bluuebunny/crossref_metadata_2025 huggingface dataset:
Enamel Proteases Reduce Amelogenin-Apatite Binding
Authors: Sun Z. , Fan D. , Fan Y. , Du C. , Moradian-Oldak J.
Published: January 2009

Organic matrix degradation and crystal maturation are extracellular events that occur simultaneously during enamel biomineralization. We hypothesized that enamel proteases control amelogenin-mineral interaction, which, in turn can affect crystal nucleation, organization, and growth. We used a recombinant amelogenin (rP172), a homolog of its major cleavage product (rP148), and a native amelogenin lacking both N- and C-termini (13k). We compared apatite binding affinity between amelogenins and their digest products during proteolysis. We further compared binding affinity among the 3 amelogenins using a Langmuir model for protein adsorption. Amelogenin-apatite binding affinity was progressively reduced with the proteolysis at the C- and N- termini by recombinant pig MMP-20 (rpMMP20) and recombinant human kallikrein-4 (rhKLK4), respectively. The binding affinity of amelogenin to apatite was found to be in the descending order of rP172, rP148, and 13k. Analysis of our data suggests that, before its complete degradation during enamel maturation, stepwise processing of amelogenin by MMP-20 and then KLK4 reduces amelogenin-apatite interaction.
Grand Challenges in Dental Informatics
Authors: Sittig D.F. , Kirshner M. , Maupomé G.
Published: January 2009

When truly significant scientific challenges are overcome, it profoundly changes the daily activities, as well as the future research activities, of everyone involved in the related field. By identifying and describing the grand challenges facing a scientific field, we can help funding agencies identify and prioritize projects for support, stimulate and encourage new investigators to work on these intellectual and technological challenges, and help define the field itself. In this article, we present an informatics-oriented, future-patient-care scenario, then describe a series of applications and the related informatics grand challenges facing the dental field today. New techniques and technologies to help us overcome these challenges would facilitate the development of truly monumental applications, such as a comprehensive electronic oral health record, an automated dental treatment planning system for all diagnoses, or a system to profile patient risk for chronic oral diseases.
A Preliminary Analysis of the Dental Informatics Literature
Authors: Schleyer T.K. , Corby P. , Gregg A.L.
Published: January 2009

Dental informatics is an emerging discipline applying computer and information science to dental practice, research, education, and management. To date, the dental informatics research literature has not been comprehensively reviewed. This study reports an initial analysis of the dental informatics literature. We developed an initial, comprehensive retrieval strategy to locate dental informatics citations in MEDLINE (1966–April 2003), including three concepts: dentistry, computers, and research. After refinement of the search, we manually classified the final set into four categories: (1) non-dental; (2) dental, but neither dental informatics nor IT-related; (3) dental informatics; and (4) IT in dentistry. We analyzed informatics and IT-related citations regarding their distribution across journals, growth rate, the number of authors and their publication frequency, and content as expressed by Medical Subject Headings (MeSH). The final set of citations (n = 3872) consisted of: 12% non-dental articles; 59% dental, but not informatics- or IT-related articles; 16% informatics-related articles; and 13% IT-related articles. Informatics-related citations appeared in 176 journals, and IT-related citations in 206 journals. Approximately 50 papers are currently published in both categories yearly. While a great many authors have contributed to this literature, very few have published more than three papers. Main topics of articles included “Imaging and Image Processing”, “Computer-aided Diagnosis and Therapy”, “Computer-aided Instruction”, and “Other”. The dental informatics literature is small, but growing. Imaging and image processing predominate as research topics.
Biomedical Informatics Training for Dental Researchers
Authors: Johnson L.A.
Published: January 2009

Dental researchers collaborating closely with biomedical informaticians have achieved many advances in oral health research, such as in mapping human genetics and addressing oral health disparities. Advances will continue to increase as dental researchers and biomedical informaticians study each others’ disciplines to increase the effectiveness of their collaborative research. The combined skills will greatly increase the effectiveness of dental research. This manuscript summarizes the core of biomedical informatics curriculum (biomedical informatics knowledge, data management, and software engineering) for dental research. It also summarizes the obstacles that must be overcome for all dental research students to receive the training in biomedical informatics they require. These issues are: a lack of biomedical informatics faculty, a lack of biomedical informatics courses, and a lack of accreditation standards. Last, intra- and inter-institutional collaboration solutions are described.

“The decades ahead will be witness to advances in science and technology as yet unforeseen. Dentistry will benefit from these advances and must be intimately involved in their progression.” ( American Dental Association, 2002 )
Adaptive Hypermedia: A New Paradigm for Educational Software
Authors: Spallek H.
Published: January 2009

Traditional online dental education courses follow the broadcast paradigm which centers on the teacher, not the student. This one-size-fits-all approach resembles a mass-production idea which cannot take individual learner characteristics into account. Most online course designs do not address the issue that users with different goals and knowledge may be interested in different pieces of information about a topic. Adaptive hypermedia (AH) is an emerging field in education research which investigates how computer systems can overcome this problem. AH can be applied to any course content. This learner-centered approach first considers the learning goal(s), then evaluates the user’s abilities and determines the individual learning style, to structure and tailor the curriculum most efficiently. The presented AH environment exploits various concepts of AH. The system collects data to create a model of the individual user, which is continuously refined based on test results throughout the course. The system then adapts the learning material dynamically, using active and passive curriculum sequencing and adaptive presentation.
Informatics Systems to Assess and Apply Clinical Research on Dental Restorative Materials
Authors: Anusavice K.J.
Published: January 2009

Dental biomaterials are used clinically for one or more of the following purposes: to restore function, to enhance esthetics, and to prevent or arrest demineralization of tooth structure. Studies of the clinical performance of restorations and prostheses made from these materials have generally focused on quality assessment and survival statistics. Data from these studies should provide probabilities of specific treatment outcomes that are useful for practicing dentists. However, the utility of these data is limited by the lack of national and international standards for assessing these clinical outcomes. Standardized approaches toward clinical informatics and treatment-decision analysis are urgently needed to minimize the variability of clinical outcomes reported in publications associated with direct and indirect restorative materials used for dental restorations and prostheses.
Informatics Challenges in Tissue Engineering and Biomaterials
Authors: Rekow D.
Published: January 2009

Both tissue engineering and biomaterials have made tremendous strides recently, yet major questions remain unanswered. Tissue-engineered products have come to the market; others are in development. A fundamental issue that informatics could address for tissue engineering is to describe and to predict the cascade of biochemical and cellular reactions that occur as a function of time and implant material: surface texture, microporosity; pore size, density, and connectivity; and three-dimensional configuration. Behavior of ceramics, a subset of tissue-engineering scaffold materials and a mainstay of dental restorations, has been studied extensively for very thin layers and for thicknesses greater than 2 mm. Until recently, little has been known about dentally relevant thickness of 1–2 mm. Results have been surprising and are continuing to develop. Still, at least one fundamental question remains that could be addressed by informatics techniques: Where, along the spectrum of flat-polished material to 10-year clinical in vivo study, can we test to predict clinical performance of all-ceramic crowns accurately?
Spectrophotometric Analysis of All-ceramic Materials and Their Interaction with Luting Agents and Different Backgrounds
Authors: Barath V.S. , Faber F.-J. , Westland S. , Niedermeier W.
Published: January 2009

In this study, two All-Ceramic (AC) materials—Empress 2 (EMP) (Ivoclar Vivadent AG, Schaan, Liechtenstein) and In-Ceram ALUMINA (ICA) (Vita Zahnfabrik, Bad Säckingen, Germany)—were analyzed, along with the effects of 3 luting agents— viz. Zinc Phosphate cement (ZNPO, PhospaCEM PL, Ivoclar Vivadent AG, Schaan, Liechtenstein), Glass Ionomer Cement (GIC, Ketac-Cem Radiopaque, ESPE Dental AG, Seefeld, Germany), and Compolute (COMP, ESPE Dental AG, Seefeld, Germany)—on the final color, using the CIELab system. Color differences (DeltaL, Deltaa, Deltab, and DeltaE) were calculated for samples with luting agents and for samples without luting agents with standard white and black backgrounds, with the use of a spectrophotometer, Luci 100 (Dr. Lange, Berlin, Germany). One-way ANOVA for DeltaL, Deltaa, Deltab, and DeltaE within both the AC systems, with and without luting agents, showed significant contributions of the background (p < 0.05). EMP was seen to be more translucent than ICA. Darker ceramics showed less color variation. Luting agents altered the final color of the restoration. ZNPO was least translucent, followed by GIC and COMP. Marginal increases in thicknesses of ICA samples (0.4 mm) do not show a statistically significant color difference. No method exists to predict the outcome of an AC restoration based on consideration of the luting agent and the background color.
Designing Clinically Useful Systems: Examples from Medicine and Dentistry
Authors: Koch S.
Published: January 2009

Despite promising results in medical informatics research and the development of a large number of different systems, few systems get beyond a prototype state and are really used in practice. Among other factors, the lack of explicit user focus is one main reason.

The research projects presented in this paper follow a user-centered system development approach based on extensive work analyses in interdisciplinary working groups, taking into account human cognitive performance. Different medical and health-care specialists, together with researchers in human-computer interaction and medical informatics, specify future clinical work scenarios. Special focus is put on analysis and design of the information and communication flow and on exploration of intuitive visualization and interaction techniques for clinical information. Adequate choice of the technical access device is made depending on the user’s work situation. It is the purpose of this paper to apply this method in two different research projects and thereby to show its potential for designing clinically useful systems that do support and not hamper clinical work. These research projects cover IT support for chairside work in dentistry ( http://www.dis.uu.se/mdi/research/projects/orquest ) and ICT support for home health care of elderly citizens ( http://www.medsci.uu.se/mie/project/closecare ).
Decision Support at the Point of Care: Challenges in Knowledge Representation, Management, and Patient-specific Access
Authors: Greenes R.A.
Published: January 2009

Many applications in a clinical information system can benefit from the incorporation of medical knowledge to provide patient-specific, point-of-care decision support. These include computer-based provider order entry, referral, clinical result interpretation, consultation, adverse event monitoring, scheduling, shared patient-doctor decision-making, and generation of alerts and reminders, among others. To be executable, knowledge must be represented in the form of rules, constraints, calculations, guidelines, and other logical/algorithmic formats. The main difficulty is that the integration of such knowledge into clinical applications, when it occurs, tends to be very system- and application-specific, often encoded in a programming language, or even in the formating specifications of a user interaction display. Also, the data references and services invoked are highly dependent on the system/platform and electronic medical record implementation. This makes it difficult and time-consuming to encode authoritative evidence-based knowledge, severely limits the ability to disseminate and share successes, and hampers efforts to review and update the logic as medical knowledge changes. Solutions to this problem involve the development of standards-based representations for medical knowledge, and tools for authoring/editing, dissemination, adaptation to local environments, and execution. Numerous approaches are being pursued, all of which will be described in this presentation.
Health Services Research
Authors: Bailit H.L.
Published: January 2009

The major barriers to the collection of primary population-based dental services data are: (1) Dentists do not use standard record systems; (2) few dentists use electronic records; and (3) it is costly to abstract paper dental records. The value of secondary data from paid insurance claims is limited, because dentists code only services delivered and not diagnoses, and it is difficult to obtain and merge claims from multiple insurance carriers. In a national demonstration project on the impact of community-based dental education programs on the care provided to underserved populations, we have developed a simplified dental visit encounter system. Senior students and residents from 15 dental schools (approximately 200 to 300 community delivery sites) will use computers or scannable paper forms to collect basic patient demographic and service data on several hundred thousand patient visits. Within the next 10 years, more dentists will use electronic records. To be of value to researchers, these data need to be collected according to a standardized record format and to be available regionally from public or private insurers.
Genetic and Molecular Characterization of a Dental Pathogen Using Genome-wide Approaches
Authors: Actis L.A. , Rhodes E.R. , Tomaras A.P.
Published: January 2009

Actinobacillus actinomycetemcomitans causes periodontitis, a costly chronic infection that affects a large number of patients. The pathogenesis of this dental infection is a multifactorial process that results in a serious degenerative disease of the periodontium. Although significant progress has been achieved after the identification of this Gram-negative bacterium as the etiological agent of this infection, much remains to be done to understand in detail the bacterial factors and host-pathogen interactions involved in the pathogenesis of this disease. Classic research approaches have resulted in the identification of important virulence factors and cellular processes, although they have provided a rather narrow picture of some of the steps of this complex process. In contrast, a much wider picture could be obtained with the application of tools such as bioinformatics and genomics. These tools will provide global information regarding the differential expression of genes encoding factors and processes that lead to the pathogenesis of this disease. Furthermore, comparative genomics has the potential of helping us to understand the emergence and evolution of this human pathogen. This genome-wide approach should provide a more complete picture of the pathogenesis process of this disease, and will facilitate the development of efficient diagnostic, preventive, and therapeutic measures for this disease.
Retrieval and Classification of Dental Research Articles
Authors: Bartling W.C. , Schleyer T.K. , Visweswaran S.
Published: January 2009

Successful retrieval of a corpus of literature on a broad topic can be difficult. This study demonstrates a method to retrieve the dental and craniofacial research literature. We explored MeSH manually for dental or craniofacial indexing terms. MEDLINE was searched using these terms, and a random sample of references was extracted from the resulting set. Sixteen dental research experts categorized these articles, reading only the title and abstract, as either: (1) dental research, (2) dental non-research, (3) non-dental, or (4) not sure. Identify Patient Sets (IPS), a probabilistic text classifier, created models, based on the presence or absence of words or UMLS phrases, that distinguished dental research articles from all others. These models were applied to a test set with different inputs for each article: (1) title and abstract only, (2) MeSH terms only, or (3) both. By title and abstract only, IPS correctly classified 64% of all dental research articles present in the test set. The percentage of correctly classified dental research articles in this retrieved set was 71%. MeSH term inclusion decreased performance. Computer programs that use text input to categorize articles may aid in retrieval of a broad corpus of literature better than indexing terms or key words alone.
Policy for Prevention of Oral Manifestations in HIV/AIDS: The Approach of the WHO Global Oral Health Program
Authors: Petersen P.-E.
Published: January 2009

The HIV/AIDS pandemic has become a human and social disaster, particularly affecting the developing countries of Africa, Southeast Asia, and Latin America. By the end of 2004, about 40 million people were estimated to be infected by HIV globally. The health sectors in many affected countries are facing severe shortages of human and financial resources, and are struggling to cope with the growing impact of HIV/AIDS. In most developed countries, the availability of antiretroviral treatment has resulted in a dramatic reduction in HIV/AIDS-related mortality and morbidity. In contrast, in the developing countries, there is little access to treatment, and access to HIV-prevention services is poor. The ’3 by 5′ initiative was launched by the WHO and UNAIDS in 2003 with the aim of providing antiretrovirals to three million people in developing countries by the year 2005. HIV infection has a significant negative impact on oral health, with approximately 40–50% of HIV-positive persons developing oral fungal, bacterial, or viral infections early in the course of the disease. Oral health services and professionals can contribute effectively to the control of HIV/AIDS through health education and health promotion, patient care, effective infection control, and surveillance. The WHO Global Oral Health Program has strengthened its work for prevention of HIV/AIDS-related oral disease. The WHO co-sponsored conference, Oral Health and Disease in AIDS, held in Phuket, Thailand (2004), issued a declaration calling for action by national and international health authorities. The aim is to strengthen oral health promotion and the care of HIV-infected persons, and to encourage research on the impact that HIV/AIDS, public health initiatives, and surveillance have on oral health.
Innate and Adaptive Mucosal Immunity in Protection against HIV Infection
Authors: Bergmeier L.A. , Lehner T.
Published: January 2009

The appalling toll on the populations of developing countries as a result of the HIV epidemic shows no signs of abatement. While costly drug therapies are effective in developed nations, the sheer scale of the epidemic elsewhere makes the need for a vaccine an ever more urgent goal. The prevalent DNA prime-viral boost strategy aims to elicit cytotoxic lymphocytes (CTL) against HIV, but this approach is undermined by the rapid mutation of HIV, which thereby escapes CTL control. Alloimmunity has been found to be protective in vertical transmission from infected mothers to their babies, in alloimmunization of women with their partners’ mononuclear cells, and in monkeys immunized with SIV grown in human T-cells. Vaginal mucosal immunization, as a result of unprotected sex with a regular partner, induced in vitro protection against HIV infection, and this was confirmed in macaques. The second type of natural protection is found in persons with the homozygous Δ32 CCR5 mutation, a 32-base-pair deletion of the CCR5 gene, which results in a lack of cell-surface expression of CCR5, which is associated with an increase in CC chemokines and the development of CCR5 antibodies. These two ‘experiments of nature’ have been used to develop vaccine strategies—first, in vaginal immunization of macaques with CCR5 peptides, in addition to HIV envelope (env) and SIV core (gag) antigens, all of which were linked to the 70-kD heat-shock protein (HSP70); and second, in mucosal allo-immunization of macaques, which also gave rise to in vitro protection from infection. Immunization with this vaccine elicited serum and vaginal IgG and IgA antibodies, IFNγ- and IL-12-producing cells, and increased concentrations of CCL-3 and CCL-4. Vaginal challenge with a simian immunodeficiency virus engineered to carry a human envelope protein (SHIV 89.6) showed significant clearance of SHIV in the immunized macaques. This platform strategy will now be developed to activate the co-stimulatory pathways with the aim of enhancing the primary allogeneic and CCR5-directed responses which are involved in natural protection against HIV infection. Abbreviations: IFN-γ, gamma interferon; IL-12, interleukin 12; MIP-1 α,β, Macrophage inflammatory protein-1; RANTES, Regulated on activation normal T-cell expressed and secreted; SDF-1, stromal-derived factor 1; SIV, simian immunodeficiency virus; and SHIV, engineered SIV carrying a human envelope protein.
Differential Mucosal Susceptibility in HIV-1 Transmission and Infection
Authors: Moutsopoulos N.M. , Greenwell-Wild T. , Wahl S.M.
Published: January 2009

HIV infection occurs primarily through mucosal surfaces, indicating that protection at mucosal sites may be crucial in prevention and treatment. The host innate and adaptive immune elements provide a level of protection, which differs between mucosal compartments, and appears to be most successful in the oral environment, where transmission is rare. In addition to the distinct oral mucosal architecture and cellular constituents, oral fluids, unlike other mucosal secretions, are rarely a vehicle for HIV infection. Multiple soluble factors may contribute to this antiviral activity, including neutralizing antibodies, secretory leukocyte protease inhibitor (SLPI), antiviral peptides such as defensins and cystatins, glycoproteins including thrombospondin and lactoferrin, and complement components. Understanding the antiviral activities of these and other potential resistance factors is becoming increasingly important in attempts to design treatments in the era of HAART resistance. In this regard, the mechanism of anti-HIV action of SLPI has recently been further elucidated by the discovery of its binding protein/receptor, which plays a key role in the infection of macrophages and may consequently be a novel therapeutic target. Continued elucidation of the unique features of mucosal HIV immunology is essential for understanding HIV pathogenesis and for developing effective vaccines and therapeutics.
Skin Lesions: Mirror Images of Oral Lesion Infections
Authors: Phanuphak N.
Published: January 2009

Skin lesions can be the presenting signs for HIV disease and are among the most prevalent manifestations throughout the course of HIV disease. Correlation of skin diseases and HIV disease staging has long been recognized and used to guide medical management in resource-limited settings. The purpose of this paper is to give a review of common skin infections presented in HIV-infected patients. Common skin infections presenting in HIV-infected patients include viral, fungal, mycobacterial, and bacterial infections, along with skin infestation. Key diagnostic points correlate with certain HIV disease staging for many skin diseases. These can help facilitate appropriate diagnosis and referral by health care personnel when treating HIV-infected patients who have skin lesions. Knowledge of common skin manifestations found in HIV-infected patients is essential for all health care personnel who work in the HIV field. Most skin infections presenting in HIV-infected patients can be treated effectively if the correct diagnosis and appropriate referral are made promptly.
Implications of HIV Disease for Oral Health Services
Authors: Robinson P.G.
Published: January 2009

This paper, by means of a quality framework, reviews health services research in relation to people with HIV infection. The relevance of oral health care services to people’s needs is considered in terms of the goal of health services to reduce the burden of disease on the everyday life of the population. Dental services may therefore have a role in primary prevention in the HIV epidemic, passing on information about HIV and promoting health through the early diagnosis and treatment of oral disease. Effectiveness research of oral health care in HIV assesses the usefulness of oral diagnosis, whether care is safe, and whether treatment is clinically effective. Few data are available on the efficiency of services. People with HIV still have problems accessing dental care, due to the volume of care available in relation to their need and acceptability of care. Access problems in the US are compounded by social inequality. Health services research data are particularly sparse in resource-poor countries, and there is a need to translate the available information into treatment guidelines appropriate to these settings. The research community and funding agencies should place greater emphasis on the quality of oral health services for people with HIV.
Candida-Host Interactions in HIV Disease: Relationships in Oropharyngeal Candidiasis
Authors: Fidel P.L.
Published: January 2009

Oropharyngeal candidiasis (OPC) caused by the commensal organism, Candida albicans, is the most common oral infection in HIV disease. Although cell-mediated immunity (CMI) by Th1-type CD4+ T-cells is considered the predominant host defense mechanism against OPC, other systemic or local immune mechanisms are critical when blood CD4+ T-cells are reduced below a protective threshold. For example, the Th cytokine profile in saliva may influence resistance or susceptibility to OPC. In OPC lesions, CD8+ T-cells become accumulated at the lamina propria-epithelium interface, suggesting some role for CD8+ T-cells against OPC. However, the absence of CD8+ T-cells close to Candida at the outer epithelium indicates that susceptibility to OPC involves a dysfunction in the CD8+ T-cells or in the micro-environment. Further evaluation of the buccal mucosa lesion showed that CD8 T-cell-associated cytokine and chemokine mRNA is increased compared with buccal mucosa from lesion-negative matched controls. The majority of CD8+ T-cells present possess the αβ T-cell receptor and several homing receptors ( i.e., α4β7, α4β1, αeβ7). While several adhesion molecules are similar in OPC+ vs. OPC− persons, E-cadherin is reduced in the tissue of OPC+ persons. These results support evidence for a role for CD8+ T-cells against OPC, but suggest that a putative dysfunction in mucosal T-cell trafficking may be associated with susceptibility to infection. Similar levels of Candida-specific antibodies in persons with and without OPC confirmed a limited role for humoral immunity. Finally, oral epithelial cells inhibit the growth of Candida in vitro in a static rather than a cidal manner. Clinically, oral epithelial cell anti- Candida activity is reduced in HIV+ persons with OPC, compared with controls. The mechanism of action includes a strict requirement for cell contact by an acid-labile moiety on intact, but not necessarily live, epithelial cells, with no role for soluble factors. Taken together, host defense against OPC involves several levels of activity. The status and efficiency of local host defenses when blood CD4+ T-cells are not available appear to play a role in protection against or susceptibility to OPC.
Oral EBV and KSHV Infection in HIV
Authors: Webster-Cyriaque J. , Duus K. , Cooper C. , Duncan M.
Published: January 2009

The gamma herpesviruses, Kaposi’s-sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are tightly associated with the development of AIDS-associated oral disease and malignancy during immune suppression. The objective of this investigation was to characterize oral infection and pathogenesis in healthy and immune-suppressed individuals. To characterize oral EBV and KSHV infection, we examined throat washings and oral epithelial cells from HIV-positive and HIV-negative individuals. Quantitative/real-time polymerase-chain-reaction (PCR) assays, transmission electronmicroscopy, immunostaining, and sequence analysis were used to identify viral infection. Virus was isolated from throat-wash samples and was used to infect epithelial and lymphoid cell lines. We detected EBV and KSHV in the oral cavity in healthy and immune-suppressed individuals. Viral strain analysis of KSHV K1 in multiple clones from the oral cavities of healthy persons and immunosuppressed patients detected several strains previously detected in KS lesions, with minor strain variation within individuals. Immunoelectron microscopy for multiple viral antigens detected consistent expression of viral proteins and oral epithelial specimens. In oral epithelial cells infected with wild-type KSHV in vitro, the K8.1 glycoprotein associated with lytic KSHV infection was detected in both primary and telomerase immortalized oral epithelial cultures by 24 hours post-infection. Virions were detected, subsequent to infection, by scanning electron microscopy. Oral epithelial cells were also infected in vitro with wild-type EBV originating from throat washes. Analysis of these data suggests that, like EBV, KSHV infection is present in the oropharynx of healthy individuals, is transmissible in vitro, and may be transmitted by saliva.
Cytomegalovirus Co-infection in AIDS-associated Oral Kaposi’s Sarcoma
Authors: Meer S. , Altini M.
Published: January 2009

The increasing appearance of AIDS-associated oral Kaposi’s sarcoma (KS) in South Africa may be ascribed to the later start of the HIV epidemic, more patients reaching stages III and IV, and the inaccessibility of most patients to anti-retroviral therapy. The objective of this study was to demonstrate cytomegalovirus (CMV) co-infection in oral KS and to consider its possible significance. We reviewed 20 cases of oral KS in known HIV-positive patients without active CMV disease. HHV8 PCR and CMV immunohistochemistry were performed. HHV8 DNA was present in all cases. CMV inclusions were detected in five cases. The significance of CMV co-infection in oral KS is unclear. The inclusions suggest active infection, although there is no evidence to support CMV in the pathogenesis of KS. Nonetheless, it is vital that physicians be alerted to active CMV infection, so that timely intervention and careful observation can be instituted, ensuring early diagnosis and treatment.
Biology of HPV in HIV Infection
Authors: Palefsky J.
Published: January 2009

HIV-positive men and women are at increased risk of anogenital and oral HPV infection. The risks for HPV-associated high-grade intra-epithelial neoplasia (IN) and cancer are also increased. The prevalence of oral, anal, and cervical HPV infection in HIV-positive individuals compared with HIV-negative individuals increases with progressively lower CD4+ levels, as does incident high-grade IN. In contrast to IN, development of cancer is not related to lower CD4+ level. With increasing grades of IN and cancer, the proportion of tissues with copy-number abnormalities (CNA) increases, with one of the most common genetic changes being amplification of chromosome 3q. The presence of CNA is associated with the integration of HPV DNA into the host genome, with loss of HPV E2 and/or E2 rearrangement. This suggests a link between CNA and increased HPV-induced chromosomal instability mediated through de-repressed E6 and E7 expression consequent to loss of functional E2 protein. In addition, epigenetic changes occur with increasing frequency in high-grade IN and cancer, such as hypermethylation leading to down-regulation of potential tumor suppressor genes. Analysis of these data together suggests that immune suppression plays a more prominent role in the earlier stages of HPV-associated disease, up to and including incident high-grade IN. Persistent high-grade IN and development of cancer may be more strongly related to the cumulative effect of HPV-associated genetic instability and the resulting host genetic changes. There are few data to suggest a direct role for HIV in the pathogenesis of HPV-associated neoplasia, but HIV-associated attenuation of HPV-specific immune responses may allow for persistence of high-grade IN and sufficient time for accumulation of genetic changes that are important in progression to cancer.
(A2) Oral Health and General Health
Authors: Johnson N.W. , Glick M. , Mbuguye T.N.L.
Published: January 2009

The interactions between oral and systemic health are bi-directional and complex, involving many pathways. Regarding health as not merely the absence of disease, but as a state of total well-being, these interactions profoundly influence the progress of many diseases, and the quality of life and economic performance of HIV-infected individuals and populations. The evidence base for specific interactions is currently weak, partly because few good-quality studies have been published, partly because of the naïveté of the instruments currently available for recording these interactions and their inherent complexity. Recording quality of life should be a fundamental aspect of all future studies. The most significant conclusion of this Workshop is the need for all involved in oral health research and oral health care to be seen as, and to act as, essential partners in comprehensive care for whole patients and communities.
(B3) Markers of Immunodeficiency and Mechanisms of HAART Therapy on Oral Lesions
Authors: Flint S.R. , Tappuni A. , Leigh J. , Schmidt-Westhausen A.-M. , MacPhail L.
Published: January 2009

Highly active anti-retroviral therapy (HAART) has revolutionized the treatment and prognosis of HIV disease and AIDS in those who can take advantage of the treatment. There are currently 20 different anti-retroviral drugs in 4 different classes that are used in specific combinations. Suppression of HIV replication and immune reconstitution are goals of therapy. Since the prevalence of some easily detectable oral manifestations of HIV/AIDS (OMHIV/AIDS) decreases with HAART, it has been suggested that they might be clinically useful surrogate markers of HAART efficacy and immune status. This might be particularly useful if their recurrence presaged or accompanied HAART failure. To date, there has been little work in this area, but its potential value to the clinical management of HIV/AIDS is apparent, especially if frequent measures of viral load and CD4 cell counts are not readily available. However, the usefulness of OMHIV/AIDS as signals for HAART failure is complicated by three phenomena: the immune reconstitution syndrome, the similarity of some adverse reactions of HAART to OMHIV/AIDS, and the direct inhibitory effect of HAART medications on some OMHIV/AIDS ( e.g., inhibition of oral candidosis by protease inhibitors). This workshop considered the current evidence and proposed pertinent research questions.
Destructive Periodontitis Lesions are Determined by the Nature of the Lymphocytic Response
Authors: Gemmell E. , Yamazaki K. , Seymour G.J.
Published: January 2009

It is now 35 years since Brandtzaeg and Kraus (1965) published their seminal work entitled "Autoimmunity and periodontal disease". Initially, this work led to the concept that destructive periodontitis was a localized hypersensitivity reaction involving immune complex formation within the tissues. In 1970, Ivanyi and Lehner highlighted a possible role for cell-mediated immunity, which stimulated a flurry of activity centered on the role of lymphokines such as osteoclast-activating factor (OAF), macrophage-activating factor (MAF), macrophage migration inhibition factor (MIF), and myriad others. In the late 1970s and early 1980s, attention focused on the role of polymorphonuclear neutrophils, and it was thought that periodontal destruction occurred as a series of acute exacerbations. As well, at this stage doubt was being cast on the concept that there was a neutrophil chemotactic defect in periodontitis patients. Once it was realized that neutrophils were primarily protective and that severe periodontal destruction occurred in the absence of these cells, attention swung back to the role of lymphocytes and in particular the regulatory role of T-cells. By this time in the early 1990s, while the roles of interleukin (IL)-1, prostaglandin (PG) E2, and metalloproteinases as the destructive mediators in periodontal disease were largely understood, the control and regulation of these cytokines remained controversial. With the widespread acceptance of the Th1/Th2 paradigm, the regulatory role of T-cells became the main focus of attention. Two apparently conflicting theories have emerged. One is based on direct observations of human lesions, while the other is based on animal model experiments and the inability to demonstrate IL-4 mRNA in gingival extracts. As part of the "Controversy" series, this review is intended to stimulate debate and hence may appear in some places provocative. In this context, this review will present the case that destructive periodontitis is due to the nature of the lymphocytic infiltrate and is not due to periodic acute exacerbations, nor is it due to the so-called virulence factors of putative periodontal pathogens.
Cell Cycle Dysregulation in Oral Cancer
Authors: Todd R. , Hinds P.W. , Munger K. , Rustgi A.K. , Opitz O.G. , Suliman Y. , Wong D.T.
Published: January 2009

The dysregulation of the molecular events governing cell cycle control is emerging as a central theme of oral carcinogenesis. Regulatory pathways responding to extracellular signaling or intracellular stress and DNA damage converge on the cell cycle apparatus. Abrogation of mitogenic and anti-mitogenic response regulatory proteins, such as the retinoblastoma tumor suppressor protein (pRB), cyclin D1, cyclin-dependent kinase (CDK) 6, and CDK inhibitors (p21WAF1/CIP1, p27KIP1, and p16INK4a), occur frequently in human oral cancers. Cellular responses to metabolic stress or genomic damage through p53 and related pathways that block cell cycle progression are also altered during oral carcinogenesis. In addition, new pathways and cell cycle regulatory proteins, such as p12DOC-1, are being discovered. The multistep process of oral carcinogenesis likely involves functional alteration of cell cycle regulatory members combined with escape from cellular senescence and apoptotic signaling pathways. Detailing the molecular alterations and understanding the functional consequences of the dysregulation of the cell cycle apparatus in the malignant oral keratinocyte will uncover novel diagnostic and therapeutic approaches.
Reflex Control of Human Jaw Muscles
Authors: Türker Kemal S.
Published: January 2009

The aim of this review is to discuss what is known about the reflex control of the human masticatory system and to propose a method for standardized investigation. Literature regarding the current knowledge of activation of jaw muscles, receptors involved in the feedback control, and reflex pathways is discussed. The reflexes are discussed under the headings of the stimulation conditions. This was deliberately done to remind the reader that under each stimulation condition, several receptor systems are activated, and that it is not yet possible to stimulate only one afferent system in isolation in human mastication experiments. To achieve a method for uniform investigation, we need to set a method for stimulation of the afferent pathway under study with minimal simultaneous activation of other receptor systems. This stimulation should also be done in an efficient and reproducible way. To substantiate our conviction to standardize the stimulus type and parameters, we discuss the advantages and disadvantages of mechanical and electrical stimuli. For mechanical stimulus to be delivered in a reproducible way, the following precautions are suggested: The stimulus delivery system (often a probe attached to a vibrator) should be brought into secure contact with the area of stimulation. To minimize the slack between the probe, the area to be stimulated should be taken up by the application of pre-load, and the delivered force should be recorded in series. Electrical stimulus has advantages in that it can be delivered in a reproducible way, though its physiological relevance can be questioned. It is also necessary to standardize the method for recording and analyzing the responses of the motoneurons to the stimulation. For that, a new technique is introduced, and its advantages over the currently used methods are discussed. The new method can illustrate the synaptic potential that is induced in the motoneurons without the errors that are unavoidable in the current techniques. We believe that once stimulation, recording, and analysis methods are standardized, it will be possible to bring out the real "wiring diagram" that operates in conscious human subjects.
Invasion of Dentinal Tubules by Oral Bacteria
Authors: Love R.M. , Jenkinson H.F.
Published: January 2009

Bacterial invasion of dentinal tubules commonly occurs when dentin is exposed following a breach in the integrity of the overlying enamel or cementum. Bacterial products diffuse through the dentinal tubule toward the pulp and evoke inflammatory changes in the pulpo-dentin complex. These may eliminate the bacterial insult and block the route of infection. Unchecked, invasion results in pulpitis and pulp necrosis, infection of the root canal system, and periapical disease. While several hundred bacterial species are known to inhabit the oral cavity, a relatively small and select group of bacteria is involved in the invasion of dentinal tubules and subsequent infection of the root canal space. Gram-positive organisms dominate the tubule microflora in both carious and non-carious dentin. The relatively high numbers of obligate anaerobes present-such as Eubacterium spp., Propionibacterium spp., Bifidobacterium spp., Peptostreptococcus micros, and Veillonella spp.-suggest that the environment favors growth of these bacteria. Gram-negative obligate anaerobic rods, e.g., Porphyromonas spp., are less frequently recovered. Streptococci are among the most commonly identified bacteria that invade dentin. Recent evidence suggests that streptococci may recognize components present within dentinal tubules, such as collagen type I, which stimulate bacterial adhesion and intra-tubular growth. Specific interactions of other oral bacteria with invading streptococci may then facilitate the invasion of dentin by select bacterial groupings. An understanding the mechanisms involved in dentinal tubule invasion by bacteria should allow for the development of new control strategies, such as inhibitory compounds incorporated into oral health care products or dental materials, which would assist in the practice of endodontics.
The Diagnostic Applications of Saliva— A Review
Authors: Kaufman Eliaz , Lamster Ira B.
Published: January 2009

This review examines the diagnostic application of saliva for systemic diseases. As a diagnostic fluid, saliva offers distinctive advantages over serum because it can be collected non-invasively by individuals with modest training. Furthermore, saliva may provide a cost-effective approach for the screening of large populations. Gland-specific saliva can be used for diagnosis of pathology specific to one of the major salivary glands. Whole saliva, however, is most frequently used for diagnosis of systemic diseases, since it is readily collected and contains serum constituents. These constituents are derived from the local vasculature of the salivary glands and also reach the oral cavity via the flow of gingival fluid. Analysis of saliva may be useful for the diagnosis of hereditary disorders, autoimmune diseases, malignant and infectious diseases, and endocrine disorders, as well as in the assessment of therapeutic levels of drugs and the monitoring of illicit drug use.
Chemotactic Signaling Pathways in Neutrophils: from Receptor to Actin Assembly
Authors: Cicchetti Gregor , Allen Philip G. , Glogauer Michael
Published: January 2009

In this review, we present an overview of the signaling elements between neutrophil chemotactic receptors and the actin cytoskeleton that drives cell motility. From receptor-ligand interactions, activation of heterotrimeric G-proteins, their downstream effectors PLC and PI-3 kinase, the activation of small GTPases of the Rho family, and their regulation of particular cytoskeletal regulatory proteins, we describe pathways specific to the chemotaxing neutrophil and elements documented to be important for neutrophil function.
Vasoactive Intestinal Peptide (VIP) and Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) as Modulators of Both Innate and Adaptive Immunity
Authors: Ganea Doina , Delgado Mario
Published: January 2009

The structurally related neuropeptides VIP and PACAP are released within the lymphoid organs following antigenic stimulation, and modulate the function of inflammatory cells through specific receptors. In activated macrophages, VIP and PACAP inhibit the production of pro-inflammatory agents (cytokines, chemokines, and nitric oxide), and stimulate the production of the anti-inflammatory cytokine IL-10. These events are mediated through the VIP/PACAP effects on de novo expression or nuclear translocation of several transcription factors, i.e., NFκB, CREB, c-Jun, JunB, and IRF-1. The in vivo administration of VIP/PACAP results in a similar pattern of cytokine and chemokine modulation, which presumably mediates the protective effect of VIP/PACAP in septic shock. In addition, VIP/PACAP reduce the expression of the co-stimulatory molecules B7.1/B7.2, and the subsequent stimulatory activity of macrophages for T-helper cells. In T-cells expressing specific VIP/PACAP receptors, VIP and PACAP inhibit the expression of FasL through effects on NFκB, NFAT, and Egr2/3. The reduction of FasL expression has several biological consequences: inhibition of antigen-induced cell death in CD4 T-cells, inhibition of the FasL-mediated cytotoxicity of CD8 and CD4 effectors against direct and bystander targets, and promotion of long-term memory Th2 cells, through a positive effect on the survival of Th2, but not Th1, effectors. The various biological effects of VIP and PACAP are discussed within the range of a general anti-inflammatory model.