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Biomedical subjects

David Chambers

Publications and source records attributed to David Chambers.

13 recordsLinked to original sources

A high throughput messenger RNA differential display screen identifies discrete domains of gene expression and novel patterning processes along the developing neural tube.

BACKGROUND: During early development the vertebrate neural tube is broadly organized into the forebrain, midbrain, hindbrain and spinal cord regions. Each of these embryonic zones is patterned by a combination of genetic pathways and the influences of local signaling centres. However, it is clear that much remains to be learned about the complete set of molecular cues that are employed to establish the identity and intrinsic neuronal diversity of these territories. In order to address this, we performed a high-resolution messenger RNA differential display screen to identify molecules whose expression is regionally restricted along the anteroposterior (AP) neuraxis during early chick development, with particular focus on the midbrain and hindbrain vesicles. RESULTS: This approach identified 44 different genes, with both known and unknown functions, whose transcription is differentially regulated along the AP axis. The identity and ontological classification of these genes is presented. The wide variety of functional classes of transcripts isolated in this screen reflects the diverse spectrum of known influences operating across these embryonic regions. Of these 44 genes, several have been selected for detailed in situ hybridization analysis to validate the screen and accurately define the expression domains. Many of the identified cDNAs showed no identity to the current databases of known or predicted genes or ESTs. Others represent genes whose embryonic expression has not been previously reported. Expression studies confirmed the predictions of the primary differential display data. Moreover, the nature of identified genes, not previously associated with regionalisation of the brain, identifies novel potential mechanisms in that process. CONCLUSION: This study provides an insight into some of the varied and novel molecular networks that operate during the regionalization of embryonic neural tissue and expands our knowledge of molecular repertoire used during development.

Animals↗

Functional genomics of early cortex patterning.

Several lines of evidence have illuminated the fundamental developmental principles involved in establishing and implementing pattern formation in the mammalian neocortex. A recent study has sought to unravel the underlying genetic control of cortex patterning by elucidating the transcriptional profile of discrete neocortical regions.

Animals↗

Blinded clinical evaluation of a new manual toothbrush.

OBJECTIVE: A new manual toothbrush with an innovative design has recently been introduced into the marketplace. The purpose of this single-blind, crossover study was to compare plaque removal associated with this new manual toothbrush (Curvex) and a best-selling commercially available manual tootbrush (Oral-B Indicator 40). METHODOLOGY: Over a five-week period, twenty-one subjects participated in this investigation. Following random assignment, ten of the subjects started with the Curvex toothbrush, and the remaining subjects began with the Oral-B Indicator 40 toothbrush. Subjects brushed twice daily for two minutes over a two-week period. After a one-week washout period, the subjects brushed with the alternate toothbrush for two weeks. At the beginning and end of each two-week trial period, subjects were scored before and after brushing using the Turesky modification of the Quigley-Hein Plaque Index (T/Q-H). Findings of reductions in plaque scores were limited to "before vs. after" assessments. Plaque scores were measured in each subject (up to 168 sites) on each of four occasions. RESULTS: The average baseline and test plaque scores for the Oral-B Indicator 40 brush were 2.41 and 1.72; for the Curvex brush these values were 2.34 and 1.69. Repeated measures ANOVA revealed no difference between brushes. Paired-comparison t-tests were conducted on each of the 168 evaluated sites, and no patterns of superiority for either brush were identified. Although both toothbrushes effectively reduced mean plaque scores, ANOVA demonstrated no significant difference between toothbrushes. CONCLUSION: The Curvex toothbrush is as effective as the Oral-B Indicator 40 toothbrush in removing plaque. Additionally, there was no evidence of any soft tissue abrasion from either brush.

Adolescent↗

Development of ultrasound tomography for breast imaging: technical assessment.

Ultrasound imaging is widely used in medicine because of its benign characteristics and real-time capabilities. Physics theory suggests that the application of tomographic techniques may allow ultrasound imaging to reach its full potential as a diagnostic tool allowing it to compete with other tomographic modalities such as x-ray computer tomography, and MRI. This paper describes the construction and use of a prototype tomographic scanner and reports on the feasibility of implementing tomographic theory in practice and the potential of ultrasound (US) tomography in diagnostic imaging. Data were collected with the prototype by scanning two types of phantoms and a cadaveric breast. A specialized suite of algorithms was developed and utilized to construct images of reflectivity and sound speed from the phantom data. The basic results can be summarized as follows. (i) A fast, clinically relevant US tomography scanner can be built using existing technology. (ii) The spatial resolution, deduced from images of reflectivity, is 0.4 mm. The demonstrated 10 cm depth-of-field is superior to that of conventional ultrasound and the image contrast is improved through the reduction of speckle noise and overall lowering of the noise floor. (iii) Images of acoustic properties such as sound speed suggest that it is possible to measure variations in the sound speed of 5 m/s. An apparent correlation with x-ray attenuation suggests that the sound speed can be used to discriminate between various types of soft tissue. (iv) Ultrasound tomography has the potential to improve diagnostic imaging in relation to breast cancer detection.

Algorithms↗

Characterization of subwavelength elastic cylinders with the decomposition of the time-reversal operator: theory and experiment.

The decomposition of the time-reversal operator provides information on the scattering medium. It has been shown [Chambers and Gautesen, J. Acoust. Soc. Am. 109, 2616-2624 (2001)] that a small spherical scatterer is in general associated with four eigenvalues and eigenvectors of the time-reversal operator. In this paper, the 2D problem of scattering by an elastic cylinder, imbedded in water, measured by a linear array of transducers is considered. In this case, the array response matrix has three nonzero singular values. Experimental results are obtained with linear arrays of transducers and for wires of different diameters smaller that the wavelength. It is shown how the singular value distribution and the singular vectors depend on the elastic velocities cL, cT, the density rho of each wire, and on the density rho0 and velocity c0 of the surrounding fluid. These results offer a new perspective towards solution of the inverse problem by determining more than scattering contrast using conventional array processing like that used in medical ultrasonic imaging.

Journal Article↗

Retinoic acid and the control of dorsoventral patterning in the avian spinal cord.

The development of neural subtypes in the dorsoventral (DV) axis of the vertebrate central nervous system (CNS) involves the integration of signalling pathways coupled with the combinatorial expression of homeodomain transcription factors. Previous studies have implicated a role for retinoic acid in the specification of a subtype of motor neurons (MN) and in the patterning of a group of interneurons within the ventral spinal cord. In this study, we use the vitamin A-deficient (VAD) quail model to further investigate the role of retinoids in the patterning of the neural tube. Using genetic markers specific to neuronal cell populations, we demonstrate that in the absence of retinoic acid, there is a disruption to the molecular mechanisms associated with the dorsoventral patterning of the spinal cord. In particular, we observe an uneven dorsal expansion of ventral-specific genes, accompanied by a reduction in the domain of roof plate and dorsal patterning genes, both of which are rescued upon addition of retinoids during development. In addition, there is a loss of V1 interneuron-specific gene expression and a decrease in the ventricular zone expression of motor neuron patterning genes. Interestingly, these effects are localised to the rostral half of the spinal cord, indicating that RA is integrated in both anteroposterior (AP) and dorsoventral patterning processes. Using differential display techniques, we have isolated 27 retinoic acid-regulated genes within the spinal cord that together reveal several interesting potential biological functions for retinoids within the avian neural tube. In summary, we propose that retinoids have an essential role in the patterning of the dorsoventral axis of the spinal cord, and are also required for the correct integration of anteroposterior patterning signals with dorsoventral determinants in the rostral spinal cord.

Amino Acid Sequence↗

The EBP50-moesin interaction involves a binding site regulated by direct masking on the FERM domain.

Members of the ezrin-radixin-moesin (ERM) protein family serve as regulated microfilament-membrane crosslinking proteins that, upon activation, bind the scaffolding protein ERM-phosphoprotein of 50 kDa (EBP50). Here we report a 3.5 A resolution diffraction analysis of a complex between the active moesin N-terminal FERM domain and a 38 residue peptide from the C terminus of EBP50. This crystallographic result, combined with sequence and structural comparisons, suggests that the C-terminal 11 residues of EBP50 binds as an alpha-helix at the same site occupied in the dormant monomer by the last 11 residues of the inhibitory moesin C-terminal tail. Biochemical support for this interpretation derives from in vitro studies showing that appropriate mutations in both the EBP50 tail peptide and the FERM domain reduce binding, and that a peptide representing just the C-terminal 14 residues of EBP50 also binds to moesin. Combined with the recent identification of the I-CAM-2 binding site on the ERM FERM domain (Hamada, K., Shimizu, T., Yonemura, S., Tsukita, S., and Hakoshima, T. (2003) EMBO J. 22, 502-514), this study reveals that the FERM domain contains two distinct binding sites for membrane-associated proteins. The contribution of each ligand to ERM function can now be dissected by making structure-based mutations that specifically affect the binding of each ligand.

Amino Acid Sequence↗

An enhancer complex confers both high-level and cell-specific expression of the human type X collagen gene.

Type X collagen expression is restricted to hypertrophic chondrocytes in the endochondral growth plate. Transient transfection of reporter constructs containing the human collagen X promoter into primary growth plate chondrocytes identified a cis-acting positive regulatory DNA element(s) that has cell-specific enhancer properties and binds a nuclear protein expressed specifically in growth plate chondrocytes. Functional disruption of this region results in a significant reduction in the activation of reporter gene transcription. The identified enhancer is a major element controlling both high-level and cell-specific expression of type X collagen gene.

Base Sequence↗

Chick gene frenzy.

The BBSRC Chick Genomics and Biology Workshop was held at UMIST, Manchester UK from 15 to 16 December 2001.

Animals↗

Neural crest: facing the facts of head development.

The cranial neural crest originates at the dorsal margin of the neural tube and produces migratory cells that populate various locations in the head. They are a crucial factor in the development of the vertebrate head because they give rise to numerous differentiated cell types, including the cartilage, bone and connective tissues of the skull. Thus, the coordinated regulation of crest cell movement and patterning is pivotal to the acquisition of organized head structure. Two recent papers cast light on the molecular mechanisms and tissue interactions employed by an embryo to achieve this goal. Here, we discuss the implications of these findings in view of pre-existing principles of neural crest patterning. Crucially, these new data implicate, for the first time, that head skeletal patterning is controlled by tissue other than the neural crest.

Animals↗

1.3 Development of professional competences.

Competency-based education, introduced approximately 10 years ago, has become the preferred method and generally the accepted norm for delivering and assessing the outcomes of undergraduate (European) or predoctoral (North America) dental education in many parts of the world. As a philosophical approach, the competency statements drive national agencies in external programme review and at the institutional level in the definition of curriculum development, student assessment and programme evaluation. It would be presumptuous of this group to prescribe competences for various parts of the world; the application of this approach on a global basis may define what is the absolute minimum knowledge base and behavioural standard expected of a 'dentist' in the health care setting, while respecting local limitations and values. The review of documents and distillation of recommendations is presented as a reference and consideration for dental undergraduate programmes and their administration.

Competency-Based Education↗

Palpable parathyroid adenomas presenting as clinical solitary thyroid nodules and cytologically as follicular thyroid neoplasms.

BACKGROUND: A palpable parathyroid mass, in a patient with primary hyperparathyroidism, is presumed to be parathyroid carcinoma until proven otherwise, with other less common causes including parathyroid cysts and adenomas. These parathyroid pathologies can be more difficult to interpret with concomitant thyroid disease. METHODS: A retrospective review was undertaken of a series of three patients with palpable parathyroid adenomas mimicking thyroid nodules. RESULTS: Two of three patients had preoperative biochemical evidence of primary hyperparathyroidism. Sestamibi scanning confirmed the presence of parathyroid pathology in one case. Fine-needle aspiration cytology revealed probable follicular neoplasms of the thyroid in all three cases. Only one of three parathyroid adenomas was diagnosed at neck exploration; the others were diagnosed at subsequent histopathology. CONCLUSION: Parathyroid and thyroid disease often occur simultaneously. Concomitant parathyroid pathology should be considered, even in the absence of biochemical and radiological evidence, at neck exploration for thyroid disease. Macroscopic identification of parathyroid disease at neck exploration can be difficult when within the thyroid gland capsule. Cytology and imaging of parathyroid adenomas may, on occasion, mimic follicular thyroid neoplasms.

Adenocarcinoma, Follicular↗