PubMed Health⌕ Search

Biomedical subjects

R R Arnold

Publications and source records attributed to R R Arnold.

At least 55 records · Page 3Linked to original sources

Hydrogen peroxide inhibits glucose metabolism and collagen synthesis in bone.

Effects of H2O2 on bone were evaluated in an organ culture system. Tibiae from chick embryos were incubated for up to 3 days in culture medium containing 0.07 to 20 mM H2O2. Glucose metabolism was monitored by measuring lactate production and oxygen consumption, and collagen synthesis was determined by hydroxylation of proline. In addition to markedly inhibiting these parameters, H2O2 also decreased bone weight and alkaline phosphatase activity. Multiple exposures to H2O2 were somewhat more effective than a single exposure. Since H2O2 inhibits bone at low concentrations in vitro, the results suggest that the potential for harmful effects of H2O2 in the oral cavity should be investigated.

Animals↗

Bactericidal effect of lactoferrin on Legionella pneumophila.

Lactoferrin, an iron-binding protein found in mucosal secretions and in specific granules of polymorphonuclear leukocytes, has been shown to be bactericidal for a variety of organisms. In this study, the effect of lactoferrin on Legionella pneumophila was investigated. Purified human apolactoferrin was bactericidal for the Knoxville 1 strain (serogroup 1), with a 4-log decrease in viability within 2 h at 37 degrees C. Killing was dependent on the iron-free state since iron-saturated lactoferrin had no activity. Guinea pig passage of this strain did not affect its sensitivity to lactoferrin. Treatment of the cells with dilutions of the lactoferrin resulted in correspondingly reduced killing. Activity was temperature dependent; there was no loss of viability at 1 or 22 degrees C and slightly enhanced killing at 41 degrees C. Addition of Mg2+ blocked bactericidal activity. In addition, mature human milk, a lactoferrin-containing mucosal secretion, was also bactericidal for L. pneumophila. As demonstrated with the purified lactoferrin, bactericidal activity was lost when the milk was iron saturated.

Animals↗

Neutrophil function in localized juvenile periodontitis. Phagocytosis, superoxide production and specific granule release.

Patients with localized juvenile periodontitis (LJP) exhibit defective neutrophil functions to a variety of environmental and host stimuli. It is not clear, however, how many of the measurable functions are defective and whether individual patients exhibit single or multiple dysfunctions. The purpose of this study was to evaluate chemotaxis, phagocytosis, specific granule release and superoxide production in a group of 23 previously unreported LJP patients. Our results indicate that all 23 of these LJP patients exhibited chemotaxis depression to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) and endotoxin-activated serum (EAS). Smaller groups from the 23 chemotactically defective LJP group were used to test other function due to inability to obtain sufficient quantities of blood. Fourteen of 14 LJP patients tested exhibited defective phagocytosis. Ten LJP patients were evaluated for specific granule release, and 14 LJP patients were evaluated for superoxide production. Both granule release and superoxide production were found to be normal in chemotactically defective LJP patients. Since both defective and normal responses noted in the same neutrophil populations are mediated by the same receptor, it is hypothesized that the cellular defect lies in a post receptor pathway.

Aggressive Periodontitis↗

Interactions between Naegleria fowleri and Legionella pneumophila.

Using electron microscopy we documented some of the intracellular events that occur in Naegleria fowleri suspended in Page amoeba saline after ingestion of Legionella pneumophila. Photomicrographs showed intracellular vacuoles containing bacteria in the process of binary fission that was accompanied by alignment of mitochondria and ribosome-like structures along the vacuole membrane. Although these intracellular events are remarkably similar to that seen in Legionella replication within human monocytes, we could not demonstrate an increase in the number of bacteria by CFU or dark-field microscopy. However, when the Naegleria cells were allowed to ingest Legionella cells while suspended in amoeba culture medium, the number of bacteria increased, and this was contingent upon the presence of viable amoebae.

Amoeba↗

Effects of alpha-amylase on in vitro growth of Legionella pneumophila.

Sterile parotid saliva inhibited growth of Legionella pneumophila on solid media, and the salivary component involved in this inhibition has been shown to be amylase. Disk diffusion and well plate assays were used to study possible mechanisms for this effect. The amylolytic activity of saliva copurified with inhibitory activity, and both activities were sensitive to proteinase K digestion and heat treatment. In addition, purified alpha-amylase from several sources (bacteria, fungi, porcine pancreas, and human saliva) exhibited similar activity. Incorporation of charcoal or bovine serum albumin into media blocked inhibition by amylase. Replacement of Bacto-Agar with Noble agar (both from Difco Laboratories) prevented growth inhibition in the absence of starch. However, when corn starch was present with Noble agar, amylase-induced growth inhibition occurred. Purification of starch by washing with methanol eliminated some toxic component. The toxic component from starch could be recovered from the methanol wash and inhibited growth of L. pneumophila in the absence of amylase activity. The results suggest that toxic substances exist in media components which may be unmasked during salivary amylase digestion of starch. This effect may explain, in part, the difficulty in recovery of the organism from clinical specimens containing amylase.

Amylases↗

Enhancement of Streptococcus mutans colonization by direct bonded orthodontic appliances.

Patients undergoing orthodontic therapy were evaluated for longitudinal changes in relative S. mutans numbers in plaque at discrete sites on the tooth surface associated with direct bond appliances. There was a significant linear increase in the percentage of S. mutans in the total streptococci isolated from the last pre-bracket sample through the last bracket sample.

Adolescent↗

Positive coooperativity in the binding of Streptococcus sanguis to hydroxylapatite.

The adherence of Streptococcus sanguis to hydroxylapatite beads has been analyzed by binding isotherms, Langmuir isotherms, and Scatchard plots. For saliva-coated beads, the Scatchard curves contained components with both positive and negative slopes. The results are interpreted as evidence for positive cooperativity in the binding process. Although all Scatchard curves were similar in shape, distinct differences were observed between saliva samples from different individuals. Salivary agglutinins against whole S. sanguis cells did not appear to influence the shapes of the curves or the extent of adherence. In addition, different strains of S. sanguis yielded similar Scatchard plots. When the binding of S. sanguis to buffer-coated hydroxylapatite beads was analyzed by Scatchard plots or binding isotherms, curves were generated which suggested that either direct ligand-ligand or nonspecific interactions were occurring. Hill plots of the adherence data yielded curves with slopes greater than unity for saliva-coated beads, providing additional support for the view that the interactions between S. sanguis and the pellicle involve cooperative phenomena. In contrast, a Hill plot for the binding data of S. sanguis to buffer-coated hydroxylapatite beads gave a curve with a slope of 0.91 +/- 0.07, suggesting negative cooperativity or limited specificity. When adherence data were plotted by the Langmuir method, curves were obtained which could not discriminate between the binding of the bacteria to the hydroxylapatite beads coated with either saliva or buffer. It was also observed that several different proteins and whole saliva tended to inhibit adherence. Scatchard plots, however, describing the binding of S. sanguis to the proteincoated beads were unique and revealed possible specific and nonspecific interactions. Scatchard analyses of binding data may be useful in understanding the mechanism(s) of adherence of streptococci to smooth surfaces.

Adhesiveness↗

Comparison fo agglutinin titers for Streptococcus mutans in tears, saliva, and serum.

The agglutinin titers for three Streptococcus mutans serotypes (AHT, BHT, and 10449, representing serotypes a, b, and c, respectively) were measured in the saliva, tears, and serum of 19 human subjects. Naturally occurring S. mutans agglutinins were routinely present in all fluids tested in the absence of overt local stimulation by antigen. The immunoglobulin A nature of this secretory agglutinin activity was suggested by blocking with alpha heavy-chain-specific antiserum and by the demonstration of S. mutans-reactive immunoglobulin A in the saliva and tears by indirect immunofluorescence. This finding is consistent with stimulation and antigen commitment of immunoglobulin A precursor lymphocytes at remote sites and subsequent homing to the lacrimal system. The relationship of anti-AHT agglutinins to anti-10449 agglutinins differed among the body fluids tested. The tears had more agglutinins for strain AHT than for strain 10449, whereas the reverse was true for saliva and serum. A possible explanation is local antigen-driven expansion of AHT-reactive committed lymphocytes in the lacrimal tissues.

Adult↗

Bactericidal activity of human lactoferrin: differentiation from the stasis of iron deprivation.

Previous studies have demonstrated a direct iron-irreversible inhibition of a variety of microorganisms by human apolactoferrin. The present study compared the bactericidal effects of lactoferrin on Streptococcus mutans with the bacteriostatic effects of iron deprivation. Growth (as determined by change in optical density) and macromolecular synthesis, as determined by incorporation of (14)C-labeled uracil, thymidine, and lysine, were inhibited by incubation of washed exponential-phase S. mutans NCTC 10449 with purified human apolactoferrin. Similarly, apolactoferrin inhibited glucose uptake and metabolism. Iron-saturated lactoferrin had no effect on bacterial growth or metabolism and was capable of serving as a source of iron in iron-depleted medium. S. mutans failed to grow, and there was no indication of macromolecular synthesis in iron-depleted partially defined medium; however, glucose metabolism continued, though at a reduced rate, and viability was retained for 72 h. There was no detectable metabolism of glucose by cells maintained for 18 h in iron-free medium. Metabolism was restored by transfer of iron-depleted S. mutans to iron-complete medium. This was in contrast to the irreversible inhibition by lactoferrin after 1 h of incubation. Inhibition could not be reversed by removal of cell surface-associated lactoferrin as detected by rhodamine isothiocyanate-labeled antilactoferrin. This inhibition of metabolism and rapid loss in viability observed with lactoferrin treatment suggest that lactoferrin has a direct bactericidal effect on S. mutans that cannot be attributed to simple iron deprivation.

Glucose↗

Bactericidal activity of human lactoferrin: influence of physical conditions and metabolic state of the target microorganism.

Lactoferrin is an iron-binding protein that is bactericidal against Streptococcus mutans and several other microorganisms. In this study, the influence of several physical conditions as well as the metabolic state of S. mutans on lactoferrin susceptibility were investigated. After exposure to lactoferrin, a 15-min lag period occurred before the initiation of killing, indicating that a two-step process is involved in lactoferrin killing. Cultures harvested during the early exponential phase were very sensitive to lactoferrin, whereas cultures harvested in the early stationary phase were markedly more resistant. The rate of killing was dependent on temperature; there was no loss of viability at 2 degrees C. Killing occurred at pH 5.0 to 6.0 in water and 20 mM glycine, but did not occur at any pH in 50 mM sodium phosphate or N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer. Addition of exogenous ferrous or ferric ions did not reverse or prevent lactoferrin killing, nor did addition of 1 mM magnesium chloride.

Humans↗

Bactericidal activity of human lactoferrin: sensitivity of a variety of microorganisms.

Lactoferrin is an iron-binding protein that has been detected in secretions that bathe human mucosal tissues. Previous studies have shown that, when this protein is in the iron-free state, it is capable of a direct bactericidal effect on Streptococcus mutans and Vibrio cholerae. The present study demonstrates variable susceptibilities for a variety of different microorganisms. The list of susceptible organisms includes gram-positive and gram-negative microbes, rods and cocci, facultative anaerobes, and aerotolerant anaerobes. Similar morphological and physiological types are represented among the lalctoferrin-resistant bacteria. S. mutans was more resistant to lactoferrin when grown on a sucrose-contaning medium than when it was grown on brain heart infusion broth without added scurose. When a lactoferrin-sensitive, avirulent strain of Streptococcus pneumoniae was passed through mice, the resultant virulent culture became lactoferrin resistant. Since organisms of the same species and even of the same strain (S. pneumoniae) can differ in susceptibility to lactoferrin, it appears that accessibility to the lactoferrin target site may account for differences in susceptibility. It appears that there may be a relation between virulence and resistance to lactoferrin.

Bacteria↗

Induction of secretory antibodies in humans following ingestion of Streptococcus mutans.

1) Ingestion of Streptococcus mutans antigen by human volunteers induced the selective appearance of antibodies in saliva and tears but not in serum. 2) These antibodies were associated with the IgA class as determined by enhanced or blocked agglutination, immunofluorescence and gel filtration. 3) A second series of antigen ingestion resulted in a secondary response in these secretions characterized by an earlier appearance of antibodies which reached higher titers than in the primary response.

Administration, Oral↗

Concept of the local and common mucosal immune response.

The available information concerning the origin of IgA-producing plasma cells and the spectrum of IgA-associated antibodies found in external secretions provide arguments that support two pathways of stimulation for a secretory humoral immune response. In addition to an explicitly local immune response induced by a topical antigen application, a second mechanism of induction operating through the sensitization of GALT, and possibly BALT, emerges. The latter pathway of stimulation leads to the appearance of specific IgA-associated antibodies in secretions of mammary, salivary, and lacrymal glands (and perhaps other sites), all of which suggests the existence of a common mucosal secretory system. Not yet explained are the mechanisms involved in the homing to secretory glands of cells sensitized in the remote lymphoid tissues (GALT and BALT), the differentiation patterns of these cells, and the regulation of selective IgA expression.

Animals↗

Effective immunity to dental caries: selective induction of secretory immunity by oral administration of Streptococcus mutans in rodents.

1) The selective induction of secretory antibody is antigen dose dependent. A dose of 10(7) or 10(8) S. mutans CFU (per gram of diet) elicited a significant response, while a higher dose (10(9) CFU/gram) resulted in an apparent state of unresponsiveness. 2) A lowly virulent mutant of S. mutans 6715 (C4) induced protective s-IgA antibodies against challenge with a highly virulent species (C211). Cross protection among serotypes of S. mutans has been achieved. 3) Bovine milk with antibodies to S. mutans significantly reduced the level of caries lesions in rats fed this lyophilized milk and challenged with the homologous, virulent S. mutans strains.

Animals↗

Secretory immunity and immunodeficiency.

1) Certain selective IgA-deficient subjects are capable of synthesizing functional secretory antibodies (s-IgM or s-IgA class) to indigenous oral microorganisms. 2) The presence or absence of these secretory antibodies in saliva can be correlated with the extent of caries involvement. 3) Lysozyme activity is significantly increased in saliva from immune deficient subjects though no correlation can be made with caries experience.

Agammaglobulinemia↗