Melbourne Dental School - Research Publications
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ItemMaxillonasal dysplasia (Binder syndrome): a lateral cephalometric assessment.(Walter de Gruyter GmbH, 2002-11)Binder syndrome or maxillonasal dysplasia was first described by Binder in 1962, and is a disorder characterised by nasomaxillary hypoplasia. The records of 33 patients who had been diagnosed clinically with Binder syndrome at the Royal Children's Hospital of Melbourne were examined. Of these 33 patients, 14 were selected because they met the incusion criteria: that they had not had prior surgical and/or orthodontic treatment, and that high-quality lateral cephalometric radiographs were available. The craniofacial morphology of these patients was determined on lateral cephalometric radiographs and compared with published age- and sex-matched norms. In agreement with published studies, the anteroposterior lengths of the anterior cranial base and maxilla were reduced, and the majority of patients had a Class III skeletal relationship. Although the lower incisors tended to be prominent, both overjet and overbite 'ell within the ranges for the normal population. Despite the fact that the orthodontic and surgical treatment for patients with Binder syndrome is normally carried out within specialised units, clinicians should be aware of the variety of ways in which this condition may present.
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ItemNo Preview AvailableRegulation of the endosomal SNARE protein syntaxin 7 by colony-stimulating factor 1 in macrophages(AMER SOC MICROBIOLOGY, 2008-10)Colony-stimulating factor 1 (CSF-1) is the main growth factor controlling the development of macrophages from myeloid progenitor cells. However, CSF-1 also regulates some of the key effector functions of macrophages (e.g., phagocytosis and cytokine secretion). The endosomal SNARE protein syntaxin 7 (Stx7) regulates vesicle trafficking events involved in phagocytosis and cytokine secretion. Therefore, we investigated the ability of CSF-1 to regulate Stx7. CSF-1 upregulated Stx7 expression in primary mouse macrophages; it also upregulated expression of its SNARE partners Vti1b and VAMP8 but not Stx8. Additionally, CSF-1 induced the rapid serine phosphorylation of Stx7 and enhanced its binding to Vti1b, Stx8, and VAMP8. Bioinformatics analysis and results from experiments with kinase inhibitors suggested the CSF-1-induced phosphorylation of Stx7 was mediated by protein kinase C and Akt in response to phosphatidylinositol 3-kinase activation. Based on mutagenesis studies, CSF-1 appeared to increase the binding of Stx7 to its SNARE partners by inducing the phosphorylation of serine residues in the Habc domain and/or "linker" region of Stx7. Thus, CSF-1 is a key regulator of Stx7 expression and function in macrophages. Furthermore, the effects of CSF-1 on Stx7 may provide a mechanism for the regulation of macrophage effector functions by CSF-1.
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ItemAn investigation on micro-Raman spectra and wavelet data analysis for pemphigus vulgaris follow-up monitoring(MDPI, 2008-06)A wavelet multi-component decomposition algorithm has been used for data analysis of micro-Raman spectra of blood serum samples from patients affected by pemphigus vulgaris at different stages. Pemphigus is a chronic, autoimmune, blistering disease of the skin and mucous membranes with a potentially fatal outcome. Spectra were measured by means of a Raman confocal microspectrometer apparatus using the 632.8 nm line of a He-Ne laser source. A discrete wavelet transform decomposition method has been applied to the recorded Raman spectra in order to overcome problems related to low-level signals and the presence of noise and background components due to light scattering and fluorescence. This numerical data treatment can automatically extract quantitative information from the Raman spectra and makes more reliable the data comparison. Even if an exhaustive investigation has not been done in this work, the feasibility of the follow-up monitoring of pemphigus vulgaris pathology has been clearly proved with useful implications for the clinical applications.
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ItemClinical Practice: Giant Cell Tumour of the Jaw Mimicking Bone Malignancy on Three-Dimensional Computed Tomography (3D CT) Reconstruction.(Bentham Science Publishers Ltd., 2008)A wide range of diseases may present with radiographic features of osteolysis. Periapical inflammation, cysts and benign tumours, bone malignancies, all of these conditions may show bone resorption on radiograph. Features of the surrounding bone, margins of the lesion, and biological behaviour including tendency to infiltration and root resorption, may represent important criteria for distinguishing benign tumours from their malign counterpart, although the radiographic aspect of the lesion is not always predictive. Therefore a critical differential diagnosis has to be reached to choose the best management. Here, we report a case of giant cell tumour (GCT) whose radiological features by computed tomography (CT) suggested the presence of bone malignancy, whereas the evaluation of a routine OPT scan comforted us about the benign nature of the lesion. A brief review of the literature on such a benign but locally aggressive neoplasm is also provided.
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ItemPhase-locked mutants of Mycoplasma agalactiae:: defining the molecular switch of high-frequency Vpma antigenic variation(WILEY, 2008-03)Mycoplasma agalactiae, an important pathogen of small ruminants, exhibits antigenic diversity by switching the expression of multiple surface lipoproteins called Vpmas (Variable proteins of M. agalactiae). Although phase variation has been shown to play important roles in many host-pathogen interactions, the biological significance and the mechanism of Vpma oscillations remain largely unclear. Here, we demonstrate that all six Vpma proteins are expressed in the type strain PG2 and all undergo phase variation at an unusually high frequency. Furthermore, targeted gene disruption of the xer1 gene encoding a putative site-specific recombinase adjacent to the vpma locus was accomplished via homologous recombination using a replicon-based vector. Inactivation of xer1 abolished further Vpma switching and the 'phase-locked' mutants (PLMs) continued to steadily express only a single Vpma product. Complementation of the wild-type xer1 gene in PLMs restored Vpma phase variation thereby proving that Xer1 is essential for vpma inversions. The study is not only instrumental in enhancing our ability to understand the role of Vpmas in M. agalactiae infections but also provides useful molecular approaches to study potential disease factors in other 'difficult-to-manipulate' mycoplasmas.
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ItemMolecular consequences of SOD2 expression in epigenetically silenced pancreatic carcinoma cell lines(NATURE PUBLISHING GROUP, 2007-10-16)Manganese superoxide dismutase (SOD2) is an enzyme that catalyses the dismutation of superoxide in the mitochondria, leading to reduced levels of reactive oxygen species. Reduced expression levels of SOD2 have been shown to result in increased DNA damage and sod2 heterozygous mice have increased incidences of cancer. It has also been shown that SOD2 expression is lost in pancreatic cell lines, with reintroduction of SOD2 resulting in decreased rate of proliferation. The mechanism of decreased SOD2 expression in pancreatic carcinoma has not been previously determined. We demonstrate, through sodium bisulphite sequencing, that the sod2 locus is methylated in some pancreatic cell lines leading to a corresponding decrease in SOD2 expression. Methylation can be reversed by treatment with zebularine, a methyltransferase inhibitor, resulting in restored SOD2 expression. Furthermore, we demonstrate that sensitivity of pancreatic carcinoma cell lines to 2-methoxyestradiol correlates with SOD2 expression and SOD2 modulation can alter the sensitivity of these cells. Using both genomics and proteomics, we also identify molecular consequences of SOD2 expression in MIA-PaCa2 cells, including dephosphorylation of VEGFR2 and the identification of both SOD2-regulated genes and transcription factors with altered binding activity in response to SOD2 expression.
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ItemLipopolysaccharide alters decorin and biglycan synthesis in rat alveolar bone osteoblasts: consequences for bone repair during periodontal disease(WILEY, 2008-06)A prime pathogenic agent associated with periodontitis is lipopolysaccharide (LPS) derived from Porphyromonas gingivalis. This study investigated the effects of P. gingivalis LPS on osteoblasts, which are responsible for alveolar bone repair. Bone cells were obtained from explants of rat alveolar bone chips and cultured with 0-200 ng ml(-1) of P. gingivalis LPS. Porphyromonas gingivalis LPS significantly increased cell proliferation and inhibited osteoblast differentiation, as judged by reduced alkaline phosphatase activity. Analysis of biglycan mRNA and protein levels indicated that P. gingivalis LPS significantly delayed the normally high expression of biglycan during the early stages of culture, which are associated with cell proliferation and early differentiation of progenitor cells. In the presence of P. gingivalis LPS, decorin expression by the alveolar bone cells was reduced during periods of culture relating to collagen fibrillogenesis and mineral deposition. Analysis of glycosaminoglycan chains conjugated to these proteoglycans suggested that in the presence of P. gingivalis LPS, dermatan sulfate persisted within the matrix. This study suggests that P. gingivalis LPS influences the expression and processing of decorin and biglycan in the matrix, altering alveolar bone cell activity and osteoblast phenotype development. The consequences of this altered expression in relation to hindering bone repair as part of the cycle of events during periodontal disease are discussed.
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ItemComparative transcriptomic analysis of Porphyromonas gingivalis biofilm and planktonic cells(BMC, 2009-01-29)BACKGROUND: Porphyromonas gingivalis in subgingival dental plaque, as part of a mature biofilm, has been strongly implicated in the onset and progression of chronic periodontitis. In this study using DNA microarray we compared the global gene expression of a P. gingivalis biofilm with that of its planktonic counterpart grown in the same continuous culture. RESULTS: Approximately 18% (377 genes, at 1.5 fold or more, P-value < 0.01) of the P. gingivalis genome was differentially expressed when the bacterium was grown as a biofilm. Genes that were down-regulated in biofilm cells, relative to planktonic cells, included those involved in cell envelope biogenesis, DNA replication, energy production and biosynthesis of cofactors, prosthetic groups and carriers. A number of genes encoding transport and binding proteins were up-regulated in P. gingivalis biofilm cells. Several genes predicted to encode proteins involved in signal transduction and transcriptional regulation were differentially regulated and may be important in the regulation of biofilm growth. CONCLUSION: This study analyzing global gene expression provides insight into the adaptive response of P. gingivalis to biofilm growth, in particular showing a down regulation of genes involved in growth and metabolic activity.
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ItemAlkaline phosphatase activity assessment of two endodontic materials: a preliminary study(University of Malaya, 2008)Objective: An in vitro assessment of MG-63 human osteosarcoma cells' alkaline phosphatase (ALP) activity when in contact with calcium hydroxide powder (CH), paste (CHP) and grey mineral trioxide aggregate (MTA). Methods: MG-63 cells were seeded to the three selected materials for durations of 0.25, 0.5, 1, 24, 48 and 72 hours. BCIP-NBT assay was used and ALP activity quantified using ELISA reader at 410 nm. Results: The overall analysis for ALP activity indicated significant interaction between test materials and control (maintenance medium). Subsequently, the test materials were paired and analysed for initial (0.25, 0.5, 1 hour) and delayed response (24, 48 and 72 hours). During the initial response, CH exhibited an increased ALP activity compared to MTA. This interaction was not dependant on duration. The delayed response exhibited elevated ALP activity with CHP when compared to MTA and CH. The interaction of CHP was dependant on duration. Conclusion: All three materials exhibited increased ALP activity.
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