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Biomedical subjects

J R Dunn

Publications and source records attributed to J R Dunn.

At least 19 recordsLinked to original sources
PubMed2006

Expression of ADAMTS-8, a secreted protease with antiangiogenic properties, is downregulated in brain tumours.

Angiogenesis and extracellular matrix degradation are key events in tumour progression, and factors regulating stromal-epithelial interactions and matrix composition are potential targets for the development of novel anti-invasive/antiangiogenic therapies. Here, we examine the expression of ADAMTS-8, a secreted protease with antiangiogenic properties, in brain tissues. Using quantitative RT-polymerase chain reaction (PCR), high, equivalent expression of ADAMTS-8 was found in normal whole brain, cerebral cortex, frontal lobe, cerebellum and meninges. ADAMTS-8 expression in 34 brain tumours (including 22 high-grade gliomas) and four glioma cell lines indicated at least two-fold reduction in mRNA compared to normal whole brain in all neoplastic tissues, and no detectable expression in 14 out of 34 (41%) tumours or four out of four (100%) cell lines. In contrast, differential expression of TSP1 and VEGF was seen in nine out of 15 (60%) and seven out of 13 (54%) tumours, with no relationship in the expression of these genes. Immunohistochemistry and Western analysis indicated downregulation of ADAMTS-8 protein in >77% tumours. Methylation-specific PCR analysis of ADAMTS-8 indicated promoter hypermethylation in one out of 24 brain tumours (a metastasis) and three out of four glioma cell lines suggesting an alternative mechanism of downregulation. These data suggest a role for ADAMTS-8 in brain tumorigenesis, warranting further investigation into its role in regulation of tumour angiogenesis and local invasion.

ADAM Proteins↗
PubMed2004

METH-2 silencing and promoter hypermethylation in NSCLC.

The antiangiogenic factor METH-2 (ADAMTS-8) was identified in a previous dual-channel cDNA microarray analysis to be at least two-fold under-represented in 85% (28 out of 33) of primary non-small-cell lung carcinomas (NSCLCs). This observation has been validated in an independent series of NSCLCs and adjacent normal tissues by comparative multiplex RT-PCR, and METH-2 mRNA expression was dramatically reduced in all 23 tumour samples analysed. Immunohistochemical analysis of the same sample set demonstrated that METH-2 was strongly expressed in 14 out of 19 normal epithelial sites examined but only one out of 20 NSCLCs. DNA methylation analysis of the proximal promoter region of this gene revealed abnormal hypermethylation in 67% of the adenocarcinomas and 50% of squamous cell carcinomas, indicating that epigenetic mechanisms are involved in silencing this gene in NSCLC. No homozygous deletions of METH-2 were found in lung cancer cell lines. Allelic imbalance in METH-2 was assessed by an intronic single nucleotide polymorphism (SNP) assay and observed in 44% of informative primary samples. In conclusion, the downregulation of METH-2 expression in primary NSCLC, often associated with promoter hypermethylation, is a frequent event, which may be related to the development of the disease.

ADAM Proteins↗
PubMed2003

On the confirmation of an effect of magnetic fields on the interictal firing rate of epileptic patients.

The effect of magnetic fields on interictal firing rates was investigated in three epileptic patients with depth electrode implantation in the hippocampus for pre-surgical evaluation. The protocol consisted of 10 min test periods, during which magnetic fields were cycled for 1 min on and 1 min off, and intervening 5 min rest periods. Only one patient revealed a 95% significant increase in the 10 s after the fields were switched on compared with the background estimate from the 10s before the fields were applied. This patient was also the only patient to show significant increases in firing rates during field-on compared with field-off periods, and during magnetic field test periods compared with intervening rest periods. This patient had a right hippocampal seizure onset. All patients showed increased firing rates during the 10 min periods of magnetic field testing compared to the 5 min rest periods between tests. This result was significant for the group at the 99% level. Two patients with right temporal lobe onset showed greater activity in the right hippocampus than the left. All patients exhibited a progressive increase in firing rates in rest periods between tests.

Electrodes, Implanted↗
PubMed2003

Labour market income inequality and mortality in North American metropolitan areas.

OBJECTIVE: To investigate relations between labour market income inequality and mortality in North American metropolitan areas. METHODS: An ecological cross sectional study of relations between income inequality and working age (25-64 years) mortality in 53 Canadian (1991) and 282 US (1990) metropolitan areas using four measures of income inequality. Two labour market income concepts were used: labour market income for households with non-trivial attachment to the labour market and labour market income for all households, including those with zero and negative incomes. Relations were assessed with weighted and unweighted bivariate and multiple regression analyses. RESULTS: US metropolitan areas were more unequal than their Canadian counterparts, across inequality measures and income concepts. The association between labour market income inequality and working age mortality was robust in the US to both the inequality measure and income concept, but the association was inconsistent in Canada. Three of four inequality measures were significantly related to mortality in Canada when households with zero and negative incomes were included. In North American models, increases in earnings inequality were associated with hypothetical increases in working age mortality rates of between 23 and 33 deaths per 100 000, even after adjustment for median metropolitan incomes. CONCLUSIONS: This analysis of labour market inequality provides more evidence regarding the robust nature of the relation between income inequality and mortality in the US. It also provides a more refined understanding of the nature of the relation in Canada, pointing to the role of unemployment in generating Canadian metropolitan level health inequalities.

Adult↗
PubMed2002

Housing and inequalities in health: a study of socioeconomic dimensions of housing and self reported health from a survey of Vancouver residents.

STUDY OBJECTIVE: To investigate the relation between housing, socioeconomic status, and self reported general and mental health. This study is an empirical investigation of social and economic dimensions of housing, specifically, demand, control, and material (affordability, dwelling type) and meaningful (pride in dwelling, home as a refuge) dimensions of everyday life as they occur in the domestic environment. DESIGN: A cross sectional telephone survey was administered to a random sample of households. Survey items included measures of demand, control, and meaningfulness of the domestic environment, as well as standard measures of socioeconomic status and social support. Main outcome measures were self reported health (excellent, very good, good, fair, poor) and self reported frequency of feeling "downhearted and blue" in the two weeks before interview (from the Rand Mental Health Index). SETTING: Households (n=650) from 12 neighbourhood areas in the city of Vancouver, Canada. PARTICIPANTS: One randomly selected adult from each of 650 households completed the interview and constitute the sample for this study. MAIN RESULTS: In bivariate analyses, measures of housing demand, control and meaningfulness exhibited strong and significantly graded relations with self reported health and somewhat less strong relations with mental health. In logistic regression analyses housing demand and control variables made significant contributions to health both general and mental health. Respondents were more likely to report fair/poor health if they: reported that they couldn't stand to be at home sometimes (OR=2.29, p<0.05); rated their domestic housework as somewhat or quite a strain (OR=5.71, p<0.001); were somewhat or very dissatisfied with their social activities (OR=3.41, p<0.001); and reported that they were constantly under stress a good bit of the time or more (OR=3.56, p<0.05). In terms of mental health, respondents were more likely to report poorer mental health if they: lived longer in their neighbourhood (OR=1.05, p<0.05); reported their housework duties to be somewhat or quite a strain (OR=5.55, p<0.001); reported that they did not have somebody that could help them if they needed it (OR=9.28, p<0.001); and reported that they were constantly under stress a good bit of the time or more in the two weeks before the interview (OR=5.26, p<0.001). One of the main hypotheses investigated-that meaningful dimensions of housing are associated with health status-found support in bivariate analyses without controls, but did not contribute to multivariable models. CONCLUSIONS: The influence of housing demand and control variables superseded a well known correlate of health status, educational attainment, attesting to their importance. The findings of this paper lend support to the hypothesis that features of the domestic environment, especially as they pertain to the exercise of control and the experience of demand, are significant predictors of self reported general and mental health status. Housing is a concrete manifestation of socioeconomic status, which has an important part to play in the development of explanations of the social production of health inequalities.

Adolescent↗
PubMed2000

Relation between income inequality and mortality in Canada and in the United States: cross sectional assessment using census data and vital statistics.

OBJECTIVE: To compare the relation between mortality and income inequality in Canada with that in the United States. DESIGN: The degree of income inequality, defined as the percentage of total household income received by the less well off 50% of households, was calculated and these measures were examined in relation to all cause mortality, grouped by and adjusted for age. SETTING: The 10 Canadian provinces, the 50 US states, and 53 Canadian and 282 US metropolitan areas. RESULTS: Canadian provinces and metropolitan areas generally had both lower income inequality and lower mortality than US states and metropolitan areas. In age grouped regression models that combined Canadian and US metropolitan areas, income inequality was a significant explanatory variable for all age groupings except for elderly people. The effect was largest for working age populations, in which a hypothetical 1% increase in the share of income to the poorer half of households would reduce mortality by 21 deaths per 100 000. Within Canada, however, income inequality was not significantly associated with mortality. CONCLUSIONS: Canada seems to counter the increasingly noted association at the societal level between income inequality and mortality. The lack of a significant association between income inequality and mortality in Canada may indicate that the effects of income inequality on health are not automatic and may be blunted by the different ways in which social and economic resources are distributed in Canada and in the United States.

Canada↗
PubMed2000

Social determinants of health in Canada's immigrant population: results from the National Population Health Survey.

As part of the Metropolis project--a large-scale investigation of immigration and integration, including well-being of immigrants in a number of areas of social life--in this paper we investigate the social determinants of health in Canada's immigrant population using Canada's National Population Health Survey (NPHS). Specifically, we examine differences in health status and health care utilization between immigrants and non-immigrants, immigrants of European and non-European origin, and immigrants of < 10 years and > 10 years' residence in Canada. We also examine social determinants of health care utilization and health status in immigrants and non-immigrants, and evaluate the utility of large-scale, national databases for these purposes. Our conceptual approach draws upon a 'population health' perspective, which suggests that the most important antecedents of human health status are not medical care inputs and health behaviours (smoking, diet, exercise, etc.), but rather social and economic characteristics of individuals and populations. We find no obvious, consistent pattern of association between socio-economic characteristics and immigration characteristics on the one hand, and health status on the other, in the NPHS data. This does not mean that socio-economic factors in Canada are not influential in shaping immigrants' health status. In fact, the results of the logistic regression models calculated for immigrants and non-immigrants on four outcome variables in this study suggest that socio-economic factors are more important for immigrants than non-immigrants, although in ways that defy a simple explanation. The complexity of immigrants' experiences, combined with the inherent limitations of cross-sectional survey data are discussed as major limitations to this kind of research.

Adult↗
PubMed2000

Social inequality, population health, and housing: a study of two Vancouver neighborhoods.

An emerging 'population health' framework for understanding inequalities in health identifies the structure of social relations as a crucial factor in shaping human health and well-being. However, there remain many unanswered questions about the mechanisms through which social relations might shape the health status of individuals and populations. Housing plays a central role in routinized, everyday life and is fundamentally bound up in one's sense of control over life circumstances. Housing and property markets are significant in the distribution of wealth and are an important arena for the exercise of power relations. Housing circumstance is crucial in the production and reproduction of social identity and social status. Yet little has been written on the influence of inequalities generated by housing and housing markets on the differential distribution of health status. This paper reports the findings of an empirical study of relationships between socioeconomic status, material and meaningful dimensions of housing and home, and health status. Our objective is to investigate ways in which material and meaningful factors related to housing, in conjunction with other dimensions of the social environment, could operate to produce systematic inequalities in health status across social strata. The data for this study were obtained through a mailed survey of residents in the Mount Pleasant (n = 322) and Sunset (n = 206) neighborhoods of Vancouver, Canada. They suggest that, in concert with commonly used measures of socioeconomic status, both material and meaningful dimensions of housing and home are associated with health status in a direction consistent with expectations following from our analytical model.

Adult↗
PubMed2000

The evolution of loss of heterozygosity on chromosome 17 during the progression to barrett's adenocarcinoma involves a unique combination of target sites in individual specimens.

We have previously identified thirteen common minimally deleted regions (MRs) on chromosome 17 in twelve Barrett's esophageal adenocarcinoma (BOA) specimens using 41 precisely mapped microsatellite markers (Dunn et al., Oncogene, 17: 987-993, 1999). The aim of the present study has been to identify the earliest sites of loss on this chromosome that arise and persist during the progression to BOA. This has been undertaken by the analysis of multiple carefully microdissected tissue samples from each of five esophagectomy specimens, several of which contained identifiable premalignant tissue. Our data demonstrate a stepwise accumulation of loss in each analyzed specimen, consistent with a single clonal pathway in four specimens and several coexisting pathways in one specimen. Several clonal anomalies (loss preceding heterozygosity and variable intrasample degrees of loss at different markers) were also observed. Within extensively deleted regions of the tumor (seen in three specimens), small deletions were detected in premalignant tissue, predominantly at the site of our identified MRs, and these losses were seen to expand and merge during the progression to BOA. Clonal losses at MRs were first detected in tissue showing early changes histologically, including Barrett's intestinal metaplasia and intermediate-grade dysplasia. Our results provide further support for many of the MRs we have previously identified, thereby adding to evidence for the existence of multiple novel cancer-associated genes on chromosome 17 involved in the development of BOA.

Adenocarcinoma↗
PubMed1999

The tylosis esophageal cancer (TOC) locus: more than just a familial cancer gene.

Tylosis (focal non-epidermolytic palmoplantar keratoderma; NEPPK) is associated with esophageal cancer in three families, two of which contain six or seven generations. The causative locus, the tylosis esophageal cancer (TOC) gene, has been localized to a small region on chromosome 17q25. Recent loss of heterozygosity (LOH) studies have indicated a role for the TOC gene in sporadic squamous cell esophageal cancer and Barrett's adenocarcinoma. We have now integrated genetic and physical mapping data from the TOC region, based on microsatellite markers and radiation hybrid, yeast (YAC), bacterial (BAC) and P1 artificial chromosomal (PAC) clones, and formed a partial minimal contig of one non-chimeric YAC (330 kb) and one PAC. Twenty-three candidate genes, including envoplakin (EVPL), were mapped against this contig, but only one was shown to be located within the minimal region. This physical map will allow further characterization of the region and identification of a gene implicated in both familial and sporadic squamous cell esophageal carcinoma and Barrett's adenocarcinoma.

Barrett Esophagus↗
PubMed1999

Photographic imaging for esthetic restorative dentistry.

Patient dental records are the most critical component of every dental practice. Whether these records are maintained in traditional cardboard folders or as digital bytes of information, the completeness of their contents is important to successful patient care. Two trends are expanding the contents of the dental record to include photographs. One of these trends is the widespread interest in esthetic restorative dentistry and the other is the increasing level of expectations by the public. More than ever, patients are seeking dental treatment to alter the appearance of their teeth. Unfortunately, esthetic restorative dentistry often is not part of a formal dental education. In addition, esthetics is a subjective topic, and patient demands and expectations can easily exceed a dentist's skill and expertise. This can ultimately lead to an "unhappy patient syndrome" and cause conflict between the patient and the dental team. Sometimes this conflict can result in litigation, which is another reason that photographs are a valuable addition to the patient record. The information that is contained in a good-quality set of "before" and "after" photographs cannot be duplicated with other components of the dental record. Taking the time to assemble adequate baseline records is always critical before any patient care is initiated. In restorative dentistry, this includes the standard of care elements: a health history, soft-tissue examination, periodontal examination, teeth and restoration examination, study casts, and an adequate radiographic survey. The use of photography in dentistry has historically been limited to the field of orthodontics. It is the standard of care for orthodontic baseline records, but has not been mandated for restorative dentistry. Memories are rarely accurate about subtle details of one's appearance and people can easily forget what their original smiles looked like even though treatment time may only be a matter of days. Baseline photographs provide an irrefutable record of pretreatment conditions in correct context. More importantly, you do not have to be a dentist to interpret the general information that is displayed on a photograph. To gain additional perspective on this issue, we consulted a panel of three dentists who are well recognized for their expertise in dental esthetics and imaging.

Dental Equipment↗
PubMed1998

Direct composites in a contemporary restorative practice.

Composite resins can restore teeth to natural appearance and function while conserving tooth structure. Adhesive technology has revolutionized tooth preparation, allowing minimum tooth removal without large retentive undercuts. Today's dental adhesives have strong bond strengths, bonding to both dentin and enamel. Many are available with fewer components, simplifying application. Composites are available in a large variety of shades in both microhybrids and microfills. Microhybrids are used in areas that need strength, whereas microfills are used in regions that require high surface gloss or decreased stiffness. Composites should be placed to natural form and shades before curing; finishing primarily involves polishing using silicone abrasives. Composites can be used to restore incisal edges, close diastemas, veneer facial surfaces, and repair defects, making teeth appear natural.

Compliance↗
PubMed1998

Dentist-prescribed home bleaching: current status.

White teeth have been an indicator of physical attractiveness throughout history. Only recently have we been able to whiten teeth with few side effects, making tooth bleaching a popular and effective dental treatment. The American Dental Association (ADA) has established guidelines on safety and effectiveness for tooth bleaching. External stains from aging or inherent dark color are more responsive to bleaching than internal stains. Dentist-prescribed home bleaching--including a careful dental exam, custom-fabricated trays, tacky high-viscosity gels, adequate instructions, and recall exams--has been shown to be an effective method for bleaching teeth. Trays can be worn overnight or during the day with similar effectiveness. The bleaching effect can last up to 3 years with more than 50% success.

American Dental Association↗
PubMed1997

Patient swallows removable partial denture: a clinical report.

The indications for a unilateral partial denture would appear to be when there is a single posterior tooth missing, bound on both sides by usable abutments. Another consideration for a unilateral partial denture is that the patient does not want to restore the space with a fixed partial denture. One drawback to this treatment modality is that the prosthesis needs to be removed after each meal and cleaned. Other more important reasons for not making a 1-tooth removable partial denture is that it provides no cross-arch stabilization and there is the chance that it may be swallowed if it becomes dislodged. This clinical and laboratory report describes how this patient was treated.

Deglutition↗
PubMed1995

Magnetic material in the human hippocampus.

Magnetic analyses of hippocampal material from deceased normal and epileptic subjects, and from the surgically removed epileptogenic zone of a living patient have been carried out. All had magnetic characteristics similar to those reported for other parts of the brain [6]. These characteristics along with low temperature analysis indicate that the magnetic material is present in a wide range of grain sizes. The low temperature analysis also revealed the presence of magnetite through manifestation of its low temperature transition. The wide range of grain sizes is similar to magnetite produced extracellularly by the GS-15 strain of bacteria and unlike that found in magnetotactic bacteria MV-1, which has a restricted grain size range. Optical microscopy of slices revealed rare 5-10 micron clusters of finer opaque particles, which were demonstrated with Magnetic Force Microscopy to be magnetic. One of these was shown with EDAX to contain AI, Ca, Fe, and K, with approximate weight percentages of 55, 19, 19, and 5, respectively.

Epilepsy↗