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Biomedical subjects

J M Tanzer

Publications and source records attributed to J M Tanzer.

At least 19 recordsLinked to original sources
PubMed2006

Streptococcus mutans: fructose transport, xylitol resistance, and virulence.

Streptococcus mutans, the primary etiological agent of human dental caries, possesses at least two fructose phosphotransferase systems (PTSs), encoded by fruI and fruCD. fruI is also responsible for xylitol transport. We hypothesized that fructose and xylitol transport systems do not affect virulence. Thus, colonization and cariogenicity of fruI(-) and fruCD(-) single and double mutants, their WT (UA159), and xylitol resistance (X(r)) of S. mutans were studied in rats fed a high-sucrose diet. A sucrose phosphorylase (gtfA(-)) mutant and a reference strain (NCTC-10449S) were additional controls. Recoveries of fruI mutant from the teeth were decreased, unlike those for the other strains. The fruCD mutation was associated with a slight loss of cariogenicity on enamel, whereas mutation of fruI was associated with a loss of cariogenicity in dentin. These results also suggest why xylitol inhibition of caries is paradoxically associated with spontaneous emergence of so-called X(r) S. mutans in habitual human xylitol users.

Animals↗
PubMed2003

Amylase-binding proteins A (AbpA) and B (AbpB) differentially affect colonization of rats' teeth by Streptococcus gordonii.

Streptococcus gordonii produces two alpha-amylase-binding proteins, AbpA and AbpB, that have been extensively studied in vitro. Little is known, however, about their significance in oral colonization and cariogenicity (virulence). To clarify these issues, weanling specific pathogen-free Osborne-Mendel rats, TAN : SPFOM(OM)BR, were inoculated either with wild-type strains FAS4-S or Challis-S or with strains having isogenic mutations of abpA, abpB, or both, to compare their colonization abilities and persistence on the teeth. Experiments were done with rats fed a sucrose-rich diet containing low amounts of starch or containing only starch. The mutants and wild-types were quantified in vivo and carious lesions were scored. In 11 experiments, S. gordonii was a prolific colonizer of the teeth when rats were fed the sucrose (with low starch)-supplemented diet, often dominating the flora. Sucrose-fed rats had several-fold higher recoveries of inoculants than those eating the sucrose-free, starch-supplemented diet, regardless of inoculant type. The strain defective in AbpB could not colonize teeth of starch-only-eating rats, but could colonize rats if sucrose was added to the diet. Strains defective in AbpA surprisingly colonized better than their wild-types. A double mutant deficient in both AbpA and AbpB (abpA/abpB) colonized like its wild-type. Wild-types FAS4-S and Challis-S had no more than marginal cariogenicity. Notably, in the absence of AbpA, cariogenicity was slightly augmented. Both the rescue of colonization by the AbpB- mutant and the augmentation of colonization by AbpA- mutant in the presence of dietary sucrose suggested additional amylase-binding protein interactions relevant to colonization. Glucosyltransferase activity was greater in mutants defective in abpA and modestly increased in the abpB mutant. It was concluded that AbpB is required for colonization of teeth of starch-eating rats and its deletion is partially masked if rats eat a sucrose-starch diet. AbpA appears to inhibit colonization of the plaque biofilm in vivo. This unexpected effect in vivo may be associated with interaction of AbpA with glucosyltransferase or with other colonization factors of these cells. These data illustrate that the complex nature of the oral environment may not be adequately modelled by in vitro systems.

Animals↗
PubMed2002

Novel sucrose-dependent adhesion co-factors in Streptococcus mutans.

Streptococcus mutans glucosyltransferases form extracellular glucans from sucrose to promote adhesion to the teeth. We tested whether additional factors are involved in S. mutans sucrose-dependent adhesion. By screening a pVA891-insertion mutant library of S. mutans LT11, we isolated four clones deficient in adhesion to glass in the presence of sucrose, but normal in glucosyltransferase activities. The genetic loci flanking the insertion sites were retrieved and identified. They encode glycerol-3-phosphate dehydrogenase, an ABC transporter, a multidrug-efflux pump, and either the ribulose monophosphate operon or ascorbate metabolism operon. The four mutants were analyzed for their phenotypic expression and in vivo colonization in rats. The multidrug efflux pump mutant failed to colonize the rats. Three other mutants colonized the rats by reverting to the wild type. Therefore, these four factors may contribute to S. mutans sucrose-dependent adhesion.

ATP-Binding Cassette Transporters↗
PubMed2001

Oral colonization and cariogenicity of Streptococcus gordonii in specific pathogen-free TAN:SPFOM(OM)BR rats consuming starch or sucrose diets.

The significance of Streptococcus gordonii in dental caries is undefined, as is that of other alpha-amylase-binding bacteria (ABB) commonly found in the mouth. To clarify the ecological and cariological roles of S. gordonii our specific pathogen-free Osborne-Mendel rats, TAN:SPFOM(OM)BR, were fed either diet 2000 (containing 56% confectioner's sugar, most of which is sucrose) or diet 2000CS (containing 56% cornstarch, in lieu of confectioner's sugar) and inoculated with S. gordonii strains. Uninoculated rats were free of both indigenous mutans streptococci (MS) and ABB, including S. gordonii, as shown by culture on mitis salivarius and blood agars of swabs and sonicates of dentitions after weanlings had consumed these diets for 26 days. ABB were detected by radiochemical assay using [125I]-amylase reactive to alpha-amylase-binding protein characteristic of the surface of S. gordonii and other ABB. No ABB were detected (detection limit < 1 colony-forming units in 10(6) colony-forming units). Thus the TAN:SPFOM(OM)BR colony presents a 'clean animal model' for subsequent study. Consequently, S. gordonii strains Challis or G9B were used to inoculate weanling rat groups consuming either the high-sucrose diet 2000 or the cornstarch diet 2000CS. Two additional groups fed each of these diets remained unioculated. Recoveries of inoculants were tested 12 and 26 days later by oral swabs and sonication of the molars of one hemimandible of each animal, respectively. Uninoculated animals were reconfirmed to be free of ABB and mutans streptococci, but inoculated ones eating diet 2000CS had S. gordonii recoveries of 1-10% or, if eating diet 2000, 10-30% of total colony-farming units in sonicates. There were no statistically significant differences among the inoculated and uninoculated animal groups' caries scores when they ate the cornstarch diet. Lesion scores for sucrose-eating rats were, however, from 2.4-5.1-fold higher than for cornstarch-eating rats, P < 0.001, and were still higher if animals had been inoculated with either Challis (1.41-fold) or G9B (1.64-fold), than if uninoculated, both P < 0.001, so long as the rats ate the sucrose diet. Therefore, TAN:SPFOM(OM)BR rats do not harbour ABB or S. gordonii but can be colonized by S. gordonii. Colonization levels of S. gordonii on the teeth are higher in the presence of high sucrose than with high starch-containing diets. Caries scores are augmented by sucrose compared with starch, and are further augmented by S gordonii colonization. S. gordonii is thus cariologically significant in the presence of sucrose, at least in this rat.

Amylases↗
PubMed2001

Caries inhibition in rats by a sodium fluoride, tripolyphosphate toothpaste with whitening and anti-tartar properties.

The anti-caries properties of a silica-based, sodium fluoride (NaF) toothpaste containing sodium tripolyphosphate (NaTPP) with tooth whitening and anti-tartar properties (Aquafresh Whitening), in specific pathogen-free Osborne-Mendel rats, were assessed in this study. A silica-based, fluoride-free placebo containing NaTPP, and a NaF-containing silica-based USP reference standard toothpaste were used as negative and positive control toothpastes, respectively. Sixty weanling rats were randomly distributed into groups of 20; all were inoculated with S. mutans 10449S, ate cariogenic diet 2000, and drank demineralized water ad libitum. Each toothpaste, packaged in coded tubes, was applied to the dentitions of the rats' teeth for one minute, twice daily on weekdays, and once daily on weekends and holidays. Both the NaF/NaTPP-containing and the NaF-containing USP standard toothpaste groups had lower total enamel caries scores (41 to 45%) than the group treated with the fluoride-free NaTPP-containing placebo. Similar dimensioned differences were evident both at smooth surface and sulcal enamel sites, and in dentinal sites. All were statistically significant at p < 0.001. There were no statistically significant differences at any tooth surface category site between the two fluoride-containing toothpastes' effects. It is thus apparent that Aquafresh Whitening has the anticaries benefit of a USP reference standard NaF toothpaste.

Analysis of Variance↗
PubMed2001

The microbiology of primary dental caries in humans.

A systematic literature review from 1966 to 2000 revealed 2,730 English-language publications on the role of bacteria in human primary dental caries in vivo. The most pertinent 313 papers were analyzed in evidence tables accessible online (http://www.nidcr.nih.gov). The search targeted all bacterial types implicated previously in caries and asked two questions. First, what is the association of specific bacteria with tooth decay and can causation be attributed to any of those bacteria? Retrieved studies were categorized as randomized-blinded-interventional, longitudinal, case-control, and cross-sectional and were weighted in descending order in terms of significance. Although many studies, due to ethical requirements, had confounding variables, they still indicate strongly: 1) the central role of the mutans streptococci in initiation of caries of smooth surfaces and fissures of crowns of teeth and suggests their potent role in induction of root surface caries; and 2) that lactobacilli are implicated as important contributory bacteria in tooth decay, but their role in induction of lesions is not well supported. Second, what is the source of infection by cariogenic bacteria? Molecular/genetic studies of implicated bacteria isolated from humans, randomized-blinded-interventional, and longitudinal studies indicate that mutans streptococci are spread vertically among humans, mostly from mothers to their children. Implications of these conclusions are briefly discussed. The most significant problems of literature interpretation include the benefits/shortcomings of salivary and plaque monitoring of the flora, the role of sugar(s) in decay as it influences the flora, and modeling strategies to predict lesion score increments as distinct from determination of the etiological role of specific bacteria. Future directions for microbiological clinical caries research are suggested, and the use of the term "caries" to describe the disease, not its lesions, is urged.

Case-Control Studies↗
PubMed1999

Caries inhibition in rats by a remineralizing toothpaste.

We tested the anti-caries properties of a prototype remineralizing toothpaste containing sodium fluoride, soluble phosphate and soluble calcium, similar but not identical to Enamelon Toothpaste in specific pathogen-free Osborne-Mendel rats. A fluoride-free placebo and sodium fluoride-containing Crest Regular were used as negative and positive control toothpastes, respectively. Sixty weanling rats were randomly distributed into groups of 20, all were inoculated with S. mutans 10449S, ate diet 2000, and drank demineralized water. Each toothpaste, contained in coded tubes, was applied to the rats' teeth, once for one minute/day, five days/week. There was no difference in bacterial recoveries from tooth swabs among the groups at either the 22- or 37-day post-inoculation recovery date. After rat sacrifice and defleshing, heads were randomly coded and scored blindly for carious lesions according to Keyes/Larson methods. Only after scoring was completed were the random codes broken and the treatment groups identified. Both the Enamelon-like product and Crest Regular treatments resulted in lower total enamel caries scores than the placebo (p < 0.001). The sum of smooth surface scores was also lower for the fluoride-containing toothpastes than for the placebo (p < 0.001). However, the Enamelon-like product had greater caries inhibitory properties than Crest Regular on sulcal and approximal tooth surface categories (p = 0.004 and p = 0.045, respectively). Therefore, the Enamelon-like product had superior caries inhibiting properties compared to Crest Regular at these tooth areas.

Administration, Topical↗
PubMed1999

Model for assessment of carious lesion remineralization, and remineralization by a novel toothpaste.

This study is of a novel toothpaste which induced remineralization of carious lesions in specific pathogen-free Osborne-Mendel rats. Randomly distributed weanlings in 7 groups (n = 10) each were initially induced to develop carious lesions as a result of a severe dietary and bacteriological challenge. Thus, all were inoculated with S. mutans 10449S, ate diet 2000CS (containing 56% cornstarch) ad libitum, and, upon weaning and for 10 additional days, drank demineralized water supplemented to 10% (w/v) with sucrose (SW) ad libitum. During these 10 days, 6 of the 7 groups of rats were topically treated with a slurried F(-)-free placebo toothpaste. On the 10th day after initial inoculation, two groups were sacrificed, one which had been treated with the placebo and the one which had been untreated. The remaining groups were then provided unsupplemented demineralized water (DW), fed diet 2000CS, and topically treated with either of 5 coded toothpastes: a slurry of the F(-)-free placebo, a similar slurry of a conventional sodium fluoride toothpaste (Crest Regular) containing about 383 ppm F-, or one of three prototype toothpastes formulated by Enamelon, Inc. containing soluble calcium and phosphate salts. Two of these contained 377 ppm F- after mixing their components, either as sodium monofluorophosphate (E-MFP) or as NaF (E-NaF). The third prototype contained 0 ppm F- (E-w/o F). Test items were applied to the dentition for one minute/day, five days/week. These 5 remaining groups were sacrificed 13 days after the DW provision. After defleshing, heads were coded randomly and scored blindly for carious lesions. The exchange of DW for SW was associated with highly significant reductions of 10449S recoveries (p < 0.001), but there were no differences in recoveries among the groups as a function of toothpaste type. Total mandibular and maxillary sulcal and smooth surface caries scores were statistically significantly lower for the E-NaF-treated group at 23 days than for the 23-day placebo-, E-w/o F(-)-, and conventional NaF toothpaste-treated group. Reductions were most impressive quantitatively on approximal tooth surfaces, where both the E-MFP and E-NaF groups had the lowest scores, but were also statistically significant at sulcal surfaces for the E-NaF group. Thus, this study model can be used to detect significant remineralization effects, as occurred with the prototype toothpaste E-NaF.

Administration, Topical↗
PubMed1997

Current trends of sugar consumption in developing societies.

This paper reviews recent data on sugar consumption in developing countries that may lead to a potential increase in caries prevalence. A search of the business, dental and nutritional literature was conducted through May 1995. There is evidence that sugar (sucrose) use was increasing in China, India, and Southeast Asia. In South and Central America (except Haiti) sugar use was either equivalent to or higher than that in most developed societies. In the Middle East, average sugar use was higher than that of other developing areas. However, it was either lower than or equivalent to the levels reported by other developed countries. Many central African countries consumed less than 15 kg of sugar/ person/year. Of particular concern is a rise in the consumption of sugar-containing carbonated beverages in a number of developing societies: China, India, Vietnam, Thailand, and other Southeast Asian countries are currently major growth markets for the soft drink industry. Consumption of high-sugar desserts and snacks may also be increasing in urban centers in some developing countries. To counteract the potential increase in the prevalence of dental caries in some developing countries, preventive and oral health promotion programs should be planned and implemented. We contend that taxation of sugar-containing products as well as efforts to reduce the level of sugar consumption to "safe" levels may be impractical, and in most countries, cannot be supported for political, economic, or health reasons. Instead, we recommend that collaboration be established between public health authorities and manufacturers/distributors of soft drinks and sweets in developing countries to establish a dental health fund that could be used to support caries preventive programs. The fund could be supported through donations from manufacturers based on the principle of the "milli-cent" (1 cent for every 1000 cents of sales). This minimal contribution would provide enough financial support for planning and implementing dental preventive and restorative programs in developing countries.

Africa, Central↗
PubMed1995

Helium-neon laser effects on conditioning-induced oral mucositis in bone marrow transplantation patients.

BACKGROUND: Oral mucositis is a common complication of bone marrow transplantation (BMT) conditioning therapy. Sequelae consist of increased risk for infection, moderate to severe pain, compromised oral function, and bleeding. This study investigated helium-neon laser treatment for prevention of conditioning-induced oral mucositis in BMT patients. Patterns and severity of mucositis for specific conditioning drug regimens also were analyzed. METHODS: Twenty patients received laser radiation to their oral mucosa, either left or right of midline. The contralateral side was sham-treated and served as a control. Mucositis severity was scored independently by two modified versions of the Oral Mucositis Index Scale (OMI-A and OMI-B) and the Eastern Cooperative Oncology Group (ECOG) Oral Toxicity Scale; pain severity was scored by subjects on a visual analogue scale (VAS). Cumulative scores were analyzed for differences between the laser-treated and sham-treated sides. RESULTS: Oral mucositis and pain scores were significantly lower for the treated versus the untreated side by OMI-A and B (P < 0.005) and VAS (P = 0.027) criteria, respectively. Ulcerative lesions occurred in all patients bilaterally; severity increased until Day +6, and lesions resolved by Day +21. Mucositis was more severe for patients conditioned with busulfan/carboplatin/thiotepa than for patients conditioned with busulfan/cyclophosphamide/etoposide. CONCLUSIONS: Helium-neon laser treatment was well-tolerated and reduced the severity of conditioning-induced oral mucositis in BMT patients.

Adult↗
PubMed1995

A pharmacokinetic and pharmacodynamic study of intravenous pilocarpine in humans.

Pilocarpine (P) is of potential utility in the treatment of xerostomia. Because optimal development of P dosage forms for humans requires that its pharmacokinetics and pharmacodynamics be defined, this intravenous study of its disposition and associated salivary responses was performed. In a hospital setting, two healthy female subjects were given a series of graded doses of intravenous P or placebo to stimulate salivary secretion. Plasma levels of P, heart rate, blood pressure, and respiratory rate were simultaneously monitored. Other objective and subjective physiological parameters were assessed. Plasma concentrations of P declined either mono- or bi-exponentially with time, and brisk initial salivation was followed by prolonged salivation at doses > or = 1 mg. At doses between 0.5 and 3.5 mg, dose-independent pharmacokinetic parameters included a small steady-state volume of distribution (2.4 to 3.0 L/kg), a high plasma clearance (0.026 to 0.03 L/kg/min), and a mean residence time of approximately 100 min. The cumulative volume of whole saliva secreted during the first 3 h post-dose was linearly related to the area under the plasma concentration-time curve. Plasma concentrations from 1 to 42 ng/mL were associated with significant levels of salivation. The pharmacokinetic linearity of the system and proportionality between the area under plasma concentration-time curves and overall salivary response have important implications for the design and utilization of pilocarpine dosage forms.

Adult↗
PubMed1995

Xylitol chewing gum and dental caries.

There is an extensive peer-reviewed literature on xylitol chewing gum as it pertains to effects on tooth decay in human subjects, on human dental plaque reduction, on inhibition of dental plaque acid production, on inhibition of the growth and metabolism of the mutans group of streptococci which are the prime causative agents of tooth decay, on reduction of tooth decay in experimental animals, and on xylitol's reported contribution to the remineralisation of teeth. The literature not only supports the conclusion that xylitol is non-cariogenic but it is now strongly suggestive that xylitol is caries inhibitory, that is, anti-cariogenic in human subjects, and it supplies reasonable mechanistic explanation(s).

Animals↗
PubMed1993

Identification of several rod loci and cloning of the rodD locus of Streptococcus mutans.

Previous work has shown that Streptococcus mutans is normally a short rod or a sphere, depending on its environment. This paper describes two distinct genetic approaches used to identify multiple loci and isolate one locus, rodD, controlling S. mutans rod shape. The first method involved isolation of a group of rod- mutants caused by transposon Tn916 insertion, and analysis of the inactivated genes by Southern hybridization. The second method involved mutagenesis via a shotgun insertion-duplication technique, isolation of a rod- mutant, and cloning the intact rod locus, employing an integration shuttle plasmid, pVA891. These approaches have led to the identification of multiple rod loci involved in determining the rod shape of S. mutans, and also cloning of one rod locus, rodD. The cloning strategy may also be useful for cloning other streptococcal genes which cannot be detected by their expression in Escherichia coli.

Blotting, Southern↗
PubMed1993

Simultaneous caries induction and calculus formation in rats.

Weanling specific pathogen-free Osborne-Mendel rats were fed a high-calcium, high-phosphorus diet with various levels of sucrose and inoculated with Streptococcus sobrinus strain 6715-13WT and Actinomyces viscosus strain OMZ-105 in order to determine whether calculus and caries could develop simultaneously. Rats consumed diets designated RC-16-5, RC-16-25, or RC-16-50 which partially replaced the corn starch component with progressively higher levels of sucrose, thus, to 5, 25, or 50% sucrose. In general, bacterial recoveries of A. viscosus declined with higher sucrose content of the diet, but a pattern of recovery for S. sobrinus was less clear with respect to dietary sucrose. S. sobrinus, however, was recovered at higher percentages from the tooth surface flora at the later two of three sampling dates. Most calculus--identified by the brittle quality, staining characteristics, and apatitic x-ray diffraction patterns of tooth surface deposits--was formed on the maxillary molars, and most carious lesions occurred on mandibular molars. While there was minimal association of the calculus score with the amount of sucrose in the diet, calculus scores increased greatly from 23 to 43 days after infectious challenge. Caries scores, of both fissure and smooth surfaces, by contrast, increased in a dose-response fashion with increasing dietary sucrose and with time. It is thus possible to induce calculus formation and caries simultaneously in specific pathogen-free Osborne-Mendel rats consuming a high-calcium and -phosphorus diet conducive to calculus formation and containing sucrose.(ABSTRACT TRUNCATED AT 250 WORDS)

Actinomyces viscosus↗
PubMed1993

Transformation efficiency of EMS-induced mutants of Streptococcus mutans of altered cell shape.

Some Streptococcus mutans strains change shape from bacillary to coccal or ellipsoid form in response to the ratio of bicarbonate to potassium or of borate to potassium in growth media. So that insight into determinants of shape of these streptococci could be gained, and future genetic studies facilitated, the shapes of a series of transformable and nontransformable strains of S. mutans were studied and attempts made to isolate a mutant of augmented transformability. Several strains were mutagenized by ethylmethane sulfonate and mutants with altered colonial and cellular morphologies isolated. Cell shapes were studied by Gram stain and Nomarski interference microscopy, and by scanning and transmission electron microscopy. Diverse shape-altered mutants were isolated from seven transformable and two nontransformable strains of S. mutans. Among these, length-to-width ratios ranged from > 10 to about 0.25. Regulation of timing of cell division, septum formation, or septum completion events may have been altered in these mutants. While most mutants substantially or completely lost transformability, mutant LT11 had transformation efficiency of 1.3 x 10(-4) to 2.3 x 10(-3), more than two to three orders of magnitude greater than its parental UA159 and the well-known transformable strain GS5(HK), respectively. There was no evidence of production of competence factor by LT11. Competence of LT11 was maintained for at least six months upon storage at -70 degrees C, facilitating its use for genetic studies. While the morphologies of several shape-altered mutants were no longer responsive to changes of the bicarbonate/potassium, unlike those of their parentals, the morphology of LT11 persisted in its response to this condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethyl Methanesulfonate↗