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Biomedical subjects

D Malamud

Publications and source records attributed to D Malamud.

At least 55 records · Page 3Linked to original sources
PubMed1988

Bacterial agglutinin activity in the saliva of human identical and fraternal twins.

The major factor in human saliva responsible for the specific aggregation of oral streptococci is a high molecular-weight glycoprotein (agglutinin). To determine if the level of this glycoprotein in whole and parotid saliva was genetically determined, agglutinin activity for Streptococcus sanguis and Streptococcus mutans in saliva obtained from identical and fraternal twins was compared. Evidence for the heritability of agglutinin activity and also parotid flow rate and total protein was obtained. There was no evidence for a significant genetic contribution to salivary sodium concentration.

Adolescent↗
PubMed1988

C31G, a new agent for oral use with potent antimicrobial and antiadherence properties.

C31G, an equimolar mixture of alkyl dimethyl glycine and alkyl dimethyl amine oxide, was evaluated for antimicrobial and antiadherence properties. The efficacy of C31G, its two components, and several commercial mouth rinses was determined in assays measuring inhibition of glycolysis, inhibition of bacterial adherence, and MICs. Inhibition of glycolysis was determined by using a saliva sediment model, with glycolytic activity expressed as the change in pH relative to that of a control. Adherence studies were undertaken with Streptococcus sobrinus 6715 to measure inhibition of adherence to nichrome wires. MICs were determined against selected microorganisms by standard methods. C31G demonstrated broad-spectrum antimicrobial properties, with activity against both gram-positive and gram-negative organisms and Candida albicans, a yeast. C31G inhibited both glycolysis by salivary bacteria and adherence of Streptococcus strains to wire mesh. C31G was more effective in the assays conducted than any commercial formulation tested and was as effective as chlorhexidine. A synergistic effect was demonstrated between the individual components of C31G, and no loss of activity was noted when it was formulated into a mouth rinse vehicle.

Anti-Bacterial Agents↗
PubMed1988

Cloning and expression of a Streptococcus sanguis surface antigen that interacts with a human salivary agglutinin.

Human saliva contains a high-molecular-weight glycoprotein (agglutinin) which binds to specific streptococci in a calcium-dependent reaction leading to the formation of bacterial aggregates. We report the cloning of a gene encoding a surface antigen from Streptococcus sanguis M5 and show that the expressed protein inhibits agglutinin-mediated aggregation and specifically binds the salivary agglutinin in a calcium-dependent fashion. Clones isolated from the immunological screening of S. sanguis M5 genomic libraries with polyclonal antibodies against whole cells were assayed for the ability to compete with S. sanguis for agglutinin. One clone, pSSP-5, expressed antigens of 165 and 130 kilodaltons (kDa) possessing this activity. A 3-kilobase-pair (kbp) insert fragment from this clone was used to screen a genomic library in lambda EMBL3 which resulted in the isolation of clone SSP-5A. This clone contained an insert of 17 kb and expressed proteins of 170 to 205 kDa that reacted with the anti-S. sanguis antibodies. Subcloning of a 5.3-kbp EcoRI-BamHI fragment from SSP-5A produced pEB-5, which expressed streptococcal components that were indistinguishable from SSP-5A. The streptococcal antigen was purified by gel permeation and ion exchange chromatography and shown to potently compete with S. sanguis M5 cells for agglutinin. The antigen also bound purified salivary agglutinin in the presence of 1 mM CaCl2. This binding was inhibited by EDTA. Both the SSP-5 antigen and a 205-kDa protein in surface protein extracts from S. sanguis M5 cross-reacted with antibodies directed against antigen B from S. mutans and SpaA from S. sobrinus 6715. These results indicate that a 205-kDa surface protein that is antigenically related to SpaA and antigen B is involved in the binding of salivary agglutinin to S. sanguis M5.

Agglutinins↗
PubMed1987

Salivary changes in solution pH: a source of individual differences in sour taste perception.

The role of saliva in sour taste perception was investigated in a series of 4 experiments. In one pair of experiments, solution pH was measured before and after acetic, citric or hydrochloric acid solutions were mixed with saliva either normally in the oral cavity or after saliva was directly added to solutions. The results showed that large increases in solution pH occurred over a wide range of acid concentrations and that the changes in pH were related to individual salivary flow rates; greater increases in solution pH occurred among those individuals with higher flow rates. The other pair of experiments measured taste threshold and suprathreshold responses to different volumes of acids. The results demonstrated that individuals with high salivary flow rates were less sensitive to the taste of acids and that large volumes of acid were more easily perceived. The pattern of findings suggest that saliva-induced changes in solution pH are important in sour taste perception.

Adolescent↗
PubMed1986

Identification of a Streptococcus sanguis receptor for salivary agglutinins.

The objective of this study was to characterize a fraction from oral streptococci containing receptor activity for salivary agglutinin molecules. Several species and strains of streptococci were disrupted in a Ribi press. The supernatant was nuclease-treated and subjected to differential centrifugation. Receptor activity in the fractions was measured by the inhibition of saliva-mediated bacterial aggregation. In addition, bacterial strains were tested for their ability to aggregate and to deplete saliva of agglutinin activity. Three patterns of activity were observed: Streptococcus sanguis M5 depleted saliva of agglutinin activity and aggregated well; Streptococcus sanguis CC5A depleted saliva of agglutinin but did not aggregate well; and Streptococcus faecalis S-161 neither depleted saliva of agglutinin nor did it aggregate. The 105,000 g supernatant fractions derived from Ribi-disrupted Streptococcus sanguis M5 and CC5A, but not from Streptococcus faecalis, showed dose-dependent inhibition of saliva-mediated aggregation. This inhibitory activity was non-dialyzable, had the same heat and trypsin sensitivity as that seen with intact bacteria, and was not due to enzymatic digestion of the salivary agglutinin. Iso-electric focusing revealed a single active region with a pI of 5.5 which was clearly separated from the bulk of the bacterial proteins.

Agglutination↗
PubMed1985

Low levels of mercury inhibit the respiratory burst in human polymorphonuclear leukocytes.

The objective of this investigation was to examine the effects of low levels of Hg(II) on the respiratory burst of PMNs by monitoring O2 consumption, superoxide radical formation, and chemiluminescence. Hg(II) at concentrations of 10-100 ng/ml profoundly inhibited zymosan-stimulated human cells. This inhibition was immediate in onset and occurred with minimal loss of cell viability. Effects of Hg(II) on the PMN respiratory burst were compared with those of Sn, Pb, Se, Au, Ag and Cu. Only in the case of Ag and Cu did the inhibitory effects approach those of Hg. The results indicate that Hg(II) may serve as a specific inhibitor of components of the respiratory burst.

Adult↗
PubMed1985

Chemiluminescence and superoxide generation by leukocytes stimulated by polyelectrolyte-opsonized bacteria. Role of histones, polyarginine, polylysine, polyhistidine, cytochalasins, and inflammatory exudates as modulators of oxygen burst.

Human blood leukocytes generate intense luminol-dependent chemiluminescence (LDCL) following stimulation by streptococci and by Gram negative rods which had been preopsonized by cationic polyelectrolytes (histone, poly L-arginine-PARG, poly L-histidine-PHSTD). Streptococci but not Gram negative rods or hyaluronic acid-rich streptococci (group C) also induced intense LDCL following opsonization with the anionic polyelectrolytes-dextran sulfate or polyanethole sulfonate (liquoid) suggesting that the outer surfaces of different bacteria bound anionic polyelectrolytes to different extents. Both normal and immune serum, synovial fluids and pooled human saliva inhibited the LDCL responses induced by streptococci preopsonized with poly cations. On the other hand, bacteria which had been first preopsonized by the various body fluids and then subjected to a second opsonization by cationic ligands ("sandwiches"), induced a very intense LDCL response in leukocytes. Streptococci which had been preopsonized by PARG, histone or by PHSTD also triggered superoxide generation by blood leukocytes, which was markedly enhanced by a series of cytochalasins. PHSTD alone induced the formation of very large amounts of superoxide. Paradoxically, the same concentrations of cytochalasins B or C which markedly boosted the generation of superoxide following stimulation of leukocytes with soluble or particulate ligands, had a strong inhibitory effect on the generation of LDCL. On the other hand cycochalasins failed to inhibit LDCL which had been induced by phorbol myristate acetate (PMA). Peritoneal macrophages which had been harvested from C. parvum-stimulated mice, generated more LDCL and superoxide following stimulation by PARG than macrophages obtained from proteose peptone-stimulated mice. Macrophages which had been activated either by proteose peptone or by C. parvum and cultivated for 2 hours on teflon surfaces, generated much more LDCL than macrophages which had been cultivated for 24 hours on teflon surfaces. Both cationic and anionic polyelectrolytes mimic the effects of antibodies as activators of the oxygen burst in blood leukocytes and in macrophages. Such polyelectrolytes can serve as models to further study leukocyte-bacteria interactions in infectious and inflammatory sites.

Adult↗
PubMed1985

Isolation of matrix vesicles by isoelectric focusing in Pevikon-Sephadex.

We have investigated the use of an isoelectric focusing (IEF) technique for isolating and characterizing matrix vesicles. Focusing was performed on crude preparations of matrix vesicles isolated from collagenase digests of chick epiphyseal cartilage and purified by discontinuous sucrose gradient centrifugation. Crude and partially purified vesicle preparations were subjected to flat bed IEF in a slurry of Pevikon-Sephadex. Partially purified matrix vesicles focused as a narrow band (pI congruent to to 6.5). Alkaline phosphatase, solubilized from matrix vesicles, focused with a pl of 4.0-4.5. The IEF profile of matrix vesicles also differed from that of chondrocyte membranes. Thus, the membrane pls were congruent to to 5.4 and 6.6-7.8, respectively. The latter peak probably corresponded to the pl of the matrix vesicle preparation. This observation lends support to the view that vesicles originate from distinct regions of the chondrocyte membrane.

Alkaline Phosphatase↗
PubMed1985

A comparison of bacterial aggregation induced by saliva, lysozyme, and zinc.

Aggregation of bacteria by zinc and lysozyme was studied and compared with aggregation induced by a high-molecular-weight salivary agglutinin. Each ligand was found to exhibit a unique profile of properties when examined by both a microradiochemical centrifugation assay and a turbidimetric assay. Significant differences in rate of aggregation and bacterial species specificity were noted. Zinc- and lysozyme-mediated aggregations were shown to be calcium independent and to proceed rapidly at 0 degree C, in contrast to the salivary agglutinin. Zinc produced large, asymmetric aggregates, saliva produced intermediate-sized aggregates, and lysozyme produced the smallest aggregates. These size differences are consistent with many of the observed reaction properties.

Agglutinins↗
PubMed1984

Poly-L-arginine and an N-formylated chemotactic peptide act synergistically with lectins and calcium ionophore to induce intense chemiluminescence and superoxide production in human blood leukocytes. Modulation by metabolic inhibitors, sugars, and polyelectrolytes.

Various cationic polyelectrolytes (poly-alpha-amino acids and histones), lectins, the chemotactic peptide, f-methionyl-leucyl-phenylalanine (fMLP), the calcium ionophore A23187, and phorbol myristate acetate (PMA) were investigated regarding their capacity to induce luminol-dependent chemiluminescence (LDCL) and superoxide production by human blood leukocytes. Although when tested individually, poly-L-arginine (PARG), phytohemagglutinin (PHA), concanavalin A (Con A), or fMLP induced only a low to moderate LDCL response, very intense synergistic CL reactions were obtained by mixtures of PARG + PHA, PARG + Con A, PARG + PHA + fMLP, Ca2 + ionophore + PARG + PHA + fMLP, and PARG + PMA. The sequence of addition of the various agents to WBC in the presence of luminol absolutely determined the intensity of the LDCL signals obtained, the highest reactions being achieved when the WBC were preincubated for 2-3 min with A23187 followed by the sequential addition of fMLP, PARG, and PHA. These "multiple hits" induced CL reactions which were many times higher than those obtained by each factor alone. On the other hand, neither poly-L-lysine, poly-L-ornithine, poly-L-histidine, nor poly-L-asparagine, when employed at equimolar concentrations, cooperated efficiently with PHA and fMLP to trigger synergistic LDCL responses in leukocytes. Concomitantly with the induction of LDCL, certain ligand mixtures also triggered the production of superoxide. The LDCL which was induced by the "cocktail" of agents was markedly inhibited by sodium azide (93% inhibition), but to a lesser extent by catalase (10% inhibition) or by superoxide dismutase (20%-60% inhibition). On the other hand, scavengers of singlet oxygen and OH (sodium benzoate, histidine) did not affect the synergistic LDCL responses induced by these multiple ligands. Cytochalasin B also markedly inhibited the LDCL responses induced either by soluble stimuli or by streptococci preopsonized either with histone or with polyanethole sulfonate. The LDCL responses which were induced by mixtures of PARG and concanavalin A were also strongly inhibited by mannose, alpha-methyl mannoside, and poly-L-glutamic acid. The data suggest that the LDCL responses induced by the soluble ligands involved a myeloperoxidase-catalyzed reaction. The possible employment of "cocktails" of ligands to enhance the bactericidal effects of PMNs, macrophages, and natural killer cells on microbial cells and mammalian targets is discussed.

Antimetabolites↗
PubMed1984

Inhibition of bacterial aggregation by serum- and blood-derived proteins.

Human and animal sera contain potent inhibitors of saliva-mediated aggregation of oral streptococci. The inhibitors consist of a high-molecular-weight heat-labile factor and a lower-molecular-weight heat-activated factor. The latter appears to be serum albumin. Analyses of purified blood-derived proteins indicated that several high-molecular-weight proteins (fibrinogen, fibronectin, and ferritin) were able to inhibit aggregation at low concentrations. These data suggest that high-molecular-weight proteins may modulate the aggregation process.

Animals↗
PubMed1984

Extraction and isolation of a leukotoxin from Actinobacillus actinomycetemcomitans with polymyxin B.

A leukotoxin from Actinobacillus actinomycetemcomitans was isolated by a procedure that includes polymyxin B extraction, ion-exchange chromatography, and gel filtration chromatography. The procedure resulted in the recovery of 48% of the toxin with a 99-fold increase in specific activity. The isolated toxin has a molecular mass of 180,000 daltons by gel filtration and 115,000 daltons by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It retains all the major biological characteristics previously documented for crude leukotoxin preparations, including susceptibility to heat and proteolytic enzymes and neutralization by sera from patients with juvenile periodontitis. The isolated leukotoxin destroys human but not rat or guinea pig polymorphonuclear leukocytes and has no apparent effect on human erythrocytes. The availability of the A. actinomycetemcomitans leukotoxin should facilitate studies on its chemistry and mode of action as well as its role in the pathogenesis of human periodontal disease.

Actinobacillus↗
PubMed1983

Characterization of a lymphokine produced by human T cells which inhibits collagen synthesis.

Human lymphocytes, isolated from peripheral blood, were cultured for 48 hr in a defined medium containing 10 mg/ml bovine serum albumin and phytohemagglutinin. A lymphokine which inhibits collagen synthesis by cultured human dermal fibroblasts was purified from the lymphocyte incubation medium by successive steps of ammonium sulfate precipitation, gel filtration chromatography, and isoelectric focusing. Good recovery of this collagen synthesis inhibitory factor (CSIF) was obtained and a factor with an approximate molecular weight of 55,000 and a pI of 6.2 was isolated. The purification of the factor should permit further studies on its mechanism of action.

Chromatography, Gel↗
PubMed1983

Modulation of bacterial aggregation by PMN and platelet extracts.

Human parotid saliva contains agglutinins which bind to the surface of streptococci and induce the formation of bacterial aggregates. Bacterial aggregation can be blocked by proteins released from viable PMNs and platelets or by sonic extracts prepared from these cells. PMN and platelet inhibitors display characteristic differences in molecular weight, protease, and temperature sensitivity. The mechanism of action of the inhibitors appears to involve a direct interaction with the salivary agglutinins rather than with the bacteria. It is thus possible that PMN and platelet-derived products might modulate saliva-mediated bacterial aggregation and thereby influence the course of infections in the oral cavity.

Agglutinins↗
PubMed1982

Characteristic differences between saliva-dependent aggregation and adhesion of streptococci.

Comparison of saliva-mediated aggregation of Streptococcus sanguis, Streptococcus mitis, and Streptococcus mutans and adhesion of these organisms to saliva-coated hydroxyapatite showed that there was no relationship between these two activities. Adsorption of salivary aggregating activity to bacteria appears to have little effect on the ability of the residual saliva to support adherence; conversely, adsorption of salivary adherence factors to hydroxyapatite does not affect aggregation. Although heating saliva significantly reduces bacterial aggregation, it has little or no effect on adherence. A comparison of aggregation and adhesion with serial dilutions of saliva demonstrated that adhesion could still be detected at 100 to 500-fold-lower concentrations of salivary protein that bacterial aggregation. These findings support the concept that aggregation and adherence involve two distinct mechanisms of microbial clearance in the oral cavity.

Adhesiveness↗
PubMed1982

Enhanced saliva-mediated bacterial aggregation and decreased bacterial adhesion in caries-resistant versus caries-susceptible individuals.

A study of saliva-mediated aggregation and adhesion has been carried out in a group of caries-resistant (CR) and caries-susceptible (CS) individuals. The submandibular saliva of the CS group had a much greater potency, as determined by dilution, in promoting adherence to hydroxyapatite beads than did the saliva of CR group. In contrast, the CR group demonstrated a twofold enhancement of saliva-mediated aggregation compared with the CS group. These observations support the hypothesis that saliva-mediated aggregation and adherence are important factors in caries resistance.

Adhesiveness↗