Long-Term Persistent GBV-B Infection and Development of a Chronic and Progressive Hepatitis C-Like Disease in Marmosets

It has been shown that infection of GB virus B (GBV-B), which is closely related to hepatitis C virus, develops acute self-resolving hepatitis in tamarins. In this study we sought to examine longitudinally the dynamics of viral and immunological status following GBV-B infection of marmosets and tamarins. Surprisingly, two of four marmosets but not tamarins experimentally challenged with GBV-B developed long-term chronic infection with fluctuated viremia, recurrent increase of alanine aminotransferase and plateaued titers of the antiviral antibodies, which was comparable to chronic hepatitis C in humans. Moreover, one of the chronically infected marmosets developed an acute exacerbation of chronic hepatitis as revealed by biochemical, histological, and immunopathological analyses. Of note, periodical analyses of the viral genomes in these marmosets indicated frequent and selective non-synonymous mutations, suggesting efficient evasion of the virus from antiviral immune pressure. These results demonstrated for the first time that GBV-B could induce chronic hepatitis C-like disease in marmosets and that the outcome of the viral infection and disease progression may depend on the differences between species and individuals

Exacerbation of daily cough and allergic symptoms in adult patients with chronic cough by Asian dust: A hospital-based study in Kanazawa

The health effects associated with Asian dust have attracted attention due to the rapid increase in the number of Asian dust events in East Asia in recent years. The aim of this study was to investigate the associations between Asian dust and daily cough, as well as allergic symptoms, in adult patients who suffer from chronic cough. We enrolled 86 adult patients from Kanazawa University Hospital, Japan, who were diagnosed with asthma, cough variant asthma, atopic cough or a combination of these conditions. From January to June 2011, subjects recorded their symptoms in a diary every day. Asian dust and non-Asian dust periods were defined according to the dust extinction coefficient, measured using the light detection and ranging (LIDAR). The daily levels of total suspended particulates, polycyclic aromatic hydrocarbons (PAHs) and coexisting factors related to allergies, such as the Japanese cedar pollen count, were measured. McNemar\u27s test showed that there were significantly more cough-positive patients during Asian dust periods than during the non-Asian dust period (p = 0.022). In addition, during Asian dust periods when the daily levels of Japanese cedar pollen, Japanese cypress pollen and PAHs were elevated, there were significantly more patients who experienced itchy eyes than during the non-Asian dust period (p < 0.05). On the other hand, there were no significant differences in the allergic symptoms, including sneezing or a runny nose and nasal congestion. This is the first report to show that Asian dust triggers cough and allergic symptoms in adult patients with chronic cough. © 2014 Elsevier Ltd. All rights reserved

Conversion of Helicobacter pylori CagA from senescence inducer to oncogenic driver through polarity-dependent regulation of p21

The Helicobacter pylori CagA bacterial oncoprotein plays a critical role in gastric carcinogenesis. Upon delivery into epithelial cells, CagA causes loss of polarity and activates aberrant Erk signaling. We show that CagA-induced Erk activation results in senescence and mitogenesis in nonpolarized and polarized epithelial cells, respectively. In nonpolarized epithelial cells, Erk activation results in oncogenic stress, up-regulation of the p21Waf1/Cip1 cyclin-dependent kinase inhibitor, and induction of senescence. In polarized epithelial cells, CagA-driven Erk signals prevent p21Waf1/Cip1 expression by activating a guanine nucleotide exchange factor–H1–RhoA–RhoA-associated kinase–c-Myc pathway. The microRNAs miR-17 and miR-20a, induced by c-Myc, are needed to suppress p21Waf1/Cip1 expression. CagA also drives an epithelial-mesenchymal transition in polarized epithelial cells. These findings suggest that CagA exploits a polarity-signaling pathway to induce oncogenesis

RELIABILITY AND VALIDITY OF THE DIGIT CANCELLATION TEST, A BRIEF SCREEN OF ATTENTION

The reliability and validity of a screening test called the D-CAT (Digit Cancellation Test) were evaluated across two studies. The D-CAT was developed to provide a highly practical and user-friendly assessment of various aspects of prefrontal cortex functioning, including information processing speed, the ability to focus attention, and executive functioning. Participants perform the D-CAT by deleting given target numbers on a sheet of randomly arranged possibilities. In Study 1, the reliability of the D-CAT was evaluated using a test-retest paradigm. Reasonably high correlations between scores on the two test sessions were obtained. In Study 2, construct validity was examined using a sample of participants with traumatic brain injury. TBI participants showed significantly lower D-CAT performance than age and education level matched healthy controls. On the basis of these findings, the D-CAT can be regarded as a reliable and valid screening test for attentional functioning. Key words: screening test for attention, digit cancellation test, traumatic brain injury, test-reliability, test-validity &quot;Higher-order cognitive functioning&quot; consists of several different facets, including attention, memory, language, and problem solving. Each of the facets interrelates with the others in complex ways, although attention is regarded as a basic aspect of executive function in so-called higher-order cognitive functioning. The assessment of attention can be regarded as one of the most important basic aspects of any neuropsychological evaluation. Various assessments of human attentional abilities have been developed, including the Paced Serial Addition Test (PASAT), Brief Test of Attention (BTA)

Synthesis of Helicobacter pylori lipid A and its analogue using p-(triuoromethyl)benzyl protecting group

Abstract Synthesis of lipid A 1 isolated from Helicobacter pylori strain 206-1 has been achieved in 2.2% total yield through 14 steps from d-glucosamine by employing a p-(tri¯uoromethyl)benzyl group for protection of the hydroxy group on the 3-hydroxy fatty acid residue. The synthetic specimen was identical with the natural counterpart in chromatographic, spectroscopic, and biological aspects. A structural analogue 2 which lacks the ethanolamine residue of 1 was also synthesized, and 2 was found to exhibit less potent IL-1b-inducing activity than 1.