Impaired autophagy: A mechanism of mitochondrial dysfunction in anoxic rat hepatocytes

Jae‐Sung Kim, Takashi Nitta, Dagmara Mohuczy, Kerri A. O'Malley, Lyle L. Moldawer, William A. Dunn, Kevin E. Behrns – 20 December 2007 – Autophagy selectively removes abnormal or damaged organelles such as dysfunctional mitochondria. The mitochondrial permeability transition (MPT) is a marker of impaired mitochondrial function that is evident in hepatic ischemia/reperfusion (I/R) injury. However, the relationship between mitochondrial dysfunction and autophagy in I/R injury is unknown.

Ciliary neurotrophic factor receptor α subunit–modulated multiple downstream signaling pathways in hepatic cancer cell lines and their biological implications

Xin Hu, Yingjun Zhao, Xianghuo He, Jinjun Li, Tao Wang, Weiping Zhou, Dafang Wan, Hongyang Wang, Jianren Gu – 19 December 2007 – Ciliary neurotrophic factor (CNTF) plays important roles in a variety of tissues including neural and non‐neural systems, but the function of CNTF and its receptor (CNTFR) in liver remains unclear. In this study, we demonstrate that CNTFRα is expressed heterogeneously in normal human liver and hepatocellular carcinoma (HCC) specimens but not in hepatoblastoma specimens.

Acute liver failure: Summary of a workshop

William M. Lee, Robert H. Squires, Scott L. Nyberg, Edward Doo, Jay H. Hoofnagle – 19 December 2007 – Acute liver failure (ALF) is a rare but challenging clinical syndrome with multiple causes; a specific etiology cannot be identified in 15% of adult and 50% of pediatric cases. The course of ALF is variable and the mortality rate is high. Liver transplantation is the only therapy of proven benefit, but the rapidity of progression and the variable course of ALF limit its use.

Hemodynamic effects of urotensin II and its specific receptor antagonist palosuran in cirrhotic rats

Jonel Trebicka, Ludger Leifeld, Martin Hennenberg, Erwin Biecker, Andreas Eckhardt, Nicolas Fischer, Andrea Schulze Pröbsting, Christoph Clemens, Frank Lammert, Tilman Sauerbruch, Jörg Heller – 19 December 2007 – In cirrhosis, splanchnic vasodilation contributes to portal hypertension, subsequent renal sodium retention, and formation of ascites. Urotensin II(U‐II) is a constrictor of large conductive vessels. Conversely, it relaxes mesenteric vessels, decreases glomerular filtration, and increases renal sodium retention. In patients with cirrhosis, U‐II plasma levels are increased.

Activation of liver X receptor sensitizes mice to gallbladder cholesterol crystallization

Hirdesh Uppal, Yonggong Zhai, Archana Gangopadhyay, Shaheen Khadem, Songrong Ren, James A. Moser, Wen Xie – 19 December 2007 – Gallstone disease is a hepatobiliary disorder due to biochemical imbalances in the gallbladder bile. In this report, we show that activation of nuclear receptor liver X receptor (LXR) sensitized mice to lithogenic diet–induced gallbladder cholesterol crystallization, which was associated with dysregulation of several hepatic transporters that efflux cholesterol, phospholipids, and bile salts.

Integration of genomic analysis and in vivo transfection to identify sprouty 2 as a candidate tumor suppressor in liver cancer

Susie A. Lee, Coral Ho, Ritu Roy, Cynthia Kosinski, Mohini A. Patil, Aaron D. Tward, Jane Fridlyand, Xin Chen – 19 December 2007 – Hepatocellular carcinoma (HCC) is 1 of the leading causes of cancer‐related deaths worldwide, yet the molecular genetics underlying this malignancy are still poorly understood. In our study, we applied statistical methods to correlate human HCC gene expression data obtained from complementary DNA (cDNA) microarrays and corresponding DNA copy number variation data obtained from array‐based comparative genomic hybridization.

Loss of the glycine N‐methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice

M. Luz Martínez‐Chantar, Mercedes Vázquez‐Chantada, Usue Ariz, Nuria Martínez, Marta Varela, Zigmund Luka, Antonieta Capdevila, Juan Rodríguez, Ana M. Aransay, Rune Matthiesen, Heping Yang, Diego F. Calvisi, Manel Esteller, Mario Fraga, Shelly C. Lu, Conrad Wagner, José M. Mato – 19 December 2007 – Glycine N‐methyltransferase (GNMT) is the main enzyme responsible for catabolism of excess hepatic S‐adenosylmethionine (SAMe).

Potential contribution of tumor suppressor p53 in the host defense against hepatitis C virus

Narayan Dharel, Naoya Kato, Ryosuke Muroyama, Hiroyoshi Taniguchi, Motoyuki Otsuka, Yue Wang, Amarsanaa Jazag, Run‐Xuan Shao, Jin‐Hai Chang, Mark K. Adler, Takao Kawabe, Masao Omata – 19 December 2007 – Infection by hepatitis C virus (HCV) usually results into chronic hepatitis that can ultimately lead to cirrhosis and hepatocellular carcinoma. Type 1 interferons (IFN‐α/β) constitute the primary cellular defense against viral infection including HCV.

Mortality attributable to cholestatic liver disease in the United States

Flavia D. Mendes, W. Ray Kim, Rachel Pedersen, Terry Therneau, Keith D. Lindor – 19 December 2007 – In the past 2 decades, important advances have been made in the treatment of cholestatic liver diseases, including primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Whether these new therapies have had demonstrable impact on mortality on a population‐wide scale has not been evaluated. This study describes the age‐specific and sex‐specific mortality rates from PBC and PSC in the United States between 1980 and 1998, based on the Multiple Cause of Death files.

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