Effect of Reader and Patient Parameters on the Performance of Last-Image-Hold for Fluoroscopic Grading of Vesicoureteric Reflux.

The purpose of this study is to determine the effect of different reader and patient parameters on the degree of agreement and the rate of misclassification of vesicoureteric reflux grading on last-image-hold frames in relation to spot-exposed frames from voiding cystourethrography (VCUG) as well as to determine the nature of reflux misclassification on last-image-hold frames. Blinded readers conducted a retrospective evaluation of last-image-hold and spot-exposed frames of the renal fossae from 191 sequential VCUG examinations performed during a five-year period. Kappa tests were used to determine the agreement between reflux gradings and to assess the impact of reader and patient parameters.

The acetylation of tau inhibits its function and promotes pathological tau aggregation.

The microtubule associated protein tau promotes neuronal survival through binding and stabilization of MTs. Phosphorylation regulates tau-microtubule interactions and hyperphosphorylation contributes to the aberrant formation of insoluble tau aggregates in Alzheimer's disease (AD) and related tauopathies. However, other pathogenic post-translational tau modifications have not been well characterized.

Effects of TNFalpha-converting enzyme inhibition on amyloid beta production and APP processing in vitro and in vivo.

Tumor necrosis factor-alpha (TNFalpha) is a proinflammatory cytokine that is elevated in Alzheimer's disease (AD) brains. Because TNFalpha is released from cell membranes by the TNFalpha-converting enzyme (TACE), inhibition of TACE has the potential to mitigate TNFalpha effects in AD brain. TACE also cleaves amyloid precursor protein (APP) and generates sAPPalpha, precluding the formation of potentially harmful amyloid beta (Abeta) peptides by beta-site APP cleaving enzymes (BACE).

Interactions between Hsp70 and the hydrophobic core of alpha-synuclein inhibit fibril assembly.

Molecular chaperones of the heat shock protein 70 (Hsp70) family counteract protein misfolding in a variety of neurodegenerative disease models. To determine whether human Hsp70 exerts similar effects on the aggregation of alpha-synuclein (alpha-Syn), the key component of insoluble fibrils present in Parkinson's disease, we investigated alpha-Syn fibril assembly in the presence of Hsp70. We found in vitro assembly was efficiently inhibited by substoichiometric concentrations of purified Hsp70 in the absence of cofactors.

Molecular and functional analyses of a human parvovirus B19 infectious clone demonstrates essential roles for NS1, VP1, and the 11-kilodalton protein in virus replication and infectivity.

In an attempt to experimentally define the roles of viral proteins encoded by the B19 genome in the viral life cycle, we utilized the B19 infectious clone constructed in our previous study to create two groups of B19 mutant genomes: (i) null mutants, in which either a translational initiation codon for each of these viral genes was substituted by a translational termination codon or a termination codon was inserted into the open reading frame by a frameshift; and (ii) a deletion mutant, in which half of the hairpin sequence was deleted at both the 5' and the 3' termini. The impact of these mutations on viral infectivity, DNA replication, capsid protein production, and distribution was systematically examined. Null mutants of the NS and VP1 proteins or deletion of the terminal hairpin sequence completely abolished the viral infectivity, whereas blocking expression of the 7.

Simian parvovirus infection: a potential zoonosis.

Introduction: Simian parvovirus (SPV) causes severe anemia in immunocompromised macaques. The closely related erythrovirus, parvovirus B19, causes anemia in susceptible humans and can be grown in human bone marrow mononuclear cells in vitro. We hypothesized that SPV may infect humans and replicate in human bone marrow mononuclear cells.