Chemical chaperone TUDCA selectively inhibits production of allergen-specific IgE in a low-dose model of allergy.

The cellular response to endoplasmic reticulum (ER) stress accompanies plasma cell maturation and is one of triggers and cofactors of the local inflammatory response. Chemical chaperones, low-molecular substances that eliminate pathological ER stress, are proposed as means of treating pathologies associated with ER stress. The aim of this study was to evaluate the effect and mechanisms of influence of chemical chaperones on the humoral response in a low-dose model of allergy.

DEPs Induce Local Ige Class Switching Independent of Their Ability to Stimulate iBALT de Novo Formation.

Background: Diesel exhaust particles (DEPs) are leading to a general increase in atopic diseases worldwide. However, it is still unknown whether DEPs induce systemic B-cell IgE class switching in secondary lymphoid organs or locally in the lungs in inducible bronchus-associated lymphoid tissue (iBALT). The aim of this work was to identify the exact site of DEP-mediated B-cell IgE class switching and pro-allergic antibody production.

Early IgE Production Is Linked with Extrafollicular B- and T-Cell Activation in Low-Dose Allergy Model.

Despite its paramount importance, the predominant association of early IgE production with harmless antigens, via germinal-center B- and T-cell subpopulations or extrafollicular activation, remains unresolved. The aim of this work was to clarify whether the reinforced IgE production following the subcutaneous immunization of BALB/c mice with low antigen doses in withers adipose tissue might be linked with intensified extrafollicular or germinal-center responses. The mice were immunized three times a week for 4 weeks in the withers region, which is enriched in subcutaneous fat and tissue-associated B cells, with high and low OVA doses and via the intraperitoneal route for comparison.

Effects of Primary Biliary Cholangitis on Quality of Life and Health Care Costs in the United Kingdom.

Background & Aims: There have been few high-quality studies of the costs, preference-based health-related quality of life (HRQoL) and cost effectiveness of treatments for primary biliary cholangitis (PBC). We aimed to estimate the marginal effects of PBC complications and symptoms, accounting for treatment, on HRQoL and the annual cost of health care in the United Kingdom (UK). These are essential components for evaluation of cost effectiveness and this information will aid in evaluation of new treatments.

Health-related quality of life and patient-reported outcome measures in NASH-related cirrhosis.

Background & Aims: Non-alcoholic steatohepatitis (NASH) is known to have a negative impact on patients' health-related quality of life (HRQoL), even before progression to cirrhosis has occurred. The burden of NASH-related cirrhosis from the patient perspective remains poorly understood. Herein, we aimed to identify the burden of disease and HRQoL impairment among patients with NASH-related compensated cirrhosis.

Characteristics of multicellular tumor spheroids formed by pancreatic cells expressing different adhesion molecules.

Aims: Multicellular tumor spheroids (MCTS) produced by different methods vary in forms, sizes, and properties. The aim of this work was to characterize MCTS formed by six pancreatic cell lines on a non-adherent surface.

Materials And Methods: Human pancreatic cells were grown in 2D and 3D conditions and compared for the expression of E- and desmosomal cadherins (PCR, confocal microscopy), growth, cell cycling, apoptosis (flow cytometry), and a response to antitumor drugs doxorubicin and gemcitabine (MTT-assay).

Making healthy homes? A pilot study of the return on investment from an external wall insulation intervention.

Objectives: External Wall Insulation (EWI) insulates and protect homes against damp. The Energy Company Obligation (ECO) scheme incentivised large energy providers in the UK delivering energy efficiency measures such as EWI to fuel impoverished households. Return on Investment (ROI) analysis is utilised to determine if EWI is a cost-effective procedure in terms of improving health related quality of life (HRQOL) measured using the EQ-5D-3L™, reducing health care expenditure, and fuel costs.

Direct versus sequential immunoglobulin switch in allergy and antiviral responses.

Allergy is characterized by IgE production to innocuous antigens. The question whether the switch to IgE synthesis occurs via direct or sequential pathways is still unresolved. The aim of this work was to analyze the distribution of immunoglobulins (Ig) to house dust mite D.

Comparison of cardiac output determined by bioimpedance and bioreactance methods at rest and during exercise.

Bioreactance is a novel non-invasive method for cardiac output measurement that involves the analysis of blood flow-dependent changes in the phase shifts of electrical currents applied across the chest. The present study (1) compared resting and exercise cardiac outputs determined by bioreactance and bioimpedance methods and those estimated from measured oxygen consumption, (2) determined the relationship between cardiac output and oxygen consumption, and (3) assessed the agreement between the bioreactance and bioimpedance methods. Twelve healthy subjects (aged 30 ± 4 years) performed graded cardiopulmonary exercise test on a recumbent cycle ergometer on two occasions, 1 week apart.

Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case-control study.

Background: Chronic fatigue syndrome (CFS) patients frequently describe difficulties with repeat exercise. Here, we explore muscle bioenergetic function in response to three bouts of exercise.

Methods: A total of 18 CFS (CDC 1994) patients and 12 sedentary controls underwent assessment of maximal voluntary contraction (MVC), repeat exercise with magnetic resonance spectroscopy and cardio-respiratory fitness test to determine anaerobic threshold.

Resistance exercise reduces liver fat and its mediators in non-alcoholic fatty liver disease independent of weight loss.

Background: Lifestyle interventions focusing on weight loss remain the cornerstone of non-alcoholic fatty liver disease (NAFLD) management. Despite this, the weight losses achieved in research trials are not easily replicated in the clinic and there is an urgent need for therapies independent of weight loss. Aerobic exercise is not well sustained and the effectiveness of the better tolerated resistance exercise upon liver lipid and mediators of liver lipid has not been assessed.

Toso regulates the balance between apoptotic and nonapoptotic death receptor signaling by facilitating RIP1 ubiquitination.

The regulation of cellular survival and apoptosis is of critical importance for the immune system to maintain immune homeostasis and to establish tolerance. Here, we demonstrate that the immune specific cell surface molecule Toso exhibits antiapoptotic effects on death receptor signaling by a novel regulatory mechanism involving the adaptor kinase RIP1. The antiapoptotic function of Toso depends on RIP1 ubiquitination and involves the recruitment of the death adaptor FADD to a Toso/RIP1 protein complex.

Impaired cardiovascular function in primary biliary cirrhosis.

Cardiovascular system dysregulation in the form of autonomic dysfunction is common at all stages of the disease process in the autoimmune liver disease primary biliary cirrhosis (PBC) and associates with the symptom of fatigue. The mechanisms underpinning autonomic dysfunction in PBC are, however, at present unclear. In this study we set out to explore, for the first time, cardiac structure and function in PBC using impedance cardiography (ICG) and magnetic resonance methodologies.

Endosomal trafficking of the ligated FcvarepsilonRI receptor.

In addition to initiating signaling cascades leading to mast cell mediator release, aggregation of the high affinity IgE receptor (FcvarepsilonRI) leads to rapid internalization of the cross-linked receptor. However, little is known about the trafficking of the internalized FcvarepsilonRI. Here we demonstrate that in RBL-2H3 cells, aggregated FcvarepsilonRI appears in the early endosomal antigen 1 (EEA1(+)) domains of the early endosomes within 15min after ligation.

The high-affinity immunoglobulin-E receptor (FcepsilonRI) is endocytosed by an AP-2/clathrin-independent, dynamin-dependent mechanism.

Aggregation of the high-affinity immunoglobulin E (IgE) receptor (FcepsilonRI), expressed on mast cells and basophils, initiates the immediate hypersensitivity reaction. Aggregated FcepsilonRI has been reported to rapidly migrate to lipid rafts in RBL-2H3 cells. We confirmed that aggregated FcepsilonRI is found in the lipid raft fractions of cellular lysates.

Importance of Protocol Immunization in Epitope Selectivity of Monoclonal Antibodies Interacting with Binding Subunit of Viscumin.

The application of two immunization protocols and two screening systems has allowed to produce five hybridomas mlb5, mlb6, mlb7, mlb9 and Mbch1, secreting mAbs against different sites of viscumin B-subunit. On the base of mlb9 and Mbch1 hybridomas, the test-system has been developed, able to detect up to 5 ng/ml of viscumin and up to 1 ng/ml of its B-chain. Produced hybridomas and monoclonal antibodies will be used for the studies of intracellular transport of plant toxins.

Specific binding of glucosaminylmuramyl peptides to histones.

Intracellular N-acetylglucosaminylmuramyl peptide-binding proteins of murine macrophages and myelomonocytic WEHI-3 cells were characterized. SDS-PAGE and Western blotting revealed proteins with molecular masses of 18, 32 and 34 kDa retaining the ability to specifically bind glucosaminylmuramyl dipeptide. The inhibition analysis demonstrated that only biologically active muramyl peptides but not inactive analogs or fragments of glucosaminylmuramyl dipeptide could inhibit glucosaminylmuramyl dipeptide-binding to these proteins.