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S Boulton

Publications and source records attributed to S Boulton.

12 recordsLinked to original sources
PubMed2004

The facilitating factors and barriers influencing change in dental practice in a sample of English general dental practitioners.

AIM: The objective of this study was to investigate the barriers and facilitators to change in dental practices among a sample of general dental practitioners (GDPs) from three regions of England. METHOD: In-depth face-to-face interviews with 60 GDPs were undertaken. The sample was selected from a group of 317 GDPs who had completed a questionnaire in the first phase of this study. The participants were selected to reflect diversity regarding the number and extent of self-reported changes reported in the questionnaire, and personal and practice characteristics. Of the 92 attempted contacts, 60 (65%) of the interviews were successfully completed. The interview schedule formed the basis of the interview. All the interviews and notes were transferred on to NUD*IST QSR version 4, a qualitative analysis package. RESULTS: No single factor was identified as being more important than another in facilitating change. The main facilitators for change were: financial factors, regular patient attendance, particularly a core patient group, staff loyalty, having regular staff meetings and open communication and having access to peer support. The main barriers to change were the reverse of the facilitators plus not having a financial stakehold in the practice. CONCLUSIONS: A range of factors were identified as influencing change in general dental practice. These include GDPs' attitudes and experience of change, patient factors, organisational issues, contact with peers and access to appropriate training courses.

Adult↗
PubMed2004

The prevalence and nature of recent self-reported changes in general dental practice in a sample of English general dental practitioners.

OBJECTIVE: To determine the extent and types of change in seven domains of dental practice in a sample of English general dental practitioners (GDPs). METHODS: A postal questionnaire was sent to 561 GDPs on the dental lists of three health authorities in diverse regions of England. Information collected included demographic details on personal and practice characteristics, self-rating of amount of change in the seven domains of practice and factors influencing change. RESULTS: The response rate was 60%. Fifty-six per cent of the sample were under 40 years old. Over a third of respondents reported "changing a lot or completely" certain clinical activities, practice management arrangements and practice amenities. The highest self-reported level of change was in clinical activities. Of the GDPs who reported changing their clinical activities, 56% reported an increase in preventive care, followed by crown and bridge (44%), periodontics (44%) and endodontics (43%). Practice management rated second in the mean rank scores for self-reported change. The main changes reported were the introduction of computer systems and employment of practice managers. A sizeable percentage (66%) reported increasing the amount of information they provided to patients and the time spent discussing care. Quality assurance activities were the area of practice least likely to have changed over a 5-year period. Over half the sample reported not being involved in any quality assurance activities in the previous 5 years. Those respondents who were younger, had a postgraduate qualification and earned more than 20% of their income from private practice reported higher levels of change. CONCLUSIONS: General dental practitioners' work patterns are dynamic and appear to be responding to changing needs and demands on their service. The main changes were in the types of clinical procedures being carried out. The low prevalence of changes reported in auditing and peer review activities needs to be investigated further.

Adult↗
PubMed2004

A dynamic clinical dental relational database.

The traditional approach to relational database design is based on the logical organization of data into a number of related normalized tables. One assumption is that the nature and structure of the data is known at the design stage. In the case of designing a relational database to store historical dental epidemiological data from individual clinical surveys, the structure of the data is not known until the data is presented for inclusion into the database. This paper addresses the issues concerned with the theoretical design of a clinical dynamic database capable of adapting the internal table structure to accommodate clinical survey data, and presents a prototype database application capable of processing, displaying, and querying the dental data.

Database Management Systems↗
PubMed2001

The C. elegans homolog of the p53 tumor suppressor is required for DNA damage-induced apoptosis.

In mammals, one of the key regulators necessary for responding to genotoxic stress is the p53 transcription factor. p53 is the single most commonly mutated tumor suppressor gene in human cancers. Here we report the identification of a C. elegans homolog of mammalian p53. Using RNAi and DNA cosuppression technology, we show that C. elegans p53 (cep-1) is required for DNA damage-induced apoptosis in the C. elegans germline. However,cep-1 RNAi does not affect programmed cell death occurring during worm development and physiological (radiation-independent) germ cell death. The DNA binding domain of CEP-1 is related to vertebrate p53 members and possesses the conserved residues most frequently mutated in human tumors. Consistent with this, CEP-1 acts as a transcription factor and is able to activate a transcriptional reporter containing consensus human p53 binding sites. Our data support the notion that p53-mediated transcriptional regulation is part of an ancestral pathway mediating DNA damage-induced apoptosis and reveals C. elegans as a genetically tractable model organism for studying the p53 apoptotic pathway.

Amino Acid Sequence↗
PubMed2001

A protein-protein interaction map of the Caenorhabditis elegans 26S proteasome.

The ubiquitin-proteasome proteolytic pathway is pivotal in most biological processes. Despite a great level of information available for the eukaryotic 26S proteasome-the protease responsible for the degradation of ubiquitylated proteins-several structural and functional questions remain unanswered. To gain more insight into the assembly and function of the metazoan 26S proteasome, a two-hybrid-based protein interaction map was generated using 30 Caenorhabditis elegans proteasome subunits. The results recapitulate interactions reported for other organisms and reveal new potential interactions both within the 19S regulatory complex and between the 19S and 20S subcomplexes. Moreover, novel potential proteasome interactors were identified, including an E3 ubiquitin ligase, transcription factors, chaperone proteins and other proteins not yet functionally annotated. By providing a wealth of novel biological hypotheses, this interaction map constitutes a framework for further analysis of the ubiquitin-proteasome pathway in a multicellular organism amenable to both classical genetics and functional genomics.

Animals↗
PubMed2000

Mechanisms of enhancement of cytotoxicity in etoposide and ionising radiation-treated cells by the protein kinase inhibitor wortmannin.

We have investigated the effects of the protein kinase inhibitor wortmannin (WM) on the cytotoxic mechanisms of etoposide and ionising radiation (IR) in the Chinese hamster ovary K1 (CHO-K1) cell line, and its radiation-sensitive derivative, xrs-6, which is defective in DNA-dependent protein kinase (DNA-PK) function. WM potentiated the cytotoxicity of etoposide and IR in CHO-K1 cells approximately 1.6 and 3-fold, respectively, and this potentiation was abolished in xrs-6 cells, which were themselves more sensitive to etoposide and IR alone. WM partially inhibited the repair of etoposide-induced DNA double-strand breaks. Etoposide treatment caused a biphasic inhibition of DNA synthesis in both cell lines, and this was abrogated by co-incubation with WM. These data suggest that WM inhibits in intact cells both DNA-PK and either or both the ataxia telangiectasia (AT) and AT-related gene products ATM and ATR.

Androstadienes↗
PubMed1999

Interactive effects of inhibitors of poly(ADP-ribose) polymerase and DNA-dependent protein kinase on cellular responses to DNA damage.

DNA-dependent protein kinase (DNA-PK) and poly(ADP-ribose) polymerase (PARP) are activated by DNA strand breaks and participate in DNA repair. We investigated the interactive effects of inhibitors of these enzymes [wortmannin (WM), which inhibits DNA-PK, and 8-hydroxy-2-methylquinazolin-4-one (NU1025), a PARP inhibitor] on cell survival and DNA double-strand break (DSB) and single-strand break (SSB) rejoining in Chinese hamster ovary-K1 cells following exposure to ionizing radiation (IR) or temozolomide. WM (20 microM) or NU1025 (300 microM) potentiated the cytotoxicity of IR with dose enhancement factors at 10% survival (DEF10) values of 4.5 +/- 0.6 and 1.7 +/- 0.2, respectively. When used in combination, a DEF10 of 7.8 +/- 1.5 was obtained. WM or NU1025 potentiated the cytotoxicity of temozolomide, and an additive effect on the DEF10 value was obtained with the combined inhibitors. Using the same inhibitor concentrations, their single and combined effects on DSB and SSB levels following IR were assessed by neutral and alkaline elution. Cells exposed to IR were post-incubated for 30 min to allow repair to occur. WM or NU1025 increased net DSB levels relative to IR alone (DSB levels of 1.29 +/- 0.04 and 1.20 +/- 0.05, respectively, compared with 1.01 +/- 0.03 for IR alone) and the combination had an additive effect. WM had no effect on SSB levels, either alone or in combination with NU1025. SSB levels were increased to 1.27 +/- 0.05 with NU1025 compared with IR alone, 1.02 +/- 0.04. The dose-dependent effects of the inhibitors on DSB levels showed that they were near maximal by 20 microM WM and 300 microM NU1025. DSB repair kinetics were studied. Both inhibitors increased net DSB levels over a 3 h time period; when they were combined, net DSB levels at 3 h were identical to DSB levels immediately post-IR. The combined use of DNA repair inhibitors may have therapeutic potential.

Androstadienes↗
PubMed1997

Low nicotinamide mononucleotide adenylyltransferase activity in a tiazofurin-resistant cell line: effects on NAD metabolism and DNA repair.

Poly(ADP-ribose) polymerase (PADPRP), which uses NAD to synthesize ADP-ribose polymers, is activated by DNA strand breaks and mediates cellular responses to DNA damage. The consequences of low cellular NAD levels in a cell line deficient in nicotinamide mononucleotide adenylyltransferase (NMNAT), an enzyme essential for NAD biosynthesis, were investigated by assessing NAD metabolism and DNA repair after treatment with alkylating agents. A tiazofurin-resistant L1210 cell line (TZR) was isolated. NAD levels were approximately 5933 and 3375 pmol mg(-1) protein for parental (wild type, WT) and TZR cells respectively, and NMNAT levels were reduced by > 95%. TZR cells were more sensitive to temozolomide (TM) and 1-methyl-3-nitro-1-nitroso-guanidine (MNNG), particularly at concentrations that caused > 50% NAD depletion. TM and MNNG treatment decreased NAD levels in both cell lines, but took longer to return to control levels in TZR cells. For example, MNNG (5 microM), depleted NAD levels at 6 h to approximately 4512 (WT) and 1442 (TZR) pmol mg(-1) protein; however, NAD levels had returned to control levels by 8 h in WT cells, but were not restored by 16 h in TZR cells. Both cell lines were equisensitive to the growth-inhibitory effects of NU1025 per se (IC50 370 microM). Co-exposure of the cell lines to TM (100 microM) with increasing concentrations of NU1025 led to a synergistic enhancement of cytotoxicity, with IC50 values for NU1025 decreasing to 17 +/- 4 microM (TZR) and 37 +/- 6 microM (WT). A similar enhanced sensitivity to NU1025 (approximately 2.7-fold) was obtained when TZR cells were co-exposed to MNNG + NU1025. TM-induced DNA strand breaks were increased by co-incubation with NU1025, and again the TZR cell line showed increased sensitivity to NU1025. There were no significant changes in NMNAT activity in response to MNNG treatment over 24 h, either in the presence or in the absence of NU1025. These data demonstrate that modest decreases in cellular NAD levels can sensitize cells to alkylating agents and PADPRP inhibitors.

Animals↗
PubMed1996

Wortmannin is a potent inhibitor of DNA double strand break but not single strand break repair in Chinese hamster ovary cells.

Wortmannin, an inhibitor of p110 PI 3-kinase, also inhibits DNA-dependent protein kinase, which is known to mediate DNA double strand break repair. It was recently demonstrated that wortmannin sensitized cells to ionizing radiation (IR) (Price and Youmell, Cancer Res., 56, 246-250, 1996). Wortmannin was used to determine if the potentiation of IR-induced cytotoxicity in Chinese hamster ovary cells could be accounted for by an inhibition of DNA double strand break (DSB) repair. Wortmannin, at concentrations which were non-toxic per se (5 and 20 microM), increased IR cytotoxicity with dose enhancement factors at 10% survival of 2.7+/-0.28 (5 microM) and 5.3+/-0.86 (20 microM). The effects of wortmannin on DSB levels were assessed by neutral elution. The effects of wortmannin on the kinetics of DSB repair were evaluated over a 3 h time course. Wortmannin (50 microM) completely inhibited DSB repair over this period, without having any effect on DSB levels itself. The concentration-dependent effects of wortmannin on DSB levels showed that inhibition of DSB repair was significant at 1 microM, and near-maximal at 20 microM. In marked contrast, it exerted no effect on the kinetics of single strand break (SSB) repair as assessed by alkaline elution, even at concentrations as high as 50 microM. There was an excellent correlation between the concentration-dependence and exposure time of wortmannin required to enhance IR cytotoxicity and inhibit DSB repair. These data implicate inhibition of DNA-dependent protein kinase, and the consequent inhibition of DSB repair, as the mechanism whereby wortmannin potentiates the cytotoxicity of IR.

Androstadienes↗
PubMed1995

Putting Yiamouyiannis into perspective.

Few names crop up so often in the context of water fluoridation as that of John Yiamouyiannis, an American who has campaigned hard to stop this public health measure not only in the United States but in other countries such as Britain. During 1993, Yiamouyiannis was given considerable air time by the BBC, appearing on its prestigious You and yours and Nature programmes where he denigrated the efforts of local health authorities to reduce tooth decay by means of fluoridating their water supplies. His dramatic claims about fluoridation--in particular, that it increases people's risk of dying of cancer--must understandably alarm those who take them at face value. So just who is John Yiamouyiannis? And do his allegations hold up? This review of his career is based on publicly documented records and statements.

Fluoridation↗
PubMed1995

Potentiation of temozolomide-induced cytotoxicity: a comparative study of the biological effects of poly(ADP-ribose) polymerase inhibitors.

Four poly(ADP-ribose) polymerase (PADPRP) inhibitors [3-aminobenzamide, benzamide, 3,4-dihydro-5-methoxyisoquinolin-1(2H)-one (PD 128763) and 8-hydroxy-2-methylquinazolin-4(3H)-one (NU1025)] were compared with respect to their effects on a number of biological end points. The following parameters were assessed: their ability to inhibit the enzyme in permeabilised L1210 cells; their ability to potentiate the cytotoxicity of temozolomide (including the cytotoxicity of the compounds per se); their ability to increase net levels of temozolomide-induced DNA strand breaks and inhibit temozolomide-induced NAD depletion. PD 128763 and NU1025 were equipotent as PADPRP inhibitors, and 40- and 50-fold more potent than benzamide and 3-aminobenzamide respectively. All the compounds acted in a concentration-dependent manner to potentiate the cytotoxicity and increase DNA strand break levels in cells treated with temozolomide. There was an excellent correlation between the potency of the compounds as PADPRP inhibitors and their effects on cell survival and DNA repair. Temozolomide treatment caused a decrease in cellular NAD levels, and this was abolished by the PADPRP inhibitors. In conclusion, the new generation of PADPRP inhibitors are at least 50-fold more effective than 3-aminobenzamide as chemopotentiators, and can be used at micromolar rather than millimolar concentrations in intact cells.

Animals↗