Abstract:
BACKGROUND & AIMS:Host cell lipid rafts form a scaffold required for replication of hepatitis C virus (HCV). Serine palmitoyltransferases (SPTs) produce sphingolipids, which are essential components of the lipid rafts that associate with HCV nonstructural proteins. Prevention of the de novo synthesis of sphingolipids by an SPT inhibitor disrupts the HCV replication complex and thereby inhibits HCV replication. We investigated the ability of the SPT inhibitor NA808 to prevent HCV replication in cells and mice. METHODS:We tested the ability of NA808 to inhibit SPT's enzymatic activity in FLR3-1 replicon cells. We used a replicon system to select for HCV variants that became resistant to NA808 at concentrations 4- to 6-fold the 50% inhibitory concentration, after 14 rounds of cell passage. We assessed the ability of NA808 or telaprevir to inhibit replication of HCV genotypes 1a, 1b, 2a, 3a, and 4a in mice with humanized livers (transplanted with human hepatocytes). NA808 was injected intravenously, with or without pegylated interferon alfa-2a and HCV polymerase and/or protease inhibitors. RESULTS:NA808 prevented HCV replication via noncompetitive inhibition of SPT; no resistance mutations developed. NA808 prevented replication of all HCV genotypes tested in mice with humanized livers. Intravenous NA808 significantly reduced viral load in the mice and had synergistic effects with pegylated interferon alfa-2a and HCV polymerase and protease inhibitors. CONCLUSIONS:The SPT inhibitor NA808 prevents replication of HCV genotypes 1a, 1b, 2a, 3a, and 4a in cultured hepatocytes and in mice with humanized livers. It might be developed for treatment of HCV infection or used in combination with pegylated interferon alfa-2a or HCV polymerase or protease inhibitors.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Katsume A,Tokunaga Y,Hirata Y,Munakata T,Saito M,Hayashi H,Okamoto K,Ohmori Y,Kusanagi I,Fujiwara S,Tsukuda T,Aoki Y,Klumpp K,Tsukiyama-Kohara K,El-Gohary A,Sudoh M,Kohara Mdoi
10.1053/j.gastro.2013.06.012subject
Has Abstractpub_date
2013-10-01 00:00:00pages
865-73issue
4eissn
0016-5085issn
1528-0012pii
S0016-5085(13)00914-1journal_volume
145pub_type
杂志文章相关文献
GASTROENTEROLOGY文献大全abstract:BACKGROUND & AIMS:Helicobacter pylori infection is mainly acquired in early childhood, but the exact routes of transmission remain elusive. To distinguish between risks of intrafamilial and extraneous child-to-child transmission, we studied H. pylori seroprevalence among Swedish school children with varying family back...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.2001.26282
更新日期:2001-08-01 00:00:00
abstract::To investigate the role of gastric inhibitory polypeptide (GIP), a potent inhibitor of gastric acid secretion, in the hypersecretion associated with duodenal ulcer, we compared the serum GIP concentrations in 11 healthy subjects and 16 duodenal ulcer patients after the stimulation of GIP release by a mixed meal. Fasti...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1977-07-01 00:00:00
abstract:BACKGROUND:Growth failure frequently complicates the clinical course of inflammatory bowel disease (IBD) in children. This study was designed to investigate the role of disease activity versus steroid therapy on growth faltering in this disorder. METHODS:We studied growth failure and its relationship to disease activi...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(93)90883-e
更新日期:1993-09-01 00:00:00
abstract:BACKGROUND & AIMS:Among the human mucin complementary DNAs thus far identified, two (MUC5AC and MUC6) were cloned from stomach libraries. This study examines the distribution of MUC6 in normal tissues and compares it with that of MUC5AC as well as with the expression of Lewis blood group antigens. METHODS:Affinity-pur...
journal_title:Gastroenterology
pub_type: 评论,杂志文章
doi:10.1016/0016-5085(95)90379-8
更新日期:1995-09-01 00:00:00
abstract:BACKGROUND & AIMS:Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) lower the risk of colorectal cancer (CRC). We investigated whether plasma inflammatory markers were associated with risk of CRC and if use of anti-inflammatory drugs was differentially associated with risk of CRC according to levels of inflamma...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2010.11.041
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND & AIMS:Lynch syndrome, a nonpolyposis form of hereditary colorectal cancer, is caused by inherited defects in DNA mismatch repair (MMR) genes. Most patients carry a germline mutation in 1 allele of the MMR genes MSH2 or MLH1. With spontaneous loss of the wild-type allele, cells with defects in MMR exist amon...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2014.07.052
更新日期:2014-11-01 00:00:00
abstract:BACKGROUND & AIMS:In the absence of a genetic test, diagnostic criteria for hereditary hemochromatosis have been imprecise. The identification of the HFE gene and the C282Y mutation allow definition of expression of this disease and reassessment of diagnostic criteria. The aim of this study was to analyze the concordan...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(98)70320-8
更新日期:1998-05-01 00:00:00
abstract::Both high-resolution manometry (HRM) and impedance-pH/manometry monitoring have established themselves as research tools and both are now emerging in the clinical arena. Solid-state HRM capable of simultaneously monitoring the entire pressure profile from the pharynx to the stomach along with pressure topography plott...
journal_title:Gastroenterology
pub_type: 杂志文章,评审
doi:10.1053/j.gastro.2008.05.048
更新日期:2008-09-01 00:00:00
abstract:BACKGROUND & AIMS:The mechanisms by which mutations in the familial intrahepatic cholestasis-1 gene cause Byler's disease (progressive familial intrahepatic cholestasis type 1) are unknown. METHODS:Interactions among the apical sodium-dependent bile acid transporter, the farnesoid X receptor (FXR), and familial intrah...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2003.12.013
更新日期:2004-03-01 00:00:00
abstract::Serum group I pepsinogen (PG I) levels have been determined before and at intervals after the administration of betazole hydrochloride (Histalog) in 50 symptomatic postoperative patients, 20 with and 30 without recurrent ulcer, after either a vagotomy and gastric resection or a drainage procedure. In patients with rec...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1976-06-01 00:00:00
abstract::The experimental production of gastric ulcers in dogs by subnucosal injection of ulcerogeic agents is described. The most satisfactory agent tested was 95% ethanol, because it produced immediate changes in the mucosa which delineated the size of the ulcer. The depth of ulceration could be controlled and the ulcer heal...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1975-07-01 00:00:00
abstract:BACKGROUND & AIMS:The evaluation of patients with chronic watery diarrhea represents a diagnostic challenge for clinicians because organic causes, including inflammatory bowel disease, microscopic colitis, and chronic infection, must be differentiated from functional diarrhea and diarrhea-predominant irritable bowel sy...
journal_title:Gastroenterology
pub_type: 杂志文章,实务指引,评审
doi:10.1053/j.gastro.2019.06.014
更新日期:2019-09-01 00:00:00
abstract:BACKGROUND & AIMS:The aim of this study was to generate an improved prognostic model for predicting recurrence in liver transplant candidates with hepatocellular carcinoma (HCC). METHODS:Predictors of recurrence were tested by a Cox model analysis in a training cohort of 537 patients transplanted for HCC. A prognostic...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2012.05.052
更新日期:2012-10-01 00:00:00
abstract::Gastric and esophageal emptying were assessed using scintigraphic techniques in 12 patients with progressive systemic sclerosis and 22 normal volunteers. Esophageal emptying was significantly delayed in the patient group, with 7 of the 12 patients beyond the normal range. Gastric emptying was slower in patients than i...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1984-10-01 00:00:00
abstract::Increasing resistance to antibiotics worldwide has adverse effects on the effectiveness of standard therapies to eradicate Helicobacter pylori infection. We reviewed guidelines developed by expert groups in Europe, Canada, and the United States for the treatment of H pylori infection. We compared the recommendations o...
journal_title:Gastroenterology
pub_type: 杂志文章,评审
doi:10.1053/j.gastro.2019.04.011
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND & AIMS:The Ki-RAS oncogene is altered in pancreatic ductal neoplasms. Pancreatic ductal cells (PDCs) were purified from cytokeratin 19 (K19)-Ki-RAS(G12V) transgenic mice and control littermates to identify properties of Ki-Ras activation in a cell-type-specific context. Because Ki-RAS mutation has prognostic...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2004.03.058
更新日期:2004-07-01 00:00:00
abstract:BACKGROUND & AIMS:Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS:...
journal_title:Gastroenterology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1053/j.gastro.2019.05.056
更新日期:2019-09-01 00:00:00
abstract::A case of spontaneous rupture of a nonparasitic liver cyst, documented by serial computed tomography scans, is reported. The patient was closely followed clinically after the rupture of the cyst and was treated conservatively, without surgical intervention. No peritonitis developed. This unusual complication of nonpar...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(89)91438-8
更新日期:1989-07-01 00:00:00
abstract::Because the esophagus is easily accessible with endoscopy, early diagnosis and curative treatment of esophageal cancer is possible. However, diagnosis is often delayed because symptoms are not specific during early stages of tumor development. The onset of dysphagia is associated with advanced disease, which has a sur...
journal_title:Gastroenterology
pub_type: 杂志文章,评审
doi:10.1053/j.gastro.2017.07.041
更新日期:2018-01-01 00:00:00
abstract::Among the components of dietary fiber, the soluble polysaccharides, primarily guaran and pectin, have been found to impair intestinal absorption. Little is known, however, about the mechanism of this effect. The direct action of guaran on small intestinal absorption was evaluated by a single-pass perfusion technique. ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1984-04-01 00:00:00
abstract:BACKGROUND & AIMS:Intrapancreatic activation of digestive enzymes is a key event in the parenchymal cell injury of pancreatitis. We hypothesized that neutrophils recruited to the pancreas during pancreatitis may contribute to such activation. METHODS:To cause experimental pancreatitis, rats and mice were treated with ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.2002.32409
更新日期:2002-04-01 00:00:00
abstract::Three analogues of the carboxyl-terminal tricosapeptide of secretin (S5-27), one with glutamine replacing glutamic acid in position 9 (9-Gln-S5-27), a second with asparagine substituted for aspartic acid in position 15 (15-Asn-S5-27), and a third with both replacements (9-Gln-15-Asn-S5-27) were tested for their abilit...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1976-12-01 00:00:00
abstract:BACKGROUND & AIMS:The long-term outcomes of patients treated for autoimmune hepatitis (AIH) are considered to be good. However, follow-up data beyond 10 years are limited and confined to tertiary referral centers. We assessed long-term outcomes and determinants of outcome in patients with AIH from a nontransplant cente...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2011.02.065
更新日期:2011-06-01 00:00:00
abstract::Wilson's disease may present with severe acute hepatocellular failure. The only effective treatment for fulminant Wilson's disease is liver transplantation, which may lead to reversal of the underlying disease. Some patients with cirrhosis who are too ill to undergo orthotopic liver transplantation have been treated w...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(90)90497-o
更新日期:1990-12-01 00:00:00
abstract:BACKGROUND & AIMS:Major histocompatibility complex (MHC) class I-restricted CD8(+) T cells are required for clearance of hepatitis C virus (HCV) infection. MHC class I expression is up-regulated by type I and II interferons (IFNs). However, little is known about the effects of HCV infection on IFN-induced expression of...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2014.01.054
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND & AIMS:A single nucleotide polymorphism (SNP) upstream of the IL28B gene has been associated with response of patients with chronic hepatitis C to therapy with pegylated interferon and ribavirin and also with spontaneous clearance of acute hepatitis C in a heterogeneous population. We analyzed the associatio...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2010.07.005
更新日期:2010-11-01 00:00:00
abstract:BACKGROUND & AIMS:Early embryogenesis involves cell fate decisions that define the body axes and establish pools of progenitor cells. Development does not stop once lineages are specified; cells continue to undergo specific maturation events, and changes in gene expression patterns lead to their unique physiological fu...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2012.04.011
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND & AIMS:Omeprazole is metabolized by cytochrome P450 (CYP2C19). The activity of this enzyme is polymorphic, with incidences of poor metabolizers (PMs), heterozygous extensive metabolizers (EMs), and homozygous EMs in white populations of 3%, 30%, and 67%, respectively. The importance of the CYP2C19 polymorphi...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.2000.16515
更新日期:2000-09-01 00:00:00
abstract:BACKGROUND & AIMS:Unlike adult antral cells, feline newborn antral cells are unable to contract in response to agonists in the absence of extracellular calcium or in response to exogenous inositol 1,4,5-triphosphate (IP3) after permeabilization. Changes in intracellular pathways that are associated with these differenc...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.1997.v113.pm9247470
更新日期:1997-08-01 00:00:00
abstract:BACKGROUND & AIMS:Celiac disease is a complex, immune-mediated disorder of the intestinal mucosa with a strong genetic component. HLA-DQ2 is the major determinant of risk, but other minor genes, still to be identified, also are involved. METHODS:We designed a strategy that combines gene expression profiling of intesti...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2007.11.041
更新日期:2008-03-01 00:00:00