Targeting IL-4/IL-13 signaling to alleviate oral allergen-induced diarrhea.

Background: Intestinal anaphylaxis (manifested by acute diarrhea) is dependent on IgE and mast cells.

Objective: We aimed to define the respective roles of IL-4 and IL-13 and their receptors in disease pathogenesis.

Methods: Wild-type mice and mice deficient in IL-4, IL-13, and IL-13 receptor (IL-13R) alpha1 (part of the type 2 IL-4 receptor [IL-4R]) were sensitized with ovalbumin (OVA)/aluminum potassium sulfate and subsequently given repeated intragastric OVA exposures.

Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a neurodegenerative condition defined clinically by lower limb spasticity and weakness. Homozygous mutations in CYP7B1 have been identified in several consanguineous families that represented HSP type 5 (SPG5), one of the many genetic forms of the disease. We used direct sequencing and multiplex ligation-dependent probe amplification to screen for CYP7B1 alterations in apparently sporadic HSP patients (n = 12) as well as index patients from non-consanguineous families with recessive (n = 8) and dominant (n = 8) transmission of HSP.

Burkholderia latens sp. nov., Burkholderia diffusa sp. nov., Burkholderia arboris sp. nov., Burkholderia seminalis sp. nov. and Burkholderia metallica sp. nov., novel species within the Burkholderia cepacia complex.

The taxonomic position of five recA gene clusters of Burkholderia cepacia complex (Bcc) isolates was determined using a polyphasic taxonomic approach. The levels of 16S rRNA and recA gene sequence similarity, multilocus sequence typing (MLST) data and the intermediate DNA-DNA binding values demonstrated that these five clusters represented five novel species within the Bcc. Biochemical identification of these species is difficult, as is the case for most Bcc species.

FIP1L1/PDGFRalpha synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome.

Expression of the fusion gene FIP1-like 1/platelet-derived growth factor receptor alpha (FIP1L1/PDGFRalpha, F/P) and dysregulated c-kit tyrosine kinase activity are associated with systemic mastocytosis (SM) and chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome (HES). We analyzed SM development and pathogenesis in a murine CEL model induced by F/P in hematopoietic stem cells and progenitors (HSCs/Ps) and T-cell overexpression of IL-5 (F/P-positive CEL mice). These mice had more mast cell (MC) infiltration in the bone marrow (BM), spleen, skin, and small intestine than control mice that received a transplant of IL-5 transgenic HSCs/Ps.

Sialyltransferase ST3Gal-IV controls CXCR2-mediated firm leukocyte arrest during inflammation.

Recent in vitro studies have suggested a role for sialylation in chemokine receptor binding to its ligand (Bannert, N., S. Craig, M.

Mitigation of patient harm from testing errors in family medicine offices: a report from the American Academy of Family Physicians National Research Network.

Objectives: Little research has focused on preventing harm from errors that occur in primary care. We studied mitigation of patient harm by analysing error reports from family physicians' offices.

Methods: The data for this analysis come from reports of testing process errors identified by family physicians and their office staff in eight practices in the American Academy of Family Physicians National Research Network.

Testing process errors and their harms and consequences reported from family medicine practices: a study of the American Academy of Family Physicians National Research Network.

Context: Little is known about the types and outcomes of testing process errors that occur in primary care.

Objective: To describe types, predictors and outcomes of testing errors reported by family physicians and office staff.

Design: Events were reported anonymously.

Distinct roles for IL-13 and IL-4 via IL-13 receptor alpha1 and the type II IL-4 receptor in asthma pathogenesis.

IL-13 and IL-4 are central T helper 2 (Th2) cytokines in the immune system and potent activators of inflammatory responses and fibrosis during Th2 inflammation. Recent studies using Il13ra1(-/-) mice have demonstrated a critical role for IL-13 receptor (IL-13R) alpha1 in allergen-induced airway responses. However, these observations require further attention especially because IL-4 can induce similar lung pathology to IL-13, independent of IL-13, and is still present in the allergic lung.

IL-9- and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity.

Previous mouse and clinical studies demonstrate a link between Th2 intestinal inflammation and induction of the effector phase of food allergy. However, the mechanism by which sensitization and mast cell responses occurs is largely unknown. We demonstrate that interleukin (IL)-9 has an important role in this process.

Surfactant protein D alters allergic lung responses in mice and human subjects.

Background: Surfactant protein (SP) D has been proposed to be protective in allergic airway responses.

Objective: We aimed to determine the effect of SP-D deficiency on murine and human airway allergy.

Methods: Immunologic responses of SP-D gene-deficient mice (Sftpd-/-) at baseline and after 4 intranasal Aspergillus fumigatus exposures were assessed.

Coamplification of eukaryotic DNA with 16S rRNA gene-based PCR primers: possible consequences for population fingerprinting of complex microbial communities.

The main aim of this study was to evaluate the specificity of three commonly used 16S rRNA gene-based polymerase chain reaction (PCR) primer sets for bacterial community analysis of samples contaminated with eukaryotic DNA. The specificity of primer sets targeting the V3, V3-V5, and V6-V8 hypervariable regions of the 16S rRNA gene was investigated in silico and by community fingerprinting of human and fish intestinal samples. Both in silico and PCR-based analysis revealed cross-reactivity of the V3 and V3-V5 primers with the 18S rRNA gene of human and sturgeon.

Comparative performance of different PCR assays for the identification of Campylobacter jejuni and Campylobacter coli.

The sensitivity and specificity of 7 PCR assays described for the identification of Campylobacter jejuni and Campylobacter coli were examined using alkaline cell lysates from a collection of 100 well characterized reference strains of C. jejuni, C. coli, Campylobacter lari and related Campylobacter, Helicobacter and Arcobacter species.

Burkholderia sartisoli sp. nov., isolated from a polycyclic aromatic hydrocarbon-contaminated soil.

A Gram-negative, rod-shaped, aerobic bacterium, designated strain RP007(T), was isolated from a polycyclic aromatic hydrocarbon-contaminated soil in New Zealand. Two additional strains were recovered from a compost heap in Belgium (LMG 18808) and from the rhizosphere of maize in the Netherlands (LMG 24204). The three strains had virtually identical 16S rRNA gene sequences and whole-cell protein profiles, and they were identified as members of the genus Burkholderia, with Burkholderia phenazinium as their closest relative.

Collimonas arenae sp. nov. and Collimonas pratensis sp. nov., isolated from (semi-)natural grassland soils.

A polyphasic taxonomic study was performed to compare 26 novel bacterial isolates obtained from (semi-)natural grassland soils and a heathland soil in the Netherlands with 16 strains that had previously been assigned to the genus Collimonas. Genomic fingerprinting (BOX-PCR), whole-cell protein electrophoresis, matrix-assisted laser desorption ionization time-of-flight mass spectrometry of intact cells and physiological characterization (Biolog) of the isolates confirmed the existence of different strain clusters (A-D) within the genus Collimonas. Until now, only cluster C strains have been formally classified, as Collimonas fungivorans.

Platelet factor 4/CXCL4-stimulated human monocytes induce apoptosis in endothelial cells by the release of oxygen radicals.

The generation of reactive oxygen species (ROS) represents a pivotal element of phagocyte defense against microbial invaders. However, oxidative stress also participates in pathophysiological processes of vascular damage leading to cell death of endothelial cells (EC). Currently, ROS-producing cells involved in this process as well as the corresponding extracellular signals required for their activation are ill-defined.

All-terrain vehicle crash factors and associated injuries in patients presenting to a regional trauma center.

Background: It is widely accepted that all-terrain vehicles (ATVs) can be dangerous to operators. Understanding the mechanisms of ATV crashes, especially rollovers, can provide important insight to consumers, legislators, and manufacturers on ATV safety and protection of the users.

Methods: From March 1, 2003 to July 31, 2005, all patients with ATV-related injuries presenting to a regional trauma center were enrolled in an ATV crash data bank.

Burkholderia bryophila sp. nov. and Burkholderia megapolitana sp. nov., moss-associated species with antifungal and plant-growth-promoting properties.

A polyphasic taxonomic study including DNA-DNA reassociation experiments and an extensive biochemical characterization was performed on 14 Burkholderia isolates from moss gametophytes of nutrient-poor plant communities on the southern Baltic Sea coast in northern Germany. The strains were classified within two novel species, for which the names Burkholderia bryophila sp. nov.

Platelet factor 4 (CXC chemokine ligand 4) differentially regulates respiratory burst, survival, and cytokine expression of human monocytes by using distinct signaling pathways.

Platelet factor 4 (PF4; CXCL4) is an abundant platelet alpha-granule CXC chemokine with unique functions. Although lacking a chemotactic activity, PF4 initiates a signal transduction cascade in human monocytes leading to the induction of a broad spectrum of acute and delayed functions including phagocytosis, respiratory burst, survival, and the secretion of cytokines. Surprisingly, although these monocyte functions are well defined, only very limited information exists on the specific signaling pathways that are involved in the regulation of these biological responses.

IL-15 constrains mast cell-dependent antibacterial defenses by suppressing chymase activities.

Sepsis remains a global clinical problem. By using the mouse cecal ligation and puncture model of sepsis, here we identify an important aspect of mast cell (MC)-dependent, innate immune defenses against Gram-negative bacteria by demonstrating that MC protease activity is regulated by interleukin-15 (IL-15). Mouse MCs express both constitutive and lipopolysaccharide-inducible IL-15 and store it intracellularly.

Platelet-derived chemokines in vascular biology.

Undoubtedly, platelets are key elements in the regulation of thrombosis and haemostasis. Along with their primary task to prevent blood loss from injured vessels, platelets have emerged as regulators of a variety of processes in the vasculature. Multiple challenges, from the contact and adhesion to subendothelial matrix after injury of the vessel wall, to interactions with blood cells in inflammatory conditions, result in platelet activation with concomitant shape change and release of numerous substances.

Identification of an efficacy switch region in the ghrelin receptor responsible for interchange between agonism and inverse agonism.

The carboxyamidated wFwLL peptide was used as a core ligand to probe the structural basis for agonism versus inverse agonism in the constitutively active ghrelin receptor. In the ligand, an efficacy switch could be built at the N terminus, as exemplified by AwFwLL, which functioned as a high potency agonist, whereas KwFwLL was an equally high potency inverse agonist. The wFw-containing peptides, agonists as well as inverse agonists, were affected by receptor mutations covering the whole main ligand-binding pocket with key interaction sites being an aromatic cluster in transmembrane (TM)-VI and -VII and residues on the opposing face of TM-III.

Barriers and motivators for making error reports from family medicine offices: a report from the American Academy of Family Physicians National Research Network (AAFP NRN).

Context: Reporting of medical errors is a widely recognized mechanism for initiating patient safety improvement, yet we know little about the feasibility of error reporting in physician offices, where the majority of medical care in the United States is rendered.

Objective: To identify barriers and motivators for error reporting by family physicians and their office staff based on the experiences of those participating in a testing process error reporting study.

Design: Qualitative focus group study, analyzed using the editing method.

Comparative in silico analysis of two vaccine candidates for group A streptococcus predicts that they both may have similar safety profiles.

Concerns of immune cross-reactivity, between epitopes of the group A streptococcal (GAS) M-proteins and host proteins have hindered the progress of an effective GAS vaccine. An ideal M-protein based subunit vaccine should not elicit heart tissue cross-reactive antibody responses and should not activate M-protein specific CD4+ T-cells. In the current study we used a bioinformatic and immunoinformatic approach to assess the safety of J8 and J14, chimeric vaccine constructs containing a GAS derived M-protein epitope embedded in flanking GCN4 region.

Molecular monitoring of the fecal microbiota of healthy human subjects during administration of lactulose and Saccharomyces boulardii.

Diet is a major factor in maintaining a healthy human gastrointestinal tract, and this has triggered the development of functional foods containing a probiotic and/or prebiotic component intended to improve the host's health via modulation of the intestinal microbiota. In this study, a long-term placebo-controlled crossover feeding study in which each subject received several treatments was performed to monitor the effect of a prebiotic substrate (i.e.

Biomechanical analysis of the percutaneous compression plate and sliding hip screw in intracapsular hip fractures: experimental assessment using synthetic and cadaver bones.

We compared the mechanical behaviour of osteosynthesis with the percutaneous compression plate (PCCP) compared with the standard osteosynthesis sliding hip screw (SHS) in intracapsular hip fractures. We created 10 stable and 10 unstable intracapsular hip fractures in 20 synthetic femurs. Each fracture was fixed with either the SHS or PCCP.