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Biomedical subjects

G R Davis

Publications and source records attributed to G R Davis.

At least 19 recordsLinked to original sources

Dentinal carious lesion in three dimensions.

AIM: The aim of this study was to show the morphology of the carious lesion in dentine in three dimensions (3D). DESIGN: A novel high-definition X-ray microtomography (XMT) scanner was used to scan 10 carious primary molars at a resolution of 15 x 15 x 15 microm3. A stack of approximately 640 XMT slices were recorded for each tooth. Using this data set and a volume rendering algorithm, each tooth was reconstructed in 3D. The VG Studio Max 1.0 visualization software package was used to make normal enamel and dentine transparent to show the carious lesions in 3D. A video film, comprised of the rendered images from 60 viewing angles rotating through 360 degrees , was produced to show the carious lesion and its relation to the pulp in a three-dimensional perspective (http://www.smd.qmul.ac.uk/dental/oralgrowdev/biophysics/xmt/images/carious.mpg). RESULTS: These images showed that carious lesions in dentine were bowl-shaped. The pulp adjacent to the carious lesion was also observed to mimic the base of the bowl-shaped lesion. CONCLUSIONS: It was concluded from the teeth studied that the shape at the base of the carious lesion in dentine is curved in 3D, rather than conical, as traditionally believed from two-dimensional image interpretation. Further 3D studies are needed to investigate whether the bowl-shaped carious lesions in dentine also apply to caries in other types of teeth.

Dental Caries↗

Assessment of the fitness impacts on Escherichia coli of acquisition of antibiotic resistance genes encoded by different types of genetic element.

OBJECTIVES: Little is known of the fitness cost that antibiotic resistance exerts on wild-type bacteria, especially in their natural environments. We therefore examined the fitness costs that several antibiotic resistance elements imposed on a wild-type Escherichia coli isolate, both in the laboratory and in a pig gut colonization model. METHODS: Plasmid R46, Tn1 and Tn7 and a K42R RpsL substitution were separately introduced into E. coli 345-2 RifC, a rifampicin-resistant derivative of a recent porcine isolate. The insertion site of Tn1 was determined by DNA sequencing. The fitness cost of each resistance element was assessed in vitro by pairwise growth competition and in vivo by regularly monitoring the recovery of strains from faeces for 21 days following oral inoculation of organic piglets. Each derivative of 345-2 RifC carrying a resistance element was grown in antibiotic-free broth for 200 generations and the experiments to assess fitness were repeated. RESULTS: RpsL K42R was found to impose a small fitness cost on E. coli 345-2 RifC in vitro but did not compromise survival in vivo. R46 imposed a cost both before and after laboratory passage in vitro, but only the pre-passage strain was at a disadvantage in vivo. The post-passage isolate had an advantage in pigs. Acquisition of Tn7 had no impact on the fitness of E. coli 345-2 RifC. Two derivatives containing Tn1 were isolated and, in both cases, the transposon inserted into the same cryptic chromosomal sequence. Acquisition of Tn1 improved fitness of E. coli 345-2 RifC in vitro and in vivo in the case of the first derivative, but in the case of a second, independent derivative, Tn1 had a neutral effect on fitness. CONCLUSIONS: The fitness impact imposed on E. coli 345-2 RifC by carriage of antibiotic resistance elements was generally low or non-existent, suggesting that once established, resistance may be difficult to eliminate through reduction in prescribing alone.

Animals↗

3D X-ray microscopic study of the extent of variations in enamel density in first permanent molars with idiopathic enamel hypomineralisation.

OBJECTIVE: To measure mineral concentration distributions within teeth with idiopathic enamel hypomineralisation, a condition in which developmental defects are seen in first permanent molars, and/or incisors. DESIGN: X-ray microtomographic and 3D x-ray microscopy. SETTING: UK University, 2001. MATERIALS AND METHODS: X-ray microtomographic measurements of the extent of hypomineralisation in two affected molars and two contralateral controls extracted from the same patient. RESULTS: The control molars were visibly normal. The affected molars showed hypomineralised yellow opaque enamel with regions of breakdown. X-ray microtomographic images showed; a 20% reduction in mineral concentration of affected enamel (most cases involved full enamel thickness); hypomineralised enamel had a mineral concentration gradient opposite to that of normal enamel; regions of hypomineralisation distributed randomly throughout affected teeth, (apart from cervical region which was less severely affected). CONCLUSIONS: The pattern of mineral concentration suggests a disturbance during the maturation process. Differences in susceptibility of the ameloblasts during different stages of dental development may explain the asymmetric distribution of the defects. Topical fluoride applications may help promote post eruption maturation of the surface layer in these teeth. The use of fissure sealants and adhesive materials appears to prevent further breakdown.

Child↗

X-ray microtomographic study of mineral concentration distribution in deciduous enamel.

OBJECTIVE: To determine the mineral concentration distribution in deciduous enamel by quantitative X-ray microtomography (XMT). DESIGN: Tooth rods ( approximately 2 mm x 2 mm) were removed from the mid-buccal region of 11 deciduous molars. Three XMT slices were taken at 1.5, 2.0 and 2.5 mm from the amelocemental junction. The distribution and variation in mineral concentration of enamel were studied from the XMT images. RESULTS: The mean mineral concentration for all the teeth was 2.81 (S.D. = 0.065) g cm(-3). There was no notable difference in the mean mineral concentration values between the three XMT slices of each tooth. However, there was up to 8% variation between different teeth (2.69-2.92 g cm(-3)). Gradients of increasing mineral concentration from the amelodentinal junction (ADJ) to the external surface were found, ranging from 0.08 to 0.60 mg cm(-3) microm(-1) with a mean of 0.366 mg cm(-3) microm(-1). The mineral concentration gradients in the occlusal slices were steeper than those in the cervical slices. The difference in mineral concentration between the inner and outer enamel ranged from 1.5 to 8.7%. CONCLUSION: In view of the large variation in both the means and the gradients of mineral concentration in deciduous molars, the mineral distribution of each experimental tooth should be measured as baseline data in studies of caries progression.

Dental Enamel↗

Sequential 3D X-ray microtomographic measurement of enamel and dentine ablation by an Er:YAG laser.

OBJECTIVE: To demonstrate the progression of crater growth during repeated sequential application of an Er:YAG laser to enamel and dentine, monitored using X-ray microtomography (XMT). DESIGN: A single centre study in which laser craters were created in blocks cut from human enamel and/or dentine under standardised and known conditions and then studied using XMT to obtain visualisation and quantification of the effects. SETTING: University setting, UK, 2001. MAIN OUTCOME MEASURES: Success was judged by an ability to obtain useful 3D XMT reconstructions of the blocks during crater development, and to make measurements from these data. These measurements were compared with data obtained from similar studies using different measurement techniques. RESULTS: Time sequences of 2D and 3D images were obtained which demonstrated the progression of laser craters in enamel and dentine. Quantitative measurements from these data enabled values to be derived for the rate of progression of crater depth per unit energy, and the volume of hard tissue removed per unit energy. These values were compared with data derived from other studies and shown to be broadly comparable. However, the present study is unique in that these values were obtained from a series of measurements of the same craters over time. CONCLUSIONS: 3D X-ray microtomography is shown to be a useful tool for quantitative measurements in dental research. For the Er:YAG laser, the relationship of laser crater depth and volume of mineral removed to applied energy was found to be linear.

Aluminum Silicates↗

Decreased expression of Wnt7a mRNA is inversely associated with the expression of estrogen receptor-alpha in human uterine leiomyoma.

Wnt-7a gene not only guides the development of the anterior-posterior axis in the female reproductive tract, but also plays a critical role in uterine smooth muscle pattering and maintenance of adult uterine function. This gene is also responsive to changes in the levels of sex steroid hormone in the female reproductive tract. To explore the molecular mechanisms underlying the pathogenesis of uterine leiomyoma, the expression of Wnt7a mRNA in the leiomyoma has been assessed. RT-PCR was performed on uterine leiomyomas and the adjacent myometria. Of 30 cases of leiomyomas studied, 67% showed a decreased mRNA level as compared to the paired myometria. On the other hand, estrogen receptor-alpha (ER-alpha) mRNA is hyper-expressed in 67% of the leiomyomas as compared to their paired myometrium. An inverse association at mRNA expression was found between Wnt7a and ER-alpha. Miller et alhas shown that fetal exposure of DES results in de-regulation of Wnt7a during uterine morphogenesis. Referring to their results, we have postulated that hypersensitivity of leiomyoma cells to estrogen may deregulate the Wnt7a expression. Decreased expression of Wnt7a may lead to loss of control in patterning of the myometrium and result in development of leiomyoma

Estrogen Receptor alpha↗

Bone fracture analysis on the short rod chevron-notch specimens using the X-ray computer micro-tomography.

Mechanical fatigue of bone leads to micro-cracking which is associated with remodeling, establishing a balance in the microcrack population of the living tissue, thus, in the steady-state, the microstructure of bone provides sites of discontinuity acting as stress raisers. Hence fracture toughness plays a decisive role in bone functionality by determining the level to which the material can be stressed in the presence of cracks, or, equivalently, the magnitude of cracking which can be tolerated at a given stress level. Cortical bone, which behaves as a quasi-brittle solid when fractured, was tested as short-rod chevron-notched tension specimens (CNT). The main features of the CNT specimen are its geometry and the V shaped notch. The notch leads to steady-state crack propagation whilst the requested geometry allows a diameter 40% smaller than the thickness of a standard compact tension specimens (CT). These features are essential to distinguish the inhomogeneties in the fracture properties of materials like bone. Bone structure and crack propagation of the CNT specimens were analyzed using X-ray computed micro-tomography (XMT), which is a non-invasive imaging technique. The unique feature of the micro-CT is the high resolution three-dimensional image which consists of multi-sliced tomographs taken in a fine pitch along the rotational axis. Fracture toughness (K(IC)) computed according to the peak load was 4.8 MNm(-3/2) while that derived from experimental calibration tests using XMT was 4.9 MNm(-3/2).

Journal Article↗

X-ray microtomographic study of mineral distribution in enamel of mandibular rat incisors.

X-ray microtomography was used to study the mineral concentrations in sequential slices of enamel of 5 mandibular incisors which showed an increase from approximately 1.0 to approximately 2.7 g cm(-3) from the apex towards the incisal end. For points at the same distance from the apex, there were differences up to 0.6 g cm(-3) between the teeth. The change of mean concentrations in the slices with distance could be modelled as (different) saturating exponentials. Under the assumption of a uniform growth rate of a mandibular incisor of 0.6 mm per day and a common time origin for the start of maturation (taken as a mineral concentration of 1 g cm(-3)), the distances were transformed to a common time frame to give a pooled data set. A single saturating exponential could be fitted to this pooled transformed data; this was: Cm = 2.84-1.94exp (-0.18d) where Cm is the mean mineral concentration (g cm(-3)) and d the time (days) from the start of maturation. This gives an asymptotic concentration of 2.84 g cm(-3) towards the incisal end, with a time constant of 7.7 days. The mineral concentration distribution functions were found to be more positively skewed closer to the apex, but more negatively skewed towards the incisal end. The difference between the higher mineral concentration in the outer enamel and the enamel near the amelodentinal junction (ADJ) was approximately 3%. The direction of maximum increase in concentration from the outer enamel surface to the ADJ meets the boundary of the ADJ at approximately 80 degrees. Three dimensional surface rendering of isodensity contours showed that the previously described C-shaped pattern of mineralisation is not solely a surface phenomenon, but extends through the depth of the enamel.

Animals↗

Determination of mineral concentration in dental enamel from X-ray attenuation measurements.

The mineral content of dental enamel is commonly measured by X-ray attenuation experiments. Most studies have used contact microradiography in which intensities are measured with photographic film which is convenient and gives high spatial resolution. However photon counting intensity measurements are to be preferred in many experiments (longitudinal and scanning microradiography, and microtomography), as illustrated here, because they have a larger dynamic range and greater sensitivity to small intensity changes. Additionally, the detector and specimen are well separated which allows the pseudo-continuous study of de- and remineralization. The mineral content is often quoted as 95 wt% or 87 vol% hydroxyapatite for permanent human enamel. This determination from attenuation experiments requires accurate values of elemental mass attenuation coefficients and a number of assumptions. The effects of possible choices of these are considered and it is shown that the most important is the density of enamel mineral used in conversion of wt% to vol%. If the density is taken as 2.99 g cm(-3), as recently suggested (J.C. Elliott, Dental Enamel, Ciba Foundation Symposium 205, Wiley, Chichester, pp. 54-72, 1997), instead of 3.15 g cm(-3) as for hydroxyapatite, the calculated vol% is approximately 93 instead of approximately 87.

Dental Enamel↗

X-ray microtomography: nondestructive three-dimensional imaging for in vitro endodontic studies.

Article shows the application of a laboratory x-ray microtomography system, a miniaturized form of conventional computerized axial tomography, to the study of root canal morphologic characteristics and changes in the course of root canal treatment in extracted teeth. After reconstruction of the three-dimensional images, the IDL software package (Research Systems, Inc., Colorado) was used to obtain cross-sectional slices of the tooth and three-dimensional views of rendered surfaces of constant mineral density. The root canal systems and changes in these were imaged at a resolution (cubic voxel side-length) of approximately 40 microns.

Anatomy, Cross-Sectional↗

X-ray microtomography: 3-dimensional imaging of teeth for computer-assisted learning.

X-ray microtomography (XMT), a miniaturised form of computed tomography, has been used to generate 3-dimensional volume data sets of the X-ray absorption of human teeth in vitro, with a resolution of approximately 40 microns (cubic voxel sidelength). Examples are presented of images relevant to dental morphology, cariology, and cavity preparation and restoration. Applications of XMT imaging to dental education are discussed in the context of new approaches to visual learning through computer-assisted methods.

Computer-Assisted Instruction↗

X-ray microtomography of bones and teeth.

X-ray microtomography is a miniaturized version of computerized axial tomography with a resolution of the order of micrometres. In the biomedical field it is particularly useful in the study of hard tissue because of its ability to accurately measure the linear attenuation coefficient. From this, the mineral concentration can be computed, which is one measure of bone quality. Using microtomography it is also possible to form three-dimensional images of bone from which structural parameters can be derived which could not be measured using conventional histomorphometry. Various types of microtomography scanner have been used, including simple translate-rotate systems which are capable of measuring x-ray attenuation at multiple energies simultaneously, and "cone-beam' systems which can acquire the necessary data for three-dimensional reconstructions in a relatively short time. Both laboratory x-ray sources and synchrotrons have been used in the study of hard tissue using microtomography. Most studies of bone have been concerned primarily with either the mineral concentration in cortical bone or the structure in cancellous bone. The mineral concentration in teeth has also been studied, in particular the loss of mineral in enamel during in vitro demineralization and the gain during subsequent remineralization. Although there are currently relatively few centres carrying out this work, interest in the technique is rapidly growing and it is likely to find a useful place both in research and ultimately in clinical practice.

Animals↗

Monitoring de- and remineralisation of enamel in vitro using an infrared reflectance meter.

The aim of this study was to design and investigate the use of an inexpensive method of monitoring the progress of demineralisation and subsequent remineralisation in artificial carious lesions. A small infrared (IR) reflectance meter was built which illuminated a 4 mm x 4 mm area on the buccal surface of a tooth and measured the reflected IR intensity. Repeated measurements were taken over a period of 25 days, during which the enamel surface was exposed to demineralising and subsequently remineralising solutions. Thirty-six teeth were studied under a variety of de- and remineralising conditions. It was observed that the IR specular reflectance of the tooth surfaces decreased with time during lesion formation and increased with time during remineralisation. It is suggested that the decrease in IR specular reflectance during demineralisation and the increase during remineralisation are a result of continuous changes in the crystals at the enamel surface during these processes.

Dental Caries Activity Tests↗

Mineral concentration gradients in rat femoral diaphyses measured by X-ray microtomography.

The bone mineral concentrations of five rat femora were measured as a function of distance from the distal metaphysis by quantitative X-ray microtomography (XMT) at a resolution of approximately 23 x 23 x 15 microns3. Assuming the mineral phase of bone to be hydroxyapatite, Ca10 (PO4)6(OH)2, the mean cortical mineral concentration (CM) per transverse section was found to range from 1.33 to 1.47 g cm-3. Detectable variations in the bone mineral concentration between sections of femora from different animals could not be attributed to the age when the particular animal was sacrificed. An increase in CM with distance, L, from the distal growth plate was observed and a saturating exponential equation, CM = a - be-alpha L, was used to describe the changes. Each section of bone tissue was considered as a population of elementary volumes of bone (EVB) and L was related to the age of the EVB (TEVB). A simple model for the mineralization process of an EVB was then proposed. Each newly formed EVB accumulated mineral rapidly to give an initial mineral concentration of approximately 1.3 g cm-3 (parameter a-b). Their mineral concentrations then increased asymptotically to approximately 1.5 g cm-3 (parameter a) with a time constant of approximately 330 days. This slow maturation process is attributed to Ostwald ripening of the bone crystals with further crystal growth using ions from the extracellular fluid.

Analysis of Variance↗

Extent and time course of restoration of descending brainstem projections in spinal cord-transected lamprey.

The purpose of the present study was to determine the numbers of descending brainstem projections to different levels of the spinal cord in normal larval sea lamprey (Petromyzon marinus) and to examine the restoration of these projections in animals 3-32 weeks after transection of the rostral spinal cord (approximately 10% of body length). In normal animals approximately 1,250, 900, and 825 brainstem neurons projected to 20%, 40%, and 60% of body length, respectively. Spinal projections originated from the diencephalon, mesencephalon, three rhombencephalic reticular nuclei, Müller and Mauthner neurons, and four cell groups in the caudal rhombencephalon. In spinal cord-transected animals the number of brainstem neurons projecting to 20% of body length increased with recovery time, and at 32 weeks post-transection the total number and distribution of brainstem neurons was not significantly different from normal animals. Brainstem projections first appeared at 40% of body length by 8 weeks post-transection, and were present at 60% of body length by 32 weeks post-transection. There was substantial restoration of brainstem projections to 40% of body length but limited restoration to 60% of body length. The approximately 50 brainstem neurons, including some Müller cells, that projected to 60% of body length at 32 weeks post-transection indicate that restoration of descending projections in excess of 50 mm can occur within the central nervous system of this vertebrate. These anatomical results are discussed in relation to the time course of recovery of locomotor function in spinal cord-transected lampreys.

Animals↗

Long distance axonal regeneration of identified lamprey reticulospinal neurons.

Retrograde labeling with horseradish peroxidase was used to examine the time course and extent of axonal regeneration of 12 pairs of individually identifiable reticulospinal Müller cells and 2 pairs of Mauthner cells in larval lamprey that received transections of the rostral spinal cord in the gill region. With increasing recovery times (3-32 weeks post-transection) the descending axons of many of these neurons regenerated to progressively more caudal levels of the spinal cord. These results confirm that some reticulospinal neurons are capable of true regeneration. However, the regenerative capacity of these neurons was not uniform, even for neurons in the same brain stem nucleus in close proximity. For example, at 32 weeks post-transection some identifiable reticulospinal neurons could regenerate their axons to 60% body length or as much as 57 mm below the transection site. In contrast, previous studies indicated regeneration distances of 5-6 mm. Other neurons showed modest axonal regeneration, while one cell type showed very limited regeneration. The factors which may be responsible for the variable extent of regeneration among these neurons are considered.

Animals↗

Deciduous enamel defects in low-birth-weight children: correlated X-ray microtomographic and backscattered electron imaging study of hypoplasia and hypomineralization.

Enamel does not remodel, and disturbances occurring during development may remain in the tooth as a permanent record of the upset. Mineralization in prenatal and postnatal deciduous enamel was studied in the shed deciduous incisors of low-birth-weight (LBW: < 2kg) children. The specific objective was to gain further insight into the mechanism of formation of developmental defects of enamel. Sections at a resolution of 22-40 microns were reconstructed using X-ray microtomography (microCT) giving absolute measurements of linear absorption coefficient for AgK alpha radiation. Detail to ca. 1 micron resolution was obtained using automated, digital backscattered electron (BSE) imaging of PMMA-embedded material. Matching the histograms of BSE and microCT images made possible the calibration of the mean atomic number-dependent signal in the BSE images. The comparison of abnormal, affected enamel regions and post-recovery, normal, unaffected regions could be made in the same teeth, since these zones were easily recognized from the distribution of hypoplasia and hypomineralization. The microCT values, converted to calculated mineral densities, ranged from 2.3 g cm-3 to 2.6 g cm-3 in LBW hypoplastic, and between 2.65 and 2.78 g cm-3 in control primary enamel and post-defect, post-natal LBW enamel. Hypoplasia with or without minimal hypomineralization indicated recovery of the ameloblasts in the maturation phase. Disturbance during late matrix formation and early maturation resulted in hypoplasia and hypomineralization.

Child, Preschool↗