Targeting oncogene expression to endothelial cells induces proliferation of the myelo-erythroid lineage by repressing the Notch pathway.

Human oncogenes involved in the development of hematological malignancies have been widely used to model experimental leukemia. However, models of myeloid leukemia rarely reproduce the human disease in full, due to genetic complexity or to difficulties in targeting leukemia initiating cells. Here, we used a zebrafish genetic model to induce the expression of oncogenic RAS in endothelial cells, including the hemogenic endothelium of the dorsal aorta that generates hematopoietic cells, and observed the development of a myelo-erythroid proliferative disorder. In larvae, the phenotype is characterized by disruption of the vascular system and prominent expansion of the caudal hematopoietic tissue. In few surviving juveniles, increased number of immature hematopoietic cells and arrest of myeloid maturation was found in kidney marrow. Peripheral blood showed increased erythroblasts and myeloid progenitors. We found that the abnormal phenotype is associated with a downregulation of the Notch pathway, whereas overexpressing an activated form of Notch together with the oncogene prevents the expansion of the myelo-erythroid compartment. This study identifies the downregulation of the Notch pathway following an oncogenic event in the hemogenic endothelium as an important step in the pathogenesis of myelo-erythroid disorders and describes a number of potential effectors of this transformation.

[Allergy to house dust mites: allergy independent symptoms dominate]. / Hausstaubmilbenallergie: Allergenunabhängige Symptome überwiegen.

A sensitisation to allergens has not always a clinical relevance. Therefore, the history has an uppermost importance for defining the relevance of a sensitisation. In contrast to the history in seasonal rhino-conjunctivitis, which causes typical complains in a restricted time period patients with house dust mite allergy seem to have less defined complaints. To define the most relevant symptoms of this frequent allergy, we evaluated 35 patients with clearly defined house dust mite allergy by a questionnaire and evaluated the same questionnaire also in a control group of 18 patients without sensitisation or asthma. The symptoms described in the patient group confirm that symptoms of house dust mite allergy are frequently not related to a direct allergen exposure. Some patients complained about itchy red eyes in the morning, but the majority of symptoms occurred independent from allergen exposure. These are blocked nose as well as exercise induced asthma. These symptoms are present all year around and are not only restricted to mite exposed areas. They are probably related to the underling eosinophilic inflammation. Thus exercise induced asthma and blocked nose are symptoms, which may indicate a mite allergy, particular in younger patients.

Decay-inhibiting restorative materials: past and present.

Clear differences exist in the fluoride release characteristics and setting reactions of glass-ionomer cements and compomers. Differences in decay inhibition associated with specific materials are less clear. Furthermore, resin added to glass ionomer cement formulations and acids added to composite resins make it difficult to distinguish composite resins from compomers and glass ionomer cements, all of which have reported fluoride release. Optimal fluoride release from a dental restorative depends on several conditions, including oral flora, saliva, diet, mineral content of the dental tissues, and marginal seal of the restoration. Presently, in vitro and in vivo studies suggest that materials which behave similarly to silicate cements in their setting reactions and hydration characteristics will behave as decay-inhibiting restoratives. Until optimal fluoride release from dental restoratives can be quantified, dental clinicians are encouraged to consider clinical outcomes as the best test for decay inhibition. Nearly a century of clinical findings support the anticariogenicity of silicate cements. This article reviews fluoride release and anticariogenicity of restorative materials using silicate cement as a model with a well-defined mechanism for preventing secondary caries. The behavior of newer materials is compared to silicate cement for predicting decay inhibition.

Time course of recovery following nitrous oxide administration.

The time course of recovery following a brief exposure to 50% N(2)O in O(2) was assessed using a standard psychomotor test, a subjective ranking of experimental pain, and somatosensory evoked potential recordings. Results of this study suggest that recovery from a brief N(2)O exposure may be prolonged and conventional methods of assessing recovery from CNS active drugs like N(2)O may be inadequate.