Effect of atrial natriuretic peptide on DOPA potentiation in mice

The effect of rat atrial natriuretic peptide (ANP1-28) on the pargyline-DOPA potentiation test was studied following its administration into the lateral brain ventricle in mice. Thirty minutes after pargyline pretreatment, three doses of ANP (200, 500, or 1,000 ng/mouse) were administered simultaneously with DOPA and animals were then observed for 2 h. ANP in doses of 500 and 1,000 ng markedly enhanced the effect of DOPA. The maximum intensity of the effect was registered 30-45 min following administration of the peptide. The data suggest that ANP might be regarded as a dopaminergic-modulating agent in the CNS.     

Beta-amyloid-induced increase in the resting intracellular calcium concentration gives support to tell Alzheimer lymphocytes from control ones

Senile plaques containing beta-amyloid peptide (betaAP) comprise the major neuropathological lesions in Alzheimer's disease (AD). In line with ongoing studies investigating alterations of various biochemical processes of cells of peripheral tissues, the authors demonstrate differences in resting intracellular free calcium levels of lymphocytes harvested from sporadic Alzheimer patients and from age-matched controls. Resting intracellular calcium concentration was measured in Fura-2AM-loaded human lymphocytes by dual wavelength spectrofluorimetry. Resting calcium level appeared to be higher in Alzheimer cells when compared to control lymphocytes. After incubating cells in 10(-7)M of beta-amyloid, the resting calcium concentration of the control cells elevated, while that of Alzheimer lymphocytes did not differ considerably.     

Application of artificial neural networks to the analysis of dynamic MR imaging features of the breast

The discriminative ability of established diagnostic criteria for MRI of the breast is assessed, and their relative relevance using artificial neural networks (ANNs) is determined. A total of 89 women with 105 histopathologically verified breast lesions (73 invasive cancers, 2 in situ cancers, and 30 benign lesions) were included in this study. A T1-weighted 3D FLASH sequence was acquired before and seven times after the intravenous administration of gadopentetate dimeglumine at a dose of 0.2 mmol/kg body weight. ANN models were built to test the discriminative ability of kinetic, morphologic, and combined MR features. The subjects were randomly divided into two parts: a training set of 59 lesions and a verification set of 46 lesions. The training set was used for learning, and the performance of each model was evaluated on the verification set by measuring the area under the ROC curve (A_z). An optimally minimized model was constructed using the most relevant input variables that were determined by the automatic relevance determination (ARD) method. ANN models were compared with the performance of a human reader. Margin type, time-to-peak enhancement, and washout ratio showed the highest discriminative ability among diagnostic criteria and comprised the minimized model. Compared with the expert radiologist (A_z=0.799), using the same prediction scale, the minimized ANN model performed best (A_z=0.771), followed by the best kinetic (A_z=0.743), the maximized (A_z=0.727), and the morphologic model (A_z=0.678). The performance of a neural network prediction model is comparable to that of an expert radiologist. A neurostatistical approach is preferred for the analysis of diagnostic criteria when many parameters are involved and complex nonlinear relationships exist in the data set.     

In vitro model of neurotoxicity of Abeta 1-42 and neuroprotection by a pentapeptide: irreversible events during the first hour

The cell biology of Alzheimer's disease (AD) is characterized mainly by the neurodegeneration caused by the beta-amyloid (Abeta) peptides and by the formation of neurofibrillary tangles. The initial events of neurodegeneration in the brain tissue include synaptic dysfunction and axonopathy. Abeta-induced axonopathy and neurite degeneration were studied in vitro on differentiated human-derived neurotypic SH-SY5Y cells. Different methods were used to investigate the mechanism of action of aggregated Abeta on neuroblastoma cells. Abeta 1-42 aggregated for 1 h induced irreversible changes in the neurite morphology. Change of tau hyperphosphorylation and cell viability (cytoplasmic redox state and active membrane uptake) was irreversible during the first hour after the addition of Abeta 1-42 to the cells. These rapid events indicate that Abeta might induce neurodegeneration even at an early stage of Abeta-cell contact. A novel pentapeptide LPYFD-amide, an analog of Soto's LPFFD, significantly decreased neurite degeneration, tau aggregation, and cell viability reduction induced by Abeta 1-42.     

A novel host defense system of airways is defective in cystic fibrosis

RATIONALE: The respiratory tract is constantly exposed to airborne microorganisms. Nevertheless, normal airways remain sterile without recruiting phagocytes. This innate immune activity has been attributed to mucociliary clearance and antimicrobial polypeptides of airway surface liquid. Defective airway immunity characterizes cystic fibrosis (CF), a disease caused by mutations in the CF transmembrane conductance regulator, a chloride channel. The pathophysiology of defective immunity in CF remains to be elucidated. OBJECTIVE: We investigated the ability of non-CF and CF airway epithelia to kill bacteria through the generation of reactive oxygen species (ROS). METHODS: ROS production and ROS-mediated bactericidal activity were determined on the apical surfaces of human and rat airway epithelia and on cow tracheal explants. MEASUREMENTS AND MAIN RESULTS: Dual oxidase enzyme of airway epithelial cells generated sufficient H(2)O(2) to support production of bactericidal hypothiocyanite (OSCN(-)) in the presence of airway surface liquid components lactoperoxidase and thiocyanate (SCN(-)). This OSCN(-) formation eliminated Staphylococcus aureus and Pseudomonas aeruginosa on airway mucosal surfaces, whereas it was nontoxic to the host. In contrast to normal epithelia, CF epithelia failed to secrete SCN(-), thereby rendering the oxidative antimicrobial system inactive. CONCLUSIONS: These data indicate a novel innate defense mechanism of airways that kills bacteria via ROS and suggest a new cellular and molecular basis for defective airway immunity in CF.     

Mutation of the Cyba gene encoding p22phox causes vestibular and immune defects in mice

In humans, hereditary inactivation of either p22(phox) or gp91(phox) leads to chronic granulomatous disease (CGD), a severe immune disorder characterized by the inability of phagocytes to produce bacteria-destroying ROS. Heterodimers of p22(phox) and gp91(phox) proteins constitute the superoxide-producing cytochrome core of the phagocyte NADPH oxidase. In this study, we identified the nmf333 mouse strain as what we believe to be the first animal model of p22(phox) deficiency. Characterization of nmf333 mice revealed that deletion of p22(phox) inactivated not only the phagocyte NADPH oxidase, but also a second cytochrome in the inner ear epithelium. As a consequence, mice of the nmf333 strain exhibit a compound phenotype consisting of both a CGD-like immune defect and a balance disorder caused by the aberrant development of gravity-sensing organs. Thus, in addition to identifying a model of p22(phox)-dependent immune deficiency, our study indicates that a clinically identifiable patient population with an otherwise cryptic loss of gravity-sensor function may exist. Thus, p22(phox) represents a shared and essential component of at least 2 superoxide-producing cytochromes with entirely different biological functions. The site of p22(phox) expression in the inner ear leads us to propose what we believe to be a novel mechanism for the control of vestibular organogenesis.