Genetic variants alter T-bet binding and gene expression in mucosal inflammatory disease.

The polarization of CD4+ T cells into distinct T helper cell lineages is essential for protective immunity against infection, but aberrant T cell polarization can cause autoimmunity. The transcription factor T-bet (TBX21) specifies the Th1 lineage and represses alternative T cell fates. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that may be causative for autoimmune diseases.

Therapeutic targets and new directions for antibodies developed for ovarian cancer.

Antibody therapeutics against different target antigens are widely used in the treatment of different malignancies including ovarian carcinomas, but this disease still requires more effective agents. Improved understanding of the biological features, signaling pathways, and immunological escape mechanisms involved in ovarian cancer has emerged in the past few years. These advances, including an appreciation of the cross-talk between cancer cells and the patient's immune system, have led to the identification of new targets.

The prognosis of translocation positive diffuse large B-cell lymphoma depends on the second hit.

A proportion of translocation positive diffuse large B-cell lymphomas (DLBCL) harbour a and/or translocation, known as double-hit DLBCL, and are clinically aggressive. It is unknown whether there are other genetic abnormalities that cooperate with translocation and form double-hit DLBCL, and whether there is a difference in clinical outcome between the double-hit DLBCL and those with an isolated translocation. We investigated gene mutations along with and translocations in a total of 234 cases of DLBCL, including 81 with translocation.

T-bet Activates Th1 Genes through Mediator and the Super Elongation Complex.

The transcription factor T-bet directs Th1 cell differentiation, but the molecular mechanisms that underlie this lineage-specific gene regulation are not completely understood. Here, we show that T-bet acts through enhancers to allow the recruitment of Mediator and P-TEFb in the form of the super elongation complex (SEC). Th1 genes are occupied by H3K4me3 and RNA polymerase II in Th2 cells, while T-bet-mediated recruitment of P-TEFb in Th1 cells activates transcriptional elongation.

Adjuvanted influenza-H1N1 vaccination reveals lymphoid signatures of age-dependent early responses and of clinical adverse events.

Adjuvanted vaccines afford invaluable protection against disease, and the molecular and cellular changes they induce offer direct insight into human immunobiology. Here we show that within 24 h of receiving adjuvanted swine flu vaccine, healthy individuals made expansive, complex molecular and cellular responses that included overt lymphoid as well as myeloid contributions. Unexpectedly, this early response was subtly but significantly different in people older than ∼35 years.

A randomised trial of secondary prophylaxis using granulocyte colony-stimulating factor ('SPROG' trial) for maintaining dose intensity of standard adjuvant chemotherapy for breast cancer by the Anglo-Celtic Cooperative Group and NCRN.

Background: Guidelines on the use of haematopoietic colony-stimulating factors for patients having adjuvant chemotherapy for breast cancer are designed to minimise the risk of neutropaenic infection (Smith TJ, Khatcheressian J, Lyman GH et al. Update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 2006; 3: 187-205; Aapro MS, Bohlius J, Cameron DA et al.

Tumour-associated macrophage polarisation and re-education with immunotherapy.

Monocytes/macrophages constitute important contributors of cancer-associated inflammation. Through their plasticity and capacity to become polarised by tumours towards less activatory and more immunosuppressive (M2) phenotypes, tumour-associated macrophages (TAM) are thought to support tumour progression. Orchestrated by T helper 2 (Th2)-biased stimuli, macrophage recruitment, activation and polarisation in tumour microenvironments is associated with poorer clinical outcomes.

Role and species-specific expression of colon T cell homing receptor GPR15 in colitis.

Lymphocyte recruitment maintains intestinal immune homeostasis but also contributes to inflammation. The orphan chemoattractant receptor GPR15 mediates regulatory T cell homing and immunosuppression in the mouse colon. We show that GPR15 is also expressed by mouse TH17 and TH1 effector cells and is required for colitis in a model that depends on the trafficking of these cells to the colon.

Enhanced and persistent levels of interleukin (IL)-17⁺ CD4⁺ T cells and serum IL-17 in patients with early inflammatory arthritis.

Prognosis of patients with early inflammatory arthritis (EIA) is highly variable. The aim of this study was to compare, longitudinally and cross-sectionally, the levels of cytokine-expressing cells in peripheral blood (PB) from patients with EIA to those in established rheumatoid arthritis (RA) and healthy controls (HC). PB mononuclear cells from HC (n = 30), patients with EIA (n = 20) or RA (n = 38) were stimulated with phorbol myristate acetate (PMA)/ionomycin for 3 h, and stained for cell markers and cytokines.

Tuberculosis, bacillus Calmette-Guérin vaccination, and allergic disease: findings from the International Study of Asthma and Allergies in Childhood Phase Two.

Some have suggested a protective effect of tuberculosis (TB) infection on allergic disease risk, but few studies have examined the association between the two. We therefore investigated whether TB disease and bacillus Calmette-Guérin (BCG) vaccination in early life protect against allergic disease. Information on allergic disease symptoms, past TB disease, and BCG vaccination as well as potential confounding factors was gathered by parental questionnaire from a randomly selected subset of 23,901 8- to 12-yr-old schoolchildren in 20 centers in both developed and developing countries.

Lack of evidence for a protective effect of prolonged breastfeeding on childhood eczema: lessons from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two.

Background: Exclusive breastfeeding for at least 4 months is recommended by many governments and allergy organizations to prevent allergic disease.

Objectives: To investigate whether exclusive breastfeeding protects against childhood eczema.

Methods: Study subjects comprised 51,119 randomly selected 8- to 12-year-old schoolchildren in 21 countries.

Biomarkers of tolerance: searching for the hidden phenotype.

Induction of transplantation tolerance remains the ideal long-term clinical and logistic solution to the current challenges facing the management of renal allograft recipients. In this review, we describe the recent studies and advances made in identifying biomarkers of renal transplant tolerance, from study inceptions, to the lessons learned and their implications for current and future studies with the same goal. With the age of biomarker discovery entering a new dimension of high-throughput technologies, here we also review the current approaches, developments, and pitfalls faced in the subsequent statistical analysis required to identify valid biomarker candidates.

The role played by contaminated surfaces in the transmission of nosocomial pathogens.

Studies in the 1970s and 1980s suggested that environmental surface contamination played a negligible role in the endemic transmission of healthcare-associated infections. However, recent studies have demonstrated that several major nosocomial pathogens are shed by patients and contaminate hospital surfaces at concentrations sufficient for transmission, survive for extended periods, persist despite attempts to disinfect or remove them, and can be transferred to the hands of healthcare workers. Evidence is accumulating that contaminated surfaces make an important contribution to the epidemic and endemic transmission of Clostridium difficile, vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, Acinetobacter baumannii, Pseudomonas aeruginosa, and norovirus and that improved environmental decontamination contributes to the control of outbreaks.

Utility of antimicrobial susceptibility-based algorithms for the presumptive identification of genotypically-defined community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital.

Purpose: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains are classically characterised by susceptibility to most non-β-lactam antimicrobial agents. We sought to determine whether antimicrobial susceptibility (AMS)-based algorithms could be used to presumptively identify CA-MRSA in a hospital MRSA collection.

Methods: Over a three-month period, all MRSA were tested for AMS, staphylococcal cassette chromosome mec (SCCmec) type, presence of the Panton-Valentine leukocidin (PVL) genes and spa type.

Strategies for translational research in the United Kingdom.

In the United Kingdom, many foundations and institutions and the government have made substantial investments in translational research. We examine the structures that surround this support and consider some of the results of this prodigious push toward enhancing translational research pursuits and thus improved clinical medicine.

Low frequency of environmental contamination with methicillin-resistant Staphylococcus aureus in an inner city emergency department and a human immunodeficiency virus outpatient clinic.

We investigated methicillin-resistant Staphylococcus aureus (MRSA) environmental contamination in an inner city outpatient clinic and emergency department (ED). Moistened cotton-tipped swabs were used to sample 63 surfaces in the outpatient clinic and 69 surfaces in the ED. MRSA was identified on none of the 63 surfaces in the outpatient clinic and on 7% of the 69 surfaces in the ED.

Bacterial contamination on touch surfaces in the public transport system and in public areas of a hospital in London.

Aims: To investigate bacterial contamination on hand-touch surfaces in the public transport system and in public areas of a hospital in central London.

Methods And Results: Dipslides were used to sample 118 hand-touch surfaces in buses, trains, stations, hotels and public areas of a hospital in central London. Total aerobic counts were determined, and Staphylococcus aureus isolates were identified and characterized.

Panton-Valentine leukocidin-encoding bacteriophage and gene sequence variation in community-associated methicillin-resistant Staphylococcus aureus.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) often produce Panton-Valentine leukocin (PVL), which is encoded by two co-transcribed genes located on lysogenized bacteriophages. Six PVL-encoding temperate phages have been described and single nucleotide polymorphisms (SNPs) in the PVL genes have been reported. In the present study, 22 PVL-positive CA-MRSA isolates were chosen to reflect the diversity of multilocus sequence type (MLST) clonal complexes (CC) identified in our hospital.

Comparison of community-associated methicillin-resistant Staphylococcus aureus from teaching hospitals in London and the USA, 2004-2006: where is USA300 in the UK?

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is increasingly common in the USA, but rare in the UK. We compared CA-MRSA from the UK and USA to examine differences in the molecular epidemiology. We investigated patients presenting with MRSA in the first 72 h of hospital admission or in out-patient settings in a UK and a US hospital from January 2004 to March 2006.

Identification and control of an outbreak of ciprofloxacin-susceptible EMRSA-15 on a neonatal unit.

We report the identification and control of an outbreak of a ciprofloxacin-susceptible strain of UK epidemic meticillin-resistant Staphylococcus aureus (EMRSA)-15 on a neonatal unit (NNU). All babies were screened for MRSA on admission using ciprofloxacin-containing media which did not detect the outbreak strain. The first identified case was a premature baby who developed MRSA bacteraemia with associated tibial osteomyelitis and multiple subcutaneous abscesses.