NKG2C, HLA-E and their association with psoriasis.

Natural killer (NK) cell activation is regulated by the integration of signals from inhibitory and activating cell surface receptors. Both NKG2A and NKG2C pair with CD94 to form inhibitory and activating receptors specific for the HLA-E-canonical peptide complex. HLA-E is a non-classical MHC class Ib molecule with limited polymorphism.

Effects of ionization on the toxicity of silver nanoparticles to Japanese medaka (Oryzias latipes) embryos.

Increase in the use of manufactured nanomaterials (NMs) has led to concerns about the environmental impacts. Especially, hazard of metal-based NMs is more severe due to ions released from surface by water quality parameters and physicochemical properties after entering into the water environment. However, little is known about the effects of ionization on the toxicity of metal-based NMs in the water environment.

The EFEMP1 gene: a frequent target for epigenetic silencing in multiple human pituitary adenoma subtypes.

Background/aims: In a genome-wide investigation we recently identified the EGF-containing fibulin-like extracellular matrix protein 1 gene, EFEMP1, as hypermethylated in growth hormone-secreting adenoma.

Methods: In an independent cohort we determined expression of EFEMP1, CpG island methylation and histone tail modification status. The causal consequences of epigenetic modification were determined through epidrug-induced reversal and enforced EFEMP1 expression in GH3 cells.

Tissues in different anatomical sites can sculpt and vary the tumor microenvironment to affect responses to therapy.

The tumor microenvironment can promote tumor growth and reduce treatment efficacy. Tumors can occur in many sites in the body, but how surrounding normal tissues at different anatomical sites affect tumor microenvironments and their subsequent response to therapy is not known.We demonstrated that tumors from renal, colon, or prostate cell lines in orthotopic locations responded to immunotherapy consisting of three agonist antibodies, termed Tri-mAb, to a much lesser extent than the same tumor type located subcutaneously.

Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells.

Purpose: To determine the antitumor efficacy and toxicity of a novel combination approach involving adoptive T-cell immunotherapy using chimeric antigen receptor (CAR) T cells with an immunomodulatory reagent for blocking immunosuppression.

Experimental Design: We examined whether administration of a PD-1 blocking antibody could increase the therapeutic activity of CAR T cells against two different Her-2(+) tumors. The use of a self-antigen mouse model enabled investigation into the efficacy, mechanism, and toxicity of this combination approach.

Molecular changes in the phosphatidylinositide 3-kinase (PI3K) pathway are common in gastric cancer.

Background And Objectives: The phosphatidylinositide 3-kinase (PI3K) pathway is an important signalling pathway that is frequently activated in cancer cells. This has led to the emergence of PI3K inhibitors as potential new treatment modalities for many cancers. We have investigated the frequency of molecular changes in the PI3K pathway in gastric cancer.

Chimeric antigen receptor-redirected T cells display multifunctional capacity and enhanced tumor-specific cytokine secretion upon secondary ligation of chimeric receptor.

Aim: The aim of the current study was to fully elucidate the functions of T cells genetically modified with an erbB2-specific chimeric antigen receptor (CAR).

Material & Methods: In this study, key functional parameters of CAR T cells were examined following antigen-specific stimulation of the chimeric anti-erbB2 receptor.

Results: Gene-modified T cells produced the cytokines IFN-γ, IL-2, IL-4, IL-10, TNF-α and IL-17, and the chemokine RANTES upon CAR ligation.

Engineering T cell function using chimeric antigen receptors identified using a DNA library approach.

Genetic engineering of cellular function holds much promise for the treatment of a variety of diseases including gene deficiencies and cancer. However, engineering the full complement of cellular functions can be a daunting genetic exercise since many molecular triggers need to be activated to achieve complete function. In the case of T cells, genes encoding chimeric antigen receptors (CARs) covalently linking antibodies to cytoplasmic signaling domains can trigger some, but not all, cellular functions against cancer cells.

Laparoscopy and peritoneal cytology: important prognostic tools to guide treatment selection in gastric adenocarcinoma.

Background: Previous studies have suggested that patients with occult peritoneal metastases not seen on preoperative imaging have poor prognosis. In this study, we aim to evaluate the utility and impact of staging laparoscopy and peritoneal cytology in patients with gastric adenocarcinoma.

Methods: A retrospective analysis of patients with gastric adenocarcinoma managed at two major metropolitan hospitals in Melbourne, Australia, between January 1999 and July 2010 was undertaken.

Preincubation of pituitary tumor cells with the epidrugs zebularine and trichostatin A are permissive for retinoic acid-augmented expression of the BMP-4 and D2R genes.

Retinoic acid (RA)-induced expression of bone morphogenetic protein-4 (BMP-4) inhibits in vitro and in vivo cell proliferation and ACTH synthesis in corticotroph-derived tumor cells. Reduced expression of BMP-4 in this adenoma subtype is associated with epigenomic silencing, and similar silencing mechanisms are also associated with the RA-responsive dopamine D2 receptor (D2R) in somatolactotroph cells. We now show that preincubation with the epidrugs zebularine and trichostatin A is obligate and permissive for RA-induced expression of the BMP-4 and the D2R genes in pituitary tumor cells.

Evolutionary stability of a refactored phage genome.

Engineered genetic systems are commonly unstable; if propagated, they evolve to reverse or modify engineered elements because the elements impair fitness. A goal of synthetic biology is thus to anticipate and avoid detrimental engineering, but little is yet known about which types of elements cause problems in different contexts. In prior work, 30% of the genome of bacteriophage T7 was "refactored" by the insertion or modification of 65 short sequences that included a useful restriction enzyme site in order to, among other goals, separate genes and their translational initiation regions from each other and from other genetic elements.

Frictional response of normal and osteoarthritic articular cartilage in human femoral head.

We evaluated the microscale frictional response of human articular cartilage in different osteoarthritis stages using an atomic force microscope. Four human femoral heads (60-80 years old) with different osteoarthritis stages were explanted, and two cylindrical cartilage samples were sectioned from each femoral head. The microscale frictional coefficient mu of human cartilage in phosphate-buffered saline increased with increasing osteoarthritis stages, resulting in mu = 0.

Toxicity of citrate-capped silver nanoparticles in common carp (Cyprinus carpio).

Juvenile common carp (Cyprinus carpio) were used as a model to investigate acute toxicity and oxidative stress caused by silver nanoparticles (Ag-NPs). The fish were exposed to different concentrations of Ag-NPs for 48 h and 96 h. After exposure, antioxidant enzyme levels were measured, including glutathione-S-transferase (GST), superoxidase dismutase, and catalase (CAT).

Quantitative, genome-wide analysis of the DNA methylome in sporadic pituitary adenomas.

DNA methylation is one of the several epigenetic modifications that together with genetic aberrations are hallmarks of tumorigenesis including those emanating from the pituitary gland. In this study, we examined DNA methylation across 27 578 CpG sites spanning more than 14 000 genes in the major pituitary adenoma subtypes. Genome-wide changes were first determined in a discovery cohort comprising non-functioning (NF), growth hormone (GH), prolactin (PRL)-secreting and corticotroph (CT) adenoma relative to post-mortem pituitaries.

Epigenomic silencing of the BMP-4 gene in pituitary adenomas: a potential target for epidrug-induced re-expression.

Bone morphogenetic protein (BMP)-4 is a key mediator of anterior pituitary organogenesis. However, through inappropriate expression patterns, BMP-4 is also pathogenic in a pituitary adenoma subtype-specific context. In these cases, increase or decrease in BMP-4 in lactotroph- and corticotroph-derived adenomas, respectively, is consistent with a bifunction role for this protein toward either promotion or inhibition of cell proliferation and hormone secretion.

18F-FDG PET/CT has a high impact on patient management and provides powerful prognostic stratification in the primary staging of esophageal cancer: a prospective study with mature survival data.

Unlabelled: The aim of this study is to evaluate the incremental staging information, management impact, and prognostic stratification of PET/CT in the primary staging of esophageal cancer in a cohort of patients with mature survival data.

Methods: Between July 2002 and June 2005, 139 consecutive patients with newly diagnosed esophageal cancer underwent conventional staging investigations (CSI), followed by PET/CT. Disease stage was classified according to the American Joint Committee on Cancer staging system (6th edition) and grouped as stage I-IIA, stage IIB-III, and stage IV reflecting broad groupings that determine therapeutic choice.

The pituitary tumour epigenome: aberrations and prospects for targeted therapy.

Global and gene-specific changes in the epigenome are hallmarks of most tumour types, including those of pituitary origin. In contrast to genetic mutations, epigenetic changes (aberrant DNA methylation and histone modifications) are potentially reversible. Drugs that specifically target or inhibit DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) can be used to restore the expression of epigenetically silenced genes.

Role of oxidative stress in methamphetamine-induced dopaminergic toxicity mediated by protein kinase Cδ.

This study examined the role of protein kinase C (PKC) isozymes in methamphetamine (MA)-induced dopaminergic toxicity. Multiple-dose administration of MA did not significantly alter PKCα, PKCβI, PKCβII, or PKCζ expression in the striatum, but did significantly increase PKCδ expression. Gö6976 (a co-inhibitor of PKCα and -β), hispidin (PKCβ inhibitor), and PKCζ pseudosubstrate inhibitor (PKCζ inhibitor) did not significantly alter MA-induced behavioral impairments.

Bidirectional esophageal dilatation in pharyngoesophageal stenosis postradiotherapy.

Severely stenosed radiation-induced benign strictures around the level of cricopharyngeus post-radical chemoradiation for head and neck or upper esophageal cancers pose significant management problems. We report our technique of bidirectional assessment and dilatation of pharyngoesophageal strictures in patients with an in situ percutaneous endoscopic gastrostomy (PEG) tube. The upper gastrointestinal surgeon approached the area of stenosis in a retrograde manner through the PEG tube to guide the otolaryngeal surgeon who performed anterograde dilatation via a rigid laryngoscope.

Effect of protein concentrations of bovine serum albumin and γ-globulin on the frictional response of a cobalt-chromium femoral head.

The study aims to identify the concentration-dependent role of bovine serum albumin (BSA) and γ-globulin in the lubricating ability of a cobalt-chromium femoral head. The frictional coefficients of the cobalt-chromium femoral head decreased with increasing BSA concentrations from 10 to 40 mg/ml and showed statistical differences between any of the BSA concentration groups, except between the 30 and 40 mg/ml concentration groups. In γ-globulin, the frictional coefficients significantly decreased at concentrations of 2.

Biodegradation of estrogen conjugates by bacteria isolated from river sediments.

The objective of this study was to investigate the ability of E. coli in river sediments to degrade estrogen conjugates. Biodegradation experiments on glucuronide estrogens (E1-GLU, E2-GLU and E3-GLU) using E.

Oncolytic virus and anti-4-1BB combination therapy elicits strong antitumor immunity against established cancer.

Oncolytic virotherapy using vaccinia virus (Vv) has shown some encouraging antitumor responses in mouse models and patients, but the breadth of efficacy in clinical trials has been somewhat limited. Given that antitumor effects have correlated with increased host immune responses, we hypothesized that improved therapeutic outcomes may be achieved by using oncolytic virus (OV) in combination with a potent immune agonist reagent. In this study, we carried out a preclinical evaluation of a genetically engineered strain of oncolytic vaccinia virus (Vvdd) for its capacity to induce antitumor responses when combined with an agonist antibody (Ab) specific for the costimulatory molecule 4-1BB (CD137).

A microfluidic device for the automated derivatization of free fatty acids to fatty acid methyl esters.

Free fatty acid (FFA) compositions are examined in feedstock for biodiesel production, as source-specific markers in soil, and because of their role in cellular signaling. However, sample preparation of FFAs for gas chromatography-mass spectrometry (GC-MS) analysis can be time and labor intensive. Therefore, to increase sample preparation throughput, a glass microfluidic device was developed to automate derivatization of FFAs to fatty acid methyl esters (FAMEs).

Regurgitation quantification using 3D PISA in volume echocardiography.

We present the first system for measurement of proximal isovelocity surface area (PISA) on a 3D ultrasound acquisition using modified ultrasound hardware, volumetric image segmentation and a simple efficient workflow. Accurate measurement of the PISA in 3D flow through a valve is an emerging method for quantitatively assessing cardiac valve regurgitation and function. Current state of the art protocols for assessing regurgitant flow require laborious and time consuming user interaction with the data, where a precise execution is crucial for an accurate diagnosis.

ICT-based visual interventions addressing social isolation for the aged.

This paper describes an approach of "visual interventions" to address the effects of social isolation imposed by independent living on the aged. This approach might be effective in situations where it is not possible to provide enough human contact or interaction to stimulate and sustain a positive outlook by the aged person. Two ICT-based visual interventions using this approach are described: a virtual "picture album" concept which can serve as a basis for positive reminiscence, and a virtual "daily assistant" concept to provide advice and reminders on health aspects encountered during daily living.