Using a murine model, we demonstrated that endobronchial administration of antibodies (Abs) to major histocompatibility complex (MHC) class I results in cellular infiltration, epithelial metaplasia, fibrosis and obstruction of the small airways (obliterative airway disease [OAD]) mediated predominantly by Th17 responses to self-antigens. This resembles bronchiolitis obliterans syndrome developed following ...

ABSTRACT: BACKGROUND: Throughout the metazoan lineage, typically gonadal expressed Piwi proteins and their guiding piRNAs (~26-32nt in length) form a protective mechanism of RNA interference directed against the propagation of transposable elements (TEs). Most piRNAs are generated from genomic piRNA clusters. Annotation of experimentally obtained piRNAs from small RNA/cDNA-libraries and ...

Like the battery bunny: The novel photoswitchable fluorescent protein rsEGFP can be cycled between its fluorescent and nonfluorescent states more than a thousand times and is, therefore, a superb marker for high-resolution RESOLFT imaging (RESOLFT=reversible saturable optical fluorescence transition) and data storage applications.

This study explored the different values of staff from two care homes for older people in which the managers had different qualifications (social worker vs. nursing). Their views were examined to explore whether the values of the staff might reflect any value difference originating in the professional backgrounds of the ...

Bacteriophages are the most abundant biological entities in our biosphere, characterized by their hyperplasticity, mosaic composition, and the many unknown functions (ORFans) encoded by their immense genetic repertoire. These genes are potentially maintained by the bacteriophage to allow efficient propagation on hosts encountered in nature. To test this hypothesis, we ...

Subtle differences: By using a combination of advanced crystallographic techniques and complementary computational approaches to assess the relative energies and conformational preferences, Me(2) Zn has been shown to form two different crystal structures. At temperatures above 180 K the methyl groups are staggered, whereas below 180 K the methyl groups ...

Neurexins are a family of transmembrane, synaptic adhesion molecules. In neurons, neurexins bind to both sub-plasma membrane and synaptic vesicle-associated constituents of the secretory machinery, play a key role in the organization and stabilization of the presynaptic active zone, and help mediate docking of synaptic vesicles. We have previously shown ...

Patients with anaplastic lymphoma kinase (ALK) gene rearrangements often manifest dramatic responses to crizotinib, a small-molecule ALK inhibitor. Unfortunately, not every patient responds and acquired drug resistance inevitably develops in those who do respond. This study aimed to define molecular mechanisms of resistance to crizotinib in patients with ALK(+) non-small ...

In order to analyze the copper-induced cross-talk between calcium, NO and H2O2 and the calcium-dependent activation of gene expression, the marine alga Ulva compressa was treated with the inhibitors of calcium channels, ned-19, ryanodine (rya) and xestospongin C (xes), of chloroplasts and mitochondrial electron transport chains, DCMU and antimycin A ...

Electromagnetic vacuum fields are omnipresent in our universe, inducing many events such as spontaneous emission, Lamb shift, and Van der Waals forces. As demonstrated here, a chemical reaction can be influenced by strongly coupling the energy landscape governing the reaction pathway to vacuum fields in an optical cavity (see picture; ...

Ascidians (tunicates) are rich sources of structurally elegant, pharmaceutically potent secondary metabolites and, more recently, potential biofuels. It has been demonstrated that some of these compounds are made by symbiotic bacteria and not by the animals themselves, and for a few other compounds evidence exists supporting a symbiotic origin. In ...

Following the success of small-molecule high-throughput screening (HTS) in drug discovery, other large-scale screening techniques are currently revolutionizing the biological sciences. Powerful new statistical tools have been developed to analyze the vast amounts of data in DNA chip studies, but have not yet found their way into compound screening. In ...

Based on the assumption that only a few genes are differentially expressed in a disease and have balanced upward and downward expression level changes, researchers usually normalise microarray data by forcing all of the arrays to have the same probe intensity distributions to remove technical variations in the data. However, ...

We describe nanoscale tools in the form of autonomous and remotely guided catalytically self-propelled InGaAs/GaAs/(Cr)Pt tubes. These rolled-up tubes with diameters in the range of 280-600 nm, move in hydrogen peroxide solutions with speeds as high as 180 µm.s-1. The effective transfer of chemical energy to translational motion has allowed ...

Background: The concomitant use of femoral and popliteal accesses has been recommended for challenging superficial femoral artery (SFA) occlusions, but no comprehensive comparison of this approach to a strategy of femoral access only is available. We thus aimed to appraise the risk-benefit balance of retrograde popliteal access as bail-out strategy ...

Aim:  In elderly patients with dementia, disturbed eating behavior is understood to be a core symptom or a behavioral and psychological symptom of dementia (BPSD). The purpose of the present study was to investigate the factors affecting self-feeding in elderly patients with Alzheimer's disease (AD). Methods:  A total of 150 ...

Dense deposit disease is a rare glomerulonephritis caused by uncontrolled stimulation of the alternative complement pathway. Allograft survival after kidney transplantation is significantly reduced by the high rate of disease recurrence. No therapeutic interventions have consistently improved outcomes for patients with primary or recurrent disease. This is the first reported ...

Few randomized trials have compared therapies in mantle cell lymphoma (MCL), and the role of aggressive induction has not been clearly defined. The NCCN Non-Hodgkin's Lymphoma Outcomes Database, a prospective cohort study collecting clinical, treatment, and outcome data at 7 NCCN centers, provides a unique opportunity to compare the effectiveness ...

ABSTRACT: BACKGROUND: Atrial fibrillation (AF) after thoracic surgery is a continuing source of morbidity and mortality. The effect of postoperative AF on long-term survival however has not been studied. Our aim was to evaluate the impact of AF on early outcome and on survival >5 years after pulmonary lobectomy for ...

PURPOSE: (11)C-Choline positron emission tomography (PET) has been exploited to detect the aberrant choline metabolism in tumors. Radiolabeled choline uptake within the imaging time is primarily a function of transport, phosphorylation and oxidation. Rapid choline oxidation, however, complicates interpretation of PET data. In this study we investigated the biological basis ...

ABSTRACT: BACKGROUND: An evidence-based Consensus on the treatment of undescended testis (UT) was recently published, recommending to perform orchidopexy between 6 and 12 months of age, or upon diagnosis and to avoid the use of hormones. In Italy, current practices on UT management are little known. Our aim was to ...

Traumatic brain injury (TBI) and intracerebral hemorrhage (ICH) are leading causes of neurological mortality and disability in the US. However, therapeutic options are limited and clinical management remains largely supportive. HMG CoA reductase inhibitors (statins) have pleiotropic mechanisms of action in the setting of acute brain injury, and have been ...

The fifth element: An efficient new synthetic method for accessing 3,6-dihydro-2H-thiopyrans (1) in one pot has been developed. This method employs an anionic cascade, which is triggered by the addition of a vinyl nucleophile to a carbonyl group followed by S to O thiophosphate migration and an intramolecular thiolate displacement. ...

Eight cyclic aliphatic amines, pyrrolidine (Py), piperidine (Pp), morpholine (M), piperazine (Pz), and the N-hydroxyethyl (HE) analogues, were employed to prepare a salt with acidic diclofenac (D). These salts were examined by thermal [differential scanning calorimetry (DSC), thermogravimetric analysis, and hot-stage microscopy (HSM)] and spectroscopic [Fourier transform infrared (FTIR), Raman, ...

Background: To date, drug-eluting stent (DES) implantation has not been compared with coronary artery bypass grafting (CABG) for ostial left main coronary artery (LMCA) lesions. Methods: Of the 263 patients in the MAIN-COMPARE registry with ostial LMCA stenosis, 123 were treated with percutaneous coronary intervention (PCI) with DES and 140 ...

Background We evaluated an open stented elephant trunk (sET) technique combined with cardiac operations for a one-stage treatment of patients with complicated Stanford type B aortic dissection (AoD) and cardiac diseases.Methods Between April 2007 and March 2010, 16 patients with Stanford B AoD and cardiac diseases (mean age 49.75 ± 13.42 years) ...

ABSTRACT: BACKGROUND: The CXCR3 receptor and its three interferon-inducible ligands (CXCL9, CXCL10 and CXCL11) have been implicated as playing a central role in directing a Th1 inflammatory response. Recent studies strongly support that the CXCR3 receptor is a very attractive therapeutic target for treating autoimmune diseases, such as rheumatoid arthritis, ...

Radiation exposure of the operator during cardiac catheter ablation procedures was assessed for an experienced cardiologist adopting various measures of radiation protection and utilised electroanatomic navigation. Chip thermoluminescent dosemeters were placed at the eyes, chest, wrists and legs of the operator. The ranges of fluoroscopy time and air kerma area ...

Cervical tumor response on posttherapy 2[(18)F]fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) is predictive of survival outcome. The purpose of this study was to use gene expression profiling to identify pathways associated with tumor metabolic response. This was a prospective tissue collection study for gene expression profiling of 62 pretreatment biopsies from patients ...

Routine incorporation of FISH into multiple myeloma (MM) diagnostic testing has led to a better appreciation of the heterogeneity of genetic abnormalities associated with this disease. We studied a group of 484 patients with newly diagnosed symptomatic MM to better understand the prevalence of the various abnormalities and the prognostic ...

Paradigm shifts in the strategies and the sciences that would enhance the quality, safety, and efficacy of traditional medicines and dietary supplements in global health care are discussed. Some of the challenges facing traditional medicine in health care are described, and the importance of defining clear goals and directions for ...

OBJECTIVE:To review the literature describing the efficacy and safety of deep brain stimulation (DBS) as an adjunct to pharmacotherapy and to determine the best treatment option for patients with Parkinson disease (PD).DATA SOURCES:Literature was obtained through MEDLINE/PubMed (1948-September, week 2, 2011) and a bibliographic review of relevant articles. Key words ...

While many cancers show a sex bias, the genetic basis and molecular mechanisms underlying sex bias are not always clear. Astrocytoma and glioblastoma show male predominance in humans. We have shown previously that glial tumors forming in the Nf1-/+; Trp53-/+cis (NPcis) mouse model also show a sex bias in some ...

Tankyrases are poly(ADP-ribose) polymerases that have many cellular functions. They play pharmaceutically important roles, at least in telomere homeostasis and Wnt signaling, by covalently ADP-ribosylating target proteins and consequently regulating their functions. These features make tankyrases potential targets for treatment of cancer. We report here crystal structures of human tankyrase ...

The phenomenon known as multiple-drug resistance, whereby anti-cancer agents are expelled from cancer cells, makes it necessary to develop methods that will reliably increase the accumulation of anti-cancer agents within cancer cells. To accomplish this goal, a new model compound, Val-SN-38, was synthesized by introducing valine to SN-38, an active ...

Gliomas are the most common type of primary brain tumor in the central nervous system of adults. Maternally Expressed Gene 3 (MEG3) is an imprinted gene located at 14q32 that encodes a non-coding RNA associated with tumorigenesis. However, little is known about whether and how MEG3 regulates glioma development. In ...

The detection rate of intracranial aneurysms has increased with the improved availability of non-invasive imaging methods. Moreover, persons who have relatives with intracranial aneurysms increasingly demand imaging to rule out aneurysms. To deal with these problems, radiologists require basic knowledge regarding the detection and treatment of unruptured intracranial aneurysms. The ...

ObjectiveTo examine the population effectiveness of nicotine replacement therapies (NRTs), either with or without professional counselling, and provide evidence needed to better inform healthcare coverage decisions.MethodsA prospective cohort study was conducted in three waves on a probability sample of 787 Massachusetts adult smokers who had recently quit smoking. The baseline ...

IL-21 is a class I cytokine that exerts pleiotropic effects on both innate and adaptive immune responses. It signals through a heterodimeric receptor complex consisting of the IL-21 receptor (IL-21R) and the common γ-chain. A hallmark of the class I cytokine receptors is the class I cytokine receptor signature motif ...

Allogeneic hematopoietic cell transplantation (HCT) is an effective treatment for adult T-cell leukemia (ATL), raising the question about the role of graft-versus-leukemia effect against ATL. In this study, we retrospectively analyzed the effects of acute and chronic graft-versus-host disease (GVHD) on overall survival, disease-associated mortality, and treatment-related mortality among 294 ...

In a variety of organisms, adulthood is divided into aging and late life, where aging is a period of exponentially increasing mortality rates and late life is a period of roughly plateaued mortality rates. In this study we used ∼57,600 Drosophila melanogaster from six replicate populations to examine the physiological ...

A large prospective, open-label, randomized trial evaluated conversion from calcineurin inhibitor (CNI)- to sirolimus (SRL)-based immunosuppression for preservation of renal function in liver transplantation patients. Eligible patients received liver allografts 6-144 months previously and maintenance immunosuppression with CNI (cyclosporine or tacrolimus) since early posttransplantation. In total, 607 patients were randomized ...

Fanconi anemia, complementation group C (FANCC)-deficient hematopoietic stem and progenitor cells are hypersensitive to a variety of inhibitory cytokines, one of which, TNFα, can induce BM failure and clonal evolution in Fancc-deficient mice. FANCC-deficient macrophages are also hypersensitive to TLR activation and produce TNFα in an unrestrained fashion. Reasoning that ...

Alzheimer's disease (AD) is the most common cause of dementia in elderly people in western countries. However important goals are unmet in the issue of early diagnosis and the development of new drugs for treatment. Magnetic resonance imaging (MRI) and volumetry of the medial temporal lobe structures are useful tools ...

ABSTRACT: BACKGROUND: Spontaneous cessation of growth is a frequent finding in uterine fibroids. Increasing evidence suggests an important role of cellular senescence in this growth control. Deciphering the underlying mechanisms of growth control that can be expected not only to shed light on the biology of the tumors but also ...

Objective: To determine the reliability of the minimum sit-to-stand height test, its responsiveness and its relationship to leg muscle strength among rehabilitation unit inpatients and outpatients.Design: Reliability study using two measurers and two test occasions. Secondary analysis of data from two clinical trials.Setting: Inpatient and outpatient rehabilitation services in three ...

Objective. The aim of this article is to provide an overview of the classical histone deacetylase (HDAC) enzymes and HDAC inhibitors. The discussion is focused on the potential anti-asthmatic effects of this group of compounds. Methods. Medline was used with the search terms, "asthma and HDAC," "asthma and Trichostatin A," ...

ABSTRACT: BACKGROUND: Digitalis purpurea is an important ornamental and medicinal plant. There is considerable interest in exploring its transcriptome. RESULTS: Through high-throughput 454 sequencing and subsequent assembly, we obtained 23532 genes, of which 15626 encode conserved proteins. We determined 140 unigenes to be candidates involved in cardiac glycoside biosynthesis. It ...

Volatile chemical profiles collected from the headspace of Aspergillus fumigatus (a pathogenic fungus that causes invasive pulmonary aspergillosis, allergic bronchopulmonary aspergillosis and chronic fungal sinusitis) grown on media with the connective tissue protein elastin, found in lung tissue, contained a large abundance of the sesquiterpene farnesene (3,7,11-trimethyl-1,3,6,10-dodecatetraene) and, depending on ...

Carboplatin remains a first-line agent in the management of epithelial ovarian cancer (EOC). Unfortunately, platinum-resistant disease ultimately occurs in most patients. Using a novel EOC cell line with acquired resistance to carboplatin: PEO1CarbR, genome-wide micro-array profiling identified the cyclin-dependent kinase inhibitor p57(Kip2) as specifically downregulated in carboplatin resistance. Presently, we ...