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Biomedical subjects

D M Walker

Publications and source records attributed to D M Walker.

At least 19 recordsLinked to original sources
PubMed2005

A case of aggressive multiple metachronous central giant cell granulomas of the jaws: differential diagnosis and management options.

We describe multiple metachronous central giant cell granulomas in a 62-year-old man who has a first degree relative with a history of a solitary central giant cell granulomas. The patient presented in 1997 with a large central giant cell granuloma of the right maxilla which was treated with a partial maxillectomy. A small recurrence was then identified and the successful management of this is described. The patient has also a histologically confirmed central giant cell granuloma previously removed from the right body of the mandible and the left angle of the mandible. The differential diagnosis of multiple central giant cell granulomas of the jaw is considered. It is possible that the present case may indeed represent a new syndrome or subtype of multiple central giant cell granulomas. The problem of treating such aggressive sub-types of giant cell granulomas is also addressed in the context of recent advances of surgical and medical management.

Diagnosis, Differential↗
PubMed2005

Primary orbital Ewing sarcoma in a middle-aged man.

A 54-year-old man presented with a painful left proptosis and a soft tissue mass at the inferolateral aspect of the left orbit with bone involvement. There was no clinical or investigational evidence of systemic disease. Both light microscopy and immunohistochemistry were required for the diagnosis of Ewing sarcoma. After failure of chemotherapy alone, management included extensive surgical excision and postoperative adjuvant radiotherapy and chemotherapy. Despite intervention, the patient died of widespread metastatic disease 17 months after initial presentation. Although rare, Ewing sarcoma should be included in the differential diagnosis of uniform round cell orbital tumors in adults.

Biopsy↗
PubMed2004

Oral mucosal immunology: an overview.

The primary function of the immune system of the mouth is to protect the teeth, jaws, gingivae and oral mucosa against infection. These host defences vary in the different oral microenvironments or domains represented by the oral mucosa, saliva and gingival crevice. This review aims to consider and contrast the main immune components in each domain and cites examples of oral diseases where the immune response is defective.

Humans↗
PubMed2003

Induction of contact-dependent endothelial apoptosis by osteosarcoma cells suggests a role for endothelial cell apoptosis in blood-borne metastasis.

Although tumour cells are believed to migrate between endothelial cells early in metastasis, the possibility remains that endothelial apoptosis may also contribute to the tumour's breach of the vascular barrier. Although seemingly inconsistent with tumour angiogenesis, one publication describes the induction of contact-dependent apoptosis in cultured endothelium by tumour cells. The cell culture data are, however, open to challenge on technical grounds while there are no confirmatory reports. The present paper describes experiments overcoming these limitations. SAOS-2 human osteosarcoma cells and two rat carcinoma cell lines were co-cultured with human umbilical vein endothelial cells (HUVECs) and cultures labelled by surface lectin histochemistry for endothelium. The HUVEC culture density was determined and SAOS-2 cells, but not rat carcinoma cells, were found significantly to reduce HUVEC survival despite the release of potent growth factors as determined in separate experiments with tumour cell conditioned medium. Lectin labelling combined with light microscopy, transmission electron microscopy, flow cytometry for both lectin binding and DNA content, and DNA gel electrophoresis of SAOS-2/HUVEC co-cultures revealed extensive HUVEC apoptosis. These findings indicate contact-dependent endothelial apoptosis by SAOS-2, while this activity appeared weaker and overwhelmed by HUVEC proliferation with rat carcinoma cells. Importantly, this study supports the suggestion that endothelial apoptosis may be important for metastasis and suggests a complex interplay between endothelial proliferation and apoptosis in tumours.

Animals↗
PubMed2003

Tongue cancer: do patients younger than 40 do worse?

BACKGROUND: Debate continues as to whether being young confers a worse prognosis for patients with squamous cell carcinoma of the tongue. Recent papers have provided conflicting views in this debate. In this study we aimed to investigate if young age at the time of diagnosis of squamous cell carcinoma of the tongue confers a worse prognosis. METHODS: Eligible patients were identified through the computer database of the Department of Radiation Oncology, Westmead Hospital, Sydney. All eligible patients were treated with radical intent. Using age 40 as a cut off multivariate and survival analysis was undertaken to compare age groups. RESULTS: Median age at diagnosis was 60 years (range, 19-86 years) in 84 males (65 per cent) and 45 females (35 per cent). Median follow-up time was 43 months (range, 2.3-203 months). Fifteen patients (12 per cent) were aged <40 years. On univariate analysis stage and age were significant determinants of disease-specific survival. There was no difference in overall survival between the young (<40 years) and middle-aged groups (40-60 years). However, the young and the middle aged were both more likely to survive than the older age group (>60 years). On multivariate analysis age remained a significant factor for determining disease-specific survival, with the older age group 2.9 times more likely to die than the younger groups. CONCLUSION: Young age (<40 years) did not portend to worse survival in comparison to older tongue cancer patients.

Adult↗
PubMed2001

Characterization of MTMR3. an inositol lipid 3-phosphatase with novel substrate specificity.

Inositol lipids play key roles in many fundamental cellular processes that include growth, cell survival, motility, and membrane trafficking. Recent studies on the PTEN and Myotubularin proteins have underscored the importance of inositol lipid 3-phosphatases in cell function. Inactivating mutations in the genes encoding PTEN and Myotubularin are key steps in the progression of some cancers and in the onset of X-linked myotubular myopathy, respectively. Myotubularin-related protein 3 (MTMR3) shows extensive homology to Myotubularin, including the catalytic domain, but additionally possesses a C-terminal extension that includes a FYVE domain. We show that MTMR3 is an inositol lipid 3-phosphatase, with a so-far-unique substrate specificity. It is able to hydrolyze PtdIns3P and PtdIns3,5P2, both in vitro and when heterologously expressed in S. cerevisiae, and to thereby provide the first clearly defined route for the cellular production of PtdIns5P. Overexpression of a catalytically dead MTMR3 (C413S) in mammalian cells induces a striking formation of vacuolar compartments that enclose membranous structures that are highly concentrated in mutant proteins.

Animals↗
PubMed2001

Mutagenicity at the Hprt locus in T cells of female mice following inhalation exposures to low levels of 1,3-butadiene.

A study was conducted to test the hypothesis that repeated low level exposures to 1,3-butadiene (BD), approaching the OSHA occupational threshold for this chemical, produce a significant mutagenic response in mice. Female B6C3F1 mice (4-5 weeks of age) were exposed by inhalation for 2 weeks (6 h/day, 5 days/week) to 0 or 3 ppm BD, and then necropsied at 4 weeks after the cessation of exposures to measure the frequency of mutations (MF) at the Hprt locus using the T-lymphocyte clonal assay. At necropsy, T cells were isolated from spleen and cultured in the presence of mitogen, growth factors, and a selection agent. Cells were scored for growth on days 8-9 after plating to determine cloning efficiencies (CEs) and Hprt MFs. There was a marginal but significant reduction in the growth of splenic T cells from mice exposed to 3 ppm (n=27) compared with control mice (n=24) (P=0.004), suggesting the occurrence of BD-induced cytotoxicity at this low exposure concentration. In addition, the average Hprt MF in mice exposed to 3 ppm BD [1.54+/-0.82 (S.D.)x10(-6)] was significantly increased by 1.6-fold over the average control value of 0.96+/-0.51 (S.D.)x10(-6) (P=0.004). Comparisons of these data to earlier Hprt mutagenicity studies of mice exposed to high concentrations of BD (where significant mutagenic but not cytotoxic effects were observed) indicate that the ability to detect the cytotoxic and mutagenic responses of T cells to low levels of BD was enhanced by using a much larger sample size than usual for both the control and treatment groups. Additional analyses of the quantitative relationships between CE and MF demonstrated that CE had no significant effect upon MF values in sham-exposed control mice or mice exposed to low-level BD. Furthermore, the approaches for assessing the impact of CE and clonality on Hprt MFs in these control and BD-exposed mice were applied with the same rigor as in in vivo Hprt mutagenicity studies in human children. The overall study results support the conclusion that short-term low-level BD exposure is mutagenic in the mouse.

Administration, Inhalation↗
PubMed2001

Calcifying epithelial odontogenic (Pindborg) tumor with malignant transformation and metastatic spread.

BACKGROUND: Pindborg tumors (calcifying epithelial odontogenic tumors) are uncommon neoplasms of odontogenic origin most often located in the posterior mandible. First described in detail in 1955 by Pindborg, these tumors are considered benign but can be locally aggressive in nature, with recurrence rates of 10% to 15% reported. The malignant form of this tumor is exceedingly rare. METHODS: We describe the case of a 64-year-old woman initially treated for a painful infected left mandibular third molar. The patient underwent extraction of the tooth and excision of an associated soft tissue component. Subsequent histologic review identified a Pindborg tumor of the left posterior mandible. RESULTS: After initial excision, this tumor recurred twice, with the recurrences exhibiting a progression to a malignant Pindborg tumor (odontogenic carcinoma) with vascular invasion and spread to a cervical lymph node. Further treatment involved radical surgery and adjuvant radiotherapy. At last review 12 months after treatment, the patient was disease free. CONCLUSIONS: This article describes only the second case of odontogenic carcinoma. The transformation from benign to malignant histologic findings has not previously been documented in this tumor. The salient clinical features of this case are presented along with supportive pathologic and radiologic evidence.

Cell Transformation, Neoplastic↗
PubMed2001

Psychiatric treatment and operational readiness: clinical guidelines for Air Force practice.

Clinical criteria for psychiatric illnesses that are career limiting to active duty Air Force personnel are defined in Air Force Instruction (AFI) 48-123. The terms used in the AFI are not sufficiently specific to the standards of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The authors review AFI 48-123 for conditions commonly seen in Air Force mental health practice and offer clinical interpretation of this AFI to bring it into line with DSM-IV. As a result of this synthesis, decisions regarding which mental health conditions warrant medical evaluation board disposition are clearer and more uniform. Clinicians and administrators are encouraged to refer to this paper for assistance in making decisions on mental health patients.

Humans↗
PubMed2001

Classical and variant Creutzfeldt-Jakob diseases and their potential impact on the practice of clinical dentistry in Australia.

Following recent published evidence regarding the experimental transmission of prion diseases via blood transfusion, dental practitioners have expressed their concern about the potential impact of these transmissible spongiform encephalopathies on dental care provision. This review provides updated information on Creutzfeldt-Jakob disease and related disorders and highlights their potential significance for the practice of clinical dentistry. The current guidelines in Australia relating to infection control and clinical dental procedures are discussed together with recommended guidelines and considerations from the United Kingdom and the World Health Organization (WHO).

Animals↗
PubMed2000

Zidovudine-didanosine coexposure potentiates DNA incorporation of zidovudine and mutagenesis in human cells.

Drug combinations that include nucleoside reverse transcriptase inhibitors (NRTIs) are remarkably effective in preventing maternal-viral transmission of HIV during pregnancy. However, there may be potential long-term risks for children exposed in utero. Examination of the genotoxic and mutagenic effects of two NRTIs, zidovudine [AZT (3'-azido-3'-deoxythymidine)] and didanosine [ddI (2',3'-dideoxyinosine)], in cultured human lymphoblastoid cells revealed multiplicative synergistic enhancement of AZT-DNA incorporation and mutant frequency induction in response to the combined drug exposure, as compared with single-drug exposures. Dose-related increases in DNA incorporation of AZT (as measured by a competitive RIA) and mutagenicity at the HPRT and TK loci (as assessed by cell-cloning assays) were observed in cells exposed in culture to AZT, or equimolar combinations of AZT + ddI, at exposure concentrations ranging from 3 to 30 times the maximum plasma levels found in humans. Because mutagenesis is strongly associated with tumor induction in experimental models, children exposed transplacentally to combinations of NRTIs may be at risk for cancer development later in life.

Anti-HIV Agents↗
PubMed2000

Analysis of the amplification refractory mutation allele-specific polymerase chain reaction system for sensitive and specific detection of p53 mutations in DNA.

The sensitivity of the amplification refractory mutation allele-specific polymerase chain reaction system (ARMAS-PCR) to detect known p53 mutations was determined using DNA extracted from two human tumour cell lines collected by cytobrush, as a model for its use in exfoliative cytology. Using DNA extracted from SW480 and CEM cell lines diluted with normal human fibroblasts, a nested ARMAS-PCR was more sensitive than a non-nested version and could detect one mutated cell amongst 100 000 normal cells. When compared with PCR-single stranded conformational polymorphism, nested ARMAS-PCR was 10 000 times more sensitive for detecting mutant p53 in extracted DNA. Primer design proved to be influential on the sensitivity and specificity of the assay; increased specificity was achieved by the use of deliberate mismatches upstream from the 3' end of mutation-specific primers. ARMAS-PCR was confirmed to be specific for the mutation that each primer was designed to detect. Nested ARMAS-PCR offered a rapid and sensitive method of analysis of cells with predetermined p53 mutations and has the potential to be applied to the study of the molecular progression of cancer, including diagnosis and detection of residual disease. It could also be extended to the in situ detection of aberrant cells.

DNA Mutational Analysis↗
PubMed2000

Synthesis of highly substituted 5-(trifluoromethyl)ketoimidazoles using a mixed-solid/solution phase motif.

Using a combination of solid phase synthesis for the preparation of N-substituted-N-acylglycines 7 followed by solution-phase ring transformation of trifluoromethylacyl munchnone intermediate 8, a library of 200 trisubstituted-5-trifluoromethylketo (TFMK) imidazoles 9 was prepared. In a sublibrary, bromoacetate resin 4 was treated with 5 amines in parallel to give N-substituted glycines 5 followed by acylation with 12 acid chlorides to provide, upon cleavage from the resin, 60 individual N-substituted-N-acylglycines 7. The glycines 7 were converted to munchnones 8 by treatment with trifluoroacetic anhydride followed by reaction with benzamidine to give trisubstituted-5-TFMK-imidazoles 9. The structural content of the library was analyzed using PlateView of the LCMS results, and individual members were isolated by automated preparative LCMS.

Databases as Topic↗
PubMed2000

In situ detection of specific p53 mutations in cultured cells using the amplification refractory mutation system polymerase chain reaction.

Accurate molecular detection of genetic mutations involved in tumorigenesis has been based predominantly on analysis of extracted DNA, but this does not provide detailed information on the location, number, type or clonal distribution of mutated cells and their precise anatomic location and clonal distribution. This study has used a sensitive and specific application of the amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) in situ, combined with in situ hybridization to localize and identify cells with defined p53 mutations. The ARMS-PCR was performed in situ in SW480 cells in suspension and in cells either cultured or cytospun onto glass slides. Amplified mutant DNA PCR products were detected in SW480 cells using digoxigenin-labeled probes, visually identifying cells harboring specific mutations in the p53 gene. In situ hybridization alone of the mutant cells without the amplification step was negative. Normal human fibroblasts or endothelial cells were refractory to in situ amplification. This reaction was mutation-specific as CEM cells with different p53 mutations reacted negatively. Mutant messenger RNA (mRNA) in tumor cells was also selectively amplified in situ by ARMS-PCR following reverse transcription (RT). This study demonstrates the potential of in situ ARMS-PCR or RT-ARMS-PCR for mutation analysis in situ and could have useful clinical applications.

Alleles↗
PubMed1999

Relationships between exposure, cell loss and proliferation, and manifestation of Hprt mutant T cells following treatment of preweanling, weanling, and adult male mice with N-ethyl-N-nitrosourea.

Experiments were performed to characterize the age-related patterns of appearance and frequency of hypoxanthine-guanine phosphoribosyl transferase (Hprt) mutant T lymphocytes in thymus and spleen following exposure of preweanling (12-day-old), weanling (22-day-old), and young adult (8-week-old) male B6C3F1 mice to ethylnitrosourea (ENU). Mice were given single i.p. injections of 0 or 40 mg ENU/kg and then groups of animals were necropsied from 2 h to 116 days after treatment to examine the relationships between exposure, cell loss and proliferation, and the frequency of Hprt mutant T cells in thymus and spleen. Hprt mutant frequency (Mf) data for thymus of ENU-exposed (0, 11.7, 35, 58, or 72 mg/kg, or five weekly doses of 1.7 mg/kg i.p.) male C57BL/6 mice (12- or 62-week-old), obtained during an earlier study of spleen cells [I.M. Jones, K. Burkhart-Schultz, C.L. Strout, T.L. Crippen, Factors that affect the frequency of thioguanine-resistant lymphocytes in mice following exposure to ethylnitrosourea, Environ. Mutagen, 9 (1987) 317-329.], were compared to results in B6C3F1 mice. Isolated T cells were cultured in the presence of mitogen, growth factor, and 6-thioguanine to detect Hprt mutants. The time required to achieve maximum Mfs in thymus was uniformly found at 2 weeks after ENU treatment, while the times needed to reach peak values in spleen were proportional to animal age at treatment. These data indicate that age-related differences in the appearance of Hprt mutant cells in spleen are largely defined by the physiologically based, age-dependent trafficking of mutant cells from or through the thymus. Three modes of handling the resulting Hprt Mf data were evaluated: (i) comparing the Mfs at a single time point, (ii) comparing the maximum Mfs observed, and (iii) comparing the change in Mfs over time (or the mutant T cell 'manifestation' curves in treated vs. control mice) in each age group post-exposure. Measuring the Mfs in spleen at multiple time points after cessation of exposure and integrating the frequency of mutants as a function of time appeared to be the superior method for comparing mutagenic responses in different age groups. Some of the underlying assumptions of this approach, as well as its strengths and weaknesses, are discussed.

Age Factors↗