Ill-Fame on Blackberry Alley: Prostitution and Sport in 19th-Century Philadelphia

The 19th century offers a view of prostitution in a time of its open celebration. A remarkably permissive attitude towards sex work defies conventional understandings of “Victorian prudery” and makes for a fascinating period of American sexual history. Though the 20th century history of prostitution is defined by efforts to regulate the practice on moral grounds, the 19th century allows an assessment of the bawdy life through the eye of the market. In the mid 19th-century, the era of established brothels as social spaces, the urban leisure and sex trade was found objectionable only as noise disturbances. This project conducts a spatial analysis of the 19th century leisure economy via a public guide, in contrast to the 20th-century post-reform accounts of prostitution in arrest records or city Vice Commission reports

Cell Junction Remodeling in Gingival Tissue Exposed to a Microbial Toxin

The gingival epithelium plays a key role in protecting the supporting structures of the teeth from bacteria and their products. In ex vivo experiments, we recently showed that the cytolethal distending toxin (Cdt) from the periodontal pathogen Aggregatibacter actinomycetemcomitans causes extensive damage to gingival tissue. Morphological changes included detachment of the keratinized outer layer, distention of spinous and basal cells in the oral epithelium, disruption of rete pegs, and apparent dissolution of cell junctions. Adherens junctions (zonula adherens) are essential for maintaining barrier function and integrity of gingival epithelium. Therefore, immunohistochemical and RT-PCR analyses of human gingival explants (HGX) and human gingival epithelial cells (HGEC) were utilized for a closer examination of the effects of the Cdt on E-cadherin, the key membrane component of adherens junctions. Although there was some variability among tissue donors, exposure of gingival tissue or isolated epithelial cells to the toxin generally resulted in a pronounced increase in the expression and cytosolic distribution of E-cadherin, accompanied by an increase in levels of the intracellular scaffolding proteins β-catenin and β-actin. These results indicate that the Cdt induced substantial remodeling of adherens junctions, with a potential impact on the barrier function of gingival epithelium. Abbreviations: cytolethal distending toxin (Cdt), 4′,6-diamidino-2-phenylindole (DAPI), human gingival epithelial cells (HGEC), human gingival explants (HGX), human gingival fibroblasts (HGF), transepithelial resistance (TER)

Evaluation of the Humoral Immune Response to the Cytolethal Distending Toxin of \u3cem\u3eAggregatibacter Actinomycetemcomitans\u3c/em\u3e Y4 in Subjects With Localized Aggressive Periodontitis

Introduction:  Cytolethal distending toxin (Cdt) is potentially one of several virulence factors of Aggregatibacter actinomycetemcomitans, the prime etiological agent of localized aggressive periodontitis (LAP). Little is known regarding the Cdt-specific antibody response in humans. The current study is a quantitative and qualitative evaluation of the toxin-specific antibody response in a cohort of LAP patients and age-, race- and sex-matched controls. Methods:  Ninety-five subjects provided a total of 692 serum samples. Sera were analysed by enzyme-linked immunosorbent assays to determine the titers of antibody against the intact Cdt holotoxin as well as the individual subunit proteins (CdtA, CdtB, and CdtC). Neutralization of growth inhibition mediated by Cdt was evaluated in a modified colony-forming assay using Chinese hamster ovary cells. Results:  Fourteen of the 95 subjects exhibited significant serum Cdt-binding activity. There were no differences in the percentages of seropositive individuals or in the mean antibody titers between the control and LAP groups. Binding activity was detected against each of the three Cdt subunit proteins in all of the positive samples. Neutralization of Cdt-mediated growth inhibition was detected in samples from all of the seropositive subjects (range 20–75%). Conclusions:  Cdt, a recently identified A. actinomycetemcomitans virulence factor, is capable of inducing a neutralizing antibody response indicating that the toxin is produced during natural infection of humans. The failure of a vast majority (20 of 23) of the LAP subjects to mount a significant anti-Cdt response may in part explain their relative susceptibility to the disease

Differential Effect of the Cytolethal Distending Toxin of Actinobacillus Actinomycetemcomitans on Co-Cultures of Human Oral Cells

The periodontal pathogen Actinobacillus actinomycetemcomitans expresses a cytolethal distending toxin (CDT) that typically arrests the growth of eukaryotic cells at either the G0/G1 or G2/M phase of the cell cycle. It was previously found that CDT failed to arrest the growth of human periodontal ligament fibroblasts (HPLFs) when grown in pure culture. In contrast, proliferation of an oral epithelial cell line was rapidly inhibited by the toxin. In this study, the feasibility of using mixed-cell cultures and cell-specific markers to evaluate the response of oral cells, when in heterogeneous populations, to CDT was established. Proliferation of epithelial cells was rapidly inhibited and the cells were selectively eliminated in co-culture with HPLFs or cementoblasts by 24–48 h post-intoxication. Epithelial cells and HPLFs were detected and counted in co-cultures following cell-specific immunolabelling with antibodies against simian virus 40 large T antigen and the Ab-1 surface antigen, respectively. These results demonstrated that the activities of potential virulence factors, such as CDT, from periodontal pathogens can be successfully examined in mixed-cell cultures. This approach is especially relevant to infectious diseases that affect tissues with a diverse cellular composition, such as the periodontium

Evaluation of the Humoral Immune Response to the Cytolethal Distending Toxin of Aggregatibacter Actinomycetemcomitans Y4 in Subjects With Localized Aggressive Periodontitis

Introduction Cytolethal distending toxin (Cdt) is potentially one of several virulence factors of Aggregatibacter actinomycetemcomitans, the prime etiological agent of localized aggressive periodontitis (LAP). Little is known regarding the Cdt-specific antibody response in humans. The current study is a quantitative and qualitative evaluation of the toxin-specific antibody response in a cohort of LAP patients and age-, race- and sex-matched controls. Methods Ninety-five subjects provided a total of 692 serum samples. Sera were analysed by enzyme-linked immunosorbent assays to determine the titers of antibody against the intact Cdt holotoxin as well as the individual subunit proteins (CdtA, CdtB, and CdtC). Neutralization of growth inhibition mediated by Cdt was evaluated in a modified colony-forming assay using Chinese hamster ovary cells. Results Fourteen of the 95 subjects exhibited significant serum Cdt-binding activity. There were no differences in the percentages of seropositive individuals or in the mean antibody titers between the control and LAP groups. Binding activity was detected against each of the three Cdt subunit proteins in all of the positive samples. Neutralization of Cdt-mediated growth inhibition was detected in samples from all of the seropositive subjects (range 20–75%). Conclusions Cdt, a recently identified A. actinomycetemcomitans virulence factor, is capable of inducing a neutralizing antibody response indicating that the toxin is produced during natural infection of humans. The failure of a vast majority (20 of 23) of the LAP subjects to mount a significant anti-Cdt response may in part explain their relative susceptibility to the disease

Differential Effect of the Cytolethal Distending Toxin of \u3cem\u3eActinobacillus actinomycetemcomitans\u3c/em\u3e on Co-Cultures of Human Oral Cells

The periodontal pathogen Actinobacillus actinomycetemcomitans expresses a cytolethal distending toxin (CDT) that typically arrests the growth of eukaryotic cells at either the G0/G1 or G2/M phase of the cell cycle. It was previously found that CDT failed to arrest the growth of human periodontal ligament fibroblasts (HPLFs) when grown in pure culture. In contrast, proliferation of an oral epithelial cell line was rapidly inhibited by the toxin. In this study, the feasibility of using mixed-cell cultures and cell-specific markers to evaluate the response of oral cells, when in heterogeneous populations, to CDT was established. Proliferation of epithelial cells was rapidly inhibited and the cells were selectively eliminated in co-culture with HPLFs or cementoblasts by 24–48 h post-intoxication. Epithelial cells and HPLFs were detected and counted in co-cultures following cell-specific immunolabelling with antibodies against simian virus 40 large T antigen and the Ab-1 surface antigen, respectively. These results demonstrated that the activities of potential virulence factors, such as CDT, from periodontal pathogens can be successfully examined in mixed-cell cultures. This approach is especially relevant to infectious diseases that affect tissues with a diverse cellular composition, such as the periodontium

Characterization of Point Mutations in the cdtA Gene of the Cytolethal Distending Toxin of Actinobacillus Actinomycetemcomitans

The Cdt is a family of gram-negative bacterial toxins that typically arrest eukaryotic cells in the G0/G1 or G2/M phase of the cell cycle. The toxin is a heterotrimer composed of the cdtA, cdtB and cdtC gene products. Although it has been shown that the CdtA protein subunit binds to cells in culture and in an enzyme-linked immunosorbent assay (CELISA) the precise mechanisms by which CdtA interacts with CdtB and CdtC has not yet been clarified. In this study we employed a random mutagenesis strategy to construct a library of point mutations in cdtA to assess the contribution of individual amino acids to binding activity and to the ability of the subunit to form biologically active holotoxin. Single unique amino acid substitutions in seven CdtA mutants resulted in reduced binding of the purified recombinant protein to Chinese hamster ovary cells and loss of binding to the fucose-containing glycoprotein, thyroglobulin. These mutations clustered at the 5′- and 3′-ends of the cdtA gene resulting in amino acid substitutions that resided outside of the aromatic patch region and a conserved region in CdtA homologues. Three of the amino acid substitutions, at positions S165N (mutA81), T41A (mutA121) and C178W (mutA221) resulted in gene products that formed holotoxin complexes that exhibited a 60% reduction (mutA81) or loss (mutA121, mutA221) of proliferation inhibition. A similar pattern was observed when these mutant holotoxins were tested for their ability to induce cell cycle arrest and to convert supercoiled DNA to relaxed and linear forms in vitro. The mutations in mutA81 and mutA221 disrupted holotoxin formation. The positions of the amino acid substitutions were mapped in the Haemophilus ducreyi Cdt crystal structure providing some insight into structure and function

Do Buffered Local Anesthetics Provide More Successful Anesthesia Over Non-Buffered Solutions in Patients Requiring Dental Therapy? – A Systematic Review & Meta-Analysis.

Background: The pH of commercially available local anesthetics (LAs) is purposefully low (pH 3–4). Decreasing the pH extends the shelf life of the solution and prevents its early oxidation. However, a low pH may produce a burning sensation on the injection site, a slower onset of anesthesia, and a decrease in its clinical efficacy. Buffering of local anesthetics (alkalinization) by adding sodium bicarbonate has been suggested to achieve better pain control, reduce the pain of injection and produce a faster onset of local anesthetics. The aim of this review is to utilize a systematic review to collate evidence on the use of buffering agents with local anesthetics and its effect on causing profound pulpal anesthesia in patients requiring dental therapy and its side effects. Methods: Electronic searches were conducted in MEDLINE, Scopus, Cochrane Library, and ClinicalTrials.gov, World Health Organization (WHO) International Trials Registry Platform, OpenGrey & Google Scholar beta. Hand searching of two books “Handbook of Local Anesthesia” & “Successful Local Anesthesia for Restorative Dentistry and Endodontics” was conducted. Also, the reference lists of all included and excluded studies were checked to identify any further trials. Weighted anesthesia success rates and 95% confidence intervals (CIs) were estimated and compared by using a random-effects model. Results: 14,011 studies were initially identified from the search; 5 double-blind, randomized clinical trials met the inclusion criteria. For combined studies, buffered local anesthetics were more likely than non-buffered solutions to achieve successful anesthesia (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.11–4.71; P = 0.0232; I2 = 66%). Conclusion: This systematic review of double-blind, randomized clinical trials comparing the use of buffered and non-buffered local anesthetics in patients requiring dental therapy provides level ‘A’ evidence that is based on the criteria given by the Strength of Recommendation Taxonomy (SORT). In conclusion, the present meta-analysis showed that in patients receiving dental therapy, buffered local anesthetics are more effective than non-buffered solutions when used for mandibular or maxillary anesthesia. Buffering local anesthetics has 2.29 times greater likelihood of achieving successful anesthesia

A novel digital approach for fixed full-mouth implant-supported rehabilitations : a case report

Successful rehabilitation of a patient?s entire dentition with implant-supported fixed prostheses requires restoration of function, esthetics and comfort. To achieve this goal, the clinician and laboratory technician must work in concert with one another to navigate the multiple steps from the patient?s initial evaluation to delivery of the final prostheses. Key to this is the ability of the clinician to provide the technician with detailed information regarding the patient?s extra- and intraoral characteristics in a manner that can be easily and accurately transferred to the lab bench where it then serves as the foundation for reconstruction of the dentition. In recent years, the impressive evolution of digital technology in dentistry has dramatically facilitated this complex process. The aim of this case report is to illustrate how digital profiles of a patient?s facial and intraoral features can be merged with one another and used to generate artificial teeth and gingival tissue of a full mouth implant supported rehabilitation via computer-aided design and computer-aided manufacturing (CAD/CAM) technology to successfully rehabilitate a patient that initially presented with a terminal dentition

Characterization of Point Mutations in the cdtA Gene of the Cytolethal Distending Toxin of Actinobacillus Actinomycetemcomitans

The Cdt is a family of gram-negative bacterial toxins that typically arrest eukaryotic cells in the G0/G1 or G2/M phase of the cell cycle. The toxin is a heterotrimer composed of the cdtA, cdtB and cdtC gene products. Although it has been shown that the CdtA protein subunit binds to cells in culture and in an enzyme-linked immunosorbent assay (CELISA) the precise mechanisms by which CdtA interacts with CdtB and CdtC has not yet been clarified. In this study we employed a random mutagenesis strategy to construct a library of point mutations in cdtA to assess the contribution of individual amino acids to binding activity and to the ability of the subunit to form biologically active holotoxin. Single unique amino acid substitutions in seven CdtA mutants resulted in reduced binding of the purified recombinant protein to Chinese hamster ovary cells and loss of binding to the fucose-containing glycoprotein, thyroglobulin. These mutations clustered at the 5′- and 3′-ends of the cdtA gene resulting in amino acid substitutions that resided outside of the aromatic patch region and a conserved region in CdtA homologues. Three of the amino acid substitutions, at positions S165N (mutA81), T41A (mutA121) and C178W (mutA221) resulted in gene products that formed holotoxin complexes that exhibited a 60% reduction (mutA81) or loss (mutA121, mutA221) of proliferation inhibition. A similar pattern was observed when these mutant holotoxins were tested for their ability to induce cell cycle arrest and to convert supercoiled DNA to relaxed and linear forms in vitro. The mutations in mutA81 and mutA221 disrupted holotoxin formation. The positions of the amino acid substitutions were mapped in the Haemophilus ducreyi Cdt crystal structure providing some insight into structure and function