Purified Timothy grass pollen major allergen Phl p 1 may contribute to the modulation of allergic responses through a pleiotropic induction of cytokines and chemokines from airway epithelial cells.

By definition, allergens are proteins with the ability to elicit powerful T helper lymphocyte type 2 (Th2) responses, culminating in immunoglobulin (Ig)E antibody production. Why specific proteins cause aberrant immune responses has remained largely unanswered. Recent data suggest that there may be several molecular paths that may affect allergenicity of proteins.

Effect-directed assessment of the bioaccumulation potential and chemical nature of Ah receptor agonists in crude and refined oils.

Recent studies have indicated that in addition to narcosis certain chemicals in crude oils and refined petroleum products may induce specific modes of action, such as aryl hydrocarbon receptor (AhR) agonism. The risks these toxic compounds pose to organisms depend on internal exposure levels, as driven by the chemicals' bioaccumulation potential. Information on this potential however is lacking, as the chemicals' identity mostly is unknown.

Does equilibrium passive sampling reflect actual in situ bioaccumulation of PAHs and petroleum hydrocarbon mixtures in aquatic worms?

Over the past couple of years, several analytical methods have been developed for assessing the bioavailability of environmental contaminants in sediments and soils. Comparison studies suggest that equilibrium passive sampling methods generally provide the better estimates of internal concentrations in organisms and thus of subsequent risks. However, field studies to validate the potential of passive sampling to predict actual in situ bioaccumulation are scarce and limited information only exists on selected, individual compounds.

Passive samplers provide a better prediction of PAH bioaccumulation in earthworms and plant roots than exhaustive, mild solvent, and cyclodextrin extractions.

A number of extraction methods have been developed to assess polycyclic aromatic hydrocarbon (PAH) bioavailability in soils. As these methods are rarely tested in a comparative manner, against different test organisms, and using field-contaminated soils, it is unclear which method gives the most accurate measure of the actual soil ecosystem exposure. In this study, PAH bioavailability was assessed in ten field-contaminated soils by using exhaustive acetone/hexane extractions, mild solvent (butanol) extractions, cyclodextrin extractions, and two passive sampling methods; solid phase micro extraction (SPME) and polyoxymethylene solid phase extraction (POM-SPE).

Renal cancer and pneumothorax risk in Birt-Hogg-Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families.

Background: Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition caused by germline FLCN mutations, and characterised by fibrofolliculomas, pneumothorax and renal cancer. The renal cancer risk, cancer phenotype and pneumothorax risk of BHD have not yet been fully clarified. The main focus of this study was to assess the risk of renal cancer, the histological subtypes of renal tumours and the pneumothorax risk in BHD.

Human testis-derived embryonic stem cell-like cells are not pluripotent, but possess potential of mesenchymal progenitors.

Background: Spontaneous in vitro transition of undifferentiated spermatogonia into the pluripotent cell state has been achieved using neonatal and adult mouse testis tissue. In an effort to establish an analogous source of human patient-specific pluripotent stem cells, several research groups have described the derivation of embryonic stem cell-like cells from primary cultures of human testis. These cells are characterized in all studies as growing in compact colonies, expressing pluripotency-associated markers and possessing multilineage differentiation capabilities in vitro, but only one study claimed their ability to induce teratomas.

CHEK2*1100delC homozygosity is associated with a high breast cancer risk in women.

Background: Mutations in the CHEK2 gene confer a moderately increased breast cancer risk. The risk for female carriers of the CHEK2*1100delC mutation is twofold increased. Breast cancer risk for carrier women is higher in a familial breast cancer setting which is due to coinheritance of additional genetic risk factors.

Intra- and interspecies variation in bioconcentration potential of polychlorinated biphenyls: are all lipids equal?

The variation among bioconcentration factors (BCFs) available in the literature is commonly ascribed to experimental parameters and metabolic capacity. Though bioconcentration is generally considered to be governed by partitioning processes and therefore to depend on the composition of the partition phases, the effect of lipid composition on BCFs measured for hydrophobic organic chemicals has largely escaped attention. The reason may be that the effect cannot easily be studied separately in a conventional BCF test setup and that any subtle effects will often be obscured by the variation normally observed when working with living organisms.

Route and type of nutrition and surgical stress influence secretory phospholipase A2 secretion of the murine small intestine.

Background: The function of secretory phospholipase A2 (sPLA2) is site dependent. In tissue, sPLA2 regulates eicosanoid production; in circulation, sPLA2 primes neutrophils; and in the intestinal lumen, sPLA2 provides innate bactericidal immunity as a defensin-related protein. Since parenteral nutrition (PN) primes leukocytes while suppressing intraluminal mucosal immunity, the authors hypothesized that (1) PN would diminish luminal sPLA2 activity but increase activity in intestinal tissue and serum and (2) stress would accentuate these changes.

Activation of WNT/β-catenin signaling in pulmonary fibroblasts by TGF-β₁ is increased in chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by abnormal extracellular matrix (ECM) turnover. Recently, activation of the WNT/β-catenin pathway has been associated with abnormal ECM turnover in various chronic diseases. We determined WNT-pathway gene expression in pulmonary fibroblasts of individuals with and without COPD and disentangled the role of β-catenin in fibroblast phenotype and function.

Single cell transcriptomics of neighboring hyphae of Aspergillus niger.

Single cell profiling was performed to assess differences in RNA accumulation in neighboring hyphae of the fungus Aspergillus niger. A protocol was developed to isolate and amplify RNA from single hyphae or parts thereof. Microarray analysis resulted in a present call for 4 to 7% of the A.

Measuring picogram per liter concentrations of freely dissolved parent and alkyl PAHs (PAH-34), using passive sampling with polyoxymethylene.

Passive sampling with nondepletive sorbents is receiving increasing interest because of its potential to measure freely dissolved concentrations of hydrophobic organic compounds (HOCs) at very low concentrations, as well as its potential for both laboratory use and field deployment. However, consistent approaches have yet to be developed for the majority of HOCs of environmental and regulatory interest. In the present study, a passive sampling method was developed which allows the freely dissolved concentrations of 18 parent and 16 groups of alkyl polycyclic aromatic hydrocarbons (PAHs) on the U.

The interleukin-2 antagonizing antibody MT204 delays allogeneic skin graft rejection in non-human primates and is well tolerated.

MT204 is a humanized IgG1 antibody specific for interleukin-2 (IL-2) of human and rhesus monkey origin. It potently antagonizes IL-2 signaling in both CD25(+) and CD25(-) cells by a unique mode of action. MT204 can not only prevent soluble IL-2 from binding to the intermediate affinity IL-2 receptors but can also antagonize IL-2 that is already bound to the CD25 subunit of high affinity IL-2 receptors on the cell surface.

Measuring and modeling adsorption of PAHs to carbon nanotubes over a six order of magnitude wide concentration range.

Understanding the interactions between organic contaminants and carbon nanomaterials is essential for evaluating the materials' potential environmental impact and their application as sorbent. Although a great deal of work has been published in the past years, data are still limited in terms of compounds, concentrations, and conditions investigated. We applied a passive sampling method employing polyoxymethylene (POM-SPE) to gain a better understanding of the interactions between polycyclic aromatic hydrocarbons (PAHs) and multiwalled carbon nanotubes (CNTs) over a 6 orders of magnitude wide concentration range.

Effects of black carbon on bioturbation-induced benthic fluxes of polychlorinated biphenyls.

It is unknown whether carbonaceous geosorbents, such as black carbon (BC) affect bioturbation by benthic invertebrates, thereby possibly affecting sediment-water exchange of sediment-bound contaminants. Here, we assess the effects of oil soot on polychlorinated biphenyl (PCB) mass transfer from sediment to overlying water, for sediments with and without tubificid oligochaeta as bioturbators. PCB levels were so low that toxicity to the oligochaeta played no role, whereas soot levels and binding affinity of PCBs to soot were so low that pore water PCB concentrations were not significantly affected by binding of PCBs to soot.

Timothy grass pollen extract-induced gene expression and signalling pathways in airway epithelial cells.

Background: Grass pollen allergy is one of the most common allergies worldwide and airborne allergens are the major cause of allergic rhinitis. Airway epithelial cells (AECs) are the first to encounter and respond to aeroallergens and are therefore interesting targets for the development of new therapeutics. Our understanding of the epithelial contribution to immune responses is limited as most studies focus on only a few individual genes or proteins.

Assessing the bioavailability of complex petroleum hydrocarbon mixtures in sediments.

Several experimental methods have been developed to assess the bioavailability of individual organic compounds. So far none of them has however been applied to complex mixtures, such as oil (petroleum hydrocarbons), which is an ubiquitous pollutant. In the present study, we tested the potential of five of these experimental methods and that of a model approach to predict bioaccumulation of oil in the aquatic worm Lumbriculus variegatus exposed to 14 field-contaminated sediments.

Parenteral nutrition impairs lymphotoxin β receptor signaling via NF-κB.

Objective: To determine effects of (1) parenteral nutrition (PN), (2) exogenous Lymphotoxin β receptor (LTβR) stimulation in PN animals, and (3) exogenous LTβR blockade in chow animals on NF-κB activation pathways and products: MAdCAM-1, chemokine (C-C motif) Ligand (CCL) 19, CCL20, CCL25, interleukin (IL)-4, and IL-10.

Background: LT stimulates LTβR in Peyer's patches (PP) to activate NF-κB via the noncanonical pathway. The p100/RelB precursor yields p52/RelB producing MAdCAM-1, cytokines, and chemokines important in cell trafficking.

Serious complications in gene-expression studies with stress perturbation: An example of UV-exposed p53-mutant mouse embryonic fibroblasts.

Reanalysis of our UV study of p53-mutant mouse embryonic fibroblasts revealed an intriguing orchestration of massive transcriptome responses. However, close scrutiny of the data uncovered an affected mRNA/rRNA ratio, effectively inhibiting valid data analysis. UV-dose range-finding showed low-dose UV specific- and high-dose stress-related responses, which represent a plea for UV dose range-finding in experimental design.

Life cycle responses of the midge Chironomus riparius to compounds with different modes of action.

Compounds with different modes of action may affect life cycles of biota differently. The aim of the present study was therefore to investigate the impact of four chemicals with different modes of action, including the essential metal copper, the nonessential metal cadmium, the organometal tributyltin, and the polycyclic aromatic compound phenanthrene, on chronic lethal and sublethal life-cycle effect parameters of the nonbiting midge Chironomus riparius, applying a 28-day sediment toxicity test. Tributyltin and cadmium delayed emergence significantly over a wide range of sublethal concentrations, while this range was narrow for copper and almost absent for phenanthrene.

Injury induces localized airway increases in pro-inflammatory cytokines in humans and mice.

Background: Secretory immunoglobulin A (sIgA) increases in the airways of humans and mice after injury to protect against infection. The pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 are linked molecularly to sIgA production and secretion and are required for sIgA increases in the airway after injury in a mouse model. We investigated the injury effect on airway and serum concentrations to determine the source of the cytokines involved in the airway IgA response.

Small intestine mucosal immune system response to injury and the impact of parenteral nutrition.

Background: Both humans and mice increase airway immunoglobulin A (IgA) after injury. This protective response is associated with TNF-α, IL-1β, and IL-6 airway increases and in mice is dependent upon these cytokines as well as enteral feeding. Parenteral nutrition (PN) with decreased enteral stimulation (DES) alters gut barrier function, decreases intestinal IgA, and decreases the principal IgA transport protein pIgR.

Finding maximal transcriptome differences between reprotoxic and non-reprotoxic phthalate responses in rat testis.

The chemical legislation of the EU, Registration, Evaluation, and Authorization of Chemicals (REACH), stipulates that about 30 000 chemical substances are to be assessed on their possible risks. Toxicological evaluation of these compounds will at least partly be based on animal testing. In particular, the assessment of reproductive toxicity is a very complicated, time-consuming and animal-demanding process.