Some enzymes in the cerebrospinal fluid and glyco-conjugates may be useful to diagnose brain disorder

科学研究費補助金研究成果報告書研究種目: 基盤研究(B)研究期間: 2003～2006課題番号: 15390212研究代表者: 西 克治（滋賀医科大学・医学部・教授）研究分担者: 大久保 岩男（滋賀医科大学・医学部・教授）研究分担者: 種子島 章男（滋賀医科大学・医学部・助教授）研究分担者: 山本 好男（滋賀医科大学・医学部・講師）研究分担者: 牛山 郁子（滋賀医科大学・医学部・助手）研究分担者: 高瀬 泉（滋賀医科大学・医学部・助手

Redox regulation of hepatitis C in nonalcoholic and alcoholic liver

Hepatitis C virus (HCV) is an RNA virus of the Flaviviridae family that is estimated to have infected 170 million people worldwide. HCV can cause serious liver disease in humans, such as cirrhosis, steatosis, and hepatocellular carcinoma. HCV induces a state of oxidative/nitrosative stress in patients through multiple mechanisms, and this redox perturbation has been recognized as a key player in HCV-induced pathogenesis. Studies have shown that alcohol synergizes with HCV in the pathogenesis of liver disease, and part of these effects may be mediated by reactive species that are generated during hepatic metabolism of alcohol. Furthenriore, reactive species and alcohol may influence HCV replication and the outcome of interferon therapy. Alcohol consumption has also been associated with increased sequence heterogeneity of the HCV RNA sequences, suggesting multiple modes of interaction between alcohol and HCV. This review summarizes the current understanding of oxidative and nitrosative stress during HCV infection and possible combined effects of HCV, alcohol, and reactive species in the pathogenesis of liver disease. (c) 2007 Elsevier Inc. All rights reserved

Time-Dependent Expression Profiles of microRNAs and mRNAs in Rat Milk Whey

<div><p>Functional RNAs, such as microRNA (miRNA) and mRNA, are present in milk, but their roles are unknown. To clarify the roles of milk RNAs, further studies using experimental animals such as rats are needed. However, it is unclear whether rat milk also contains functional RNAs and what their time dependent expression profiles are. Thus, we prepared total RNA from whey isolated from rat milk collected on days 2, 9, and 16 postpartum and analyzed using microarrays and quantitative PCR. The concentration of RNA in colostrum whey (day 2) was markedly higher than that in mature milk whey (days 9 and 16). Microarray analysis detected 161 miRNAs and 10,948 mRNA transcripts. Most of the miRNAs and mRNA transcripts were common to all tested milks. Finally, we selected some immune- and development-related miRNAs and mRNAs, and analysed them by quantitative PCR (in equal sample volumes) to determine their time-dependent changes in expression in detail. Some were significantly more highly expressed in colostrum whey than in mature milk whey, but some were expressed equally. And mRNA expression levels of some cytokines and hormones did not reflect the protein levels. It is still unknown whether RNAs in milk play biological roles in neonates. However, our data will help guide future <i>in vivo</i> studies using experimental animals such as rats.</p></div

Functions of transcripts detected in whey.

<p>Transcripts detected by microarray analysis were examined by Ingenuity Pathway Analysis. Ranks were determined by the right-tailed Fisher's Exact Test and were corrected by Benjamini-Hochberg Multiple Testing Correction.</p><p>B-H <i>P</i>-value  =  Benjamini-Hochberg <i>P</i>-value.</p

Quantitative PCR analysis of selected mRNAs in equal volumes of whey and serum.

<p>An aliquot of total RNA from 0.5-µL was used for each mRNA. Non-detected mRNAs were assigned a Ct value of 50. Values are the mean ± SEM (n = 3). Means without letters in common differ (<i>P</i><0.05, Tukey-Kramer HSD test).</p

Quantitative PCR analysis of selected miRNAs in equal volumes of whey and serum.

<p>An aliquot of total RNA from 0.5-µL was used for each miRNA. Values are the mean ± SEM (n = 3). Means without letters in common differ (<i>P</i><0.05, Tukey-Kramer HSD test).</p