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Biomedical subjects

Richard Thomas

Publications and source records attributed to Richard Thomas.

At least 19 recordsLinked to original sources
PubMed2006

Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation.

The transcription factor Gata-3 is a defining marker of the 'luminal' subtypes of breast cancer. To gain insight into the role of Gata-3 in breast epithelial development and oncogenesis, we have explored its normal function within the mammary gland by conditionally deleting Gata-3 at different stages of development. We report that Gata-3 has essential roles in the morphogenesis of the mammary gland in both the embryo and adult. Through the discovery of a novel marker (beta3-integrin) of luminal progenitor cells and their purification, we demonstrate that Gata-3 deficiency leads to an expansion of luminal progenitors and a concomitant block in differentiation. Remarkably, introduction of Gata-3 into a stem cell-enriched population induced maturation along the alveolar luminal lineage. These studies provide evidence for the existence of an epithelial hierarchy within the mammary gland and establish Gata-3 as a critical regulator of luminal differentiation.

Animals↗
PubMed2006

Presenting risk information to people with diabetes: evaluating effects and preferences for different formats by a web-based randomised controlled trial.

OBJECTIVE: Web-based patient information is widespread and information on the benefits and risks of treatments is often difficult to understand. We therefore evaluated different risk presentation formats - numerical, graphical and others - addressing the pros and cons of tight control versus usual treatment approaches for diabetes. METHOD DESIGN: Randomised controlled trial. SETTING: Online. Publicity disseminated via Diabetes UK. PARTICIPANTS: People with diabetes or their carers. INTERVENTIONS: Control group information based on British Medical Journal 'Best Treatments'. Four intervention groups received enhanced information resources: (1) detailed numerical information (absolute/relative risk, numbers-needed-to-treat); (2) 'anchoring' to familiar risks or descriptions; (3) graphical (bar charts, thermometer scales, crowd figure formats); (4) combination of 1-3. OUTCOMES: Decision conflict scale (DCS, a measure of uncertainty); satisfaction with information; further free text responses for qualitative content analysis. RESULTS: Seven hundred and ten people visited the website and were randomised. Five hundred and eight completed the questionnaire for quantitative data. Mean DCS scores ranged from 2.12 to 2.24 for the five randomisation groups, indicating neither clear delay or vacillation about decisions (usually DCS>2.5) nor tending to make decisions (usually DCS<2.0). There were no statistically significant effects of the interventions on DCS, or satisfaction with information. Two hundred and fifty-six participants provided responses for qualitative analysis: most found graphical representations helpful, specifically bar chart formats; many found other graphic formats (thermometer style, crowd figures/smiley faces) and 'anchoring' information unhelpful, and indicated information overload. Many negative experiences with healthcare indicate a challenging context for effective information provision and decision support. CONCLUSION: Online evaluation of different risk representation formats was feasible. There was a lack of intervention effects on quantitative outcomes, perhaps reflecting already well-informed participants from the Diabetes UK patient organisation. The large qualitative dataset included many comments about what participants found helpful as formats for communicating risk information. PRACTICE IMPLICATIONS: These findings assist the design of online decision aids and the representation of risk information. The challenge is to provide more information, in appropriate and clear formats, but without risking information overload. Interactive web designs hold much promise to achieve this.

Audiovisual Aids↗
PubMed2006

The production of de novo folded proteins by a stepwise chain elongation: a model for prebiotic chemical evolution of macromolecular sequences.

We describe an experimental procedure to mimic the formation of long (over 40 residues) co-oligopetide sequences in many identical copies which may have occurred in the prebiotic molecular evolution. The basic hypothesis is that chain formation is based on the stepwise fragment condensation of randomly generated short oligopeptides, whereby the elongation takes place under the contingent environmental constraints (solubility, pH, salinity), which eliminate most of the products, and thus determine the selection towards one particular small set of chains. The present work aims at verifying the validity of this scheme. In order to do so, we utilize a classic synthetic procedure based on the Merrifield solid-phase synthesis of peptides for the synthesis of randomly produced peptides as well as for their stepwise fragment condensation. Thus, starting from a library of peptides with n=10, the first condensation step produces a library of 16 peptides with 20 residues each (n=20), of which only four remain water-soluble and, therefore, capable to undergo the next fragment condensation step. This gives rise to 16 peptides with n=30, out of which twelve precipitate out under the chosen pH and buffer conditions and are eliminated. Finally, a 44-residue-long water-soluble de novo protein is obtained. This has no homologies or similarities with extant proteins, and, based on circular dichroism (CD), it assumes a stable three-dimensional folding. In agreement with CD data, molecular-modelling simulations suggest an helical fold for the protein with poor, if any, structural homology with known proteins. The implication of this procedure as a general mechanism for the etiology of de novo macromolecular sequences and globular proteins in the origin of life is briefly discussed.

Amino Acid Sequence↗
PubMed2006

Attachment of Yersinia pestis to human respiratory cell lines is inhibited by certain oligosaccharides.

Pneumonic plague is an aggressive disease that is clinically difficult to treat. Inhibition of attachment using oligosaccharide receptor mimics may provide an alternative to antibiotics. The virulent Yersinia pestis strain GB was demonstrated to attach to the murine monocyte cell line (J774A.1) and a range of human respiratory epithelial cell lines: nasal (RPMI-2650), bronchial (BEAS2-B) and alveolar (A549). Attachment was greatest to the A549 and BEAS2-B cell lines. Pre-treatment of the cell lines with tunicamycin reduced attachment by 55-65 %, indicating the importance of cell-surface carbohydrates in adhesion. The cell lines displayed differences in the oligosaccharides that inhibited attachment. p-Nitrophenol was the best inhibitor for each cell line. Disaccharides such as GalNAcbeta1-3Gal and GalNAcbeta1-4Gal were also good inhibitors, particularly for the RPMI-2650 cell line. This demonstrates the potential of oligosaccharides as potential anti-adhesion therapeutics.

Animals↗
PubMed2005

The role of local and global processing in the recognition of living and nonliving things.

We report a study on a patient (DW) with integrative visual agnosia and a category-specific recognition impairment for living things. We assessed DW's local and global processing and tested if his integrative agnosia could have led directly to his category-specific impairment. The main findings were: (i) DW was faster at identifying local compared to global letters. (ii) DW showed no local-to-global (or global-to-local) interference effects in selective attention tasks. (iii) DW showed a congruency effect in a divided attention task, suggesting that, when his attention was cued to both levels, he could process information simultaneously and integrate local and global information. (iv) Controls were poorer at naming nonliving compared to living things when presented with silhouettes. These data suggest that local and global information are differentially weighted in the visual recognition of living and nonliving things, and that an impairment in processing the overall shape of an object can lead to a category-specific deficit for living things. Crucially, this implies that category-specific impairments do not necessarily reflect damage to the semantic system, and models of semantic memory based on this assumption need to be revised.

Agnosia↗
PubMed2005

Shared representations in body perception.

The ability to understand events that happen to other people is a characteristic feature of the human mind. Here, we investigate whether the links between mental representation of one's own body and the bodies of other people could form the basis of human social representations. We studied interpersonal body representation (IBR) in a series of behavioural cueing experiments. Subjects responded to tactile events on their own body after a visual event was presented in either the corresponding anatomical location on a model's body, or in a non-corresponding location. We found that reactions were faster when the visual cue was in register with the tactile stimulation. This effect was absent when identical visual events were presented on a non-body control stimulus, suggesting a body specific mechanism for interpersonal registration of purely sensory events. Similar interpersonal systems have been demonstrated previously for the coding of action and emotion, but we believe that our results provide the first behavioural evidence for interpersonal body representation at the purely sensory level. We show that a sensory processing mechanism specific for bodies is automatically activated when viewing another person. Interpersonal body representation may be an important precursor to empathy and theory of mind. In our social world, we understand the percepts of others by registering them against the representations used to perceive our own body, and this mechanism involves an interpersonal somatotopic map.

Adolescent↗
PubMed2005

Housing improvement and self-reported mental distress among council estate residents.

This paper is concerned with how housing improvements instigated either publicly or privately influence the degree of psychological stress reported by council estate residents in South Manchester. Stress is measured on the GHQ12 scale containing standard symptomatic items. Potential sources of variation in this indicator are analysed within a geographical setting where repeated samples of residents were drawn from two adjacent suburban council housing estates before and after the implementation of a single regeneration budget (SRB) housing initiative in late 1999. The residents of one of these estates (Wythenshawe) were targeted by this funding while those in the other (Mersey Bank) were not. The latter, therefore, serve as a control for the effects of the enhanced incidence of housing improvement activity promoted by this SRB. Regression analyses revealed that stress was raised significantly among the SRB residents perhaps on account of the additional environmental nuisance they encountered. The experience of stress among all residents, however, was dominated by measures of personal psychosocial risk and it is argued that future regeneration initiatives should address the manifestation of these risks in the effort to achieve better mental health.

Adult↗
PubMed2005

HIV health care access issues for women living with HIV, mental illness, and substance abuse.

Nurses at the Well-Being Institute, a community-based nursing outreach clinic in Detroit, Michigan, located 75 women living with HIV, mental illness, and substance abuse who were lost to follow-up at their HIV medical clinic as part of a nursing research study. Women who had been scheduled for an appointment in the last 4 months but who had missed that appointment were considered "lost to follow-up" in the HIV clinic. The purpose of the research was to study factors related to health care access in women not participating in regular health care for their HIV infection. Women were randomly assigned to two study groups. Women assigned to "care as usual" study group (n = 37) received no additional services beyond study interviews for 1 year. Women assigned to the "nursing intervention" group (n = 38) were provided with nursing services designed to facilitate their return to and continued connection with their HIV clinic. Findings showed that factors related to the women's vulnerability, such as mental illness and drug use, were more related to their use of expensive health care services such as hospital emergency departments or hospital inpatient admissions than was assignment to either the "nursing intervention" or "care as usual" study groups. Two case studies describing the cost of care for 2 of the multiply diagnosed women in the study is presented. The women differed on whether they had stable housing and were accessing care for their mental illness.

Adolescent↗
PubMed2005

A type IV pilin, PilA, Contributes To Adherence of Burkholderia pseudomallei and virulence in vivo.

The Burkholderia pseudomallei K96243 genome contains multiple type IV pilin-associated loci, including one encoding a putative pilus structural protein (pilA). A pilA deletion mutant has reduced adherence to human epithelial cells and is less virulent in the nematode model of virulence and the murine model of melioidosis, suggesting a role for type IV pili in B. pseudomallei virulence.

Animals↗
PubMed2004

Extraordinary branching ratios in astrophysically important dissociative recombination reactions.

Branching ratios of the dissociative recombination reactions of the astrophysically relevant ions DCO+, N2H+ and DOCO+ (as substitute for HOCO+) have been measured using the CRYRING storage ring at the Manne Siegbahn Laboratory at the University of Stockholm, Sweden. For DCO+, the channel leading to D and CO was by far the most important one (branching ratio 0.88), only small contributions of the CD + O and OD + C product pathways (branching ratios 0.06 each) were recorded. In the case of N2H+ the surprising result of a break-up of the N-N bond to N and NH (branching ratio 0.64) was found with the branching ratio of the N2 + H product channel therefore displaying a branching ratio of only 0.36. In the case of DOCO+, the three-body break-up into D + O + CO dominated (branching ratio 0.68), whereas the contribution of the CO2 + H channel was only minute (0.05). The remaining share (branching ratio 0.27) was taken by the pathway leading to OH + CO. For the dissociative recombination of N2H+ and DOCO+ also absolute reaction cross sections were obtained in the collisional energy range between 0 and 1 eV. From these cross sections it was possible to work out the thermal rate constants, which were found to be k(T) = 1.0+/-0.1 x 10(-7) (T/300 K)(-0.51+/-0.02) cm3 s(-1) and k(T) = 1.2+/-0.1 x 10(-6) (T/300 K)(-0.64+/-0.02) cm3 S(-1) for N2H+ and DOCO+, respectively.

Journal Article↗
PubMed2004

Common oligosaccharide moieties inhibit the adherence of typical and atypical respiratory pathogens.

Intervention in bacterial adhesion to host cells is a novel method of overcoming current problems associated with antibiotic resistance. Antibiotic-resistant strains of bacteria that cause respiratory tract infections are a problem in hospitals and could be used in bioterrorist attacks. A range of bacterial species was demonstrated to attach to an alveolar epithelial (A549) cell line. In all cases, cell surface oligosaccharides were important in attachment, demonstrated by reduced adhesion when A549 cells were pre-treated with tunicamycin. Bacillus anthracis and Yersinia pestis displayed a restricted tropism for oligosaccharides compared to the environmental, opportunistic pathogens, Pseudomonas aeruginosa, Burkholderia cenocepacia, Burkholderia pseudomallei and Legionella pneumophila. The compound with the greatest anti-adhesion activity was p-nitrophenol. Other generic attachment inhibitors included the polymeric saccharides (dextran and heparin), GalNAcbeta1-4Gal, GalNAcbeta1-3Gal, Galbeta1-4GlcNAc and Galbeta1-3GlcNAc. Burkholderia pseudomallei attachment was particularly susceptible to oligosaccharide inhibition. Combinations of such compounds may serve as a novel generic therapeutics for respiratory tract infections.

Bacteria↗
PubMed2004

Shocking abdominal trauma: review of an uncommon disorder of small intestine perfusion.

'Shock bowel' is a rare disorder of gastrointestinal physiology with characteristic radiological features. It usually occurs in the setting of blunt abdominal trauma and hypovolaemia, with complete reversibility of these findings following resuscitation. We present a case demonstrating the classic features of this complex of imaging findings thought to be caused by end-organ hypoperfusion.

Abdominal Injuries↗