High abundances of neurotrophin 3 in atopic dermatitis mast cell

Background  

Neurotrophin 3 (NT-3) is a member of the neurotrophin family, a group of related proteins that are known to regulate neuro-immune interactions in allergic diseases. Their cellular sources and role in the recruitment of mast cell precursors in atopic dermatitis have not been characterized in detail so far.     

The Nursing Outcomes Classification: Validation by Rehabilitation Nurses

Measuring patient outcomes is important to rehabilitation nurses and the patients they serve. This article describes research conducted at the University of Iowa College of Nursing to develop the Nursing Outcomes Classification (NOC) and the validation of this research by surveys conducted through specialty nursing organizations, particularly the Association of Rehabilitation Nurses. Nurses responded to surveys designed to validate (a) the importance of outcome indicators to the achievement of an outcome and (b) nursing's contribution to the achievement of the indicators. The results of the surveys indicated that rehabilitation nurses believe that nursing makes a substantial contribution to most outcomes and indicators.     

Synthetic Colloids Attenuate Leukocyte-Endothelial Interactions by Inhibition of Integrin Function

Background: It has been suspected that synthetic colloids may interfere with leukocyte adhesion by down-regulation of endothelial cell adhesion molecules. Although inhibition of endothelial inflammation might reduce leukocyte-related tissue injury, the same mechanism may be detrimental for host defense during severe infection. Regarding the widespread use of colloids, the authors performed a laboratory investigation to determine the mechanisms by which synthetic colloids interfere with leukocyte-endothelial interactions.

Methods: Adhesion molecule expression on native and cytokine-activated endothelium from umbilical veins was measured after pretreatment with gelatin and various preparations of dextran or hydroxyethyl starch. Inhibition of neutrophil adhesion to activated endothelium was examined in a flow chamber by perfusion of untreated and colloid-treated neutrophils over colloid-pretreated endothelium at 2 dyn/cm2. Comparisons were made between untreated controls, colloid-pretreated endothelium, and colloid-cotreated neutrophils.

Results: Intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin, and P-selectin were not attenuated by any colloid. Accordingly, colloid pretreatment of endothelium alone did not reduce neutrophil adhesion. In contrast, when neutrophils were cotreated by addition of colloids to the perfusate immediately before perfusion, adhesion decreased by 31-51% (P < 0.05) regardless of the colloid type. As indicated by the twofold increased rolling fractions, this reduction was due to an inhibition of neutrophil integrins.     

Post-1950 mortality trends and medical care: gains in life expectancy due to declines in mortality from conditions amenable to medical intervention in The Netherlands

In order to assess the impact of medical care innovations on post-1950 mortality in The Netherlands, we analysed trends in mortality from a selection of conditions suggested by Rutstein et al.'s lists of "unnecessary untimely mortality". This selection covers 11 types of innovation, and includes 35 conditions which have become amenable to medical care. Loglinear regression analysis shows that for most of these conditions mortality declined during each of two subperiods (1950-1968; 1969-1984). Mortality decline accelerated in the second subperiod for many conditions. Reductions in mortality from these conditions between 1950/54 and 1980/84 added 2.96 and 3.95 years to life expectancy at birth of Dutch males and Dutch females respectively. A priori evidence indicates that these mortality reductions are due to some extent to 'spontaneous' incidence declines. Although the exact contribution of medical care innovations to these changes in mortality thus cannot be determined, the impact of medical care on post-1950 mortality in The Netherlands could well have been substantial.     

Regional differences in mortality from conditions amenable to medical intervention in The Netherlands: a comparison of four time periods.

In The Netherlands, as in many other countries, important geographical variation in mortality from conditions amenable to medical intervention exists. Associations with a number of simple medical care supply characteristics (general practitioner density, hospital bed density, and percentage of regional hospital beds located in university and small hospitals) are generally weak and inconsistent, both before and after controlling for possible confounding factors. We explored one of the possible reasons for this lack of consistency, which is the time dependency of the relationship between medical care supply and avoidable mortality. A comparison of associations in four time periods (1950-54, 1960-64, 1970-74 and 1980-84) shows that the percentage of variance in regional mortality levels which can be "explained" by the medical care supply variables has changed over time. Although the patterns of change differ little from what one would expect on the basis of the time of introduction of medical care innovations, the exact nature of the associations is puzzling. Apart from some expected negative associations between mortality and the presence of university hospitals, we also found a few unexpected positive associations with general practitioner density. Possible explanations for these findings are discussed, and it is concluded that further study is necessary to reveal the causes of a higher or lower mortality level for conditions considered to be amenable to medical intervention.     

Differential increases in brain levels of neuropeptide Y and vasoactive intestinal polypeptide after kainic acid-induced seizures in the rat

Summary Changes in immunoreactivities of neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) were investigated in the brain of rats after severe kainic acid (KA, 10 mg/kg, i.p.) induced limbic seizures. Decreased levels of both neuropeptides were observed in the frontal cortex, striatum, dorsal hippocampus and amygdala/pyriform cortex subsequently to the period of acute seizures (3 h after injection of the toxin). Then NPY increased consistently in the frontal cortex, hippocampus and amygdala/pyriform cortex. Highest levels (290% of controls) were found in the frontal cortex after two months. Anticonvulsant therapy with phenobarbital (20 mg/kg, i.p., twice daily for three weeks) partially suppressed the rise in NPY levels. Immunoreactivity of VIP increased (to 150%) in the frontal cortex only transiently 3 days after injection of kainic acid. At the subsequently examined time intervals (10–60 days after kainic acid) it declined to control values. Levels decreasing subsequently to acute seizures reflect increased release and degradation of the respective peptide. Increased NPY levels suggest upregulation of NPY/ somatostatin/GABA neurons due to the decreased seizure threshold of the animals. The early, reversible rise of VIP in the cortex points to a short-lasting activation of this peptide system contained in local cholinergic neurons. This may be a consequence either of the acute seizures or subsequent neuropathological changes. Send offprint requests to G. Sperk at the above address     

Rescue of lethal molybdenum cofactor deficiency by a biosynthetic precursor from Escherichia coli

Substitution therapies for orphan genetic diseases, including enzyme replacement methods, are frequently hampered by the limited availability of the required therapeutic substance. We describe the isolation of a pterin intermediate from bacteria that was successfully used for the therapy of a hitherto incurable and lethal disease. Molybdenum cofactor (Moco) deficiency is a pleiotropic genetic disorder characterized by the loss of the molybdenum-dependent enzymes sulphite oxidase, xanthine oxidoreductase and aldehyde oxidase due to mutations in Moco biosynthesis genes. An intermediate of this pathway-'precursor Z'-is more stable than the cofactor itself and has an identical structure in all phyla. Thus, it was overproduced in the bacterium Escherichia coli, purified and used to inject precursor Z-deficient knockout mice that display a phenotype which resembles that of the human deficiency state. Precursor Z-substituted mice reach adulthood and fertility. Biochemical analyses further suggest that the described treatment can lead to the alleviation of most symptoms associated with human Moco deficiency.