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Biomedical subjects

J Knowles

Publications and source records attributed to J Knowles.

At least 19 recordsLinked to original sources
PubMed2007

Mechanisms of endothelin 1-stimulated proliferation in colorectal cancer cell lines.

BACKGROUND: The peptide endothelin (ET) 1 promotes proliferation in a number of epithelial cancers. The aim of this study was to identify the mechanism of ET-1-stimulated proliferation in colorectal cancer cells in vitro. METHODS: The effects of ET-1 on colorectal cancer cell lines HT29, LIM1215 and SW620 were studied. Cells were cultured with ET-1 plus antagonists/inhibitors to ET(A) or ET(B) receptors, G protein subtypes, phosphoinositide 3-kinase (PI3K) or protein kinase C (PKC). DNA replication and apoptosis were investigated by 5-bromo-2'-deoxyuridine incorporation and Annexin V staining. Transactivation of the epidermal growth factor (EGF) receptor was investigated by blockade of the receptor in the presence of ET-1, measurement of levels of phosphorylated EGF receptor in the presence of ET-1, and comparing the effects of ET-1 and EGF on cell proliferation. RESULTS: ET-1 significantly stimulated growth of all cell lines via ET(A) receptors. ET-1 stimulated DNA replication, not apoptosis. ET-1-stimulated growth was inhibited by antagonism of pertussis toxin-sensitive G proteins, PI3K and PKC. Inhibition of the EGF receptor reduced the effect of ET-1. ET-1 increased levels of phosphorylated EGF receptor via the ET(A) receptor. CONCLUSION: ET-1 increased DNA replication in colorectal cancer cells via the ET(A) receptor. This mitogenic action was mediated via pertussis toxin-sensitive G proteins, PI3K, PKC and transactivation of the EGF receptor.

Analysis of Variance↗
PubMed2006

Ant-based clustering and topographic mapping.

Ant-based clustering and sorting is a nature-inspired heuristic first introduced as a model for explaining two types of emergent behavior observed in real ant colonies. More recently, it has been applied in a data-mining context to perform both clustering and topographic mapping. Early work demonstrated some promising characteristics of the heuristic but did not extend to a rigorous investigation of its capabilities. We describe an improved version, called ATTA, incorporating adaptive, heterogeneous ants, a time-dependent transporting activity, and a method (for clustering applications) that transforms the spatial embedding produced by the algorithm into an explicit partitioning. ATTA is then subjected to the most rigorous experimental evaluation of an ant-based clustering and sorting algorithm undertaken to date: we compare its performance with standard techniques for clustering and topographic mapping using a set of analytical evaluation functions and a range of synthetic and real data collections. Our results demonstrate the ability of ant-based clustering and sorting to automatically identify the number of clusters inherent in a data collection, and to produce high quality solutions; indeed, we show that it is particularly robust for clusters of differing sizes and for overlapping clusters. The results obtained for topographic mapping are, however, disappointing. We provide evidence that the solutions generated by the ant algorithm are barely topology-preserving, and we explain in detail why results have--in spite of this--been misinterpreted (much more positively) in previous research.

Algorithms↗
PubMed2005

Adolescents' and their parents' views on the acceptability and design of a new diabetes education programme: a focus group analysis.

BACKGROUND: The present study was conducted as part of an ongoing project to develop an innovative educational intervention for young people with type 1 diabetes. We aimed to seek the views of children and adolescents with type 1 diabetes and their parents regarding (i) the acceptability of the new programme and (ii) practical aspects regarding course design and delivery. METHODS: Twenty-four children and 29 parents attended one of eight separate focus groups. Semi-structured interview schedules were developed around two main areas of discussion: views on the education programme; and views on the design and delivery of current and future education. Discussions were tape-recorded and transcribed, before undergoing systematic qualitative analysis. RESULTS: Participants agreed that the proposed intervention was feasible, and were enthusiastic that it could improve quality of life and 'normality'. Potential problems included self-management during school-time and parental anxiety. In terms of course design/delivery, participants emphasized the need to maximize enjoyment on the course (e.g. integrating fun and practical sessions, holding parts of the course outside of the clinic setting), and encourage effective learning and adherence to the regimen (e.g. including separate parent education, and using IT-based reference material). CONCLUSIONS: The qualitative methodology proved an effective way of eliciting child and parent views and informing the development of the proposed intervention. These findings can now be incorporated into the development of the education programme.

Adolescent↗
PubMed2001

Public perceptions of child abuse and neglect in a midwestern urban community.

This study found that the majority of urban adults did not believe that any of the characteristics of children posed to them predisposed a child to abuse. In contrast, 40% of respondents claimed child abuse could not occur in a family like the one in which they grew up. The majority perceived only one characteristic, alcohol abuse, as a characteristic of child abusers. Few respondents (10%) believed that child abusers could not be helped, and 25% were not sure. Adults' perceptions of child abuse and abusers varied by sex, age, socioeconomic status, and whether the respondents had children. The data indicate that there are significant deficits in the respondents' knowledge of child abuse and neglect.

Adult↗
PubMed2001

Effect of exposing dentine to sodium hypochlorite and calcium hydroxide on its flexural strength and elastic modulus.

AIM: The aim of this study was to evaluate the effect of sodium hypochlorite (NaOCl) solutions (3%, 5%) and saturated calcium hydroxide (Ca(OH)2) solution, individually and consecutively, on the flexural strength and modulus of elasticity of standardized dentine bars. METHODOLOGY: Standardized plano-parallel dentine bars (n = 121) were divided into five test groups and one control group. The control group 1 consisted of dentine bars, stored in normal saline until testing. The dentine bars in the five test groups were treated by exposure to the following solutions; group 2--3% NaOCl, 2 h; group 3--5% NaOCl, 2 h; group 4--saturated Ca(OH)2 solution, 1 week; group 5--3% NaOCl, 2 h and then saturated Ca(OH)2 solution 1 week; group 6--5% NaOCl, 2 h and then saturated Ca(OH)2 solution 1 week. The dentine bars were then loaded to failure in a three-point bend test. RESULTS: The data revealed a significant (P < 0.001) decrease in the modulus of elasticity and flexural strength of the dentine bars treated with 3% and 5% NaOCl. There was no significant difference in the flexural strength and the modulus of elasticity between the 3% and 5% NaOCl groups. Exposure to Ca(OH)2 significantly (P < 0.001) reduced the flexural strength but had no significant effect on the modulus of elasticity. The groups treated with sodium hypochlorite followed by calcium hydroxide did not have moduli of elasticity and flexural strengths that were significantly different from those treated only with sodium hypochlorite. CONCLUSIONS: NaOCl (3 & 5%) reduced the modulus of elasticity and flexural strength of dentine. Saturated Ca(OH)2 reduced the flexural strength of dentine but not the modulus of elasticity. Sequential use of NaOCl and Ca(OH)2 has no additional weakening effect.

Calcium Hydroxide↗
PubMed2001

An overview of tritium behaviour in the Severn Estuary (UK).

Measurements of tritium (3H) activity in marine species in the Severn Estuary (UK) show concentrations significantly above those predicted by standard models. Concentration factors of 10(4) between seawater and marine species are observed; standard models assume a concentration factor of 1. In addition, the vast majority of activity is present in the form of organically bound tritium (OBT). The critical group dose from tritium--to consumers of local flounder--is estimated as approximately 36 microSv per annum. The measurements are related to the authorised release of wastes, via the sewer system, from the Amersham plc plant at Cardiff. The radiochemical plant manufactures a wide range of isotopically labelled compounds for use in life science research. The elevated levels of tritium observed in marine species have led to a programme of investigative work by specialist organisations. This paper describes the various definitions, measurements and significance of the term OBT. It also outlines the environmental observations and preliminary conclusions from the investigative programme to date.

Animals↗
PubMed2001

Efficacy of chitosan, carvacrol, and a hydrogen peroxide-based biocide against foodborne microorganisms in suspension and adhered to stainless steel.

The ability of natural compounds to inactivate foodborne organisms adhered to surfaces was investigated with the ultimate aim of replacing synthetic biocides by more environmentally friendly, natural alternatives. The antimicrobial efficacy of 0.5, 1.0, and 2.0% chitosan and Spor-Klenz RTU (a commercial biocide based on hydrogen peroxide and peroxyacetic acid) and 0.5, 1.25, and 2.0 mM carvacrol was determined at 20 degrees C against Listeria monocytogenes, Salmonella enterica serovar Typhimurium, Staphylococcus aureus, and Saccharomyces cerevisiae adhered to stainless steel disks. Treatment with up to 2.0% chitosan reduced the viable cell count in the microbial films of the four test organisms by 2.4, 1.8, 2.3, and 0.9 log CFU/test surface (t.s.), respectively. By contrast, planktonic counts of the same organisms were reduced by 0.8 to 1.7 log CFU/ml at 2.0% chitosan. Treatment with 2 mM carvacrol reduced the viable counts of adhered listeriae, salmonellae, and yeasts by 2 to 3 log CFU/t.s. but S. aureus counts were reduced by only 0.9 log CFU/t.s. The efficacy of any single compound was species specific. In the case of microbial films prepared using listeriae and salmonellae, Spor-Klenz RTU was most biocidal, followed by carvacrol and then chitosan. However, dried films of S. aureus were most sensitive to chitosan and relatively resistant to carvacrol and Spor-Klenz RTU. By contrast, yeast films were most sensitive to carvacrol and least sensitive to chitosan. It was concluded that carvacrol and chitosan may have potential for use as natural biocides although optimization of conditions would be necessary.

Bacteria↗
PubMed2000

No association between a presenilin 1 polymorphism and Alzheimer disease.

BACKGROUND: Homozygosity of allele 1 of a presenilin 1 intron 8 polymorphism (PS1-1) has been associated with doubling of the risk of sporadic late-onset Alzheimer disease (LOAD), in some, but not all studies. OBJECTIVE: To genotype the PS1 intron 8 polymorphism in predominantly Hispanic families with LOAD to test for association and for linkage between this polymorphism and LOAD. DESIGN: A family-based, case-control, genetic-linkage study. SETTING: Predominantly Hispanic families were selected from probands who were part of a random sample of 2128 Medicare beneficiaries aged 65 years or older who were residing in the community of Washington Heights, which is located in the northern part of Manhattan, NY. PARTICIPANTS: Fifty-one families with 103 affected family members, 67 unaffected family members, and 7 family members with other diagnoses were genotyped for the PS1 polymorphism. All patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for either probable or possible Alzheimer disease. Age was truncated at 55 years or older. MAIN OUTCOME MEASURES: Association analyses, conditional logistic regression, and traditional linkage methods were applied to the families for the PS1 polymorphism and for the presence of the gene for apolipoprotein E (APOE). Results of the association and conditional logistic regression analyses of PS1 intron 8 polymorphism were subsequently adjusted for the effect of APOE-epsilon4, sex, age, and education of each sibling. RESULTS: No association between the PS1 intron 8 polymorphism and LOAD was observed (relative risk, 0.99; 95% confidence interval, 0.3-3.4). An association between presence of the APOE-epsilon4 allele and LOAD (relative risk 4.05; 95% confidence interval, 1.3-12.5) was observed. CONCLUSION: We could not confirm the relationship between the PS1 intron 8 polymorphism and LOAD in this collection of families.

Aged↗
PubMed2000

Behaviour in early treated phenylketonuria: a systematic review.

UNLABELLED: A search was made of the literature on behaviour in early treated phenylketonuria (PKU). Some 34 publications were selected for systematic review in order to answer the following questions: (1) does behaviour in early treated subjects with PKU differ from that in the general population?, (2) if so, do the differences show any consistent pattern?, matter in real life?, relate to intellectual status, phenylalanine (Phe) control or social factors? and (3) can behavioural problems be precipitated or reversed by changes in Phe control?. Eleven reports based on four studies of > 20 subjects provided the most useful data. There was good evidence of differences between subjects with PKU and their unaffected peers in behaviour and perception of self. The pattern of results was consistent across nations and age groups (higher scores on emotional/neurotic items and lower scores on anti-social/aggressive items) and suggested that subjects with PKU are more prone to depression, anxiety, phobic tendencies, isolation from their peers and a less "masculine" self image. Features of attention deficit hyperactivity disorder and associations between behaviour problems and both lower IQ and a worse quality of Phe control were well documented in several studies. CONCLUSION: The literature did not allow for definite conclusions on the cause of the behavioural problems but, taken together, the findings suggest that both the stressful dietary intervention and a degree of neurobiological impairment are likely to play a part.

Adolescent↗
PubMed2000

Continuous circadian measurements of ventilation in behaving adult rats.

Body temperature (Tb) and oxygen consumption (V(O(2))) are important determinants of ventilation (VE). While the circadian rhythms in Tb and V(O(2)) have been well described, the daily pattern of VE has not due to limitations in the available methods for measuring VE. Here we describe an adaptation of the barometric method using a chamber in which a large flow through very small restrictions was generated by the combined action of a positive pressure pump on the entrance and a negative pressure pump at the outlet. In this way the chamber effectively behaved as a closed system, despite having a high enough flow for long-term recording in freely moving, undisturbed small animals. This system was then used to test the hypothesis that VE oscillates with a circadian pattern similar to that of Tb(.) Measurements of tidal volume (VT) and breathing rate (f), in combination with Tb and activity by telemetry, were made in eight adult rats over 4-6 days under 12:12 light:dark conditions. Both VT, f, and thus VE, showed a circadian pattern similar to that of Tb and activity; that is, values were higher during the dark compared to the light phase. The differences in VE levels according to the time of the day suggest that mechanisms involved in the control of breathing may also have circadian patterns.

Animals↗
PubMed1999

Statistical mechanical simulation of polymeric DNA melting with MELTSIM.

MOTIVATION: MELTSIM is a windows-based statistical mechanical program for simulating melting curves of DNAs of known sequence and genomic dimensions under different conditions of ionic strength with great accuracy. The program is useful for mapping variations of base compositions of sequences, conducting studies of denaturation, establishing appropriate conditions for hybridization and renaturation, determinations of sequence complexity, and sequence divergence. RESULTS: Good agreement is achieved between experimental and calculated melting curves of plasmid, bacterial, yeast and human DNAs. Denaturation maps that accompany the calculated curves indicate non-coding regions have a significantly lower (G+C) composition than coding regions in all species examined. Curves of partially sequenced human DNA suggest the current database may be heavily biased with coding regions, and excluding large (A+T)-rich elements. AVAILABILITY: MELTSIM 1.0 is available at: //www.uml.edu/Dept/Chem/UMLBIC/Apps/MEL TSIM/MELTSIM-1.0-Win/meltsim. zip. Melting curve plots in this paper were made with GNUPLOT 3.5, available at: http://www.cs.dartmouth.edu/gnuplot_inf o.html Contact : blake@maine.maine.edu;

Base Composition↗
PubMed1998

Effect of heat treatment on pulsed laser deposited amorphous calcium phosphate coatings.

Amorphous calcium phosphate coatings were produced by pulsed laser deposition from targets of nonstoichiometric hydroxyapatite (Ca/P = 1.70) at a low substrate temperature of 300 degrees C. They were heated in air at different temperatures: 300, 450, 525 and 650 degrees C. Chemical and structural analyses of these coatings were performed using X-ray diffraction (XRD), FTIR, and SEM, XRD analysis of the as-deposited and heated coatings revealed that their crystallinity improved as heat treatment temperature increased. The main phase was apatitic, with some beta-tricalcium phosphate in the coatings heated at 525 and 600 degrees C. In the apatitic phase there was some carbonate substitution for phosphate and hydroxyl ions at 450 degrees C and almost solely for phosphate at 525 and 600 degrees C as identified by FTIR. This was accompanied by a higher hydroxyl content at 525 and 600 degrees C. At 450 degrees C a texture on the coating surface was observable by SEM that was attributable to a calcium hydroxide and calcite formation by XRD. These phases almost disappeared at 600 degrees C, probably due to a transformation into calcium oxide.

Calcium Phosphates↗