Factor analysis reveals differences in brain metabolism in macaques with SIV/AIDS and those with SIV-induced encephalitis

MRS has often been used to study metabolic processes in the HIV-infected brain. However, it remains unclear how changes in individual metabolites are related to one another in this context of virus-induced central nervous system dysfunction. We used factor analysis (FA) to identify patterns of metabolite distributions from an MRS study of healthy macaques and those infected with simian immunodeficiency virus (SIV) which were moribund with AIDS. FA summarized the correlations from nine metabolites into three main factors. Factor 3 identified patterns that discern healthy animals from those with SIV/AIDS. Factor 2 was able to differentiate between animals that had encephalitis and those moribund with AIDS but lacking encephalitis. Specifically, Factor 2 was able to distinguish animals with moderate to severe encephalitis from animals with mild or no encephalitis as well as uninfected controls. FA not only confirmed the involvement of neuronal metabolites (N-acetylaspartate and glutamate) in disease severity, but also detected changes in creatine and myo-inositol that have not been observed in the SIV macaque model previously. These results suggest that the divergent pathways of N-acetylaspartate and creatine in this disease may enable the commonly reported ratio N-acetylaspartate/creatine to be a more sensitive marker of disease severity. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Differential proteomic analysis of human glioblastoma and neural stem cells reveals HDGF as a novel angiogenic secreted factor

Presence in glioblastomas of cancer cells with normal neural stem cell (NSC) properties, tumor initiating capacity, and resistance to current therapies suggests that glioblastoma stem-like cells (GSCs) play central roles in glioblastoma development. We cultured human GSCs endowed with all features of tumor stem cells, including tumor initiation after xenograft and radio-chemoresistance. We established proteomes from four GSC cultures and their corresponding whole tumor tissues (TTs) and from human NSCs. Two-dimensional difference gel electrophoresis and tandem mass spectrometry revealed a twofold increase of hepatoma-derived growth factor (HDGF) in GSCs as compared to TTs and NSCs. Western blot analysis confirmed HDGF overexpression in GSCs as well as its presence in GSC-conditioned medium, while, in contrast, no HDGF was detected in NSC secretome. At the functional level, GSC-conditioned medium induced migration of human cerebral endothelial cells that can be blocked by anti-HDGF antibodies. In vivo, GSC-conditioned medium induced neoangiogenesis, whereas HDGF-targeting siRNAs abrogated this effect. Altogether, our results identify a novel candidate, by which GSCs can support neoangiogenesis, a high-grade glioma hallmark. Our strategy illustrates the usefulness of comparative proteomic analysis to decipher molecular pathways, which underlie GSC properties.     

A tick-borne encephalitis virus vaccine based on the European prototype strain induces broadly reactive cross-neutralizing antibodies in humans

After vaccination of humans with tick-borne encephalitis virus (TBEV) vaccine, the extent of cross-neutralization between viruses of the European, Far Eastern, and Siberian subtypes of TBEV and Omsk hemorrhagic fever virus (OHFV) was analyzed. Hybrid viruses that encode the TBEV surface proteins for representative viruses within all subtypes, and OHFV, were constructed using the West Nile virus (WNV) backbone as vector. These viruses allow for unbiased head-to-head comparison in neutralization assays because they exhibit the antigenic characteristics of the TBEV strains from which the surface proteins were derived and showed equivalent biologic properties in cell culture. Human serum samples derived from a TBEV vaccine trial were analyzed and revealed comparable neutralizing antibody titers against European, Far Eastern, and Siberian subtype viruses, indicating equally potent cross-protection against these TBEV strains and a somewhat reduced but still protective neutralization capacity against more distantly related viruses, such as OHFV.     

The possible role of neuropeptide Y after spontaneous subarachnoid hemorrhage

Objective  

Neuropeptide Y (NPY), a highly potent vasoconstrictive neuropeptide, is widely expressed in the human brain, regulating vessel diameter and cerebral blood flow. Earlier studies focusing on the possible role of NPY in the context of aneurismal subarachnoid hemorrhage (SAH) and vasospasm have produced conflicting results. However, despite extensive research efforts, the pathophysiological mechanisms underlying the SAH-related vasospasm and delayed cerebral ischemia (DCI) have not been clarified. We, therefore, attempted to investigate the role of NPY in SAH-induced vasospasm in a larger, well documented patient population utilizing modern analytical tools. We focused on the release of the potent vasoconstrictor NPY in cerebrospinal fluid (CSF) and blood, and its correlation to vasospasm and stroke in the early clinical stage.     

Differentiation,Quantification and Identification of Abrin and Abrus precatorius Agglutinin

Abrin, the toxic lectin from the rosary pea plant Abrus precatorius, has gained considerable interest in the recent past due to its potential malevolent use. However, reliable and easy-to-use assays for the detection and discrimination of abrin from related plant proteins such as Abrus precatorius agglutinin or the homologous toxin ricin from Ricinus communis are sparse. To address this gap, a panel of highly specific monoclonal antibodies was generated against abrin and the related Abrus precatorius agglutinin. These antibodies were used to establish two sandwich ELISAs to preferentially detect abrin or A. precatorius agglutinin (limit of detection 22 pg/mL for abrin; 35 pg/mL for A. precatorius agglutinin). Furthermore, an abrin-specific lateral flow assay was developed for rapid on-site detection (limit of detection ~1 ng/mL abrin). Assays were validated for complex food, environmental and clinical matrices illustrating broad applicability in different threat scenarios. Additionally, the antibodies turned out to be suitable for immuno-enrichment strategies in combination with mass spectrometry-based approaches for unambiguous identification. Finally, we were able to demonstrate for the first time how the developed assays can be applied to detect, identify and quantify abrin from a clinical sample derived from an attempted suicide case involving A. precatorius.     

Minimal-invasive versus open hepatectomy for hepatocellular carcinoma: Comparison of postoperative outcomes and long-term survivals using propensity score matching analysis

Background

Minimal-invasive hepatectomy (MIH) has been increasingly performed for benign and malignant liver lesions with most promising results. However, the role of MIH for the treatment of patients with hepatocellular carcinoma (HCC) needs further investigation.