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E Dickinson

Publications and source records attributed to E Dickinson.

At least 37 records · Page 2Linked to original sources

Delayed involution of the mammary epithelium in BALB/c-p53null mice.

In mammals, weaning of neonates and subsequent milk stasis initiates removal of the secretory epithelium of the mammary gland by apoptosis. The p53 tumor suppressor gene is induced rapidly following weaning of neonates, but its role in the process of involution has not been defined. Therefore, experiments were performed to identify the cell types in which the p53 gene is expressed during involution and determine the consequences of its absence in BALB/c-p53null mice. Both p53 mRNA and protein were detected in the mammary epithelium within 48 h following weaning and resulted in an eightfold increase in levels of p21WAF1 mRNA. Induction of p21WAF1 mRNA was absent in BALB/c-p53null mice, and therefore, was shown to be p53-dependent. The BALB/c-p53null mice exhibited delayed involution of the mammary epithelium, as measured by 60% greater epithelial area compared to BALB/c-p53(wt) mice through 5 days post-weaning. The delay was transient with no differences being apparent at 7 days post-weaning. Expression of the stromal protease stromelysin-1 was unaffected by the absence of p53 suggesting that stromal responses were intact. These data demonstrate that p53 participates in the first stage of involution initiated by the epithelium itself, but does not affect the second phase during which stromal proteases are induced.

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Rheology and Flocculation of Oil-in-Water Emulsions Made with Mixtures of alphas1-Casein + beta-Casein.

The influence of the composition of a mixed binary protein emulsifier composed of alphas1-casein + beta-casein on the rheology of concentrated oil-in-water emulsions (45 vol% oil, 5 wt% protein, pH 7) has been investigated over the temperature range 0-40 degreesC. Controlled stress viscometric data are reported over the shear stress range 0.1-30 Pa for systems with alphas1-casein/beta-casein ratios of 100:0, 98:2, 95:5, 90:10, 75:25, 50:50, and 0:100. The pure casein emulsions showed substantially different temperature-dependent rheology, and there was observed to be a pronounced maximum in the small-deformation complex modulus of the pure alphas1-casein emulsion in the range 30-40 degreesC. In the emulsions containing >/=90% alphas1-casein in the emulsifier mixture, all of the beta-casein present was found to be associated with the surface of the droplets. Average droplet sizes and protein surface coverages were higher in the mixed casein systems than in the equivalent pure casein systems. The strongly pseudoplastic character of the emulsions is consistent with extensive reversible flocculation caused probably by a depletion mechanism involving unadsorbed protein. The degree of flocculation is sensitive to temperature and to the alphas1-casein/beta-casein ratio. The results can be interpreted in terms of changes in protein self-assembly and adsorbed layer structure which influence the strength of the interdroplet interactions and hence the rheological behavior of the emulsions. There is some evidence of a specific role for alphas1-casein-beta-casein complexes in these systems. Copyright 1998 Academic Press.

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Viscoelastic Properties of Protein-Stabilized Emulsions: Effect of Protein-Surfactant Interactions.

Viscoelastic properties of whey protein isolate-stabilized emulsions have been investigated by determining storage and loss moduli of both fresh emulsions and heat-set emulsion gels. Gel strength increases with the increase of protein concentration in the system. The flocculated protein-covered oil droplets behave as active fillers and hence dramatically enhance the gel strength. The presence of water-soluble surfactant Tween 20 induces a dramatic reduction in emulsion gel strength, which is attributable to protein displacement from the oil-water interface. Oil droplets that are fully covered with Tween 20 do not adhere to protein gel matrix and do not contribute to gel strength. The presence of oil-soluble monopalmitin increases the viscous character of fresh emulsions and substantially reduces the modulus of heat-set emulsion gels. The viscoelastic properties of heat-set emulsion gels containing monopalmitin are only slightly frequency-dependent, and these gels can be classified as "strong gels".

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Influence of Protein Interfacial Composition on Salt Stability of Mixed Casein Emulsions.

The influence of casein surface composition on the stability toward flocculation by sodium chloride has been investigated for oil-in-water emulsions (20 vol % oil, 1 wt % total protein) prepared with a mixture of alpha(s1)-casein + beta-casein. It has been observed that the poor salt stability of emulsions containing 100% alpha(s1)-casein is greatly enhanced by the replacement of about one-third of the alpha(s1)-casein by beta-casein. With around half of the adsorbed protein layer consisting of beta-casein, emulsions remain stable at ionic strengths of 2 M NaCl in the presence or absence of calcium ions (5 mM). At the point of droplet flocculation in these emulsions, most of the casein present is associated with the surface of the droplets. These results provide definitive evidence for the important influence of the compositional balance in sodium caseinate on the colloidal stability behavior of casein-based emulsions.

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Influence of Alcohol on Stability of Oil-in-Water Emulsions Containing Sodium Caseinate

The effect of alcohol on the stability of oil-in-water emulsions of similar mean droplet size made with 4 wt% sodium caseinate and 35 vol% n-tetradecane was investigated. Controlled stress viscometry showed that, shortly after preparation, emulsions containing 25 vol% ethanol are of low viscosity and almost Newtonian in character. In contrast, emulsions containing little or no alcohol (</=10 vol%) exhibit psuedoplastic behavior with a much higher limiting low-stress viscosity. Time-dependent creaming profiles were determined at 30&deg;C using an ultrasound velocity scanning technique with a linear renormalization data analysis. The addition of alcohol was found to have relatively little effect on the long-term creaming stability, which was uniformly characteristic of a flocculated emulsion. The presence of alcohol leads to Ostwald ripening, as demonstrated by the gradual shift in monomodal droplet-size distribution during prolonged storage. Ostwald ripening is probably the main reason for the stepwise reduction in oil concentration in the serum phase of the stored alcohol-containing emulsions. Time-dependent rheology measurements of alcohol-rich emulsions showed an apparent shear viscosity increasing steadily over a matter of hours, suggesting that flocculation was not eliminated, but merely slowed, by the presence of the alcohol. It is proposed that the presence of alcohol modifies the average size and composition of the unadsorbed caseinate submicelles which are putatively responsible for the depletion flocculation. Reducing the mean diameter of droplets in alcohol-containing emulsions by prolonged homogenization was found to enhance the short-term emulsion creaming stability, but the long-term stability was essentially unaffected due to the predominant influence of Ostwald ripening. Copyright 1998 Academic Press. Copyright 1998Academic Press

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Clinical effectiveness for health care quality improvement.

This paper describes the work of the Research Unit of the Royal College of Physicians on clinical effectiveness and links with other national initiatives. The overall goal is to improve the quality of care by basing routine care on research evidence, an approach referred to as the 'bridge for health'. Systematic reviews bring together research evidence and are largely carried out by the Cochrane Collaboration, the NHS Centre for Reviews and Dissemination and the NHS Health Technology Assessment programme. Clinical guidelines, now produced according to a more rigorous methodology, are used to package research to support decisions about health care by clinicians, patients and others. Clinical audit, along with outcomes development, is carried out at a national level to support the implementation of clinical guidelines by clinical teams in local health services. To achieve this, it matches the best principles of quality improvement. Future identified trends in clinical effectiveness include a greater emphasis on better integration of effort and exchange of best practice.

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Rheology of Sodium Caseinate Stabilized Oil-in-Water Emulsions

We report on shear rheological measurements at 30&deg;C of fine oil-in-water emulsions (volume-surface average diameter < 0.5 &mgr;m) prepared at pH 6.8 with sodium caseinate as the sole emulsifier (1-6 wt%) and n -tetradecane as the dispersed phase (10, 35, or 45 vol%). Strong sensitivity of rheological behavior to total protein concentration was indicated by both steady-state viscometry and small-deformation oscillatory experiments. The behavior can be classified into three types, depending on the protein/oil ratio. (1) Emulsions containing insufficient protein for (near-) saturation protein surface coverage develop a time-dependent increase in low-stress apparent viscosity and associated shear-thinning behavior; this can be attributed to bridging flocculation. (2) Emulsions having full protein surface coverage but relatively little excess unadsorbed protein in the continuous phase are stable Newtonian liquids. (3) Emulsions containing a substantial excess of unadsorbed sodium caseinate exhibit considerable pseudoplasticity which can be attributed to depletion flocculation. Taken as a whole, the time-dependent rheological properties for this set of emulsions as a function of protein content and oil volume fraction are largely consistent with our previous results on the creaming stability and the particle gel microstructure for these same emulsion systems. In particular, the reversible flocculation of emulsion samples of high protein content is readily explicable in terms of depletion flocculation of droplets by unadsorbed protein existing in the form of approximately spherical caseinate submicelles.

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On the "Anomalous" Adsorption Behavior of Phosvitin

A statistical analysis based on the Scheutjens-Fleer theory can explain the "anomalous" adsorption behavior of the egg yolk protein phosvitin. The predicted adsorbed layer structure consists of a low surface coverage of looplike polyelectrolyte chains attached to the surface at the two ends.

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Modeling of Combined Creaming and Flocculation in Emulsions

A computer model is presented which simulates the simultaneous creaming and flocculation of emulsions. A cubic lattice model is used, with particles bonding together and breaking apart according to predefined probabilities. Creaming and diffusion are included, with different rates for different sizes of floc. Results are presented in the form of concentration profiles as a function of height, and as the variation of the pseudo-fractal dimension of the particle networks formed. In the numerical simulations, an increase in creaming rate was observed before a particle network formed which prevented further creaming. A sharp serum interface was seen. In the presence of bond breakage, creaming proceeded for a longer period and a more compact network was formed. These results explain some features observed experimentally in creaming and flocculating emulsions, but do not reproduce the rapid serum development seen in some cases.

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Creaming and Flocculation of Oil-in-Water Emulsions Containing Sodium Caseinate

The influence of protein content on the stability of concentrated oil-in-water emulsions (35 or 45 vol% oil, droplet diameter approximately 0.5 &mgr;m, pH 6.8) containing sodium caseinate as the sole emulsifying agent has been investigated. Time-dependent creaming profiles were determined at 30&deg;C using an ultrasound velocity scanning technique with data analysis based on a Urick equation renormalization technique. The results indicate that creaming kinetics has a complex dependence on caseinate content. At low protein content (1 wt%), corresponding to less than half that required for saturation monolayer coverage, the emulsion is destabilized by bridging flocculation (accompanied by some coalescence). At higher protein content (2 wt%), where individual droplets are fully protected against protein bridging or coalescence by the thick adsorbed protein layer, the unflocculated emulsion has good stability over a period of several weeks. With further increase of protein content (>/=3 wt%), the observed creaming stability is reduced again, with the rate of serum separation at the bottom of the sample now greatly increased. This is attributed here to depletion flocculation by unadsorbed caseinate, probably in the form of small particles called "casein submicelles." Light microscopy has confirmed that the visually observable extent of reversible depletion flocculation in concentrated emulsions of this type is very sensitive to overall protein content. Once the caseinate concentration reaches a high value (6 wt%), the strength of the depletion interaction is such that it produces a very strong emulsion droplet network which can reorganize only slowly, and is hence much more stable to creaming and serum separation.

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The Genome Sequence DataBase version 1.0 (GSDB): from low pass sequences to complete genomes.

The Genome Sequence DataBase (GSDB) has completed its conversion to an improved relational database. The new database, GSDB 1.0, is fully operational and publicly available. Data contributions, including both original sequence submissions and community annotation, are being accomplished through the use of a graphical client-server interface tool, the GSDB Annotator, and via GIO (GSDB Input/Output) files. Data retrieval services are being provided through a new Web Query Tool and direct SQL. All methods of data contribution and data retrieval fully support the new data types that have been incorporated into GSDB, including discontiguous sequences, multiple sequence alignments, and community annotation.

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Evaluation of specialists' outreach clinics in general practice in England: process and acceptability to patients, specialists, and general practitioners.

OBJECTIVES: The wider study aimed to evaluate specialists' outreach clinics in relation to their costs, processes, and effectiveness, including patients' and professionals' attitudes. The data on processes and attitudes are presented here. DESIGN: Self administered questionnaires were drawn up for patients, their general practitioners (GPs) and specialists, and managers in the practice. Information was sought from hospital trusts. The study formed a pilot phase prior to a wider evaluation. SETTING: Nine outreach clinics in general practices in England, each with a hospital outpatient department as a control clinic were studied. SUBJECTS: The specialties included were ear, nose, and throat surgery; rheumatology; and gynaecology. The subjects were the patients who attended either the outreach clinics or hospital outpatients clinics during the study period, the outreach patients' GPs, the outreach patients' and outpatients' specialists, the managers in the practices, and the NHS trusts which employed the specialists. MAIN OUTCOME MEASURES: Process items included waiting lists, waiting times in clinics, number of follow up visits, investigations and procedures performed, treatment, health status, patients' and specialists' travelling times, and patients' and doctors' attitudes to, and satisfaction with, the clinic. RESULTS: There was no difference in the health status of patients in relation to the clinic site (ie, outreach and hospital outpatients' clinics) at baseline, and all but one of the specialists said there were no differences in casemix between their outreach and outpatients' clinics. Patients preferred, and were more satisfied with, care in specialists' outreach clinics in general practice, in comparison with outpatients' clinics. The outreach clinics were rated as more convenient than outpatients' clinics in relation to journey times; those outreach patients in work lost less time away from work than outpatients' clinic patients due to the clinic attendance. Length of time on the waiting list was significantly reduced for gynaecology patients; waiting times in clinics were lower for outreach patients than outpatients across all specialties. In addition, outreach patients were more likely to be first rather than follow up attenders; rheumatology outreach patients were more likely than hospital outpatients to receive therapy. GPs' referrals to hospital outpatients' clinics were greatly reduced by the availability of outreach clinics. Both specialists and GPs saw the main advantages of outreach clinics in relation to the greater convenience and better access to care for patients. Few of the specialists and GPs in the outreach practices held formal training and education sessions in the outreach clinic, although over half of the GPs felt that their skills/expertise had broadened as a result of the outreach clinic. CONCLUSIONS: The processes of care (waiting times, patient satisfaction, convenience to patients, follow up attendances) were better in outreach than in outpatients' clinics. However, waiting lists were only significantly reduced for gynaecology patients, despite both GPs and consultants reporting reduced waiting lists for patients as one of the main advantages of outreach. Whether these improvements merit the increased cost to the specialists (in terms of their increased travelling times and time spent away from their hospital base) and whether the development of what is, in effect, two standards of care between practices with and without outreach can be stemmed and the standard of care raised in all practices (eg, by sharing outreach clinics between GPs in an area) remain the subject of debate. As the data were based on the pilot study, the results should be viewed with some caution, although statistical power was adequate for comparisons of sites if not specialties.

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Evidence based health care in old age psychiatry.

OBJECTIVE: The purpose of this article is to present the current status and future needs of old age psychiatry in relation to evidence-based health care. METHOD: The opportunities and difficulties of evidence-based medicine as applied to old age psychiatry are described. Depression is used as a specific example. The role of the Cochrane Collaboration and of clinical guidelines in dealing with these difficulties are discussed. RESULTS: There has been a tendency for drug studies to focus on younger age groups and to exclude patients with comorbidity or polypharmacy. Aspects of clinical management separate from drugs are given insufficient attention. The generalizability of current studies is a problem in old age psychiatry. CONCLUSIONS: Psychiatry is no less part of medicine than any other specialty. Increased attention to studies of effectiveness, as opposed to efficacy, is indicated. The Cochrane Collaboration is an international network which promotes and conducts systematic reviews of the effectiveness of health care. Systematic reviews can increase the generalizability of the current knowledge base and better define the needs for future research.

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