Original Article Guidelines and diagnostic algorithm for patients with suspected systemic mastocytosis: a proposal of the Austrian competence network (AUCNM)

Abstract: Systemic mastocytosis (SM) is a hematopoietic neoplasm characterized by pathologic expansion of tissue mast cells in one or more extracutaneous organs. In most children and most adult patients, skin involvement is found. Childhood patients frequently suffer from cutaneous mastocytosis without systemic involvement, whereas most adult patients are diagnosed as suffering from SM. In a smaller subset of patients, SM without skin lesions develops which is a diagnostic challenge. In the current article, a diagnostic algorithm for patients with suspected SM is proposed. In adult patients with skin lesions and histologically confirmed mastocytosis in the skin (MIS), a bone marrow biopsy is recommended regardless of the serum tryptase level. In adult patients without skin lesions who are suffering from typical mediator-related symptoms, the basal serum tryptase level is an important diagnostic parameter. In those with slightly elevated tryptase (15-30 ng/ml), additional non-invasive investigations, including a KIT mutation analysis of peripheral blood cells and sonographic analysis, is performed. In adult patients in whom i) KIT D816V is detected or/and ii) the basal serum tryptase level is clearly elevated (> 30 ng/ml) or/and iii) other clinical or laboratory features are suggesting the presence of occult mastocytosis, a bone marrow biopsy should be performed. In the absence of KIT D816V and other indications of mastocytosis, no bone marrow investigation is required, but the patient's course and the serum tryptase levels are examined in the follow-up

NOx- REDUCTION WITH STAGED COMBUSTION - COMPARISON OF EXPERIMENTAL AND MODELLING RESULTS

INTRODUCTION The IVD of the University of Stuttgart carries out investigations of in-furnace DeNOx technologies using an electrically heated bench-scale test facility where the different process parameters are evaluated independently. The DeNOx technologies of air and fuel staging have been demonstrated to be effective control techniques to reduce NO x from coal-fired utility boilers. In order to assure a good reduction efficiency the process parameters temperature, stoichiometry and residence time must be carefully controlled. The importance of and interest in applying mathematical models is growing as they are a tool giving information about the combustion behaviour inside full-scale power station combustors. Until today discretization has been fairly coarse, and simple `global' reaction models are used for the pyrolysis of coal, the burnout of the char and the formation or reduction of NO. The NO formation and reduction in substoichiometric regions is strongly infl

Conversion of RP models to investment castings

The Tooling and Casting subgroup of the European Action on Rapid Prototyping (EARP) has undertaken a project to investigate the problems associated with using rapid prototype models as sacrificial patterns for investment casting. The accuracy and surface finish of the models and the castings were also assessed so that a comparison could be made. Models from each process were manufactured by different members of EARP and then three foundries were each given a set of models to convert to castings. Observes that one of the oldest metal manufacturing techniques, which dates back to 4000-6000 BC, is being used with one of the most modern - rapid prototyping

Nitric Oxide Promotes Airway Epithelial Wound Repair through Enhanced Activation of MMP-9

The airway epithelium provides a protective barrier against inhaled environmental toxins and microorganisms, and epithelial injury initiates a number of processes to restore its barrier integrity, including activation of matrix metalloproteinases such as MMP-9 (92-kD gelatinase B). Airway epithelial cells continuously produce nitric oxide (NO), which has been linked to cell migration and MMP-9 regulation in several cell types, but the importance of epithelial NO in mediating airway epithelial repair or MMP-9 activation is unknown. Using primary or immortalized human bronchial epithelial cells, we demonstrate that low concentrations of NO promote epithelial cell migration and wound repair in an in vitro wound assay, which was associated with increased localized expression and activation of MMP-9. In addition, in HBE1 cells that were stably transfected with inducible NOS (NOS2), to mimic constitutive epithelial NOS2 expression in vivo, NOS inhibition decreased epithelial wound repair and MMP-9 expression. The stimulatory effects of NO on epithelial wound repair and MMP-9 expression were dependent on cGMP-mediated pathways and were inhibited by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase. Inhibition of cGMP-dependent protein kinase (PKG) attenuated NO-mediated epithelial wound closure, but did not affect MMP-9 expression. However, pharmacologic MMP inhibition and siRNA knockdown of MMP-9 expression demonstrated the contribution of MMP-9 to NO-mediated wound closure. Overall, our results demonstrate that NOS2-derived NO contributes to airway epithelial repair by both PKG-dependent and -independent mechanisms, and involves NO-dependent expression and activation of MMP-9

Identification of Ustilago maydis Aurora Kinase As a Novel Antifungal Target

Infestation of crops by pathogenic fungi has continued to have a major impact by reducing yield and quality, emphasizing the need to identify new targets and. develop new agents to improve methods of crop protection. Here we present Aurora kinase from the phytopathogenic fungus Ustilago maydis as a novel target for N-substituted diaminopyrimidines, a class of small-molecule kinase inhibitors. We,, show that Aurora kinase is essential in U. maydis and that diaminopyrimidines inhibit its activity in vitro. Furthermore, we observed an overall good correlation between in vitro inhibition of Aurora kinase and growth inhibition of diverse fungi in vivo. In vitro inhibition assays with Ustilago and human Aurora kinases indicate that some compounds of the N-substituted diaminopyrimidine class show specificity for the Ustilago enzyme, thus revealing their potential as selective fungicides