Biomedical subjects
Publications and source records attributed to M J Aldred.
The solitary fibrous tumour is an uncommon, benign neoplasm of adults involving the pleura. It is now recognised to occur in extrapleural sites. Only a limited number of cases have been reported in the oral cavity. This paper reports two further cases, which presented as clinically benign masses in the palate and buccal mucosa respectively.
Amelogenesis imperfecta of the hypomaturation-hypoplasia type with taurodontism (AIHHT) is inherited as a highly penetrant autosomal dominant trait. These dental findings are similar to those of another autosomal dominant condition, the tricho-dento-osseous syndrome (TDO), from which AIHHT differs primarily by lack of changes in the hair and bones. TDO is characterized by a highly variable clinical phenotype. While enamel hypoplasia and taurodontism appear to be present in all TDO cases, non-dental features may be absent, with approximately half of TDO cases losing the kinky/curly hair phenotype seen in infancy by adolescence, and in almost 20% of cases, osseous changes are not evident. The genetic basis for AIHHT is unknown and it has been questioned whether AIHHT and TDO are separate conditions or a spectrum of disease. The genetic basis for TDO has recently been identified as a deletion mutation in the distal-less 3 (DLX3) transcription factor gene. To determine if AIHHT and TDO represent variable expression of a common DLX3 gene mutation, allelic mutations of the DLX3 gene, or mutations in DLX7 (the linked paralogue to DLX3 on chromosome 17), we have performed mutational analysis and sequencing studies of the DLX3 and DLX7 genes in three individuals (two affected and one unaffected) from a family with AIHHT. Results of the analysis demonstrate that AIHHT and TDO are not due to a common DLX3 gene mutation. Sequence analyses of the DLX3 and DLX7 genes suggest AIHHT is not due to genetic mutations or polymorphisms in the exons of these genes. These results suggest that AI-HHT and TDO are two genetically distinct conditions.
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This paper reviews past and present applications of quantitative and molecular genetics to dental disorders. Examples are given relating to craniofacial development (including malocclusion), oral supporting tissues (including periodontal diseases) and dental hard tissues (including defects of enamel and dentine as well as dental caries). Future developments and applications to clinical dentistry are discussed. Early investigations confirmed genetic bases to dental caries, periodontal diseases and malocclusion, but research findings have had little impact on clinical practice. The complex multifactorial aetiologies of these conditions, together with methodological problems, have limited progress until recently. Present studies are clarifying previously unrecognized genetic and phenotypic heterogeneities and attempting to unravel the complex interactions between genes and environment by applying new statistical modelling approaches to twin and family data. Linkage studies using highly polymorphic DNA markers are providing a means of locating candidate genes, including quantitative trait loci (QTL). In future, as knowledge increases; it should be possible to implement preventive strategies for those genetically-predisposed individuals who are identified to be at risk.
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Amelogenesis imperfecta is a disfiguring inherited condition affecting tooth enamel. X-Linked and autosomal dominant and recessive inheritance patterns occur. X-Linked amelogenesis imperfecta has been studied extensively at the molecular level. Linkage analysis has shown that there is genetic hetetogeneity in X-linked amelogenesis imperfecta with two identified loci: AIH1 and AIH3. The AIH1 locus corresponds to the location of the amelogenin gene on the distal short arm of the X chromosome; various mutations in the amelogenin gene have been found in families with X-linked amelogenesis imperfecta. The AIH3 locus maps to the Xq24-q27.1 region on the long arm of the X chromosome. Linkage to the long arm of chromosome 4 has been established in three families with autosomal dominant amelogenesis imperfecta. There is as yet no published evidence for genetic heterogeneity in autosomal dominant amelogenesis imperfecta as in X-linked amelogenesis imperfecta. Candidate genes for autosomal dominant amelogenesis imperfecta include tuftelin (1q), albumin (4q) and ameloblastin (4q) but the involvement of these genes in the disease has yet to be demonstrated. In view of the variable clinical appearances within families with autosomal dominant amelogenesis imperfecta and X-linked amelogenesis imperfecta, together with the finding that different X-linked amelogenesis imperfecta phenotypes result from mutations within the same gene, an alternative classification based on the molecular defect and mode of inheritance rather than phenotype has been proposed.
This article describes a series of 21 consecutive cases, each involving a solitary median maxillary central incisor; the patients were seen in the Department of Dentistry or the Victorian Clinical Genetics Unit, Murdoch Institute, at the Royal Children's Hospital, Melbourne, from 1966 to 1997. The spectrum of anomalies and associated features present in these cases--solitary median maxillary central incisor, choanal atresia, and holoprosencephaly--is described, and the literature related to the features, including genetic studies in these conditions, is reviewed. We relate our findings in these cases to current knowledge of developmental embryology. It is hoped that the findings, together with our interpretation of them, will help to clarify understanding of solitary median maxillary central incisor syndrome. This syndrome was previously considered a simple midline defect of the dental lamina, but it is now recognized as a possible predictor of holoprosencephalies of varying degrees in the proband, in members of the proband's family, and in the family's descendants.
Orofacial granulomatosis is a condition that may be difficult to diagnose for those unfamiliar with the entity. This paper describes two cases and addresses the presentation, pathogenesis and treatment. The clinical recognition of this condition is important as is the subsequent investigation by an appropriate specialist. Management of patients needs to take into account the results of further investigations, the patient's expectations, and the severity of the condition.
E-selectin is an adhesion molecule, expressed by cytokine-activated endothelial cells, that participates in the binding of neutrophils. Recent studies in our laboratory documented binding of the E-selectin-specific monoclonal antibody H4/18 to keratinocytes in inflamed human oral mucosa, particularly gingival epithelium. To determine whether this immunoreactivity was due to expression of authentic E-selectin, the presence of E-selectin mRNA in gingival epithelium was analysed using the polymerase chain reaction (PCR). Reverse transcription of epithelial RNA and amplification of cDNA with E-selectin-specific primers resulted in the formation of a 178 nucleotide PCR product identical to that obtained from cytokine-activated endothelial cells. Sequencing of the PCR product revealed 100% homology between epithelial and endothelial E-selectin fragments. Epithelial preparations did not contain mRNA for von Willebrand factor, excluding the possibility of contamination by endothelial cells. These results confirm immunohistochemical studies of E-selectin immunoreactivity in human oral mucosa and demonstrate that E-selectin expression is not confined to endothelium.
UNLABELLED: To study V beta gene expression in oral lichen planus (OLP) lesional T lymphocytes cell lines. MATERIALS AND METHODS: Lesional T lymphocytes were isolated from eight OLP patients and cell lines established. The total RNA was extracted from these lymphocyte cell lines and reverse transcribed. cDNA was amplified by the polymerase chain reaction (PCR) using a panel of 26 V beta-specific oligonucleotide primers followed by qualitative analysis of the electrophoresed reaction products. RESULTS: V beta 1, 2, 3, 5.1, 6.1-3, 7, 8, 9, 22, 23, and 24 were represented consistently in all of the OLP samples, V beta 11, 12, and 17 were consistently negative, while the other V beta families (V beta 4, 5.2-3, 10, 13.1, 13.2, 14, 15, 16, 18, 19, 20, and 21) were variable. V beta 22 and 23 were the most strongly expressed in all patients. CONCLUSIONS: A limited T cell receptor (TCR) gene usage indicates a degree of oligoclonality within these lesional T lymphocyte cell lines from OLP. This implies that OLP may be an antigen-specific disease or linked to a limited number of superantigens.
This editorial reviews the history of the classification of amelogenesis imperfecta (AI). The limitations of the existing classification systems are discussed. An alternative classification is proposed based upon the molecular defect, biochemical result, mode of inheritance and phenotype in the family involved. While not all of the criteria for the proposed classification can yet be addressed, this scheme is proposed for future classification of AI cases and families.
UNLABELLED: Porphyromonas gingivalis is generally recognized as a major periodontopathogen such that a study of T cell responses to this organism may help to elucidate immune regulation in periodontal disease. OBJECTIVE: The aim of this study was to examine interleukin (IL)-4, interferon (IFN)-gamma and IL-10 production by P. gingivalis-responsive T cell lines and clones derived from the peripheral blood of two P. gingivalis-infected subjects with different disease expression and from the gingival tissues of one of the P. gingivalis-infected subjects. MATERIALS AND METHODS: FACS analysis was used to determine the percentage of T cells staining positive for cytoplasmic IL-4, IFN-gamma and IL-10 and reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the presence of mRNA for IL-4 and IFN-gamma in the T cell lines and clones. RESULTS: FACS analysis showed that virtually all the T cell lines and clones contained IL-4- and IFN-gamma-producing T cells. The RT-PCR results generally supported this trend. However, a higher percentage of cells in the clones derived from one subject produced IL-4 while a lower percentage produced IFN-gamma compared with the clones derived from the other subject. FACS analysis also demonstrated that the lines and clones derived from the two subjects showed differences in IL-10 production. CONCLUSION: This study has demonstrated that there may be differences in IL-4 and IL-10 production by the P. gingivalis responsive lines and clones derived from P. gingivalis-infected subjects with different disease expression. Any relationship to disease however, remains to be determined.
Hereditary gingival fibromatosis can occur as an isolated trait or as part of a syndrome. We report on three generations of one family featuring an autosomal dominant syndrome with variable expression of gingival fibromatosis with associated hearing deficiencies, hypertelorism, and supernumerary teeth. We propose that this represents a new syndrome within the spectrum of those including gingival enlargement.
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A Brazilian family with hereditary gingival fibromatosis is described with multiple affected subjects in four generations. A total of 50 (48%), of 105 at-risk offspring in a family of 132 members were affected, consistent with an autosomal dominant mode of inheritance. This family appears to represent the largest pedigree with this condition reported in the literature.