Biomedical subjects

R M Davies

Publications and source records attributed to R M Davies.

At least 37 records · Page 2Linked to original sources

PubMed2001

Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18.

Salmonella enterica serovar Typhi (S. typhi) is the aetiological agent of typhoid fever, a serious invasive bacterial disease of humans with an annual global burden of approximately 16 million cases, leading to 600,000 fatalities. Many S. enterica serovars actively invade the mucosal surface of the intestine but are normally contained in healthy individuals by the local immune defence mechanisms. However, S. typhi has evolved the ability to spread to the deeper tissues of humans, including liver, spleen and bone marrow. Here we have sequenced the 4,809,037-base pair (bp) genome of a S. typhi (CT18) that is resistant to multiple drugs, revealing the presence of hundreds of insertions and deletions compared with the Escherichia coli genome, ranging in size from single genes to large islands. Notably, the genome sequence identifies over two hundred pseudogenes, several corresponding to genes that are known to contribute to virulence in Salmonella typhimurium. This genetic degradation may contribute to the human-restricted host range for S. typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis.

Chromosome Mapping↗

PubMed2001

Genome sequence of Yersinia pestis, the causative agent of plague.

The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague (nineteenth century to the present day). The recent identification of strains resistant to multiple drugs and the potential use of Y. pestis as an agent of biological warfare mean that plague still poses a threat to human health. Here we report the complete genome sequence of Y. pestis strain CO92, consisting of a 4.65-megabase (Mb) chromosome and three plasmids of 96.2 kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion sequences and displays anomalies in GC base-composition bias, indicating frequent intragenomic recombination. Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins). The genome contains around 150 pseudogenes, many of which are remnants of a redundant enteropathogenic lifestyle. The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve.

Animals↗

PubMed2001

The use of fibre-optic transillumination in general dental practice.

OBJECTIVE: To assess the use of fibre-optic transillumination (FOTI) as a diagnostic tool in general dental practice. DESIGN: A cross-over quantitative study for the diagnosis of approximal carious lesions by two clinical methods with a qualitative component. SUBJECTS AND METHODS: Seven GDPs were trained to use FOTI as an adjunct to their usual clinical examination to diagnose approximal caries. After 12 weeks of use in their practices four of the GDPs took part in two assessment sessions, set a week apart, using 29 volunteer patients. Each patient was examined on two separate occasions by each GDP using either their standard clinical examination technique alone or supplemented by FOTI examination. The order of the techniques was randomised. Radiographs of each patient were also examined separately. An experienced FOTI user also examined the patients to provide a benchmark. From standard charts the number of enamel and dentinal lesions on approximal surfaces was summed and comparisons made between the techniques. Six GDPs took part in one-to-one interviews. MAIN OUTCOME MEASURES: Mean numbers ofcarious lesions recorded by each clinician using each technique. RESULTS: There was a trend for all GDPs to find more enamel and dentinal lesions using FOTI, than with their standard clinical examination with or without radiographs. All GDPs found the FOTI technique a useful adjunct. They used FOTI in different ways and found a variety of uses for it other than caries diagnosis. CONCLUSIONS: The

Cross-Over Studies↗

PubMed2001

Mutation of the gene encoding the enamel-specific protein, enamelin, causes autosomal-dominant amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a group of inherited defects of dental enamel formation that shows both clinical and genetic heterogeneity. To date, mutations in the gene encoding amelogenin have been shown to underlie a subset of the X-linked recessive forms of AI. Although none of the genes underlying autosomal-dominant or autosomal-recessive AI have been identified, a locus for a local hypoplastic form has been mapped to human chromosome 4q11-q21. In the current investigation, we have analysed a family with an autosomal-dominant, smooth hypoplastic form of AI. Our results have shown that a splicing mutation in the splice donor site of intron 7 of the gene encoding the enamel-specific protein enamelin underlies the phenotype observed in this family. This is the first autosomal-dominant form of AI for which the genetic mutation has been identified. As this type of AI is clinically distinct from that localized previously to chromosome 4q11-q21, these findings highlight the need for a molecular classification of this group of disorders.

Amelogenesis Imperfecta↗

PubMed2001

Massive gene decay in the leprosy bacillus.

Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.

Animals↗

PubMed2001

The contribution of industry to the decline in dental caries.

The contribution of the oral care industry to the reduction in dental caries extends beyond the provision of safe and clinically proven products containing fluoride. The industry has contributed to the scientific base that underpins the use of fluoride, delineated factors that influence the clinical performance of toothpaste, raised the public's awareness of dental health and provided funding to support both undergraduate and postgraduate students in clinical training and basic research.

Cariostatic Agents↗

PubMed2000

An SNP map of human chromosome 22.

The human genome sequence will provide a reference for measuring DNA sequence variation in human populations. Sequence variants are responsible for the genetic component of individuality, including complex characteristics such as disease susceptibility and drug response. Most sequence variants are single nucleotide polymorphisms (SNPs), where two alternate bases occur at one position. Comparison of any two genomes reveals around 1 SNP per kilobase. A sufficiently dense map of SNPs would allow the detection of sequence variants responsible for particular characteristics on the basis that they are associated with a specific SNP allele. Here we have evaluated large-scale sequencing approaches to obtaining SNPs, and have constructed a map of 2,730 SNPs on human chromosome 22. Most of the SNPs are within 25 kilobases of a transcribed exon, and are valuable for association studies. We have scaled up the process, detecting over 65,000 SNPs in the genome as part of The SNP Consortium programme, which is on target to build a map of 1 SNP every 5 kilobases that is integrated with the human genome sequence and that is freely available in the public domain.

Cell Line↗

PubMed2000

Dental fluorosis in permanent incisor teeth in relation to water fluoridation, social deprivation and toothpaste use in infancy.

OBJECTIVES: To determine the prevalence and severity of fluorosis in permanent incisor teeth in young children in a fluoridated and a fluoride-deficient community and to establish what relationship, if any, there was between the occurrence of dental fluorosis and the reported use of fluoride toothpaste in childhood. DESIGN: A prevalence study of children aged 8-9 years who had been continuous residents in fluoridated Newcastle or fluoride-deficient Northumberland. METHOD: The permanent maxillary central incisor teeth were examined clinically and photographically by one examiner using the Thylstrup-Fejerskov index; the photographs were read blind to child identity and clinical score. A closed-response questionnaire enquired into the child's early experiences of toothbrushing and use of fluoride toothpastes. Social deprivation was measured by a Jarman score. The study took place in 1998. OUTCOME MEASURE: Prevalence of dental fluorosis measured by the Thylstrup-Fejerskov index. RESULTS: Complete data were available for 78% (n = 409) and 79% (n = 403) of eligible sampled children in the two areas, respectively. Clinical and photographic results agreed closely and had high reproducibility. The prevalence of fluorosis was 54% in the fluoridated area and 23% in the fluoride-deficient area when all grades (> 0) of fluorosis were included; percentage prevalence of mild to moderate fluorosis (> or = 3) was 3% and 0.5% in the two areas, respectively. Multivariate analysis indicated that area of residence (odds ratio = 4.5), Jarman score (odds ratio = 0.99 per Jarman unit) and type of toothpaste (odds ratio = 1.6) were statistically significantly related to presence or absence of fluorosis: the risk factors were--fluoridated area, affluence, and use of adult toothpaste. CONCLUSIONS AND RECOMMENDATIONS: The prevalence of aesthetically important dental fluorosis was low, although higher in the fluoridated area. Use of a child's toothpaste (with lower fluoride concentration) could decrease risk in a fluoridated area. Adherence to the guidelines published by the British Society of Paediatric Dentistry is recommended.

Child↗

PubMed2000

Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491.

Neisseria meningitidis causes bacterial meningitis and is therefore responsible for considerable morbidity and mortality in both the developed and the developing world. Meningococci are opportunistic pathogens that colonize the nasopharynges and oropharynges of asymptomatic carriers. For reasons that are still mostly unknown, they occasionally gain access to the blood, and subsequently to the cerebrospinal fluid, to cause septicaemia and meningitis. N. meningitidis strains are divided into a number of serogroups on the basis of the immunochemistry of their capsular polysaccharides; serogroup A strains are responsible for major epidemics and pandemics of meningococcal disease, and therefore most of the morbidity and mortality associated with this disease. Here we have determined the complete genome sequence of a serogroup A strain of Neisseria meningitidis, Z2491. The sequence is 2,184,406 base pairs in length, with an overall G+C content of 51.8%, and contains 2,121 predicted coding sequences. The most notable feature of the genome is the presence of many hundreds of repetitive elements, ranging from short repeats, positioned either singly or in large multiple arrays, to insertion sequences and gene duplications of one kilobase or more. Many of these repeats appear to be involved in genome fluidity and antigenic variation in this important human pathogen.

Antigenic Variation↗

PubMed2000

The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences.

Campylobacter jejuni, from the delta-epsilon group of proteobacteria, is a microaerophilic, Gram-negative, flagellate, spiral bacterium-properties it shares with the related gastric pathogen Helicobacter pylori. It is the leading cause of bacterial food-borne diarrhoeal disease throughout the world. In addition, infection with C. jejuni is the most frequent antecedent to a form of neuromuscular paralysis known as Guillain-Barré syndrome. Here we report the genome sequence of C. jejuni NCTC11168. C. jejuni has a circular chromosome of 1,641,481 base pairs (30.6% G+C) which is predicted to encode 1,654 proteins and 54 stable RNA species. The genome is unusual in that there are virtually no insertion sequences or phage-associated sequences and very few repeat sequences. One of the most striking findings in the genome was the presence of hypervariable sequences. These short homopolymeric runs of nucleotides were commonly found in genes encoding the biosynthesis or modification of surface structures, or in closely linked genes of unknown function. The apparently high rate of variation of these homopolymeric tracts may be important in the survival strategy of C. jejuni.

Amino Acid Sequence↗

PubMed2000

An examination of 'unidentified' Prevotella (formerly PINLO) using RAPD-PCR and partial 16S rRNA gene sequencing.

Prevotella intermedia- and Prevotella nigrescens-like organisms (PINLO) have been described as organisms which are phenotypically and biochemically similar to P. intermedia and P. nigrescens and the species P. pallens was created to include some of them. Other PINLO groups which do not fit the definition of P. pallens exist, and in this study these 'unidentified' Prevotella sp. were compared with P. corporis, P. intermedia, P. nigrescens and P. pallens using commercial identification kits, GLC, RAPD-PCR and partial 16S rRNA gene sequencing. The Rapid ID 32 A and the RapID ANA II system both identified all 'unidentified' Prevotella as P. intermedia. Similarly they gave this identification to all the species tested (with the exception of P. corporis using the RapID ANA II system) clearly demonstrating biochemical similarities. Gas liquid chromatography (GLC) analysis of the volatile end-products of fermentation could not distinguish between strains. RAPD-PCR using arbitrary primer L10 demonstrated intra-species homogeneity within PINLO strains with amplification profiles which differed from other Prevotella species tested. Cluster analysis of the amplification profiles confirmed species divisions and yielded a distinct 'unidentified' Prevotella cluster. Comparison of partial 16S rDNA sequences displayed 98% sequence similarity between the 'unidentified' Prevotella strains, although 2 strains, HST 1156 and HST 2160 displayed 100% identity. The highest similarity between groups was seen between 'unidentified' Prevotella strains and P. corporis (approximately 94% similarity). The DNA techniques used here confirm that 'unidentified' Prevotella strains are distinct from the other species of Prevotella tested, including P. pallens. Partial 16S rDNA sequence comparisons suggested a close relationship with P. corporis.

Journal Article↗

PubMed2000

Restorative treatment provided over five years for adults regularly attending general dental practice.

OBJECTIVES: To investigate the distribution and type of restorative treatment, including re-treatment, provided for adults who attend annually. METHODS: In 1991 a selected group of 24 general dental practitioners in the North West of England recruited 4211 of their regularly attending adult patients. Dentists recorded the reason for and type of treatment provided during the following 5 years. RESULTS: Approximately 40% of the participants received treatment (restorations and/ or extractions) at each annual examination. Of the 2293 patients who attended every examination 1959 (85%) had received a restoration and/ or extraction during the 5 years. A total of 8187 teeth, 15% of those present at baseline, received treatment, 3030 (37%) for caries and 5157 (63%) for other reasons. The proportion of adults who received treatment by age group differed significantly with those aged 25-34 years (80%) being least likely and those 35-44 years of age (89%) most likely. Of the 1744 teeth restored in the first year of the study, 170 (10%) were retreated within 1 year and 402 (23%) during the subsequent 4 years. The 4 year survival of amalgam and tooth coloured fillings was 84% and that of crowns 92%. CONCLUSIONS: This study documented the extent and type of restorative care provided for regularly attending adults during a 5-year period. The majority of treatment was provided for reasons other than caries. Of the teeth restored over the first year, 23% were retreated in the subsequent 4 years.

Adult↗

PubMed2000

Cryopreservation and image enhancement of juvenile and adult dentine mineral.

The inorganic component of bone and related hard tissues is generally described as sheets of uniform needle- and plate-like crystals. However, cryofixation has become the method of choice for ultrastructural studies of bone mineral when ladder-like arrangements of filaments contained within deformable microspheres about 1 microm in diameter are apparently the prime structural feature and are consistent with the optical image. The same methodology has now been applied to mature human dentine in caries-free juvenile and adult teeth. These were fixed, sliced, stained for mineral and examined optically or were snap frozen, fragmented under liquid nitrogen, freeze-substituted with methanol or acetone and embedded without thawing in Lowicryl K4M for electron microscopy. Others were processed by traditional transmission electron microscopy methods. To obtain maximum resolution, the electron micrographs were photographically printed as negatives and image-enhanced by digitisation using a Polaroid Sprint Scan 45 and laser printer. In both optical and cryopreparations of juvenile and adult dentine, mineral microspheres up to 1 microm in diameter, were present in the dentinal tubules and peritubular dentine. Within these objects, the mineral was primarily in the form of sinuous electron dense filaments, 5 nm thick, which had a characteristic periodicity. In these preparations needle-like and plate-like structures were rare. In contrast, after traditional transmission electron microscopy preparation although similar filamentous structures remained, the mineral more generally had the familiar form of needles measuring approximately 50 nm in the long axis. The cryopreserved calcified filaments were apparently particularly densely distributed in the intertubular dentine where their parallel ladder-like arrays often formed highly orientated struts and stays. It was concluded that early dentine mineral has the form of filamentous microspheres and as in bone (and other calcifying tissues and cells) has no specific association with collagen. It was also concluded that these structures compact and deform with maturity into a sub-structural framework which may relate to powerful biomechanical forces transmitted through the tissue. Needle- or plate-like mineral is probably rare in vivo in dentine, only becoming commonplace after extensive chemical processing.

Adolescent↗

PubMed1999

The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum.

Analysis of Plasmodium falciparum chromosome 3, and comparison with chromosome 2, highlights novel features of chromosome organization and gene structure. The sub-telomeric regions of chromosome 3 show a conserved order of features, including repetitive DNA sequences, members of multigene families involved in pathogenesis and antigenic variation, a number of conserved pseudogenes, and several genes of unknown function. A putative centromere has been identified that has a core region of about 2 kilobases with an extremely high (adenine + thymidine) composition and arrays of tandem repeats. We have predicted 215 protein-coding genes and two transfer RNA genes in the 1,060,106-base-pair chromosome sequence. The predicted protein-coding genes can be divided into three main classes: 52.6% are not spliced, 45.1% have a large exon with short additional 5' or 3' exons, and 2.3% have a multiple exon structure more typical of higher eukaryotes.

Animals↗

PubMed1999

Fluoride ingestion from toothpaste by young children.

OBJECTIVE: To investigate the reported and observed brushing habits of young children and their ingestion of fluoride from toothpaste. DESIGN: In 1997, a random sample of 50 children, aged 30 months, from three districts in the North West region of England, were visited at home. METHODS: The reported and observed toothbrushing behaviour was determined and the weight of toothpaste applied to the toothbrush was measured. The amount of fluoride retained in the mouth after brushing with either a 400 ppm F or 1,450 ppm F toothpaste was determined. RESULTS: All parents claimed that their children's teeth were being brushed with a fluoride toothpaste at least once daily. The mean amount of toothpaste applied on the brush was 0.36 g of which 0.27 g (72%) was retained in the mouth. The mean amount of fluoride ingested per brushing was 0.42 mg when using the 1,450 ppm F toothpaste and 0.10 mg when using the 400 ppm F toothpaste. Although most parents applied a small amount of toothpaste a small minority applied a large amount. If using the 400 ppm F toothpaste twice daily no children of average weight would have exceeded ingestion of 0.05 mgF/kg body weight whereas 14 average weight children would have exceeded this value if using the 1450 ppm F toothpaste. CONCLUSIONS: It is essential that parents of children aged less than 7 years apply a small (pea-sized) amount of fluoride toothpaste on the toothbrush and discourage swallowing.

Child↗

PubMed1999

An in-vitro evaluation of a dental subtraction radiography system using bone chips on dried human mandibles.

The aim of this in vitro study was to evaluate the ability of digital subtraction radiography to detect small differences in bone density between 2 dental images captured with the Digora radiographic imaging system. 5 dried human mandibles were held in a fixed position and cortical bone chips were superimposed on the alveolar bone between the 1st molar and 2nd premolar teeth. For each mandible, a reference image was obtained without bone chip placement. Subsequently, another image without a bone chip and a series of 10 images with bone chips ranging from 1.2 to 35.3 mg, were recorded. Each of the initial images of the 5 mandibles was then compared to the 11 subsequent images using digital subtraction radiography. The difference in density between the 2 images, at the site between the 1st molar and 2nd premolar, was calculated and represented as a volume equivalent of aluminium. Regression analysis demonstrated a close relationship between the weight of the bone chips and the aluminium equivalent density difference between the 2 radiographs (r2 = 0.96). Good results were obtained with the smaller bone chips that more closely resembled the dimensions of bone changes likely to be of clinical interest (1-8 mg). It is concluded that this subtraction radiography system is suitable for clinical investigations of localised small changes in alveolar bone and for the diagnosis and monitoring of destructive forms of periodontal diseases.

Absorptiometry, Photon↗

PubMed1999

A cluster randomized controlled trial testing the effectiveness of a school-based dental health education program for adolescents.

OBJECTIVES: This trial investigated the value of a school-based dental health education program in terms of changes in knowledge, reported behavior, and plaque scores. METHODS: A total of 2,678 pupils with a mean age of 12.1 years attending 28 schools participated in a school-based dental health education program. The study used a cluster randomized controlled study design. The health service administrators stipulated that all participants receive the intervention; to meet this requirement, a rolling program of two six-month periods was utilized. During the first six months, half the adolescents received the intervention program, the other half acting as controls. Throughout a further six-month period, all participants received the intervention program. This research design allowed comparisons between participants receiving the program for six and 12 months. At baseline, six, and 12 months, a random subsample of 40 children in each participating school had their plaque scores recorded and a questionnaire was used to record their knowledge of dental health and reported dental behavior. RESULTS: The analysis used the subjects clustered within the schools, which were the units of randomization. The intervention program produced statistically significant improvements (P < .001) in knowledge about periodontal disease and the frequency of sugar intake and dental caries in both assessment time periods. The reported frequency of brushing did not change, but the group who had received 12 months of the intervention were more likely (P < .05) to brush for over a minute. At six months the early intervention group had a statistically significant, 13 percent reduction in the mean proportion of sites with plaque compared with the late intervention group (P = .043). This difference was sustained at 12 months (P = .037). CONCLUSION: This cluster randomized control trial demonstrated that the intervention program resulted in an improvement in knowledge of dental disease and an increase in the reported duration of brushing. These improvements were accompanied by a significant improvement in oral hygiene and a reported reduction in gingival bleeding.

Adolescent↗

PubMed1998

Occlusal caries diagnosis: an in vitro histological validation of the Electronic Caries Monitor (ECM) and other methods.

OBJECTIVES: The aim of this in vitro study was to validate the use of the Electronic Caries Monitor (ECM) for the detection of enamel and dentinal caries on the occlusal surfaces of posterior teeth, and to compare it with visual examination, fibre-optic transillumination, conventional and digital bitewing radiography. METHODS: One-hundred and three extracted posterior permanent teeth with no apparent occlusal cavitation were selected and examined using each system. Thirty teeth were re-examined with each system to assess repeatability. Each tooth was then serially sectioned and examined histologically for occlusal caries. RESULTS: The occlusal surfaces of 25 teeth had caries in enamel and 37 had dentinal carious lesions. The sensitivity and specificity of the ECM were 0.78 and 0.80 for the diagnosis of occlusal dentinal lesions (cut-off = 0.391) and 0.65 and 0.73 for enamel lesions (cut-off = 0.501). The weighted kappa value for repeatability of the ECM was 0.68. Of the other diagnostic systems, visual examination provided the best combination of sensitivity and specificity, 0.24 and 0.97 for dentinal caries and 0.60 and 0.73 for enamel caries, respectively. CONCLUSION: The ECM was the most accurate diagnostic tool for the in vitro diagnosis of early, non-cavitated occlusal lesions on posterior teeth.

Bicuspid↗