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Biomedical subjects

P Warren

Publications and source records attributed to P Warren.

At least 19 recordsLinked to original sources
PubMed2003

Demystified. Human endogenous retroviruses.

Human endogenous retroviruses (HERVs) are a family of viruses within our genome with similarities to present day exogenous retroviruses. HERVs have been inherited by successive generations and it is possible that some have conferred biological benefits. However, several HERVs have been implicated in certain cancers and autoimmune diseases. This article demystifies these retroviruses by providing an insight into HERVs, their means of classification, and a synopsis of HERVs implicated in cancer and autoimmunity. Furthermore, the biological roles of HERVs are explored.

Antibodies, Viral↗
PubMed2001

Identification of critical staphylococcal genes using conditional phenotypes generated by antisense RNA.

Comprehensive genomic analysis of the important human pathogen Staphylococcus aureus was achieved by a strategy involving antisense technology in a regulatable gene expression system. In addition to known essential genes, many genes of unknown or poorly defined biological function were identified. This methodology allowed gene function to be characterized in a comprehensive, defined set of conditionally growth-defective/lethal isogenic strains. Quantitative titration of the conditional growth effect was performed either in bacterial culture or in an animal model of infection. This genomic strategy offers an approach to the identification of staphylococcal gene products that could serve as targets for antibiotic discovery.

Animals↗
PubMed2001

In vitro targeted killing of prostate tumor cells by a synthetic amoebapore helix 3 peptide modified with two gamma-linked glutamate residues at the COOH terminus.

Prostate-specific membrane antigen (PSMA) is a trans-membrane protein specifically expressed in LNCaP cells, malignant human prostate tissues, and the surrounding neovasculature. PSMA is a unique exopeptidase with reactivity toward poly-gamma-glutamated folates. It can sequentially remove the poly-gamma-glutamyl termini. To target prostate tumor cells, a novel procytolytic peptide was designed with a backbone consisting of an amoebapore H3 domain modified by two gamma-linked glutamate residues at the epsilon-amino group of the COOH-terminal lysine residue. The strategy behind the design of this prolytic peptide was to inactivate the lytic amoebapore H3 peptide by replacing its functionally important COOH-terminal positive charge with negatively charged groups, which in turn might be selectively removed by the PSMA exopeptidase. This peptide exhibited little cytolytic activity toward PSMA-negative cells, such as PC-3 cells. On the other hand, this peptide exhibited strong cytolytic activity toward PSMA-positive LNCaP cells in a concentration-dependent manner. The carboxypeptidase inhibitor 4,4'-phosphonicobis (butane-1,3-dicarboxylic acid) can inhibit this activity. Moreover, this peptide also exhibited cytolytic activity toward PSMA cDNA-transfected PC-3 cells.

Amino Acid Sequence↗
PubMed2001

Identification, substrate specificity, and inhibition of the Streptococcus pneumoniae beta-ketoacyl-acyl carrier protein synthase III (FabH).

In the bacterial type II fatty acid synthase system, beta-ketoacyl-acyl carrier protein (ACP) synthase III (FabH) catalyzes the condensation of acetyl-CoA with malonyl-ACP. We have identified, expressed, and characterized the Streptococcus pneumoniae homologue of Escherichia coli FabH. S. pneumoniae FabH is approximately 41, 39, and 38% identical in amino acid sequence to Bacillus subtilis, E. coli, and Hemophilus influenzae FabH, respectively. The His-Asn-Cys catalytic triad present in other FabH molecules is conserved in S. pneumoniae FabH. The apparent K(m) values for acetyl-CoA and malonyl-ACP were determined to be 40.3 and 18.6 microm, respectively. Purified S. pneumoniae FabH preferentially utilized straight short-chain CoA primers. Similar to E. coli FabH, S. pneumoniae FabH was weakly inhibited by thiolactomycin. In contrast, inhibition of S. pneumoniae FabH by the newly developed compound SB418011 was very potent, with an IC(50) value of 0.016 microm. SB418011 also inhibited E. coli and H. influenzae FabH with IC(50) values of 1.2 and 0.59 microm, respectively. The availability of purified and characterized S. pneumoniae FabH will greatly aid in structural studies of this class of essential bacterial enzymes and facilitate the identification of small molecule inhibitors of type II fatty acid synthase with the potential to be novel and potent antibacterial agents active against pathogenic bacteria.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗
PubMed2000

Intonational disambiguation in sentence production and comprehension.

Speakers' prosodic marking of syntactic constituency is often measured in sentence reading tasks that lack realistic situational constraints on speaking. Results from such studies can be criticized because the pragmatic goals of readers differ dramatically from those of speakers in typical conversation. On the other hand, recordings of unscripted speech do not readily yield the carefully controlled contrasts required for many research purposes. Our research employs a cooperative game task, in which two speakers use utterances from a predetermined set to negotiate moves around gameboards. Results from a set of early versus late closure ambiguities suggest that speakers signal this syntactic difference with prosody even when the utterance context fully disambiguates the structure. Phonetic and phonological analyses show reliable prosodic disambiguation in speakers' productions; results of a comprehension task indicate that listeners can successfully use prosodic cues to categorize syntactically ambiguous fragments as portions of early or late closure utterances.

Humans↗
PubMed1999

An evaluation of video instruction for an electric toothbrush. Comparative single-brushing cross-over study.

Instructions on the use of electric toothbrushes are usually derived from the written and/or diagrammatic leaflets provided with the device or perhaps less often instruction from a professional. Videos are now widely used for information transfer and the direction of physical activities. The aim of this study was to determine whether video instruction in the use of an electric toothbrush could promote efficient use of the device. The 2-min video demonstrated the use of an oscillating, rotating electric toothbrush used by a hygienist for 15 s in each buccal and lingual quadrant. A voice-over directed the observer to follow the hygienist's movements. The study was planned as a 2-phase, single-examiner blind, randomised, cross-over study accepting there would be confounding of the 2nd period by carry-over from the 1st. A group of 24 healthy volunteers participated who had average oral hygiene and never used an electric toothbrush. 12 subjects received the video first (VN) and 12 subjects the instructional leaflet with the device (NV). Single brushings were performed after suspending tooth cleaning for 48 h. Plaque was scored before and after brushing. A 2-week washout period was permitted before the crossover. In period 1, plaque removal with the video was overall significantly greater than with written instructions. The effects for posterior teeth were greater than anterior and comparison between groups for posterior minus anterior differences were highly significant in favour of the VN group. In period 2, the effect of period was dominant with both groups achieving greater plaque removal in period 2 than period 1. Plaque removal by group VN remained considerably greater than group NV Despite the confounding influences of carry-over in this particular design of study, the results support the idea that video instruction for electric toothbrushes could be a simple and efficient way of improving plaque removal by these devices. The methodology needs to be verified in a home-use type of investigation.

Adult↗
PubMed1999

Conversion of plaque-area measurements to plaque index scores. An assessment of variation and discriminatory power.

Plaque areas recorded graphically or photographically provide a permanent record of plaque accumulations on teeth at a moment in time. As such, these records could be re-evaluated and converted into other index scores. The purpose of this study was to determine the reproducibility of scoring a plaque index from previously recorded plaque areas and to compare such scores with the original scores of the same index. A randomised blind, crossover study comparing 5 treatments for plaque inhibition scored by plaque area and index was chosen. 2 examiners, the original scorer PRH and another, NC, 2x scored the plaque area tooth charts according to the criteria of the plaque index system used in the original study. Standard deviations of the differences showed intra-examiner repeatability to be high particularly for the original examiner. Inter-examiner reproducibility for the original index scores was considered good but less than for intra-examiner repeatability. Correlation coefficients were complimentary to the differences analysis, being very high within examiners and less high for between examiners and original and rescored index. Separation between distributions of plaque area measurements for consecutive values of the index were particular good for scores 2 versus 3 and 3 versus 4 and less good for 1 versus 2 and 4 versus 5. Reanalysis of the study for treatment differences using rescored data revealed a similar level of significance as using the original data. Rescored index had similar discriminatory power for the study as plaque area and original plaque index when both were derived from the same buccal tooth surfaces. However, discriminatory power was less by comparison with original plaque index derived from the buccal surfaces of all teeth. It is concluded that plaque area provides a permanent record of plaque distribution which can be converted into index data at a later date. Such data collection could make possible comparisons between studies using different indices.

Cross-Over Studies↗
PubMed1999

Comparison of video and written instructions for plaque removal by an oscillating/rotating/reciprocating electric toothbrush.

A previous crossover study showed that a watch-and-follow instructional video improved plaque removal by an electric toothbrush compared to the use of the instructional leaflet. This study employed a parallel design to assess the value of an instructional video for plaque removal by a new model oscillating/rotating/reciprocating electric toothbrush. 2 groups of 26 dentate subjects with average oral hygiene, who had never used an electric toothbrush, participated in this single blind, randomised parallel group designed study. On day 1 of the study, subjects received a professional prophylaxis to remove all plaque. Oral hygiene measures were then suspended and subjects returned on day 3 when a prebrushing plaque score was recorded by plaque index and area. Subjects withdrew and either read the manufacturers instructional leaflet (group L) or observed the instructional video (group V). Groups L and V then performed toothbrushing with toothpaste for 2 minutes and with group V brushing in time with the instructional video. Post-brushing plaque indices and areas were then recorded. Whole mouth, lingual, upper, lower, anterior and posterior but not buccal % reductions in plaque index and area were significantly greater in group V compared to group L. % plaque removal was also significantly greater by area at mid and distal sites but not mesial sites. Whole-mouth plaque reductions were 10% greater in group V but reached >15% at lingual surfaces. Within group differences in plaque removal at paired sites e.g., buccal/lingual, remained similar, suggesting that further improvement could be achieved by modifying the video to devote more time to the difficult-to-clean areas. In conclusion, in the early period of learning the use of an electric toothbrush, plaque removal can be improved by using an instructional video. Such watch-and-follow video routines could be extended to other areas of oral hygiene practices.

Adult↗
PubMed1999

A review of 1019 consecutive cases of polycystic ovary syndrome demonstrated by ultrasound.

Analysis of a cohort of 1019 consecutive subjects with ultrasonically demonstrable polycystic ovary (PCO) syndrome demonstrated a significant relationship between biochemical parameters and clinical symptoms such as menstrual frequency and severity of hirsutism. One hundred and forty-four subjects presented with involuntary infertility and only eight cases had unexplained infertility apart from PCO.

Anthropometry↗
PubMed1998

A practice-based randomised controlled trial of the efficacy of an electric and a manual toothbrush on gingival health in patients with fixed orthodontic appliances.

OBJECTIVES: The aim of the present study was to evaluate the efficacy of an electric toothbrush with a specially designed orthodontic brush head compared with a manual toothbrush in controlling plaque and gingivitis in patients with fixed orthodontic appliances over an 8-week period in a dental practice setting. METHODS: This was a randomised controlled, single blind, stratified, parallel group trial conducted in two specialist orthodontic dental practices by a specialist orthodontist. Group 1 comprised 41 subjects who used the electric toothbrush and Group 2 consisted of 43 subjects who brushed with a manual toothbrush around the orthodontic appliance for a timed 2 minutes twice daily for 8 weeks. Plaque around the fixed appliance attachments was measured using an orthodontic modification to the Silness and Loe plaque index, while gingival condition was scored using the gingival index and Eastman interdental bleeding index. RESULTS: There was baseline balance for all clinical variables (p > 0.05). Both groups had significantly less plaque after 8 weeks than at baseline (p < 0.001) but the group using the electric brush also had significantly less interdental gingival bleeding, as determined by the Eastman interdental bleeding index both at week 4 (p < 0.001) and week 8 (p = 0.004). The majority of subjects (n = 54, 64.3%) preferred the electric toothbrush. CONCLUSIONS: In conclusion, the results from this study would suggest that use of an electric toothbrush with an orthodontic brush head may be of benefit in promoting gingival health in fixed orthodontic appliance patients; however, the long-term effects (over at least 6 months) need to be evaluated.

Adolescent↗
PubMed1998

Home use oral hygiene product trials; timing of the last brushing before scoring; an assessment of variation.

Home use studies to evaluate oral hygiene products often standardise the time lag between plaque scoring and the previous toothbrushing. Most protocols have favoured an evening before brushing regimen, but the rationale and even the validity of this approach has not been evaluated. In this study, a group of 30 adult subjects participated in a 4-period randomised single-blind crossover evaluation of within-subjects and between-subjects variation in plaque levels after two different brushing times. Thus, on 2 occasions, plaque was scored after an "evening before" brushing and on the other 2 occasions plaque was scored after a "morning before" brushing. As expected, mean plaque levels were lower after morning brushing, but only by 11%. There was little difference for lingual plaque (4%) but a greater difference for buccal plaque (18%). Comparisons for within-subjects variation, which ideally should be low, favoured morning brushing but differences were small and not significant. Comparisons for between subjects variation, which ideally should be high to permit discrimination between high and low plaque formers, also favoured morning brushing but were only significant for lingual plaque. Intraclass correlation coefficients of reliability revealed that overall repeatability was high for both morning and evening regimens; marginally favouring morning brushing. Analyses using all four scores per subject disregarding timing of brushing increased within subjects variation and decreased repeatability, particularly for buccal plaque. In conclusion, the data support the concept of standardising the time between plaque scoring and the previous tooth-brushing. There were no clear statistically significant grounds for preferring one brushing regimen to the other, however the data favoured the morning brushing.

Adult↗