1999 Distinguished Service Award: Alice Horowitz, PhD.
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Biomedical subjects
Publications and source records attributed to B A White.
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BACKGROUND: Failure to replace a missing posterior tooth is assumed to result in host of adverse consequences, which include shifting of teeth and loss of alveolar bone support. METHODS: A retrospective longitudinal study (median follow-up period 6.9 years), using the radiographs of 111 patients who had an untreated bounded edentulous space, or BES, was conducted to determine the extent to which these adverse outcomes occurred. RESULTS: The majority of patients lost 1 millimeter or less of the distance between teeth adjacent to the space, extrusion of the opposing tooth was < or = 1 mm in 99 percent of the cases, and the amount of alveolar bone loss next to the adjacent teeth was < or = 1 mm in 83 percent of the cases. CONCLUSIONS: Within the follow-up time in this study, this group of patients did not exhibit the expected adverse consequences with either the frequency or severity generally assumed to be associated with nonreplacement of a single posterior tooth. CLINICAL IMPLICATIONS: These findings suggest that for the large majority of patients who experience a single-tooth posterior BES, immediate treatment may not be critical to the maintenance of arch stability. Instead, regular follow-up assessments to monitor change in stability and periodontal health may be warranted.
BACKGROUND: No reliable evidence is available regarding the effect of periodontal therapy on major disease endpoints such as tooth loss, edentulism, or quality of life. The primary objective of this study was to assess the association between tooth loss and the non-surgical periodontal treatment history of 1,021 members of the Kaiser Permanente Dental Care Program. METHODS: Tooth loss rates were estimated using Poisson regression models, adjusting for some of the potentially confounding variables such as initial disease severity and extent. RESULTS: Continuous non-surgical therapy (one or more non-surgical procedures performed during 3 successive years), as opposed to no therapy during such a 3-year period, reduced the subsequent tooth mortality rate by 58% (relative rate, 0.42; 95% confidence interval, 0.29-0.61). Intermittent non-surgical therapy reduced the tooth mortality rate by 48% (RR = 0.52; 95% confidence interval, 0.34-0.80). As the number of non-surgical procedures increased, tooth loss rates decreased. CONCLUSIONS: These findings suggest that non-surgical periodontal therapy may be associated with a substantial reduction in tooth mortality. Different study designs and populations are needed to confirm these findings.
The objective of this study was to characterize the extracellular proteolytic activity of Streptococcus bovis. Strains KEG, JB1, NCFB 2476, and K11.21.09.6C produced very similar large molecular weight (160-200 kDa) extracellular proteases that were specifically inhibited by PMSF, a serine protease inhibitor. Further experiments with S. bovis KEG indicated that cultures grown with casein as the sole added N source produced the greatest level of proteolytic activity, and the level of proteolytic activity was independent of growth rate. Clarified ruminal fluid (CRF) decreased proteolytic activity by 54% compared with cultures grown with casein alone, and addition of exogenous peptides and carbohydrates (CHO) to the CRF further reduced the level of proteolytic activity by 44% and 52%, respectively. These results suggested that the proteolytic activity of S. bovis KEG was modulated by available N source and that the proteolytic activity was present for reasons other than providing N for growth. The role of S. bovis in ruminal proteolysis requires further definition, but phenotypic similarity among some ruminal strains would suggest a common niche in ruminal proteolysis. The uniformity of proteolytic activities could make S. bovis a prime candidate for manipulation in ruminal proteolysis control strategies.
The current research was aimed at comparing proteolytic activities among ruminal Prevotella spp. Growth rates of Prevotella sp. 2202, Prevotella ruminicola D31d, P. brevis GA33, P. albensis M384, and P. bryantii B(1)4 varied with N source, and no one N source produced the fastest growth in all species. Proteolytic activity was greatest with casein compared with peptides, AA, and NH(4)Cl in all species. Proteolytic activity of Prevotella sp. 2202, P. brevis GA33, and P. bryantii B(1)4 was modulated by N source. With gelatin co-polymerized SDS-PAGE, the extracellular activities of the Prevotella spp. showed wide variation in number, size, and type of proteases. Prevotella sp. 2202 and P. albensis M384 produced metalloproteases of low molecular weight (40 kDa). P. ruminicola D31d produced one cysteine protease (100-200 kDa) and two metalloproteases (90-100 kDa). P. brevis GA33 generated a diffuse clearing zone (95-160 kDa) containing serine, cysteine, and metalloproteases. P. bryantii B(1)4 produced a metalloprotease greater than 200 kDa in size. The molecular sizes provided are estimations and served only to differentiate among the bacterial species in this study. Large variations in proteolytic activities among species and the known genetic diversity of the Prevotella taxon suggested that targeting this bacterial assemblage for genetic manipulation in order to alter the bacterial impact on ruminal protein degradation would be difficult.
The porcine gastrointestinal tract (GIT) microbiota has been studied to increase production efficiency, improve product quality, and help attempt to reduce disease. During the developmental period from birth through weaning, the intestinal microbiota undergoes a rapid ecological succession. There is interest in developing a monitoring technique that allows for analysis of bacterial population levels and shifts within the pig intestine. The objective of this study was to determine if denaturant gradient gel electrophoresis (DGGE) could be effectively applied to measure changes in bacterial populations of the pig GIT, as influenced by age, diet or compartment. Bacterial genetic diversity was determined using DGGE analysis of the V3 region of 16S rDNA PCR products (approximately 200 bp) obtained from primers specific for the domain Bacteria. Protocol development included optimization of: DNA extraction procedures, PCR amplification, removal of PCR artifacts, and optimization of gel preparation and image capture. DGGE analysis revealed diverse bacterial populations between pigs of different ages and among individual gut compartments. Comparison of fecal DNA from different aged pigs revealed several unique PCR product bands indicating the presence of unique bacterial populations. Comparison of different gut compartments demonstrated that bacterial populations were most similar (C, value > 50%) within a single compartment and between adjacent ones. Thus, DGGE can be used to examine bacterial diversity and population shifts in the pig GIT.
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OBJECTIVES: Standardized measures to assess clinical aspects of the performance of managed dental care plans are not available. This project sought to develop and evaluate measures for effectiveness of care and use of services that could be calculated using a plan's administrative data. METHODS: Two panels of stake holders representing dental plans, purchasers, and dental providers participated in a modified Delphi process to refine initial sets of effectiveness of care and use of services measures modeled after HEDIS measures for medical care. The refined measures were then pilot tested in two dental health maintenance organizations. RESULTS: The development process resulted in specification of seven effectiveness of care measures assessing disease activity classification, and prevention and outcomes for caries, periodontal disease, and tooth loss. Six use of services measures focusing on prophylaxes, third molar surgery, preventive, restorative, prosthetic, surgical, and endodontic care also were specified. Pilot testing of the measures indicated reasonable reliability and sensitivity, but also demonstrated the need for supervision or auditing of the process. CONCLUSIONS: These standardized measures for dental care plan performance are available for immediate use. However, because the measures depend on diagnostic information (periodontal probing data and diagnoses associated with restorative treatments) in the administrative data set, their adoption will require changes in most plans' data systems and data collection policies.
OBJECTIVES: Although a set of clinical performance measures, i.e., a report card for dental plans, has been designed for use with administrative data, most plans do not have administrative data systems containing the data needed to calculate the measures. Therefore, we evaluated the use of a set of proxy clinical performance measures calculated from data obtained through chart audits. METHODS: Chart audits were conducted in seven dental programs--three public health clinics, two dental health maintenance organizations (DHMO), and two preferred provider organizations (PPO). In all instances audits were completed by clinical staff who had been trained using telephone consultation and a self-instructional audit manual. The performance measures were calculated for the seven programs, audit reliability was assessed in four programs, and for one program the audit-based proxy measures were compared to the measures calculated using administrative data. RESULTS: The audit-based measures were sensitive to known differences in program performance. The chart audit procedures yielded reasonably reliable data. However, missing data in patient charts rendered the calculation of some measures problematic--namely, caries and periodontal disease assessment and experience. Agreement between administrative and audit-based measures was good for most, but not all, measures in one program. CONCLUSIONS: The audit-based proxy measures represent a complex but feasible approach to the calculation of performance measures for those programs lacking robust administrative data systems. However, until charts contain more complete diagnostic information (i.e., periodontal charting and diagnostic codes or reason-for-treatment codes), accurate determination of these aspects of clinical performance will be difficult.
OBJECTIVES: The reliability of practicing dentists' classifications of patients' caries risk and periodontal disease risk and reason for treatment for individual teeth were determined. The risk classification protocols had been in use in a group practice for more than a year, and the reason-for-treatment protocol had been introduced six months previously. METHODS: Eight dentists' classifications for caries (n = 66) and periodontal disease risk (n = 66), and six dentists' classifications for reason for treatment (n = 73) were compared to those of a nominal standard examiner. Reliability was expressed as percent agreement and kappa values. RESULTS: Percent agreement was 76 percent, 83 percent, and 74 percent for caries, periodontal disease, and reason for treatment, respectively, with kappa values of 0.56, 0.70, and 0.69. CONCLUSIONS: Dentists can attain reasonable levels of reliability using simple classification protocols with little formal training, although misclassification may be problematic for specific administrative or research-related purposes.
The manA gene of Thermoanaerobacterium polysaccharolyticum was cloned in Escherichia coli. The open reading frame of manA is composed of 3,291 bases and codes for a preprotein of 1,097 amino acids with an estimated molecular mass of 119,627 Da. The start codon is preceded by a strong putative ribosome binding site (TAAGGCGGTG) and a putative -35 (TTCGC) and -10 (TAAAAT) promoter sequence. The ManA of T. polysaccharolyticum is a modular protein. Sequence comparison and biochemical analyses demonstrate the presence of an N-terminal leader peptide, and three other domains in the following order: a putative mannanase-cellulase catalytic domain, cellulose binding domains 1 (CBD1) and CBD2, and a surface-layer-like protein region (SLH-1, SLH-2, and SLH-3). The CBD domains show no sequence homology to any cellulose binding domain yet reported, hence suggesting a novel CBD. The duplicated CBDs, which lack a disulfide bridge, exhibit 69% identity, and their deletion resulted in both failure to bind to cellulose and an apparent loss of carboxymethyl cellulase and mannanase activities. At the C-terminal region of the gene are three repeats of 59, 67, and 56 amino acids which are homologous to conserved sequences found in the S-layer-associated regions within the xylanases and cellulases of thermophilic members of the Bacillus-Clostridium cluster. The ManA of T. polysaccharolyticum, besides being an extremely active enzyme, is the only mannanase gene cloned which shows this domain structure.
The ability of the estrogen receptor signaling pathway to regulate cell-cell adhesion, and N-cadherin and beta-catenin expression was examined in rat somatolactotropic GH3 cells cultured in serum-free, phenol red-free medium (SFM). Estradiol-17beta (E2) promoted a nonadherent phenotype, whereas the steroidal antiestrogen, ICI 182,780, induced the formation of tightly adherent aggregates of cells. The antiestrogen-induced cell-cell adhesion was associated with the presence of adherens junctions, and was Ca2+-dependent. E2 reduced surface N-cadherin protein to barely detectable levels, whereas ICI 182,780-treated cells displayed abundant punctate immunoreactive N-cadherin. Antiestrogen failed to induce adhesion in the presence of a blocking antibody to N-cadherin. ICI 182,780 increased the protein levels for N-cadherin and the cadherin-binding protein, beta-catenin, by twofold over SFM controls or E2-treated samples. ICI 182,780 also increased the mRNA levels for N-cadherin and beta-catenin by two- to fivefold. In GH3 cells cultured in growth medium, ICI 182,780 increased N-cadherin and beta-catenin levels by twofold over untreated controls, and inhibited cell proliferation by 53%. These results provide the first demonstration of the regulation of N-cadherin-mediated cell-cell adhesion by the estrogen receptor (ER) signaling pathway in pituitary somatolactotrophs through the coordinate regulation of N-cadherin and beta-catenin expression. The inverse relationship between ICI 182,780-induced adhesion and proliferation raises the possibility that these two processes are functionally related.
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Steroidogenic factor-1 (SF-1) is a transcription factor that is expressed by many cell types within the ovary and has been shown to inhibit granulosa cell proliferation. The present studies were designed to determine whether: 1) SF-1 is expressed by primary and transformed rat ovarian surface epithelial cells (i.e. ROSE cells); and 2) SF-1 expression effects the proliferation of both normal and neoplastic ROSE cells. These studies used immature, gonadotropin-primed and mature rat ovaries, as well as ROSE-179 cells from early passages (EP) and late passages (LP), T-sv-40 transformed ROSE cells, and T-ras transformed ROSE cells. In situ hybridization studies demonstrated that SF-1 was detected in the surface epithelium of rat ovaries, independent of age or gonadotropin treatment. Further, Northern blot and quantitative in situ hybridization studies revealed that significant amounts of SF-1 messenger RNA (mRNA) were present in EP-ROSE-179 cells but not in the other cell lines. Interestingly, EP-ROSE-179 cells proliferated at a significantly slower rate than the other cell lines. Further, SF-1 mRNA levels were higher in EP-ROSE-179 cells in the G0/G1 stage than in the S-, G2/M stage of the cell cycle. These observations suggest that a cause and effect relationship exists between the level of SF-1 expression and cell proliferation. To test this hypothesis, LP, T-sv-40, and T-ras ROSE cells were transfected with either control vector or SF-1 expression vector. Forty-eight hours after transfection, SF-1 expression was assessed by in situ hybridization, and the fold increase in cell number/24 h was determined. For each cell line, about 30% of the cells were successfully transfected. The fold increase in the number of cells observed after transfection with the SF-1 expression vector was significantly less than the increase in cell number after transfection with the control vector (P < 0.05). To confirm that the forced expression of SF-1 prevented proliferation, LP cells were cotransfected with a green fluorescent protein (GFP) expression vector and either control vector or SF-1 expression vector. This study demonstrated that virtually none of the GFP/SF-1-transfected cells proliferated over a 24-h period, whereas GFP/Control vector-transfected cells proliferated. Further, approximately 40% of the GFP/SF-1-transfected cells underwent apoptosis after 24 h of culture in serum-supplemented medium. These data demonstrate that: 1) normal ovarian surface epithelial cells express SF-1; 2) SF-1 is also expressed by EP-ROSE-179 cells, but its expression seems to be suppressed when the cells enter the cell cycle; 3) LP-, T-sv, and T-ras ROSE cells do not express SF-1 mRNA; and 4) the inability to express SF-1 is associated with an increase in cell proliferation. Finally, forced SF-1 expression interferes with serum-induced proliferation and leads to apoptosis.
It is widely assumed that if posterior bounded edentulous spaces, or BESs, are not treated, the adjacent teeth ultimately will be lost. The authors examined this assumption by determining the survival of teeth adjoining 569 treated and untreated BESs. In the short term, the assumption was not supported. The great majority of untreated BESs did not result in loss of an adjacent tooth. Treatment with a removable partial denture did not increase the likelihood of adjacent tooth survival, while treatment with a fixed partial denture did result in modestly improved survival of adjacent teeth.
OBJECTIVE: To review the current status of oral health related quality of life measures as used in dental managed care plans and discuss the potential for their application in such delivery settings. METHODS: Three questions guided this analysis. First, what additional work is needed in the development or application of quality of life measures in dental managed care settings? Secondly, how can existing quality of life measures be used most effectively now in dental managed care settings? Finally, can existing data be used for secondary analyses of 'generic questions' concerning the relationship between oral health care and quality of life outcomes in dental managed care settings? Oral health related quality of life measures presented at the conference were considered. CONCLUSIONS: Currently available oral health related quality of life measures have limited applicability in dental managed care settings. Additional work is needed--involving dental plan administrators, purchasers, patients, and practitioners--to develop a set of questions. Such a set of questions should be able to provide inter alia information on the relationship between oral health related quality of life measures and plan structure and administration, level of dental benefits, and effectiveness and appropriateness of dental treatment. Without additional work, existing measures cannot be used effectively in managed dental care settings. Data currently available from dental managed care plans are sparse, limiting the potential for further analysis.
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