Neutrophil-specific expression of JAK2-V617F or CALRmut induces distinct inflammatory profiles in myeloproliferative neoplasia.

Background: Neutrophils play a crucial role in inflammation and in the increased thrombotic risk in myeloproliferative neoplasms (MPNs). We have investigated how neutrophil-specific expression of JAK2-V617F or CALRdel re-programs the functions of neutrophils.

Methods: Ly6G-Cre JAK2-V617F and Ly6G-Cre CALRdel mice were generated.

Directional mast cell degranulation of tumor necrosis factor into blood vessels primes neutrophil extravasation.

Tissue resident mast cells (MCs) rapidly initiate neutrophil infiltration upon inflammatory insult, yet the molecular mechanism is still unknown. Here, we demonstrated that MC-derived tumor necrosis factor (TNF) was crucial for neutrophil extravasation to sites of contact hypersensitivity-induced skin inflammation by promoting intraluminal crawling. MC-derived TNF directly primed circulating neutrophils via TNF receptor-1 (TNFR1) while being dispensable for endothelial cell activation.

Mast Cell Functions Linking Innate Sensing to Adaptive Immunity.

Although mast cells (MCs) are known as key drivers of type I allergic reactions, there is increasing evidence for their critical role in host defense. MCs not only play an important role in initiating innate immune responses, but also influence the onset, kinetics, and amplitude of the adaptive arm of immunity or fine-tune the mode of the adaptive reaction. Intriguingly, MCs have been shown to affect T-cell activation by direct interaction or indirectly, by modifying the properties of antigen-presenting cells, and can even modulate lymph node-borne adaptive responses remotely from the periphery.

Mast cells as protectors of health.

Mast cells (MCs), which are well known for their effector functions in T2-skewed allergic and also autoimmune inflammation, have become increasingly acknowledged for their role in protection of health. It is now clear that they are also key modulators of immune responses at interface organs, such as the skin or gut. MCs can prime tissues for adequate inflammatory responses and cooperate with dendritic cells in T-cell activation.

Engulfment of mast cell secretory granules on skin inflammation boosts dendritic cell migration and priming efficiency.

Background: Mast cells (MCs) are best known as key effector cells of allergic reactions, but they also play an important role in host defense against pathogens. Despite increasing evidence for a critical effect of MCs on adaptive immunity, the underlying mechanisms are poorly understood.

Objective: Here we monitored MC intercellular communication with dendritic cells (DCs), MC activation, and degranulation and tracked the fate of exocytosed mast cell granules (MCGs) during skin inflammation.

Although Abundant in Tumor Tissue, Mast Cells Have No Effect on Immunological Micro-milieu or Growth of HPV-Induced or Transplanted Tumors.

High numbers of mast cells populate the stroma of many types of neoplasms, including human papilloma virus-induced benign and malignant tumors in man and mouse. Equipped with numerous pattern recognition receptors and capable of executing important pro-inflammatory responses, mast cells are considered innate sentinels that significantly impact tumor biology. Mast cells were reported to promote human papilloma virus (HPV)-induced epithelial hyperproliferation and neo-angiogenesis in an HPV-driven mouse model of skin cancer.

Mast cells acquire MHCII from dendritic cells during skin inflammation.

Mast cells (MCs) and dendritic cells (DCs) are essential innate sentinels populating host-environment interfaces. Using longitudinal intravital multiphoton microscopy of DC/MC reporter mice, we herein provide in vivo evidence that migratory DCs execute targeted cell-to-cell interactions with stationary MCs before leaving the inflamed skin to draining lymph nodes. During initial stages of skin inflammation, DCs dynamically scan MCs, whereas at a later stage, long-lasting interactions predominate.

The Neurobeachin-like 2 Protein Regulates Mast Cell Homeostasis.

The neurobeachin-like 2 protein (Nbeal2) belongs to the family of beige and Chediak-Higashi (BEACH) domain proteins. Loss-of-function mutations in the human gene or Nbeal2 deficiency in mice cause gray platelet syndrome, a bleeding disorder characterized by macrothrombocytopenia, splenomegaly, and paucity of α-granules in megakaryocytes and platelets. We found that in mast cells, Nbeal2 regulates the activation of the Shp1-STAT5 signaling axis and the composition of the c-Kit/STAT signalosome.

Mast Cells Are Critical Regulators of Bone Fracture-Induced Inflammation and Osteoclast Formation and Activity.

Mast cells, important sensor and effector cells of the immune system, may influence bone metabolism as their number is increased in osteoporotic patients. They are also present during bone fracture healing with currently unknown functions. Using a novel c-Kit-independent mouse model of mast cell deficiency, we demonstrated that mast cells did not affect physiological bone turnover.

MK2/3 Are Pivotal for IL-33-Induced and Mast Cell-Dependent Leukocyte Recruitment and the Resulting Skin Inflammation.

The IL-1R family member IL-33R mediates Fcε-receptor-I (FcεRI)-independent activation of mast cells leading to NF-κB activation and consequently the production of cytokines. IL-33 also induces the activation of MAPKs, such as p38. We aimed to define the relevance of the p38-targets, the MAPK-activated protein kinases 2 and 3 (MK2 and MK3) in IL-33-induced signaling and the resulting mast cell effector functions in vitro and in vivo.

Mast-Cell-Derived TNF Amplifies CD8(+) Dendritic Cell Functionality and CD8(+) T Cell Priming.

Mast cells are critical promoters of adaptive immunity in the contact hypersensitivity model, but the mechanism of allergen sensitization is poorly understood. Using Mcpt5-CreTNF(FL/FL) mice, we show here that the absence of TNF exclusively in mast cells impaired the expansion of CD8(+) T cells upon sensitization and the T-cell-driven adaptive immune response to elicitation. T cells primed in the absence of mast cell TNF exhibited a diminished efficiency to transfer sensitization to naive recipients.

Mast cell promotion of T cell-driven antigen-induced arthritis despite being dispensable for antibody-induced arthritis in which T cells are bypassed.

Objective: The function of mast cells (MCs) in autoimmune disorders has been a subject of controversy recently. MC-deficient Kit(W/W-v) mice were found to be resistant to K/BxN serum-transfer arthritis, whereas Kit(W-sh/W-sh) mice and a genetic model of MC deficiency independent of the Kit mutation were found to be fully susceptible. This debate might lead to the assumption that MCs are dispensable in autoimmunity in general.

Increased bone remodelling around titanium implants coated with chondroitin sulfate in ovariectomized rats.

Coating titanium implants with artificial extracellular matrices based on collagen and chondroitin sulfate (CS) has been shown to enhance bone remodelling and de novo bone formation in vivo. The aim of this study was to evaluate the effect of estrogen deficiency and hormone replacement therapy (HRT) on the osseointegration of CS-modified Ti implants. 30 adult female, ovariectomized Wistar rats were fed either with an ethinyl-estradiol-rich diet (E) to simulate a clinical relevant HRT or with a genistein-rich diet (G) to test an alternative therapy based on nutritionally relevant phytoestrogens.

Practical blood flow restriction training increases muscle hypertrophy during a periodized resistance training programme.

Background: Resistance training in combination with practical blood flow restriction (pBFR) is thought to stimulate muscle hypertrophy by increasing muscle activation and muscle swelling. Most previous studies used the KAATSU device; however, little long-term research has been completed using pBFR.

Objective: To investigate the effects of pBFR on muscle hypertrophy.

Effects of 8 weeks of Xpand® 2X pre workout supplementation on skeletal muscle hypertrophy, lean body mass, and strength in resistance trained males.

Background: Xpand® 2X is a proprietary blend comprised of branched chain amino acids, creatine monohydrate, beta-alanine (CarnoSyn®), quercetin, coenzymated B-vitamins, alanyl-glutamine (Sustamine®), and natural nitrate sources from pomegranate and beet root extracts purported to enhance the neuromuscular adaptations of resistance training. However to date, no long-term studies have been conducted with this supplement. The purpose of this study was to investigate the effects of a multi-ingredient performance supplement (MIPS) on skeletal muscle hypertrophy, lean body mass and lower body strength in resistance-trained males.

The effects of 8 weeks of whey or rice protein supplementation on body composition and exercise performance.

Consumption of moderate amounts of animal-derived protein has been shown to differently influence skeletal muscle hypertrophy during resistance training when compared with nitrogenous and isoenergetic amounts of plant-based protein administered in small to moderate doses. Therefore, the purpose of the study was to determine if the post-exercise consumption of rice protein isolate could increase recovery and elicit adequate changes in body composition compared to equally dosed whey protein isolate if given in large, isocaloric doses.

Mast cells are key promoters of contact allergy that mediate the adjuvant effects of haptens.

A prominent feature of sensitizing environmental compounds that cause allergic contact dermatitis is the rapid induction of an innate inflammatory response that seems to provide danger signals for efficient T cell priming. We generated mouse models of mast cell deficiency, mast cell-specific gene inactivation, and mast cell reporter mice for intravital imaging and showed that these adjuvant effects of contact allergens are mediated by mast cells and histamine. Mast cell deficiency resulted in impaired emigration of skin DCs to the lymph node and contact hypersensitivity was dramatically reduced in the absence of mast cells.

Immature mast cells exhibit rolling and adhesion to endothelial cells and subsequent diapedesis triggered by E- and P-selectin, VCAM-1 and PECAM-1.

Mast cell numbers are markedly increased at sites of chronic inflammation. However, the underlying mechanisms of mast cell accumulation including mast cell progenitor trafficking remain to be identified in detail. Thus, the aim of this study was to identify the adhesion molecules involved in rolling, firm adhesion and transendothelial diapedesis of murine bone marrow-derived cultured mast cells (BMCMC) as a model for immature mast cells.

Changes in Medical Documentation over the Last Five Decades.

In medical documentation, standardized coding schemes are used to facilitate sharing, transformation and reusability of data. First, classification systems coding schemes have been introduced. While classification systems are mainly used for statistical purposes, individual care documentation moves towards the use of nomenclatures coding schemes.

A reference model for clinical tumour documentation.

The definition of common system semantics is an explicit and generally accepted precondition for comparability and exchangeability of data from different systems. We have looked back on 15 years of experience with a data model that was developed in a co-operative effort by experts from various hospital cancer registries as the foundation of a new tumour documentation system (GTDS). The data model is based on the definition of a common basic data set for hospital cancer registries which is agreed by the German Association of Comprehensive Cancer Centres (ADT).

The Giessen Tumor Documentation System (GTDS)--review and perspectives.

Objectives: GTDS is a documentation system used by more than 40 German hospital cancer registries. This paper discusses the factors that contributed to its success concerning design, development, and routine use.

Methods: Success is measured in terms of the system's financial independence of public grants and its successful use by the registries.

Advanced Information Retrieval Using XML Standards.

The bulk of clinical data is available in an electronic form. About 80% of the electronic data, however, is narrative text and therefore limited with respect to machine interpretation. As a result, the discussion has shifted from "electronic versus paper based data" towards "structured versus unstructured electronic data".

Standardized Semantic Markup for Reference Terminologies, Thesauri and Coding Systems: Benefits for distributed E-Health Applications.

With the introduction of the ICD-10 as the standard for diagnosis, the development of an electronic representation of its complete content, inherent semantics and coding rules is necessary. Our concept refers to current efforts of the CEN/TC 251 to establish a European standard for hierarchical classification systems in healthcare. We have developed an electronic representation of the ICD-10 with the extensible Markup Language (XML) that facilitates the integration in current information systems or coding software taking into account different languages and versions.

Implementing health care systems using XML standards.

Most healthcare data is narrative text and often not accessible and easy to find at the clinical workstation. XML related standards (XML schema, XForms, XSL, Topic Maps, etc.) provide an infrastructure that might change the situation.