Expansion and de novo generation of potentially therapeutic regulatory T cells in patients with autoimmune hepatitis

Maria Serena Longhi, Francesca Meda, Pengyun Wang, Marianne Samyn, Giorgina Mieli‐Vergani, Diego Vergani, Yun Ma – 26 January 2008 – CD4+CD25+ regulatory T cells (T‐regs) are central to the maintenance of immune tolerance and represent an immune intervention candidate in autoimmune hepatitis (AIH), a condition characterized by impaired T‐reg number and function. We investigated whether T‐regs can be expanded from the existing CD4+CD25+ T cell pool and generated de novo from CD4+CD25− T cells in AIH patients and healthy controls.

Liver: An organ with predominant innate immunity

Bin Gao, Won‐Il Jeong, Zhigang Tian – 26 January 2008 – Blood circulating from the intestines to the liver is rich in bacterial products, environmental toxins, and food antigens. To effectively and quickly defend against potentially toxic agents without launching harmful immune responses, the liver relies on its strong innate immune system. This comprises enrichment of innate immune cells (such as macrophages, natural killer, natural killer T, and γδ T cells) and removal of waste molecules and immunologic elimination of microorganisms by liver endothelial cells and Kupffer cells.

S‐adenosylmethionine prevents mallory denk body formation in drug‐primed mice by inhibiting the epigenetic memory

Jun Li, Fawzia Bardag‐Gorce, Jennifer Dedes, Barbara Alan French, Fataneh Amidi, Joan Oliva, Samuel William French – 26 January 2008 – In previous studies, microarray analysis of livers from mice fed diethyl‐1,4‐dihydro‐2,4,6‐trimethyl‐3,5‐pyridine decarboxylate (DDC) for 10 weeks followed by 1 month of drug withdrawal (drug‐primed mice) and then 7 days of drug refeeding showed an increase in the expression of numerous genes referred to here as the molecular cellular memory. This memory predisposes the liver to Mallory Denk body formation in response to drug refeeding.

Intrahepatic cholestasis of pregnancy: Amelioration of pruritus by UDCA is associated with decreased progesterone disulphates in urine

Anna Glantz, Sarah‐Jayne Reilly, Lisbet Benthin, Frank Lammert, Lars‐Åke Mattsson, Hanns‐Ulrich Marschall – 26 January 2008 – Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus, elevated bile acids, and, specifically, elevated disulphated progesterone metabolites. We aimed to study changes in these parameters during treatment with dexamethasone or ursodeoxycholic acid (UDCA) in 40 out of 130 women included in the Swedish ICP intervention trial (26 randomized to placebo or UDCA, 14 randomized to dexamethasone).

Isolation and characterization of a novel oncogene, amplified in liver cancer 1, within a commonly amplified region at 1q21 in hepatocellular carcinoma

Ning‐Fang Ma, Liang Hu, Jackie M. Fung, Dan Xie, Bo‐Jian Zheng, Leilei Chen, Dong‐Jiang Tang, Li Fu, Zhenguo Wu, Muhan Chen, Yan Fang, Xin‐Yuan Guan – 26 January 2008 – Amplification of 1q21 is the most frequent genetic alteration in human hepatocellular carcinoma (HCC), being detected in 58%‐78% of primary HCC cases by comparative genomic hybridization. Recently, we isolated a candidate oncogene, Amplified in Liver Cancer 1 (ALC1), from 1q21 by hybrid selection. Here we demonstrate that ALC1 was frequently amplified and overexpressed in HCC.

Leptin's mitogenic effect in human liver cancer cells requires induction of both methionine adenosyltransferase 2A and 2β

Komal Ramani, Heping Yang, Meng Xia, Ainhoa Iglesias Ara, José M. Mato, Shelly C. Lu – 26 January 2008 – Leptin is an adiopokine that plays a pivotal role in the progression of liver fibrogenesis and carcinogenesis. Recently, leptin was shown to be mitogenic in human liver cancer cell lines HepG2 and Huh7. Whether leptin can act as a mitogen in normal hepatocytes is unclear. Methionine adenosyltransferase (MAT) is an essential enzyme that catalyzes the formation of S‐adenosylmethionine (SAMe), the principal methyl donor and precursor of polyamines.

The methionine connection: Homocysteine and hydrogen sulfide exert opposite effects on hepatic microcirculation in rats

Eleonora Distrutti, Andrea Mencarelli, Luca Santucci, Barbara Renga, Stefano Orlandi, Annibale Donini, Vijay Shah, Stefano Fiorucci – 26 January 2008 – Increased intrahepatic resistance in cirrhotic livers is caused by endothelial dysfunction and impaired formation of two gaseous vasodilators, nitric oxide (NO) and hydrogen sulfide (H2S). Homocysteine, a sulfur‐containing amino acid and H2S precursor, is formed from hepatic methionine metabolism. In the systemic circulation, hyperhomocystenemia impairs vasodilation and NO production from endothelial cells.

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