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We explore the local negotiation of regulatory practice at the UK Stem Cell Bank, the first Bank of its type in the world. Basing our empirical work on a detailed analysis of one aspect of the Bank’s regulatory commitment – the completion of the Cell Line Information form – we make visible the necessary judgements and labour involved in interpreting and operationalizing externally imposed regulation. The discussion opens by detailing the problems encountered when the Bank completes the form: reconciling a bureaucratic system of accountability with craft-like laboratory skills involving multiple kinds of tacit knowledge. We follow this by explicating the emergent ‘bridging strategies’ pursued by the Bank to address these issues, highlighting their reliance upon the formation of trust and social networks. The closing discussion emphasizes the contingent assembly of regulatory practices that emerge in the local setting. [ABSTRACT FROM PUBLISHER]

Summary: For a disease initially described in 1958 as a leukaemic reticulo‐endotheliosis associated with poor outcomes, we have come a long way in our understanding of Hairy cell leukaemia. The vast majority of patients diagnosed with this rare, often diagnostically challenging, leukaemia can now expect a lifespan that is similar to the general population. This article covers some of the highlights from the last 6 decades that have led to our current understanding of this fascinating leukaemia ‐ from elucidation of its B‐cell origin to discovery of the almost universal occurrence of the BRAF V600E mutation; from the initial successes reported with splenectomy to the more recent development of targeted therapies such as Vemurafenib and Moxetumomab Pasudotox. It also pays tribute to some of the outstanding research in this field focusing particularly on the significant contributions made by the clinical and scientific community in the UK. [ABSTRACT FROM AUTHOR]

The article presents a medical research in Great Britain on the alternative pathways of T-cell development. It is said that the recent report of immunity revealed the common need for signalling through the signalling lymphocytic activation molecule (SLAM) family of receptors. However, the studies featured in the paper helped define pathways of T-cell selection on haematopoietic cells and indicate an important role for SLAM receptor signalling in these alternative pathways of T-cell development.

Mesenchymal stem cells (MSCs) possess immunosuppressive properties and have been described in the tumor microenvironment of glioblastoma multiforme (GBM). This manuscript has two major topics—first, to describe isolated and cultured MSCs derived from GBM (GB-MSCs) and second, to examine their in vitro immunosuppressive capacity. Our results display cells with morphology and phenotype, clonogenic ability, and osteogenic potential, typical for MSCs. Furthermore, the cultured cells show intracellular expression of the neural markers Nestin and GFAP. They express PD-L1 and secrete TGFβ, CCL-2, PGE2, IL-6, and sVEGF. Coculturing of GB-MSCs with PBMCs isolated from healthy donors results in a decreased percentage of Th17 lymphocytes and an increased percentage of Tregs. Regarding the impact of GB-MSCs on monocytes, we establish an augmented expression of CD14 and CD86 along with diminished expression of HLA-DR and CD80, which is associated with tolerogenic phenotype monocyte-derived cells. In conclusion, our results describe in detail GBM-derived and cultured cells that meet the criteria for MSCs but at the same time express Nestin and GFAP. GB-MSCs express and secrete suppressive molecules, influencing in vitro T cells and monocytes, and are probably another factor involved in the immune suppression exerted by GBM. [ABSTRACT FROM AUTHOR]

Harnessing the unparalleled properties of human embryo stem cells (hESCs) for the therapeutic treatment of disease and injury will require a convergence of scientific developments with regulatory standards. In the case of the latter, it is especially critical that standards for clinically assisted reproduction be harmonized with those governing human cell and tissue transplantation, most notably with respect to procurement, donation, testing, processing, preservation, storage and distribution of cells. In the UK, existing infrastructure to address these considerations is undergoing extensive reorganization to keep pace with evolving European Union standards. The present best paradigm for defining standards for the therapeutic use of embryo-derived stem cells is experience with adult haematopoietic stem cells (HSC). However, compared with adult-derived stem cell, the origin of embryo-derived stem cells from limiting quantities of tissue and their absolute dependence on in vitro culture to realise their therapeutic potential, makes optimization of their isolation and cultivation of even greater importance. Most notable is the requirement to create animal cell product-free culture environments to reduce the risk of cross-specific disease transmission. In the present paper, we review present and emerging standards in the isolation and banking of human embryo-derived stem cells for therapeutic use in the UK and international progress in the development of defined culture systems for this purpose. [ABSTRACT FROM AUTHOR]

Objectives: Cell-free DNA (cfDNA) analysis of maternal blood for detection of trisomies 21, 18 and 13 is superior to other methods of screening but is expensive. One strategy to maximize performance at reduced cost is to offer cfDNA testing contingent on the results of the first-trimester combined test that is used currently. The objectives of this study were to report the feasibility of implementing such screening, to examine the factors affecting patient decisions concerning their options for screening and decisions on the management of affected pregnancies and to report the prenatal diagnosis of fetal trisomies and outcome of affected pregnancies following the introduction of contingent screening.Methods: We examined routine clinical implementation of contingent screening in 11,692 singleton pregnancies in two National Health Service (NHS) hospitals in the UK. Women with a risk ≥ 1 in 100 (high-risk group) were offered options of invasive testing, cfDNA testing or no further testing, and those with a risk between 1 in 101 and 1 in 2500 (intermediate-risk group) were offered cfDNA testing or no further testing. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or by examination of the neonates.Results: In the study population of 11,692 pregnancies, there were 47 cases of trisomy 21 and 28 of trisomies 18 or 13. Screening with the combined test followed by invasive testing for all patients in the high-risk group potentially could have detected 87% of trisomy 21 and 93% of trisomies 18 or 13, at a false-positive rate of 3.4%; the respective values for cfDNA testing in the high- and intermediate-risk groups were 98%, 82% and 0.25%. However, in the high-risk group, 38% of women chose invasive testing and 60% chose cfDNA testing; in the intermediate-risk group 92% opted for cfDNA testing. A prenatal diagnosis was made in 43 (91.5%) pregnancies with trisomy 21 and all pregnancies with trisomies 18 or 13. In many affected pregnancies the parents chose to avoid testing or termination and 32% of pregnancies with trisomy 21 resulted in live births.Conclusions: Screening for fetal trisomies by cfDNA analysis of maternal blood, contingent on the results of the combined test, can be implemented easily in routine clinical practice. In the high-risk group from the combined test, most but not all women chose cfDNA testing rather than invasive testing. Performance of screening for trisomy 21 was superior by the cfDNA test than by the combined test. However, prenatal detection of trisomies and pregnancy outcome depend not only on performance of screening tests but also on parental choice. [ABSTRACT FROM AUTHOR]

Enhancements in sensitivity now allow DNA profiles to be obtained from only tens of picograms of DNA, corresponding to a few cells, even for samples subject to degradation from environmental exposure. However, low-template DNA (LTDNA) profiles are subject to stochastic effects, such as "dropout" and "dropin" of alleles, and highly variable stutter peak heights. Although the sensitivity of the newly developed methods is highly appealing to crime investigators, courts are concerned about the reliability of the underlying science. High-profile cases relying on LTDNA evidence have collapsed amid controversy, including the case of Hoey in the United Kingdom and the case of Knox and Sollecito in Italy. I argue that rather than the reliability of the science, courts and commentators should focus on the validity of the statistical methods of evaluation of the evidence. Even noisy DNA evidence can be more powerful than many traditional types of evidence, and it can be helpful to a court as long as its strength is not overstated. There have been serious shortcomings in statistical methods for the evaluation of LTDNA profile evidence, however. Here, I propose a method that allows for multiple replicates with different rates of dropout, sporadic dropins, different amounts of DNA from different contributors, relatedness of suspected and alternate contributors, "uncertain" allele designations, and degradation. R code implementing the method is open source, facilitating wide scrutiny. I illustrate its good performance using real cases and simulated crime scene profiles. [ABSTRACT FROM AUTHOR]

Objective: To describe our experience in recognizing an unusual presentation of severe dyskaryosis at two large cytology centres using ThinPrep liquid-based cytology (LBC). LBC has been introduced in England following successful pilot studies. It is clear that LBC improves visualization and preservation of cells, and that sensitivity for high-grade dyskaryosis is at least as good as for conventional cytology, and may be better. Several variants of high-grade dyskaryosis have been described on conventional cytology, including small and pale cell dyskaryosis. These are also seen on LBC. We are reporting a new variant of dyskaryosis which in our experience is seen only in LBC specimens prepared by the Thinprep® method, which we have named bland dyskaryosis. This has not to our knowledge been previously described. Bland dyskaryosis is characterized by cells with a high nuclear/cytoplasmic ratio, nuclear hyperchromasia and is present in groups with a chaotic architecture. The chromatin pattern appears bland at low power screening examination. On high power examination, however, the chromatin pattern can be seen to be subtly abnormal. Nuclear membranes are smooth. These changes mimic endocervical cells or immature squamous metaplasia at low power. Method: Identification and description of cytological appearances observed in routine practice and correlation with histological diagnosis. Conclusion: The features of bland dyskaryosis should be disseminated through teaching activities. Recognition of this previously undescribed variant will prevent false negative reporting of LBC samples. [ABSTRACT FROM AUTHOR]

Cell salvage is widely used in many surgical specialties to reduce the use of allogeneic blood, which is associated with well-recognized significant complications such as incorrect transfusion, acute and delayed immunological transfusion reactions and transfusion-transmitted infection. Theoretical concerns over the use of cell salvage in obstetrics have focused on the risk of Rhesus immunization and the risk of contamination of the cell-saved blood with traces of amniotic fluid. This article examines the in vitro and in vivo evidence for the safety of the technique, presents current usage figures from Wales and the entire UK, and discusses the current perception of amniotic fluid embolus as an anaphylactoid reaction. It suggests that patients will have to choose between the risks of allogeneic or cell-saved blood, and concludes that the balance of evidence is now in favour of cell salvage in obstetrics. [ABSTRACT FROM AUTHOR]

Tracheal mites have been associated with the condition in honey bees that devastated colonies in Britain and Ireland in the early 1900s. The first outbreak of this condition, that became known as the 'Isle of Wight' disease, coincided with the period when brood-cell size was increased from about 5.0 mm to about 5.5 mm in width. We undertook an inoculation experiment over a 7-day period to establish if the act of increasing the brood-cell size could have triggered the onset of tracheal mites in honey bees. The standard-sized cells used had a cell width of 5.44 mm and the small-sized cells a width of 5.07 mm. Using callow (newly emerged) bees, from three colonies that had mixed cell sizes, we compared the susceptibility of bees reared in standard-sized cells with that of those raised in small-sized cells. The results indicated similar levels of female mite abundance (0.49 vs. 0.52 mites per bee) and mean fecundity (4.33 vs. 4.22 offspring per female mite), and produced no evidence of any difference in the overall susceptibility between the bees raised in the standard-sized cells versus small-sized brood cells. [ABSTRACT FROM AUTHOR]

Evaluates several advancements concerning the understanding of mechanisms controlling normal craniofacial development in connection to the evolutionary diversity among species. Components of the craniofacial complex; Role of the neural crest in the production of facial structures; Impact of the early embryonic development of facial tissues on several cellular processes.

A seasonal study of field-collected individuals of Porphyra leucosticta at Sidmouth, Devon, UK showed that the blade phase was present from April to September 2001. Specimens of P. leucosticta were epiphytic on Fucus serratus, Mastocarpus stellatus, Chondrus crispus and Osmundea pinnatifida, and epizoic on Mytilus edulis, often found growing in layers on the host. Field material was monoecious, with male and female gametangia in separate sori, but intermixed along the margins of thalli. Mean size (wet mass and dry mass, length and width) was lowest in April and greatest in July. All spores released in culture from field-collected material developed into conchocelis, except one individual, which released archeospores that developed into blades. The life history was completed in culture at both 15°C/long days (16:8 h light:dark cycle) and 15°C/short days (8:16 h light:dark cycle). A protothallus developed directly on the vegetative conchocelis filament by divisions of one of the vegetative cells and either detached and dropped to the bottom of the culture dish or remained as part of the conchocelis. The protothallus produced either archeosporangia or male and female gametangia or both. Chromosome numbers of n=3 in male gametangia, 2n=6 in zygotosporangia and 2n=6 in the conchocelis phase suggest that fertilisation had taken place. [ABSTRACT FROM AUTHOR]

Reports on the controversy about adult versus embryonic stem cell research in Great Britain as of April 2002. Decision of a committee of the British House of Lords to permit scientists to proceed with experiments on human embryos; Concerns raised by pro-life groups with regard to the need for embryonic stem cell research; Potential flaws of adult stem cell studies.