Search PubMed⌕ Search

Biomedical subjects

C A Evans

Publications and source records attributed to C A Evans.

At least 37 records · Page 2Linked to original sources
PubMed2001

The sequence of the human genome.

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Algorithms↗
PubMed2001

Nramp1 is expressed in neurons and is associated with behavioural and immune responses to stress.

The gene Nramp1 encoding the natural resistance-associated macrophage protein (Nramp1) influences susceptibility to intracellular infections and autoimmune diseases, and the humoral response to stress. Nramp1 functions as a proton/divalent cation antiporter in the membranes of late endosomes/lysosomes, regulating cytoplasmic iron levels in macrophages. The Drosophila homologue of Nramp1 is expressed in sensory neurons and macrophages, and influences taste behaviour directly through divalent cation transport. Here we demonstrate that murine Nramp1 is also expressed on neurons as well as microglial cells in the brain and influences the behavioural response to stress, hypothalamus-pituitary-adrenal (HPA) axis activation and mortality following Toxoplasma gondii infection in control and prestressed mice. We hypothesise that, although differences in HPA activation translate into differences in adrenal enlargement and basal circulating corticosterone levels, the primary influence of Nramp1 is at the level of the neuronal response to stress. These results provide new insight into the possible roles of divalent cation transporters of the Nramp gene family in regulating metal ion homeostasis in the brain and its pathological implications.

Adrenal Glands↗
PubMed2001

Hypodontia in hemifacial microsomia.

OBJECTIVE: The purpose of this study was twofold: (1) to describe the patterns of missing teeth in patients with hemifacial microsomia (HFM) and (2) to compare the prevalence of missing teeth in subjects with HFM with a group of unaffected subjects. STUDY DESIGN: A descriptive study was conducted comparing HFM subjects with a group of patients selected from an orthodontic clinic. METHODS: The prevalence of missing teeth was assessed by evaluation of panoramic radiographs. At the time of the study, records of 125 patients with HFM were available from the Craniofacial Center at Boston's Children's Hospital. Seventy-six met inclusion criteria for radiographic analysis of hypodontia. Fifty-two patients met inclusion criteria into the comparison study in which the prevalence of hypodontia was compared with a group of patients from the Department of Orthodontics at Harvard School of Dental Medicine. A Fisher's exact test was conducted to test the hypothesis that HFM patients have a greater prevalence of missing teeth than individuals without the anomaly. A chi-square test for trend was conducted to determine whether hypodontia was more prevalent with increasing severity of the mandibular deformity in HFM. RESULTS: Hypodontia was more common among HFM patients (26.9%) versus the comparison group in which no missing teeth were recorded (p < .0001). Additionally, the degree of hypodontia was correlated with the grade of mandibular hypoplasia (p = .024). CONCLUSION: Hypodontia was found to be more prevalent in patients with HFM than in comparison subjects, possibly indicating an etiologic link between the two conditions.

Adolescent↗
PubMed2000

The genome sequence of Drosophila melanogaster.

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

Animals↗
PubMed2000

Metalloporphyrins inhibit beta-hematin (hemozoin) formation.

Metal-substituted protoporphyrin IXs (Cr(III)PPIX (1), Co(III)PPIX (2), Mn(III)PPIX (3), Cu(II)PPIX (4), Mg(II)PPIX (5), Zn(II)PPIX (6), and Sn(IV)PPIX (7)) act as inhibitors to beta-hematin (hemozoin) formation, a critical detoxification biopolymer of malarial parasites. The central metal ion plays a significant role in the efficacy of the metalloprotoporphyrins to inhibit beta-hematin formation. The efficacy of these compounds correlates well with the water exchange rate for the octahedral aqua complexes of the porphyrin's central metal ion. Under these in vitro reaction conditions, metalloporphyrins 5, 6 and 7 are as much as six times more efficacious than the free ligand protoporphyrin IX in preventing beta-hematin formation and four times as efficacious as chloroquine, while metalloporphyrins 3 and 4 are three to four times more effective at preventing beta-hematin formation than the free protoporphyrin IX base. In contrast, the relatively exchange inert metalloporphyrins 1 and 2 are only as efficacious as the free ligand and only two-thirds as effective as chloroquine. Aggregation studies of the heme:MPPIX using UV-Vis and fluorescence spectroscopies are indicative of the formation of pi-pi hetero-metalloporphyrin assemblies. Thus, hemozoin inhibition is likely prevented by the formation of heme:MPPIX complexes through pi-stacking interactions. The ramifications of such hetero-metalloporphyrin assemblies, in the context of the emerging structural picture of hemozoin, are discussed.

Hemeproteins↗
PubMed2000

Developing the Guide to Community Preventive Services--overview and rationale. The Task Force on Community Preventive Services.

When the GUIDE TO COMMUNITY PREVENTIVE SERVICES: Systematic Reviews and Evidence-Based Recommendations (the Guide) is published in 2001, it will represent a significant national effort in encouraging evidence-based public health practice in defined populations (e.g., communities or members of specific managed care plans). The Guide will make recommendations regarding public health interventions to reduce illness, disability, premature death, and environmental hazards that impair community health and quality of life. The Guide is being developed under the guidance of the Task Force on Community Preventive Services (the Task Force)-a 15-member, nonfederal, independent panel of experts. Subject matter experts, methodologists, and scientific staff are supporting the Task Force in using explicit rules to conduct systematic literature reviews of evidence of effectiveness, economic efficiency, and feasibility on which to base recommendations for community action. Contributors to the Guide are building on the experience of others to confront methodologic challenges unique to the assessment of complex multicomponent intervention studies with nonexperimental or nonrandomized designs and diverse measures of outcome and effectiveness. Persons who plan, fund, and implement population-based services and policies to improve health at the state and local levels are invited to scrutinize the work in progress and to communicate with contributors. When the Guide is complete, readers are encouraged to consider critically the value and relevance of its contents, the implementation of interventions the Task Force recommends, the abandonment of interventions the Task Force does not recommend, and the need for rigorous evaluation of the benefits and harms of promising interventions of unknown effectiveness.

Decision Making↗
PubMed2000

The Surgeon General's report on America's oral health: opportunities for the dental profession.

BACKGROUND AND OVERVIEW: The release this year of "Oral Health in America: A Report of the Surgeon General"--the first such report on this topic in U.S. history--gives national visibility to the scope and breadth of oral health and disease in America. The report emphasizes oral health's inextricable link to general health and well-being. Although the country has seen major improvements in oral health, some population groups have yet to benefit from these improvements. To address health disparities and improve quality of life for all Americans, the surgeon general's report calls for the development of a National Oral Health Plan. CONCLUSIONS: "Oral Health in America" identifies opportunities for the dental profession on behalf of the nation's overall health. The profession is uniquely positioned to ensure that all components of the National Oral Health Plan are addressed: changing perceptions to ensure that oral health is seen as integral to general health; removing barriers to care; enhancing health infrastructure; accelerating the transfer of science into practice; and continuing to participate in private/public partnerships. CLINICAL IMPLICATIONS: The report's findings highlight the importance of assessing patients' known risks of experiencing oral diseases and of educating patients about health-promoting behaviors. The integral role of oral health in general health, as described in the report, makes it imperative for health professionals to ensure appropriate referrals to practitioners in all areas of health care.

Dental Caries↗
PubMed1999

Activation of granulocyte-macrophage colony-stimulating factor and interleukin-3 receptor subunits in a multipotential hematopoietic progenitor cell line leads to differential effects on development.

Activation of specific cytokine receptors promotes survival and proliferation of hematopoietic progenitor cells but their role in the control of differentiation is unclear. To address this issue, the effects of human interleukin-3 (hIL-3) and human granulocyte-macrophage colony-stimulating factor (hGM-CSF) on hematopoietic development were investigated in hematopoietic progenitor cells. Murine multipotent factor-dependent cell-Paterson (FDCP)-mix cells, which can self-renew or differentiate, were transfected with the genes encoding the unique alpha and/or shared beta(c) human hIL-3 receptor (hIL-3 R) or hGM-CSF receptor (hGM R) subunits by retroviral gene transfer. Selective activation of hIL-3 Ralpha,beta(c) or hGM Ralpha,beta(c) transfects by hIL-3 and hGM-CSF promoted self-renewal and myeloid differentiation, respectively, over a range of cytokine (0.1 to 100 ng/mL) concentrations. These qualitatively distinct developmental outcomes were associated with different patterns of protein tyrosine phosphorylation and, thus, differential signaling pathway activation. The cell lines generated provide a model to investigate molecular events underlying self-renewal and differentiation and indicate that the alpha subunits act in combination with the hbeta(c) to govern developmental decisions. The role of the alpha subunit in conferring specificity was studied by using a chimeric receptor composed of the extracellular hIL-3 Ralpha and intracellular hGM Ralpha subunit domains. This receptor promoted differentiation in response to hIL-3. Thus, the alpha subunit cytosolic domain is an essential component in determining cell fate via specific signaling events.

Animals↗
PubMed1999

Mandibular lengthening using preprogrammed intraoral tooth-borne distraction devices.

PURPOSE: This report describes the application of an intraoral device for treatment of malocclusions characterized by mandibular deficiency and the surgical technique for its placement. PATIENTS AND METHODS: In an office setting, 5 retrognathic patients underwent mandibular lengthening via distraction osteogenesis with an intraoral tooth-borne distraction device. Under local anesthesia and sedation, mandibular corticotomies, mobilization, and placement of the distractors were performed. Preoperative, intradistraction, and postoperative dental casts, photographs, and cephalometric radiographs were used to analyze the results. RESULTS: In 3 of the 5 cases, distraction occurred along the planned vector. The remaining 2 cases showed opening rotations of the mandibular anterior segment along with the advancement. CONCLUSIONS: This study documents that the mandible and the dental arch can be lengthened successfully using this technique.

Adolescent↗
PubMed1999

Tensile and shear stresses in the orthodontic attachment adhesive layer with 3D finite element analysis.

The tests commonly used for the evaluation of orthodontic adhesives measure tensile and shear bond strength. The two methods were compared with finite element analysis using a three-dimensional model and the effect of misalignment of the tensile and shear forces was calculated. Applying a shear load produces significant compressive and tensile stresses in the adhesive layer. Under ideal conditions of shear loading, the induced tensile stress is over 5 times the induced shear stress. The model shows that a tensile load induces predominantly tensile stresses in the adhesive layer. The calculations indicate that the tensile test method is a robust testing method with low sensitivity to misalignment of the applied load.

Adhesives↗
PubMed1999

Assessment of 3-dimensional computer-generated cephalometric measurements.

The purpose of this study was to assess the reliability of 3-dimensional computer-generated linear and angular measurements produced by different computer algorithms and various combinations of cephalogram projections compared with direct and CT measurements. A computer program was written to provide 4 computer algorithms and 4 combinations of cephalogram projections generating 22 linear and 10 angular 3-dimensional measurements from 20 landmarks. A new technique to produce biplanar cephalograms from a single x-ray source using a special facebow was developed, and its reliability was assessed. Sets of lateral, frontal, and basilar cephalograms of a human dried skull were taken both with 20 radiopaque landmark markers and without markers. Paired t tests based on marker position demonstrated reliability of the facebow; there were no statistically significant differences in repositioning the skull over time using the facebow at P <.05. In the ideal situation, with minimal head rotation and landmark identification error (with the facebow and radiopaque markers), the average error of linear measurements was 1. 5 mm and 3.5(o) for the angular measurements. Subsequent trials evaluated the errors in head position (within 5(o) of head rotation) and in landmark identification (by removing all markers); two-way ANOVA with Scheffé groupings concluded that the vector intercept with manual adjustment algorithm using the lateral-frontal biplanar projection provides not only greater accuracy but also clinical practicality for both linear (mean of 2.2 mm error) and angular (mean of 4.0(o) error) measurements compared with direct or CT measurements (P <.05). The effect of landmark identification error was found to be slightly greater than the head rotation error in the accuracy of 3-dimensional linear and angular measurements (mean, 2.85 mm error for linear and 4.4(o) error for angular measurements). Lastly, this study concluded that linear measurements in the transverse direction were found to have a slightly larger error than vertical measurements. Anteroposterior measurements have the least error.

Algorithms↗
PubMed1999

Comparison of preferences in lip position using computer animated imaging.

The objectives of this study were to examine the esthetic preferences of lip position in males and females, and to compare them with each other and with a common orthodontic standard using a custom computer animation program. The sample consisted of 53 young adult subjects, 25 males and 28 females. The sample was divided into orthodontically treated and untreated subjects. ANOVA and Scheffé tests were carried out to determine differences between the responses of the various groups. Also, t-tests were used to compare subjects' responses to a commonly used orthodontic standard (Ricketts' E-line). The results indicated a sex-effect, with females preferring fuller lips than males. Significant differences were also found between orthodontically treated subjects and untreated subjects, with untreated subjects preferring fuller lips. Differences were significant at p<0.05. Furthermore, both males and females preferred lip fullness greater than the Ricketts' values.

Adolescent↗
PubMed1999

Comparison of perceptions of computer-animated left- and right-facing profiles.

PURPOSE: Although scientific publications differ in displaying left- or right-facing profiles, there are few systematic studies of the possible effects of directional biases and laterality on patients' and clinicians' perceptions of treatment need, outcomes, and satisfaction. As part of a research program to quantitate the physical bases of the perceived zone of acceptability and most-pleasing facial profiles, responses to computer-animated left- and right-facing soft-tissue profile images were compared and related to eye and hand preference. MATERIALS AND METHODS: Standardized left-facing, soft-tissue profile images were captured in color and digitized. The right-facing profile was created by reversing the left profile image to display a mirror image. Using imaging and customized morphing software, retrusive and protrusive extremes were created, from which transitional frames were developed to display five features of the soft-tissue profile: upper lip, chin, bimaxillary position, lower face height, and mandible. One left- and one right-facing profile for a Class II division 1 female, and Class III male were randomly presented to 24 subjects who were asked to indicate: 1) acceptability by pressing a mouse button and releasing the button when the images were no longer acceptable; and 2) most-pleasing image by pressing the mouse button once. RESULTS: No differences were found between left- and right-profile images for zone of acceptability, midpoint of the zone of acceptability, or most pleasing; nor was there any relation to laterality measures. However, consistently higher intercorrelations among the features for the zone of acceptability were found for the left- than for the right-facing profiles for retrusive to protrusive and protrusive to retrusive excursions measured in millimeters (p < .001). The bimaxillary position accounted for most of the variance in judgments of acceptability with greater influence on the left than on the right profile. CONCLUSION: With the increasing use of computer-imaging in dental practices, the influence of psychophysical and other environmental variables on perception must be considered.

Adolescent↗
PubMed1999

Computer-animated comparison of self-perception with actual profiles of orthodontic and nonorthodontic subjects.

To determine if motivation for adult orthodontic treatment is influenced by self-perception, a computer morphing program was developed to animate discrete digitized photographs of facial profiles. It was hypothesized that orthodontic patients are less tolerant of variations in their profiles than nonorthodontic patients. Sixteen orthodontic and 14 nonorthodontic adult patients were presented with animated distortions of 5 features of the lower third of their own profiles. They were asked to identify the zone of acceptability in the changing profile and to indicate the single most pleasing distortion and their perceived and preferred profiles, for comparison with their actual profile. Although orthodontic subjects did not differ from nonorthodontic subjects in the zone of acceptability of their own profiles, they were less tolerant (smaller zone of acceptability) of variation in features of a standard control face. Orthodontic subjects, however, had a larger disparity between the most pleasing and at least one feature of their actual profile than did the nonorthodontic subjects. Orthodontic and nonorthodontic subjects were equally accurate in their ability to identify their own profile features. This unique method of measuring self-perception offers the clinician the advantage of providing a dynamic range rather than a single point of acceptable change to the patient. Moreover, this interactive computer program will enable patients to actively participate in treatment planning decisions by communicating preferences for variations in facial profile distortions.

Adult↗