% protein and gave an absorption maximum at 260 nm and a minimum at 235 nm and ribosomal particles were approximately 150-180 X 190-220 A as determined by electron microscopy. Immunodiffusion analysis of pooled antiserum raised by injecting the ribosomal preparation into rabbits disclosed precipitin lines with glucosyltransferase and lipoteichoic acid preparations from S. mutans. Gas chromatography showed rhamnose and glucose to be present in the ribosomal preparation indicating the presence of nonribosomal carbohydrate materials. The ribosomes were able to synthesize precipitable polypeptides when exogenous mRNA and tRNA were added and anti-ribosomal antibodies reduced this activity. Protease treatment rendered the ribosomal preparation less immunogenic in rats and less antigenic when the ribosomal preparation was used to coat erythrocytes for passive haemagglutination assays, while RNase treatment of the ribosomal preparation had no effect, suggesting that a protein(s) is the principal immunogenic moiety of the ribosomal antigen. Polyacrylamide gel electrophoresis of the ribosomal preparation revealed 27 protein bands of which five were found to react with hyperimmune rabbit antisera to the S. mutans ribosomal preparation by Western blot analysis. Washing the ribosomal preparation with 1 M NH4Cl did not remove any of the five immunogenic ribosomal protein antigens indicating that these were innate ribosomal proteins.

Amino Acids↗

Prevention of Streptococcus mutans colonization by salivary IgA antibodies.

The levels of salivary and serum IgA, IgG, and IgM antibodies to the seven serotypes (a-g) of Streptococcus mutans were established in 12 laboratory volunteers using a sensitive enzyme-linked immunosorbent assay. Salivary IgA antibody levels to the serotype c organism were significantly lower (P less than 0.005) than antibody levels to the other six serotypes of S. mutans. Similar results were found with a purified S. mutans serotype c carbohydrate. Serum IgG and IgM antibody titers to the serotype c whole cells were significantly higher (P less than 0.05) than to four other S. mutans serotypes (a, e-g). The abilities of S. mutans serotypes c and d to colonize molar tooth surfaces were examined in eight volunteers. S. mutans serotype d was cleared from the tooth surfaces within 24 hr of challenge, whereas S. mutans serotype c was detected in six of the eight volunteers after 2 weeks and in three of eight after 3 weeks. These results provide additional evidence for the role of salivary IgA antibodies in regulating S. mutans infection and suggest that the low levels of salivary IgA antibodies to S. mutans serotype c may contribute to the predominance of this serotype in the U.S. population.

Adult↗

Movement nulling: for heterochromatic photometry and isolating channels for 'real' and 'apparent' motion.

Null measurements given by cancelling forces, voltages, or whatever, are used in physics for gaining 'objectivity'--by avoiding 'subjective' perceptions; but, somewhat paradoxically, null methods can be useful for studying perception itself. Here we consider cancelling opposed movements for photometry with coloured lights, and some recent experiments, carried out with John Harris, on nulling 'real' against opposed 'apparent' motion for teasing out some neural movement channels.

Adaptation, Ocular↗