Abstract:
BACKGROUND/AIMS:Replication deficient recombinant adenoviruses represent an efficient means of transferring genes in vivo into a wide variety of dividing and quiescent cells from many different organs. Although the gastrointestinal tract is a potentially attractive target for gene therapy approaches, only a few studies on the use of viral gene transfer vehicles in the gut have been reported. The prospects of using recombinant adenoviruses for gene delivery into epithelial and subepithelial cells of the normal and inflamed colon are here analysed. METHODS:An E1/E3 deleted recombinant adenovirus (denoted AdCMVbetaGal) and an adenovirus with modified fibre structure (denoted AdZ.F(pk7)) both expressing the bacterial lacZ gene under the control of a human cytomegalovirus promoter were used for reporter gene expression in vitro and in vivo. beta-Galactosidase activity was determined by specific chemiluminescent reporter gene assay. RESULTS:Intravenous or intraperitoneal injection of AdCMVbetaGal into healthy Balb/c mice caused strong reporter gene expression in the liver and spleen but not in the colon. In contrast, local administration of AdCMVbetaGal resulted in high reporter gene expression in colonic epithelial cells and lamina propria mononuclear cells. A local route of adenovirus administration in mice with experimental colitis induced by the hapten reagent trinitrobenzenesulphonic acid was next evaluated. Interestingly, rectal administration of AdCMVbetaGal caused a higher beta-galactosidase activity in isolated lamina propria cells from infected mice with experimental colitis than in those from controls. Furthermore, isolated lamina propria cells from mice with colitis infected in vitro showed a significant increase in reporter gene activity compared with controls. Finally, AdZ.F(pk7) adenoviruses with modified fibre structure produced 10- to 40-fold higher reporter gene activity in spleen T cells and lamina propria mononuclear cells of colitic mice compared with standard AdCMVbetaGal vectors. CONCLUSIONS:Local administration of recombinant adenoviruses with normal or modified fibre structure could provide a new reliable method for targeted gene expression in the inflamed colon. Such gene delivery could be used to specifically express signal transduction proteins with therapeutic potential in inflamed colonic tissue. In particular, adenoviruses with modified fibre structure may be useful in T cell directed therapies in intestinal inflammation.
journal_name
Gutjournal_title
Gutauthors
Wirtz S,Galle PR,Neurath MFdoi
10.1136/gut.44.6.800keywords:
subject
Has Abstractpub_date
1999-06-01 00:00:00pages
800-7issue
6eissn
0017-5749issn
1468-3288journal_volume
44pub_type
杂志文章相关文献
GUT文献大全abstract:OBJECTIVE:To highlight the contribution of the gut microbiota to the modulation of host metabolism by dietary inulin-type fructans (ITF prebiotics) in obese women. METHODS:A double blind, placebo controlled, intervention study was performed with 30 obese women treated with ITF prebiotics (inulin/oligofructose 50/50 mi...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gutjnl-2012-303304
更新日期:2013-08-01 00:00:00
abstract::Endoscopic sphincterotomy was undertaken in 186 patients with common bile duct stones and an intact gall bladder who were considered unfit for surgery. One hundred and seventy one patients had jaundice of whom 18 also had clinical cholangitis. The mean age of treated patients was 79.7 years (range 27-92) and only 13 w...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.30.8.1129
更新日期:1989-08-01 00:00:00
abstract::Recent evidence suggests that the production of colorectal carcinogens is facilitated when the pH of the colonic contents is alkaline. It follows that the colonic intraluminal pH of patients with colorectal neoplasms should be higher than in normal subjects. Gastrointestinal pH has been measured in 30 patients with co...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.31.12.1355
更新日期:1990-12-01 00:00:00
abstract:OBJECTIVE:The natural course of chronic hepatitis C varies widely. To improve the profiling of patients at risk of developing advanced liver disease, we assessed the relative contribution of factors for liver fibrosis progression in hepatitis C. DESIGN:We analysed 1461 patients with chronic hepatitis C with an estimat...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gutjnl-2014-306997
更新日期:2015-10-01 00:00:00
abstract::The influence of carbenoxolone on the synthesis of glycoproteins in the surface mucous cells and the production of new cells in the rat gastric mucosa was studied by means of a vascular perfusion system. The rate of incorporation of tritiated galactose, glucosamine, serine, and sulphate in surface mucous cells, studie...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.22.10.782
更新日期:1981-10-01 00:00:00
abstract::The aims of the present study were to determine the relative amplitudes of intragastric motor responses evoked by different vagal branches and to establish whether the effects of acute or chronic vagotomy could be predicted from these data. Intragastric pressure responses to electrical stimulation of the vagus were me...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.21.10.811
更新日期:1980-10-01 00:00:00
abstract:BACKGROUND:MicroRNAs (miRNAs) are important in hepatic pathophysiology and the development of liver cancer. OBJECTIVE:To explore miRNAs that are regulated with the progression of liver fibrosis caused by chronic liver disease. DESIGN:The regulated miRNAs in human livers infected with hepatitis C virus were identified...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gutjnl-2011-300717
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND:Activated hepatic stellate cells (HSCs) are an attractive target for antifibrotic therapy based on their key role in extracellular matrix accumulation during liver injury. AIM:: To develop a system for regulable and cell-specific gene expression in HSCs to enable targeted delivery of therapeutic genes. MET...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.2005.085704
更新日期:2007-03-01 00:00:00
abstract::Ileal disease or resection causes bile salt malabsorption and a reduction in the bile salt content of bile. Since cholesterol solubility requires adequate bile salt concentrations, depletion of the bile salt content of bile might, therefore, jeopardize cholesterol solubility and predispose to cholesterol gallstone for...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.13.6.415
更新日期:1972-06-01 00:00:00
abstract::Although colorectal cancer (CRC) is a common cause of cancer-related death, it is fortunately amenable to screening with faecal tests for occult blood and endoscopic tests. Despite the evidence for the efficacy of guaiac-based faecal occult blood tests (gFOBT), they have not been popular with primary care providers in...
journal_title:Gut
pub_type: 杂志文章,评审
doi:10.1136/gutjnl-2014-308074
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:There is considerable evidence indicating that the severity of hepatic damage in individuals with cholestatic liver disease is causally associated with the extent of intrahepatic oxidative stress. Increased levels or accelerated generation of reactive oxygen species and toxic degradative products of lipid pe...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.47.5.710
更新日期:2000-11-01 00:00:00
abstract:BACKGROUND:Watery stools are equated with rapid and hard stools with slow intestinal transit; however, the relation between stool form and transit through specific regions of the gut is not clear cut. In addition, more information is needed on interindividual variability of these measurements. AIM:To examine the relat...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.39.1.109
更新日期:1996-07-01 00:00:00
abstract::The effect of 28 days' continuous administration of oral indomethacin on gastroduodenal morphology, gastric mucosal blood flow, and gastric mucosal prostaglandin E2 (PGE2) metabolism in man was studied to define further the mechanisms of mucosal injury induced by indomethacin. Indomethacin caused acute gastroduodenal ...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.33.2.164
更新日期:1992-02-01 00:00:00
abstract::Thirty eight patients with Crohn's disease and 30 patients with ulcerative colitis have been assessed using the technique of faecal excretion of 111Indium granulocytes to quantify precisely acute inflammatory activity. At the time of each faecal granulocyte measurement the serum concentration of the acute phase protei...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.27.7.809
更新日期:1986-07-01 00:00:00
abstract:BACKGROUND/AIMS:Transjugular intrahepatic portosystemic stent shunt (TIPSS) is effective in the prevention of variceal rebleeding but requires invasive portographic follow up. This randomised controlled trial aims to test the hypothesis that combining variceal band ligation (VBL) with TIPSS can obviate the need for lon...
journal_title:Gut
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1136/gut.2003.013532
更新日期:2004-03-01 00:00:00
abstract:OBJECTIVE:Loss of surface maturation and cytonuclear atypia have been regarded as the pathological 'gold standard' for the diagnosis of oesophageal squamous cell intraepithelial neoplasia. However, there has been no satisfactory endomicroscopic method similar to this pathological approach to detect surface maturation a...
journal_title:Gut
pub_type: 临床试验,杂志文章
doi:10.1136/gutjnl-2011-301946
更新日期:2013-11-01 00:00:00
abstract:BACKGROUND:Overexpression of tissue plasminogen activator (t-PA) in pancreatic cancer cells promotes invasion and proliferation in vitro and tumour growth and angiogenesis in vivo. AIMS:To understand the mechanisms by which t-PA favours cancer progression, we analysed the surface membrane proteins responsible for bind...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.2003.026831
更新日期:2004-07-01 00:00:00
abstract:BACKGROUND:Hereditary pancreatitis (HP) is a rare autosomal dominant disorder with variable expression and an overall lifetime penetrance of 80%. We hypothesised that (1) monozygotic twins within similar environments would develop the typical signs of HP at a similar age, and (2) if penetrance were due to modifier gene...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.48.4.542
更新日期:2001-04-01 00:00:00
abstract::The experience of The Middlesex Hospital in the investigation and management of chronic intestinal arterial occlusion (IAO) over a 20 year period is presented. Of some 100 patients referred only 28 were found to have IAO and these were critically evaluated in terms of insorptive and exsorptive function. No relation wa...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.26.7.656
更新日期:1985-07-01 00:00:00
abstract::Patients with the Peutz-Jeghers syndrome carry a slight, though definite, increased risk of gastrointestinal carcinoma. The malignant potentiality of Peutz-Jeghers hamartomatous polyps, generally considered benign, is supported by this report. Two cases of metastasising gastrointestinal carcinoma associated with the P...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.20.2.169
更新日期:1979-02-01 00:00:00
abstract::A further patient with watery diarrhoea and hypokalaemia in association with a non-beta islet cell tumour of the pancreas is reported. The mechanism by which fluid and electrolyte losses are produced is discussed and cases previously reported are reviewed. ...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.11.11.911
更新日期:1970-11-01 00:00:00
abstract:BACKGROUND AND AIMS:In acute liver failure (ALF), the brain is exposed to high levels of ammonia. Human studies defining the clinical significance of ammonia in ALF are lacking. This prospective study evaluated the relationship of arterial ammonia levels at admission to complications and survival among patients with AL...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.2004.061754
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVE:miR-21 was found to be overexpressed in the colon tissues and serum of patients with UC and colorectal cancer (CRC); however, the exact roles of miR-21 in colitis-associated CRC remain unclear. The aim of our study was to investigate the biological mechanisms of miR-21 in colitis-associated colon cancer (CAC)...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gutjnl-2014-308455
更新日期:2016-09-01 00:00:00
abstract:BACKGROUND:Despite the recent discovery of four genes responsible for up to 90% of all cases of hereditary non-polyposis colorectal cancer (HNPCC), there will still be families in whom predictive testing is not possible. A phenotypic biomarker would therefore be useful. An upwards shift of the proliferative compartment...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.43.1.85
更新日期:1998-07-01 00:00:00
abstract:BACKGROUND:The major potential site of acid nitrosation is the proximal stomach, an anatomical site prone to a rising incidence of metaplasia and adenocarcinoma. Nitrite, a pre-carcinogen present in saliva, can be converted to nitrosating species and N-nitroso compounds by acidification at low gastric pH in the presenc...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.2007.128587
更新日期:2007-12-01 00:00:00
abstract::The isoenzyme pattern of lactic dehydrogenase was measured in rectal biopsies from six patients with ulcerative colitis in whom precancerous histological changes had been independently recognized. There was a highly significant increase in the ratio of isoenzymes IV + V to I + II. This suggests that lactic dehydrogena...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.12.1.16
更新日期:1971-01-01 00:00:00
abstract:OBJECTIVE:The death rate of mature hepatocytes is chronically increased in various liver diseases, triggering responses that prevent liver atrophy, but often cause fibrosis. Mice with targeted disruption of inhibitor kappa B kinase (Ikk) in hepatocytes (HEP mice) provide a model to investigate this process because inhi...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.2009.204354
更新日期:2010-05-01 00:00:00
abstract:BACKGROUND:Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed medications, but they are associated with a number of serious adverse effects, including hypertension, cardiovascular disease, kidney injury and GI complications. OBJECTIVE:To develop a set of multidisciplinary recommenda...
journal_title:Gut
pub_type: 杂志文章,实务指引
doi:10.1136/gutjnl-2019-319300
更新日期:2020-04-01 00:00:00
abstract:BACKGROUND AND AIM:The treatment of ulcerative colitis (UC) with 5-aminosalicylic acid (5-ASA) does not have the same therapeutic effect in all patients. We tested the hypothesis that the effectiveness of the drug is related to its mucosal concentration. PATIENTS:Twenty one UC patients receiving oral 5-ASA (2.4-3.2 g/...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.47.3.410
更新日期:2000-09-01 00:00:00
abstract::Three cases of apparent primary villous atrophy of the terminal ileum in women with chronic diarrhoea are reported. Eight cases have previously been reported in the literature. Clinical characteristics are the presence of severe chronic secretory diarrhoea with episodes of hypokalaemia combined with signs of ileal mal...
journal_title:Gut
pub_type: 杂志文章,评审
doi:10.1136/gut.41.4.561
更新日期:1997-10-01 00:00:00