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Biomedical subjects

Sarah Phillips

Publications and source records attributed to Sarah Phillips.

6 recordsLinked to original sources
PubMed2025

Diverse defense systems and prophages in human-associated Bifidobacterium species reveal coevolutionary "arms race" dynamics.

Bacteria of the genus Bifidobacterium are pivotal for human health, especially in early life, where they dominate the gut microbiome in healthy infants. Bacteriophages, as drivers of gut bacterial composition, can affect bifidobacterial abundance. Here, we use a bioinformatics approach to explore direct interactions between human-associated Bifidobacterium spp. and prophages, as evidenced by their genomes. Analysis of 1,086 bifidobacterial genomes reveals the presence of complex systems that prevent viral invasion, with 34 defense systems and 56 subtypes detected, including several different CRISPR-Cas systems. CRISPR spacers target almost three-quarters of bifidobacteria-derived prophages, indicating dynamic interactions. At least one prophage is present in ∼67% of strains, with phages exhibiting high genomic diversity and evidence of historical recombination. These prophages encode various defense and anti-defense systems, such as anti-CRISPR genes and restriction-modification mechanisms. Overall, this investigation reveals that coevolutionary "arms race" dynamics drive genomic diversity in both bifidobacteria and their phages.

Prophages↗
PubMed2006

Exploring consensus in practice with youth who are sexually abusive: findings from a Delphi study of practitioner views in the United Kingdom and the Republic of Ireland.

This article presents the findings of a study exploring current levels of consensus among practitioners in the United Kingdom (UK) and the Republic of Ireland (ROI) about good practice in relation to youth who are sexually abusive. A three-stage Delphi procedure was used to survey the views of 78 practitioners, experienced in this field, on a range of matters relating to preferred responses to this population. The exercise indicated high levels of agreement that youth who are sexually abusive should be seen as a group clinically distinct from adult sex offenders and that all of their developmental needs, and their problematic behavior, should be targeted in intervention. A strong level of consensus was found among respondents about the goals and content of ideal practice with this user group, although there was less consensus about the theoretical models that should underpin practice.

Adolescent↗
PubMed2002

The AML1-ETO fusion gene promotes extensive self-renewal of human primary erythroid cells.

The t(8;21) translocation, which encodes the AML1-ETO fusion protein (now known as RUNX1-CBF2T1), is one of the most frequent translocations in acute myeloid leukemia, although its role in leukemogenesis is unclear. Here, we report that exogenous expression of AML1-ETO in human CD34(+) cells severely disrupts normal erythropoiesis, resulting in virtual abrogation of erythroid colony formation. In contrast, in bulk liquid culture of purified erythroid cells, we found that while AML1-ETO initially inhibited proliferation during early (erythropoietin [EPO]-independent) erythropoiesis, growth inhibition gave way to a sustained EPO-independent expansion of early erythroid cells that continued for more than 60 days, whereas control cultures became growth arrested after 10 to 13 days (at the EPO-dependent stage of development). Phenotypic analysis showed that although these cells were CD13(-) and CD34(-), unlike control cultures, these cells failed to up-regulate CD36 or to down-regulate CD33, suggesting that expression of AML1-ETO suppressed the differentiation of these cells and allowed extensive self-renewal to occur. In the early stages of this expansion, addition of EPO was able to promote both phenotypic (CD36(+), CD33(-), glycophorin A(+)) and morphologic differentiation of these cells, almost as effectively as in control cultures. However, with extended culture, cells expressing AML1-ETO became refractory to addition of this cytokine, suggesting that a block in differentiation had been established. These data demonstrate the capacity of AML1-ETO to promote the self-renewal of human hematopoietic cells and therefore support a causal role for t(8;21) translocations in leukemogenesis.

Antigens, CD34↗
PubMed2002

Protein kinase C mediates mutant N-Ras-induced developmental abnormalities in normal human erythroid cells.

RAS mutations are one of the most frequent molecular abnormalities associated with myeloid leukemia and preleukemia, yet there is a poor understanding of how they contribute to the pathogenesis of these conditions. Here, we describe the consequences of ectopic mutant N-Ras (N-Ras*) expression on normal human erythropoiesis. We show that during early (erythropoietin [EPO]-independent) erythropoiesis, N-Ras* promoted the amplification of a phenotypically primitive but functionally defective subpopulation of CD34(+) erythroblasts. N-Ras* also up-regulated the expression of megakaryocyte antigens on human erythroblasts. Although early erythroblasts expressing N-Ras* were able to respond to erythropoietin and generate mature progeny, this occurred with greatly reduced efficiency, probably explaining the poor colony growth characteristics of these cells. We further report that this oncogene promoted the expression and activation of protein kinase C (PKC) and that the effects of N-Ras* on erythropoiesis could be abrogated or attenuated by inhibition of PKC. Similarly, the effects of this oncogene could be partially mimicked by treatment with PKC agonist. Together, these data suggest that expression of N-Ras* is able to subvert the normal developmental cues that regulate erythropoiesis by activating PKC. This gives rise to phenotypic and functional abnormalities commonly observed in preleukemia, suggesting a direct link between RAS mutations and the pathogenesis of preleukemia.

Antigens, CD↗
PubMedDate not supplied

A structured learning programme for venepuncture and cannulation.

This article discusses a structured learning programme that offers a standardised assessment for all healthcare staff to learn venepuncture and/or cannulation. Nurses from four NHS trusts in London and the south east, with a special interest and expertise in cannulation and venepuncture, devised the programme to reduce the need for repeated training and assessment when staff take up new posts within these trusts. The authors in their respective trusts have used the tool over a four-year period and findings from a study in Chelsea and Westminster Healthcare NHS Trust are presented to demonstrate its use by staff. The tool has recently been reviewed by its authors and is being disseminated to organisations across the United Kingdom (UK). These organisations will evaluate it, with a long-term objective to standardise the training and assessment of venepuncture and cannulation across the UK.

Catheterization↗