Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists最新文献

Mast cells are mobile granule-containing secretory cells that are distributed preferentially about the microvascular endothelium in oral mucosa and dental pulp. The enzyme profile of mast cells in oral tissues resembles that of skin, with most mast cells expressing the serine proteases tryptase and chymase. Mast cells in oral tissues contain the pro-inflammatory cytokine tumour necrosis factor-alpha in their granules, and release of this promotes leukocyte infiltration during evolving inflammation in several conditions, including lichen planus, gingivitis, pulpitis, and periapical inflammation, through induction of endothelial-leukocyte adhesion molecules. Mast cell synthesis and release of other mediators exerts potent immunoregulatory effects on other cell types, while several T-lymphocyte-derived cytokines influence mast cell migration and mediator release. Mast cell proteases may contribute to alterations in basement membranes in inflammation in the oral cavity, such as the disruptions that allow cytotoxic lymphocytes to enter the epithelium in oral lichen planus. A close relationship exists among mast cells, neural elements, and laminin, and this explains the preferential distribution of mast cells in tissues. Mast cells are responsive to neuropeptides and, through their interaction with neural elements, form a neural immune network with Langerhans cells in mucosal tissues. This facilitates mast cell degranulation in response to a range of immunological and non-immunological stimuli. Because mast cells play a pivotal role in inflammation, therapies that target mast cell functions could have value in the treatment of chronic inflammatory disorders in the oral cavity.

The oral cavity is a complex ecosystem in which several hundred microbial species normally cohabit harmoniously. However, under certain special conditions, the growth of some micro-organisms with a pathogenic potential is promoted, leading to infections such as dental caries, periodontal disease, and stomatitis. The physiology and pathogenic properties of micro-organisms are influenced by modifications in environmental conditions that lead to the synthesis of specific proteins known as the heat-shock proteins (HSPs). HSPs are families of highly conserved proteins whose main role is to allow micro-organisms to survive under stress conditions. HSPs act as molecular chaperones in the assembly and folding of proteins, and as proteases when damaged or toxic proteins have to be degraded. Several pathological functions have been associated with these proteins. Many HSPs of oral micro-organisms, particularly periodontopathogens, have been identified, and some of their properties-including location, cytotoxicity, and amino acid sequence homology with other HSPs-have been reported. Since these proteins are immunodominant antigens in many human pathogens, studies have recently focused on the potential contributions of HSPs to oral diseases. The cytotoxicity of some bacterial HSPs may contribute to tissue destruction, whereas the presence of common epitopes in host proteins and microbial HSPs may lead to autoimmune responses. Here, we review the current knowledge regarding HSPs produced by oral micro-organisms and discuss their possible contributions to the pathogenesis of oral infections.

The concept of a two-step process of cancer development in the oral mucosa, i.e., the initial presence of a precursor subsequently developing into cancer, is well-established. Oral leukoplakia is the best-known precursor lesion. The evidence that oral leukoplakias are pre-malignant is mainly derived from follow-up studies showing that between < 1 and 18% of oral pre-malignant lesions will develop into oral cancer; it has been shown that certain clinical sub-types of leukoplakia are at a higher risk for malignant transformation than others. The presence of epithelial dysplasia may be even more important in predicting malignant development than the clinical characteristics. Three major problems, however, are attached to the importance of epithelial dysplasia in predicting malignant development: (1) The diagnosis is essentially subjective, (2) it seems that not all lesions exhibiting dysplasia will eventually become malignant and some may even regress, and (3) carcinoma can develop from lesions in which epithelial dysplasia was not diagnosed in previous biopsies. There is, therefore, a substantial need to improve the histologic assessment of epithelial dysplasia or, since epithelial dysplasia does not seem to be invariably associated with or even a necessary prerequisite for malignant development, it may be necessary to develop other methods for predicting the malignant potential of pre-malignant lesions. As a consequence of these problems, numerous attempts have been made to relate biological characteristics to the malignant potential of leukoplakias. Molecular biological markers have been suggested to be of value in the diagnosis and prognostic evaluation of leukoplakias. Markers of epithelial differentiation and, more recently, genomic markers could potentially be good candidates for improving the prognostic evaluation of precursors of oral cancer. As yet, one or a panel of molecular markers has not been determined that allows for a prognostic prediction of oral pre-cancer which is any more reliable than dysplasia recording. However, these new markers could be considered complementary to conventional prognostic evaluation.

Field cancerization was first described in 1953 as histologically altered epithelium surrounding tumor samples taken from the upper aerodigestive tract. Since then, the term has been used to describe multiple patches of pre-malignant disease, a higher-than-expected prevalence of multiple local second primary tumors, and the presence of synchronous distant tumors within the upper aerodigestive tract. Molecular techniques such as karyotype analysis, microsatellite analysis, p53 mutation screening, and X-chromosome inactivation studies have further refined the relationship among these lesions. While there are differences in the techniques used to identify the clonal origins of the lesions, these studies indicate that there is often lateral clonal spread of pre-malignant or malignant disease, and a significant portion of local second primary tumors are in fact genetically related. Distant second primary tumors found in the esophagus are often not related to concurrent head and neck cancer, whereas synchronous squamous lung tumors with a head and neck primary are often, in fact, metastases, rather than independently arising malignancies. These observations help to explain the high incidence of recurrent disease, despite excision or other therapy--pre-malignant or malignant clones often have the ability to migrate and persist outside of the field of treatment. Therefore, alternative means of prevention or therapy that can affect the entire head and neck region may be of benefit to such patients. Future studies will further refine the relationship among these lesions and perhaps identify key molecular alterations to be used as targets for gene therapy.

Helicobacter pylori infection is one of the most common in man. The bacterium primarily resides in the human stomach, where it plays a significant role in gastric disease. If the spread of H. pylori is to be prevented, an understanding of the transmission process is essential. The oral cavity has been proposed as a reservoir for gastric H. pylori, which has been detected by culture and PCR in both dental plaque and saliva. This review will discuss the evidence for the role of the oral cavity in the transmission of gastric H. pylori. Moreover, the difficulties encountered in addressing this topic, possible directions for future research, and the implications for the dental profession are discussed.

Oral fungal infections (mycoses) have come into particular prominence since the advent of infection with Human Immunodeficiency Virus (HIV), and recognition of the Acquired Immune Deficiency Syndrome (AIDS), as well as the phenomenal increase in world travel with increased exposure to infections endemic in the tropics. Paracoccidioidomycosis is a rare mycosis worldwide but common in Brazil and some other areas in Latin America. It can be life-threatening and can manifest with a spectrum of clinical presentations, including frequent oral lesions. This paper reviews the more recent information on Paracoccidioidomycosis, emphasizing those areas most relevant in dental science.

The synthesis of extracellular glucan is an integral component of the sucrose-dependent colonization of tooth surfaces by species of the mutans streptococci. In investigators' attempts to understand the mechanisms of plaque biofilm development, several glucan-binding proteins (GBPs) have been discovered. Some of these, the glucosyltransferases, catalyze the synthesis of glucan, whereas others, designated only as glucan-binding proteins, have affinities for different forms of glucan and contribute to aspects of the biology of their host organisms. The functions of these latter glucan-binding proteins include dextran-dependent aggregation, dextranase inhibition, plaque cohesion, and perhaps cell wall synthesis. In some instances, their glucan-binding domains share common features, whereas in others the mechanism for glucan binding remains unknown. Recent studies indicate that at least some of the glucan-binding proteins modulate virulence and some can act as protective immunogens within animal models. Overall, the multiplicity of GBPs and their aforementioned properties are testimonies to their importance. Future studies will greatly advance the understanding of the distribution, function, and regulation of the GBPs and place into perspective the facets of their contributions to the biology of the oral streptococci.

Advances in bacterial genetics came with the discovery of the genetic code, followed by the development of recombinant DNA technologies. Now the field is undergoing a new revolution because of investigators' ability to sequence and assemble complete bacterial genomes. Over 200 genome projects have been completed or are in progress, and the oral microbiology research community has benefited through projects for oral bacteria and their non-oral-pathogen relatives. This review describes features of several oral bacterial genomes, and emphasizes the themes of species relationships, comparative genomics, and lateral gene transfer. Genomics is having a broad impact on basic research in microbial pathogenesis, and will lead to new approaches in clinical research and therapeutics. The oral microbiota is a unique community especially suited for new challenges to sequence the metagenomes of microbial consortia, and the genomes of uncultivable bacteria.

This review will focus on the impact of molecular genetic approaches on elucidating the bacterial etiology of oral diseases from an historical perspective. Relevant results from the pre- and post-recombinant DNA periods will be highlighted, including the roles of gene cloning, mutagenesis, and nucleotide sequencing in this area of research. Finally, the impact of whole-genome sequencing on deciphering the virulence mechanisms of oral pathogens, along with new approaches to control these organisms, will be discussed.

High-risk genotypes of the human papillomavirus (HPV), particularly HPV type 16, are found in a distinct subset of head and neck squamous cell carcinomas (HNSCC). Thus, these HPV-associated HNSCC may be prevented or treated by vaccines designed to induce appropriate HPV virus-specific immune responses. Infection by HPV may be prevented by neutralizing antibodies specific for the viral capsid proteins. In clinical trials, vaccines comprised of HPV virus-like particles (VLPs) have shown great promise as prophylactic HPV vaccines. However, given that capsid proteins are not expressed at detectable levels by infected basal keratinocytes, vaccines with therapeutic potential must target other non-structural viral antigens. Two HPV oncogenic proteins, E6 and E7, are important in the induction and maintenance of cellular transformation and are co-expressed in the majority of HPV-containing carcinomas. Therefore, therapeutic vaccines targeting these proteins may have potential to control HPV-associated malignancies. Various candidate therapeutic HPV vaccines are currently being tested whereby E6 and/or E7 is administered in live vectors, in peptides or protein, in nucleic acid form, as components of chimeric VLPs, or in cell-based vaccines. Encouraging results from experimental vaccination systems in animal models have led to several prophylactic and therapeutic vaccine clinical trials. Should they fulfill their promise, these vaccines may prevent HPV infection or control its potentially life-threatening consequences in humans.