Derivation and propagation of human embryonic stem cell lines from frozen embryos in an animal product-free environment.

The protocols described here are comprehensive instructions for deriving human embryonic stem (hES) cell lines in xeno-free conditions from cryopreserved embryos. Details are included for propagation, cryopreservation and characterization. Initial derivation is on feeder cells and is followed by adaptation to a feeder-free environment; competent technicians can perform these simplified methods easily.

Umbilical cord blood stem cells: clinical trials in non-hematological disorders.

Background: Umbilical cord blood (UCB) has become the second most common source of stem cells for cell therapy. The recent boom in stem cell research and public fascination with promises of stem cell-based therapies, fueled by the media, have led researchers to explore the potential of UCB stem cells in therapy for non-hematological disorders.

Sources Of Data: ClinicalTrials.

T cell receptor signalling in γδ cell development: strength isn't everything.

γδ cells have been conserved across ∼450 million years of evolution, from which they share the distinction, alongside αβ T cells and B cells, of forming antigen receptors by somatic gene recombination. However, much about these cells remains unclear. Indeed, although γδ cells display 'innate-like' characteristics exemplified by rapid tissue-localised responses to stress-associated stimuli, their huge capacity for T cell receptor (TCR)γδ diversity also suggests 'adaptive-like' potential.

Butyrophilins: an emerging family of immune regulators.

Butyrophilins (Btns) and butyrophilin-like (Btnl) molecules are emerging as novel regulators of immune responses in mice and humans. Several clues point to their probable importance: many of the genes are located within the MHC; they are structurally related to B7-co-stimulatory molecules; they are functionally implicated in T cell inhibition and in the modulation of epithelial cell-T cell interactions; and they are genetically associated with inflammatory diseases. Nonetheless, initial immersion into the current literature can uncover confusion over even basic information such as gene names and expression patterns, and seemingly conflicting data regarding the biological activities of different family members.

Derivation and feeder-free propagation of human embryonic stem cells under xeno-free conditions.

Background Aims: Human embryonic stem (hES) cells hold great potential for cell therapy and regenerative medicine because of their pluripotency and capacity for self-renewal. The conditions used to derive and culture hES cells vary between and within laboratories depending on the desired use of the cells. Until recently, stem cell culture has been carried out using feeder cells, and culture media, that contain animal products.

Skint-1 identifies a common molecular mechanism for the development of interferon-γ-secreting versus interleukin-17-secreting γδ T cells.

Murine T cell development begins with the generation of a unique Vγ5(+)Vδ1(+) epidermal γδ T cell compartment and a unique, more broadly distributed Vγ6(+)Vδ1(+) subset that is an important source of interleukin-17 (IL-17). This study showed that these respective functional programs were determined by Skint-1, a thymic epithelial cell determinant. By engaging Skint-1(+) cells, Vγ5(+)Vδ1(+) thymocytes induced an Egr3-mediated pathway, provoking differentiation and the potential to produce IFN-γ while suppressing the γδ T cell lineage factor, Sox13, and a RORγt transcription factor-associated IL-17-producing capacity.

The Th1 life cycle: molecular control of IFN-γ to IL-10 switching.

Control of IFN-γ-secreting T helper (Th) 1 cells prevents autoimmunity and immunopathology during infection. IL-10-mediated suppression of Th1 cells is achieved not only through IL-10 produced extrinsically, but also through a negative feedback loop that induces "intrinsic" IL-10 expression in cells also expressing IFN-γ, during Th1 lineage differentiation. Targeting this Th1 cell IFN-γ to IL-10 switching is a tantalising prospect for developing therapeutics for Th1-mediated diseases.

Butyrophilin-like 1 encodes an enterocyte protein that selectively regulates functional interactions with T lymphocytes.

Although local regulation of T-cell responses by epithelial cells is increasingly viewed as important, few molecules mediating such regulation have been identified. Skint1, a recently identified member of the Ig-supergene family expressed by thymic epithelial cells and keratinocytes, specifies the murine epidermal intraepithelial lymphocyte (IEL) repertoire. Investigating whether Skint1-related molecules might regulate IEL in other compartments, this study focuses on buytrophilin-like 1 (Btnl1), which is conspicuously similar to Skint1 and primarily restricted to small intestinal epithelium.

Cutting edge: adaptive versus innate receptor signals selectively control the pool sizes of murine IFN-γ- or IL-17-producing γδ T cells upon infection.

γδ T lymphocytes are commonly viewed as embracing properties of both adaptive and innate immunity. Contributing to this is their responsiveness to pathogen products, either with or without the involvement of the TCR and its coreceptors. This study clarifies this paradoxical behavior by showing that these two modes of responsiveness are the properties of two discrete sets of murine lymphoid γδ T cells.

Photoprotection and vitamin D status.

The adverse effects of solar ultraviolet radiation on the skin are well documented, especially in fair-skinned people. These can be ameliorated by photoprotection strategies advocated by many public health bodies and typically include sun avoidance, sunscreen use and clothing. The UVB waveband which is the main cause of all adverse effects investigated in the laboratory to date is also the waveband for vitamin D photosynthesis which is the only established benefit of solar exposure.

Surface Transmission or Polarized Egress? Lessons Learned from HTLV Cell-to-Cell Transmission.

Commentary on Pais-Correia, A.M.; Sachse, M.

Latest developments in peri-operative monitoring of the high-risk major surgery patient.

Peri-operative monitoring technology has made great strides in the last 20 years with the introduction of minimally invasive devices to measure inter alia stroke volume, cardiac output, depth of anaesthesia and cerebral and tissue oxygen monitoring. Despite these technological advances, peri-operative management of the high risk major surgery patient has remained virtually unchanged. The vast majority of patients undergo a pre-operative assessment which is neither designed to quantify functional capacity nor predict outcome.

Matrix mediates the functional link between human immunodeficiency virus type 1 RNA nuclear export elements and the assembly competency of Gag in murine cells.

Human immunodeficiency virus type 1 (HIV-1) assembles poorly in murine cells, reflecting inefficient targeting of the Gag structural polyprotein to the plasma membrane. Virus particle production can be restored by replacing the cis-acting Rev response element (RRE) in Gag-Pol mRNAs with multiple copies of the CTE (4xCTE), suggesting a mechanistic link between HIV-1 RNA trafficking and productive Gag assembly. In this report, we demonstrate that Gag molecules generated from RRE-dependent transcripts are intrinsically defective for assembly in murine 3T3 cells.

A longer duration of schizophrenic illness has sex-specific associations within the working memory neural network in schizophrenia.

An association has previously been demonstrated between prefrontal cortex (PFC) volume decreases and illness progression in schizophrenia. The impact of illness duration on the fronto-parietal working memory neural network, however, remains unexplored. We investigated the effect of ageing and duration of illness, and explored possible sex-specific effects of duration of illness, in working memory-related brain activity in schizophrenia.

What have we learnt about the development and progression of early RA from RCTs?

Most randomized controlled trials (RCTs) investigating the treatment of early rheumatoid arthritis (RA) use the core set of measures proposed by consensus meetings in the 1990s; these include tender and swollen joint counts, pain, global assessments, disability, and acute-phase responders such as the erythrocyte sedimentation rate (ESR). Trials in early RA generally assess three key outcomes based on this core data set: symptoms and signs of inflammatory arthritis, progression of disability, and erosive damage. Adverse events are also recorded.

Vascular progenitor cells and translational research: the role of endothelial and smooth muscle progenitor cells in endogenous arterial remodelling in the adult.

There has been much recent research into the therapeutic use of stem and progenitor cells for various diseases. Alongside this, there has also been considerable interest in the normal roles that endogenous precursor cells may play in both physiological and pathological settings. In the present review, we focus on two types of progenitor cell which are of potential relevance to vascular homoeostasis, namely the EPC (endothelial progenitor cell) and the smooth muscle progenitor cell.

Protein acylation and localization in T cell signaling (Review).

Many proteins with pivotal roles in T cell activation are modified by fatty acylation. Examples of these include transmembrane proteins such as the co-receptors CD4 and CD8, the adaptors LAT and Cbp/PAG, the pre-TCR as well as proteins synthesized on free cytosolic ribosomes, such as the Src-related tyrosine kinases Lck and Fyn. The two main types of fatty acylations in eukaryotic cells are N-myristoylation and S-acylation, the latter being more commonly referred to as palmitoylation.

Brokering the peace: the origin of intestinal T cells.

In designating the thymic origin of the cells, the T in T cell seems simple enough, and the impressive unfolding of how the differentiation and selection of conventional CD4 and CD8 T cells are supported by the uniquely capable thymic stroma seems prima facie to leave little left to uncover. But, as the initial uncovering of T-cell receptor (TCR) gamma-chain genes forewarned, there are myriad "unconventional T cell" subtypes whose development is not easily explained by current understanding. Such cells, either TCR alphabeta(+) or TCR gamma delta(+), rarely express either CD4 (a coreceptor for major histocompatibility complex (MHC) II) or CD8 alphabeta (a coreceptor for MHC I).

Robotic renal surgery.

Robotic surgery is being increasingly used for prostatectomy. Its use in renal surgery has been limited by a perception that it does not offer any extra benefit. This article explores the use of robot assistance in renal surgery.

Robotic-assisted radical cystectomy.

Objective: To evaluate the emerging role of robotic-assisted radical cystectomy (RARC) in the management of bladder cancer.

Methods: Review of the published literature on robotic-assisted radical cystectomy, including data from our cystectomy series of 30 patients.

Results: Nearly 150 procedures have been performed worldwide.

HCV and autoimmunity.

Hepatitis C virus (HCV) infection is characterized by a number of autoreactive manifestations, such as autoantibody production, cryoglobulinemia and thyroid disorders. We will analyse critically the mechanisms invoked, and partially documented, to explain such manifestations arising in genetically predisposed individuals exposed to HCV. In particular we will examine the available evidence implicating the virus in lowering the B cell activation threshold, in directly infecting lymphocytes and in inducing self-reactivity through a mechanism of molecular mimicry.

Synchronized mechanical ventilation for respiratory support in newborn infants.

Background: During synchronized mechanical ventilation, positive airway pressure and spontaneous inspiration coincide. If synchronous ventilation is provoked, adequate gas exchange should be achieved at lower peak airway pressures, potentially reducing baro/volutrauma, air leak and bronchopulmonary dysplasia. Synchronous ventilation can potentially be achieved by manipulation of rate and inspiratory time during conventional ventilation and employment of patient triggered ventilation.