Biomedical subjects

D V Dawson

Publications and source records attributed to D V Dawson.

At least 19 recordsLinked to original sources

PubMed2004

The timing of subsequent treatment for teeth restored with large amalgams and crowns: factors related to the need for subsequent treatment.

Crowns and large amalgams protect structurally compromised teeth to various degrees in different situations. The aim of this investigation was to evaluate the survival of teeth with these two types of restorations and the factors associated with better outcomes. Retrospective administrative and chart data were used. Survival was defined and modeled as: (1) receipt of no treatment and (2) receipt of no catastrophic treatment over five- and 10-year periods. Analyses included: Kaplan-Meier survival curves, Log-Rank tests, and Cox proportional hazards regression modeling. Crowns survived longer with no treatment and with no catastrophic treatment; however, mandibular large amalgams were least likely to have survived with no treatment, and maxillary large amalgams were least likely to have survived with no catastrophic treatment. Having no adjacent teeth also decreased survival. Crowns survived longer than large amalgams, but factors such as arch type and the presence of adjacent teeth contributed to the survival of large amalgams.

Bicuspid↗

PubMed2002

Vasectomy and the risk of prostate cancer: a meta-analysis examining vasectomy status, age at vasectomy, and time since vasectomy.

The aim of this study was to conduct a quantitative review of prostate cancer studies to pool relative risk (RR) estimates on the association between prostate cancer and vasectomy, in an attempt to determine whether there is an association, and if so, its magnitude. Random-effects models were examined along with a linear model for time since vasectomy. The pooled RR estimate was 1.37 (95% CI=1.15-1.62) based on five cohort studies and 17 case-control studies. The RR estimate varied by study design with the lowest risk for population-based case-control studies. No difference was seen in risk by age at vasectomy. A linear trend based on the 16 studies reporting time since vasectomy suggested an 10% increase for each additional 10 y or a RR of 1.32 (95% CI=1.17-1.50) for 30 y since vasectomy. When null effects were assumed for the six studies not reporting information, the linear RR for the 22 studies was 1.07 (1.03-1.11) and 1.23 (1.11-1.37) for 10 and 30 y since vasectomy, respectively. These results suggest that men with a prior vasectomy may be at an increased risk of prostate cancer, however, the increase may not be causal since potential bias cannot be discounted. The overall association was small and therefore could be explained by bias. The latency effect shown here for time since vasectomy should be examined further.

Age Factors↗

PubMed2001

Longitudinal study of the carrier testing process for fragile X syndrome: perceptions and coping.

This paper reports the results of a longitudinal study of women at-risk to inherit the fragile X mutation. It addresses 1) how upsetting the women perceived their carrier information to be, 2) how serious a problem they perceive fragile X syndrome to be, and 3) descriptions of feelings about the carrier testing process. The study sample consisted of 42 women (20 carriers and 22 noncarriers). There were two measurement times (just prior to carrier testing and after learning actual carrier status). The measures used were a Fragile X Visual Analog Scale and a structured interview. At time 1, being at-risk was reported to be upsetting and fragile X syndrome was perceived to be a serious problem. For the women found to be carriers there was no change from time 1 to time 2 on any of the items. Significant change occurred in the non-carriers. They were significantly less upset at time 2 after receiving the results of their carrier test than at time 1. They also perceived fragile X syndrome to be a more serious problem than they did at time 1 and a more serious problem than the carriers at time 2. Themes found included concerns that carrier status for fragile X syndrome presented a barrier for having healthy biological children and concern for children's and grandchildren's adaptation to their own carrier status. Coping behaviors were activated to manage the emotions related to these concerns. The coping behaviors identified were minimization, acceptance of the possibility of being a carrier, a sense of being able to deal with the outcome of the carrier test, positive comparison, problem solving, and positive interpretation.

Adaptation, Psychological↗

PubMed2001

Ramifications of HLA class I polymorphism and population genetics for vaccine development.

HLA polymorphism can complicate the design and development of vaccines, especially those that contain a selected number of epitopes and are directed at pathogens prevalent worldwide. Because of HLA class I restricted antigen recognition and ethnic variation in HLA distribution, such vaccines may not be uniformly effective across populations. We, therefore, considered whether it is possible to assemble a panel of HLA-A and/or HLA-B alleles that would allow the formulation of a single vaccine for a set of Caucasian, Black, or Asian populations. In applying an algorithm to predict levels of favorable response, we identified predominant alleles in 15 representative populations. Approximately 80% of the individuals in one African Black population and five Asian populations were positive for at least one of three HLA-A alleles. Eighty percent coverage was also theoretically possible in five Caucasian populations with only five HLA-A alleles. Four of five Black populations analyzed also required five alleles, but the allelic combinations differed. Our findings suggest that HLA-A alleles may be preferred targets because of the increased heterogeneity at HLA-B, although addition of a single HLA-B allele to a set of HLA-A alleles improved coverage. This approach provides for the identification of combinations of alleles that represent a desired percentage of a population and that could be targeted in designing vaccines. For vaccines with known HLA-restricted epitopes, it allows a prediction of theoretical levels of "responder" and "non-responder" status. Finally, these results might be used in the analysis of protein sequences to identify potential CD8+ T-cell epitopes in populations of interest. Biologic variables that may have further relevance are discussed.

Algorithms↗

PubMed2001

Epidemiology of periodontal disease: a review and clinical perspectives.

The purpose of this paper is to assimilate epidemiological evidence for the prevalence of periodontal disease in human populations, and for comprehensive understanding of the disease for health care providers. Periodontal disease is a pathological condition affecting the supporting structures of teeth. It is characterised by a bacterial challenge that can instigate a destructive host response leading to periodontal attachment loss, bone loss and ultimately, possible tooth loss. The specifics of the disease process are obscured by our incomplete understanding of the role of various risk factors. Periodontal epidemiology literature lacks consistency in methodology of research, which includes various definitions for periodontal disease and health; different approaches to measuring periodontal indices of pocket depth, and attachment loss; inconsistent study designs and lack of adjustments to known risk factors. These inconsistencies do not allow for effective comparison of epidemiological studies, which is essential to find strong associations of risk factors with periodontal disease, which in turn is necessary for the interpretation of risk and causality. This paper will address several areas within the topic of periodontal disease epidemiology, including definitions of periodontal disease instituted by researchers, approaches to epidemiological studies in periodontitis, and risk factors in periodontal disease. Consideration is given to aspects of design and analyses relevant to evaluation of reports in the literature. For the clinical practitioner this review provides a theoretical framework to approach patients with comprehensive knowledge of not only the disease presentation, but also the environmental factors that govern past history, present condition and future response to treatments and interventions.

Alveolar Bone Loss↗

PubMed2000

Identification of highly conserved and broadly cross-reactive HIV type 1 cytotoxic T lymphocyte epitopes as candidate immunogens for inclusion in Mycobacterium bovis BCG-vectored HIV vaccines.

One of the fundamental goals of current strategies to develop an efficacious vaccine for AIDS is the elicitation of cytotoxic T lymphocyte (CTL) reactivities capable of recognizing cells infected with different subtypes of the human immunodeficiency virus type 1 (HIV-1). In efforts to explore new vaccine candidates by the UNAIDS/WHO Vaccine Committee, we review the most recent data concerning CTL epitopes that are conserved among the different HIV-1 subtypes. Moreover, we examine HLA allelic frequencies in several different populations, to determine those that could contribute to the goal of a cumulative phenotype frequency (CP) of at least 80%. By analyzing conserved epitopes in the context of HLA restricting alleles, we define a set of HIV-1 gene regions that may have the greatest potential to induce cross-clade reactive CTLs. The absence of well-defined correlates of immune protection that link CTL epitopes to delayed disease progression and/or prevention of infection does not permit an assignment of rank order of the most relevant component of a candidate vaccine. Thus far, most of the studies conducted in clade B-infected patients to define conserved and immunodominant epitopes indicate gag and pol gene products to be the most conserved among the HIV-1 subtypes. Moreover, anti-Pol and -Gag CTL responses appear to correlate inversely with disease progression, suggesting that they should be among the first choice of antigens to be included in a candidate vaccine construct aimed at induction of broad CTL responses. The impact of a clade B-based vaccine as a worldwide candidate capable of inducing protective immune responses can be determined only after "in vivo" studies. Meanwhile, extensive parallel studies in populations infected with non-clade B HIV-1 subtypes should define the patterns of immunodominant epitopes and HLA for comparison with the data already collected in clade B-infected subjects.

AIDS Vaccines↗

PubMed2000

Carrier testing in fragile X syndrome: effect on self-concept.

The purpose of the study was to explore self-concept in women at risk for inheriting the fragile X mutation. Time 1 measures were obtained prior to carrier testing and Time 2 measures were collected approximately 5 months after learning carrier status. The sample consisted of 42 women from 17 families. Measures included the Tennessee Self-Concept Scale (TSCS), the fragile X Visual Analog Scale (VAS), and a structured interview. The TSCS provided a global measure of self-concept and the fragile X VAS and structured interview provided a contextual measure of self related to carrier status. Results indicated that there were no differences initially between carriers and noncarriers and no change from Time 1 to Time 2 on the TSCS. Analysis of the Time 1 fragile X VAS means for the total sample found a reduction in positive feelings about self. Analysis of the Time 2 fragile X VAS found that noncarriers reported improvement in feelings about self, with no change in feelings about self found in the carriers. Responses from the structured interview indicated that the feelings regarding self in the context of genetic testing are not related to global self-concept, but result from concerns regarding the implications of a positive carrier test for themselves and their families. This information highlights areas related to carrier testing that warrant further investigation and may ultimately result in modifications to the genetic counseling.

Adult↗

PubMed2000

Physical characteristics of young boys with fragile X syndrome: reasons for difficulties in making a diagnosis in young males.

Fragile X syndrome is the leading form of hereditary mental retardation, but the condition is still underdiagnosed in young children. Because of concern that the fragile X phenotype is subtle in young boys and therefore contributes to underdiagnosis of the disorder, we evaluated 73 boys (36 with fragile X and 37 same-age boys who were fragile X negative) using a checklist that we devised to learn which characteristics might be the most useful for alerting professionals to this diagnosis. After a multiple comparisons adjustment, only 4 of 42 characteristics differed significantly in their distributions between the two groups of boys (P < 0.0012), but 10 other items may also have predictive value for fragile X syndrome (P < 0.01). Four additional items occurred in at least 80% of boys with fragile X and may also be helpful for the clinician. Professionals who work with developmentally delayed children should be aware of these 18 clinical characteristics and some of the behavior characteristics commonly seen in boys with fragile X so that they can readily diagnose patients.

Child↗

PubMed2000

Relation between informant-rated personality and clinician-rated depression in patients with memory disorders.

OBJECTIVE: The goal of this study was to examine the convergent validity of informant-rated changes in depressive and related personality traits with clinician-assessed depression in memory-disordered patients. BACKGROUND: Depressive symptoms are frequent complications in persons with dementias such as Alzheimer disease, and caregiver informants consistently report changes in depression and related neurotic traits on the NEO Personality Inventory (NEO-PI) in dementia patients. METHODS: In 78 patients undergoing evaluation of memory complaints at an Alzheimer disease clinic, depression was characterized by clinical diagnosis, a clinician-rated scale, and informant ratings of premorbid versus current depression, anxiety, vulnerability, and neuroticism on the NEO-PI. RESULTS: The diagnostic groups differed in meaningful patterns on the NEO-PI measures. Those with a diagnosis of major depression differed from never-depressed patients in all personality areas, although those with depressed mood differed only on NEO-PI depression. The clinician-rated depression scale correlated modestly with current personality and change from baseline personality. CONCLUSIONS: The NEO-PI provides a useful measure of informants' perspectives on depressive personality changes in patients with memory disorders but does not correspond fully with a clinical syndrome of depression.

Aged↗

PubMed1999

Chain length of the polylysine in receptor-targeted gene transfer complexes affects duration of reporter gene expression both in vitro and in vivo.

Complexes composed of peptide ligand for the serpin enzyme complex receptor covalently coupled to poly-L-lysine condensed by charge interaction with plasmid DNA direct gene transfer into receptor bearing cells. We compared intensity and duration of reporter gene expression in vitro and in vivo from serpin-enzyme receptor-directed gene transfer complexes prepared with poly-L-lysine of different chain lengths. When substituted with linker and ligand to comparable extents, DNA complexes containing short chain poly-L-lysine were larger and gave higher peak expression but significantly shorter duration of expression than those containing long chain poly-L-lysine. Both peak expression and duration of expression exceeded that observed with Lipofectin. Neither naked DNA nor DNA complexed with unsubstituted polylysine was effective in gene transfer. For in vivo experiments, complexes containing optimal ligand and degree of substitution (based on in vitro data, peptide C105Y, 11 ligands/plasmid DNA molecule) were prepared with either short chain or long chain polylysine and a beta-galactosidase expression plasmid. Following injection into the tail veins of mice, longer chain complexes gave significantly higher expression of reporter gene in lung and spleen that lasted for a significantly longer period of time than the shorter chain complexes. The short chain poly-L-lysine-DNA complexes were larger in diameter, as assessed by electron microscopy or atomic force microscopy, and gave less protection against DNase digestion in vitro than longer chain complexes. Thus, for gene transfer complexes directed at the serpin enzyme complex receptor, longer chain poly-L-lysine gave a much longer duration of expression both in vitro and in vivo. We speculate that this may be due to protection against degradation afforded the plasmid DNA by the tighter compaction produced by long chain poly-L-lysine.

Amino Acid Sequence↗

PubMed1999

Parental attitudes regarding carrier testing in children at risk for fragile X syndrome.

Sixty-five parents of individuals affected by fragile X syndrome who attended the National Fragile X Conference in Portland, Oregon (1996), were asked to complete a survey assessing parental level of concern about carrier testing in children at risk for fragile X syndrome. All subjects completed a 15-item paper and pencil Likert response scale measure that was developed specifically for this study. The items included parental rights and duties, psychological adjustment, adaptation, discrimination, harm, childbearing, and interpersonal relationships. The major concern of the parents was that their children have knowledge of their carrier status prior to becoming sexually active and that their children be able to marry informed of their genetic risk. Mothers were significantly more concerned than fathers about raising their children with the knowledge of their carrier status. A sense of parental right to make the decision regarding carrier testing for children was associated with concerns about (1) behavioral or educational problems, (2) knowledge of carrier status prior to sexual activity or marriage, and (3) adjustment of the children to knowledge of their carrier status. As the sample was drawn from a unique population of parents, the results of this survey should be interpreted with caution. The findings of this study suggest a model of parents providing anticipatory guidance for their children to help them adjust to carrier information and for their children to have this knowledge prior to the possibility of reproduction.

Attitude to Health↗

PubMed1999

A meta-analysis of risk estimates for prostate cancer related to tire and rubber manufacturing operations.

Studies investigating the association between prostate cancer and exposure to the tire and rubber manufacturing environment have reported weak and inconsistent results. A meta-analysis of nine cohort studies that used standard mortality ratios and three case-control studies that used odds ratios was conducted. The pooled results from the nine cohort studies showed a standard mortality ratio of 101 (95% confidence interval [CI] = 93,110), whereas the pooled results from the three case-control studies showed on odds ratio of 1.10 (95% CI = 0.94, 1.29). The standard mortality ratios were converted to odds ratios by dividing by 100. The overall pooled risk estimate from all 12 studies was 1.03 (95% CI = 0.96, 1.11). The conclusion of this meta-analysis is that work exposure in a rubber and tire manufacturing environment does not result in an increased risk of prostate cancer.

Adult↗

PubMed1999

IL-10 attenuates excessive inflammation in chronic Pseudomonas infection in mice.

Cystic fibrosis (CF) lung disease is characterized by an excessive inflammatory response associated with chronic Pseudomonas aeruginosa endobronchial infection. Compared with bronchoalveolar lavage fluid from healthy subjects, lavage fluid from patients with CF contains elevated proinflammatory cytokines but negligible amounts of the anti-inflammatory cytokine interleukin-10 (IL-10). We sought to determine whether IL-10 deficiency results in increased local and systemic morbidity in mice with chronic endobronchial infection with P. aeruginosa embedded in agar beads and to determine if exogenous IL-10 might reduce these effects. Infected IL-10 knockout mice had more severe weight loss (p = 0.04) and increased area of lung inflammation (28 +/- 4 versus 10 +/- 2%, p < 0.002) but no alterations in bacterial burden compared with wild-type mice. Infected CD-1 mice treated with IL-10 had improved survival (p = 0. 035), less severe weight loss (p < 0.005), fewer bronchoalveolar lavage neutrophils (3 x 10(5)/ml versus 5 x 10(6)/ml, p < 0.02), and decreased area of lung inflammation (11 +/- 2 versus 35 +/- 7%, p < 0.01) but no alterations in bacterial burden compared with placebo-treated mice. These data suggest that IL-10 is an important regulator of the inflammatory response to P. aeruginosa endobronchial infection and that further investigation into the use of IL-10 in CF is warranted.

Animals↗

PubMed1999

Assessment of familial patterns of microbial infection in periodontitis.

The purpose of this article is to review approaches to the assessment of familial patterns of microbial infection and disease in periodontitis, and to identify statistical methods appropriate to such considerations of family data. Previous studies have provided evidence for the presence of familial aggregation of periodontal pathogens and periodontitis and have alluded to possible transmissibility of these organisms within families. Modern statistical techniques permit the appropriate analysis of the correlated data inherent in families, properly allowing for these statistical dependencies while including the possibility of adjustment for risk factors which may also aggregate in families. Such approaches as multiple linear regression, multivariate logistic regression, and regressive modeling provide the necessary tools to assess the familial aggregation of risk factors and disease in periodontitis. In particular, regressive models permit the analysis of familiality (membership to family) as a risk factor without reference to a specific underlying biologic mechanism, and also permit the possibility of adjustment for covariates, such as age and access to dental care. They also allow consideration of specific mechanisms, e.g., susceptibility genes of major effect. Using such techniques, it is possible to more completely explore and describe familial patterns of periodontal infection and other aspects of periodontal disease.

Disease Transmission, Infectious↗

PubMed1998

Magnetic resonance imaging correlates of depression in early- and late-onset Alzheimer's disease.

BACKGROUND: Depressive symptoms are frequent complications of Alzheimer's disease (AD). We hypothesized that AD patients with depression would be more likely than nondepressed AD patients to show deep white-matter, subcortical gray-matter, and periventricular hyperintensities on magnetic resonance imaging (MRI). METHODS: In a retrospective study of 31 AD patients, depression was characterized by clinical diagnosis (DSM-III-R major depression, depressive symptoms, or no depression), a clinician-rated depression scale, and informant ratings of premorbid (before memory disorder) as well as current depression using the NEO Personality Inventory (NEO-PI), and related to qualitative and quantitative ratings of MRI hyperintensities. RESULTS: In contrast to reports in nondemented elderly patients, there was no relationship between clinical diagnosis of major depressive episode and hyperintensities; however, clinician-rated depressive symptoms were higher in subjects with large anterior hyperintensities. In the early-onset AD group only, MRI abnormalities were related to greater premorbid depression, and less increase in depression after the onset of dementia, as rated by informants on the NEO-PI. CONCLUSIONS: Results highlight the need to consider early- and late-onset AD separately when assessing relationships between personality and MRI abnormalities, and to consider premorbid personality style when drawing conclusions about the etiology of depressive features seen in AD.

Age of Onset↗

PubMed1998

Evidence of independent origin of multiple tumors from patients with prostate cancer.

BACKGROUND: In men with prostate cancer, the gland usually contains two or more widely separate tumors. A critical issue of prostatic carcinogenesis is whether these multiple tumors are independent in origin. Molecular analysis of microsatellite (i.e., highly repeated, short nucleotide sequences) alterations in the DNA from separate tumors in the same prostate can be used to determine whether or not these separate tumors arise independently. METHODS: Four microsatellite polymorphic markers (D8S133, D8S136, and D8S137, for a putative tumor suppressor gene on chromosome 8p, and D17S855, for the BRCA1 gene on chromosome 17q) were used to examine the pattern of allelic loss in prostate cancer from 19 patients who had two or more distantly separate tumors (i.e., located on contralateral sides or separated by at least half the anterior-posterior diameter of the prostate). Forty distantly separate tumors were microdissected, DNA samples were prepared from formalin-fixed, paraffin-embedded wholemount prostate tissue section, and the overall frequencies of loss of heterozygosity at the four loci were determined. RESULTS: The pattern of allelic loss was compatible with independent tumor origin in 15 of 18 informative cases. A random discordant pattern of allelic deletion was observed in distantly separate tumors, whereas the same allele was consistently lost in cells from different regions of the same tumor. For three patients, the results were compatible with either intraglandular dissemination or independent origin of prostate cancer. CONCLUSIONS: Our data suggest that multiple tumors in some patients with prostate cancer have independent origin.

Chromosome Deletion↗

PubMed1998

Ligand substitution of receptor targeted DNA complexes affects gene transfer into hepatoma cells.

We have targeted the serpin enzyme complex receptor for gene transfer in human hepatoma cell lines using peptides < 30 amino acids in length which contain the five amino acid recognition sequence for this receptor, coupled to poly K of average chain length 100 K, using the heterobifunctional coupling reagent sulfo-LC SPDP. The number of sulfo-LC SPDP modified poly-L-lysine residues, as well as the degree of peptide substitution was assessed by nuclear magnetic resonance spectroscopy. Conjugates were prepared in which 3.5%, 7.8% or 26% of the lysine residues contained the sulfo-LC SPDP moiety. Each of these conjugates was then coupled with ligand peptides so that one in 370, one in 1039, or one in 5882 lysines were substituted with receptor ligand. Electron microscopy and atomic force microscopy were used to assess complex structure and size. HuH7 human hepatoma cells were transfected with complexes of these conjugates with the plasmid pGL3 and luciferase expression measured 2 to 16 days after treatment. All the protein conjugates in which 26% of the K residues were modified with sulfo-LC SPDP were poor gene transfer reagents. Complexes containing less substituted poly K, averaged 17 +/- 0.5 nm in diameter and gave peak transgene expression of 3-4 x 10(6) ILU/mg which persisted (> 7 x 10(5) ILU) at 16 days. Of these, more substituted polymers condensed DNA into complexes averaging 20 +/- 0.7 nm in diameter and gave five-fold less luciferase than complexes containing less substituted conjugates. As few as eight to 11 ligands per complex are optimal for DNA delivery via the SEC receptor. The extent of substitution of receptor-mediated gene transfer complexes affects the size of the complexes, as well as the intensity and duration of transgene expression. These observations may permit tailoring of complex construction for the usage required.

Animals↗

PubMed1997

HLA class I polymorphism: structure and function and still questions.

The HLA-A, HLA-B and HLA-C molecules have turned out to be highly polymorphic and functionally complex. They not only serve as peptide receptors, but also interact with beta 2-microglobulin, an alpha beta T cell receptor, CD8 and NK inhibitory molecules, all at different sites. The fact that more than 300 class I alleles have now been defined prompted us to ask the question of where polymorphism really occurs in a class I molecule. We have used a database of 275 HLA-A, HLA-B and HLA-C alleles to illustrate how extensive the polymorphism is. The data is presented here for comparison of alleles and allele families and to facilitate studies of class I structure and function.

Alleles↗