Abstract:
BACKGROUND AND AIMS:Fer kinase is activated by a number of growth factors and cytokines, and phosphorylates cortactin during cell shape change induced cortical actin reorganisation. In addition, Fer participates in cytoskeletal interactions mediated by cadherins, platelet endothelial cell adhesion molecule 1 (PECAM-1), and integrins, and has recently been implicated in limiting the innate immune response. Here we examined the role of Fer in modulating leucocyte recruitment and epithelial barrier function in the gut in response to lipopolysaccharide (LPS). METHODS:Mice targeted with a kinase inactivating mutation (FerDR) or strain matched wild-type (129Sv/J) mice were studied after intraperitoneal injection of LPS. Intravital microscopy was used to examine intestinal leucocyte kinetics, and leucocyte infiltration was assessed by fluorescence activated cell sorting. Systemic inflammation was assessed by measuring lung myeloperoxidase activity. Epithelial barrier function was assessed in vivo using blood to lumen 51Cr-EDTA clearance, with or without antibody based depletion of circulating neutrophils. RESULTS:LPS induced a significant increase in leucocyte adhesion and neutrophil infiltration into the intestinal tissue, and increased blood to lumen 51Cr-EDTA clearance. Pretreatment with neutrophil depleting antibody completely abrogated this response in wild-type mice. In FerDR mice, LPS induced leucocyte adhesion within the intestinal venules was exacerbated and associated with a trend towards increased neutrophil transmigration relative to wild-type mice. Surprisingly, LPS induced epithelial barrier permeability was increased 2.5-fold in FerDR mice relative to wild-type mice, and this barrier defect was only partly attenuated by depleting circulating neutrophils by >93 %. CONCLUSIONS:Fer plays a role in regulating LPS induced epithelial barrier dysfunction in vivo through both neutrophil dependent and neutrophil independent mechanisms.
journal_name
Gutjournal_title
Gutauthors
Qi W,Ebbert KV,Craig AW,Greer PA,McCafferty DMdoi
10.1136/gut.2004.061887keywords:
subject
Has Abstractpub_date
2005-08-01 00:00:00pages
1091-7issue
8eissn
0017-5749issn
1468-3288pii
54/8/1091journal_volume
54pub_type
杂志文章相关文献
GUT文献大全abstract:BACKGROUND:Human growth factors are potential therapeutic agents for various inflammatory disorders affecting the gastrointestinal tract. However, they are unstable when administered orally and systemic administration requires high doses increasing the risk of unwanted side effects. Live microorganism-based delivery sy...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.2008.176131
更新日期:2010-04-01 00:00:00
abstract::Heat shock proteins (HSPs) are a highly conserved family of proteins which inhabit almost all subcellular locations and cellular membranes. Depending on their location, these proteins perform a variety of chaperoning functions including folding of newly synthesised polypeptides. HSPs also play a major role in the prot...
journal_title:Gut
pub_type: 杂志文章,评审
doi:10.1136/gut.2007.140194
更新日期:2009-07-01 00:00:00
abstract::Patients with chronic active hepatitis or alcoholic cirrhosis have serum antibodies to many more serotypes of Escherichia coli than do patients with primary biliary cirrhosis or cryptogenic cirrhosis, or normal controls. They also have antibodies against more serotypes than cirrhotic patients with a portacaval shunt. ...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.16.11.871
更新日期:1975-11-01 00:00:00
abstract::Nodular regenerative hyperplasia of the liver usually presents with signs of portal hypertension with little evidence of obvious liver disease. We report a 47 year old man who presented with clinical signs of decompensated cirrhosis, recurrent encephalopathy, and tense ascites but at liver transplant was found to have...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.31.6.725
更新日期:1990-06-01 00:00:00
abstract::This experimental study was undertaken to follow the influence of phenobarbital on bile chemistry and gallstone formation. Phenobarbital (400 mg/kg/day) was administered to golden hamsters receiving a diet known to induce cholesterol gallstones. After a 28-day period none of the control animals had gallstones whereas ...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.14.12.956
更新日期:1973-12-01 00:00:00
abstract::A 24 hour gastric aspiration study was carried out on nine Polya gastrectomy, eight pernicious anaemia, and nine matched control subjects. Intragastric pH, bacteria, nitrite, and N-nitroso compounds were assessed half hourly whilst ambulant and hourly when in bed. Both total and nitrate reducing bacterial counts were ...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.27.5.491
更新日期:1986-05-01 00:00:00
abstract::The free primary amines present in the faeces of 44 infants (1-18 months) with gastroenteritis have been examined by field desorption mass spectrometry of the lactone form of their fluorescamine derivatives without their prior separation. p-Tyramine, 2-phenylethylamine, the diamines, putrescine and cadaverine and seve...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.27.10.1173
更新日期:1986-10-01 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::The small bowel of 44 rats has been made ischaemic for 120 minutes by occluding the superior mesenteric artery. Gaseous oxygen was introduced into the small bowel lumen of 18 of the rats, and gaseous nitrogen into the bowel lumen of a further eight, 30 minutes after the start of the ischaemia. The mortality rate of th...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.17.12.1001
更新日期:1976-12-01 00:00:00
abstract::The increase in activities of hepatic thymidylate synthetase (EC 2.1.1.45) and thymidine kinase (EC 2.7.1.21), which catalyse the formation of thymidylate through the de novo and salvage pathways, respectively, were significantly suppressed during liver regeneration in rats which were given glucocorticoids (hydrocorti...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.30.3.387
更新日期:1989-03-01 00:00:00
abstract::Relatives of patients with colorectal cancer have on average a two to threefold increased risk for developing bowel neoplasia although in some families the risk is much higher. This study examined the compliance for endoscopic screening and faecal occult blood testing among first degree relatives of patients with colo...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.34.1.96
更新日期:1993-01-01 00:00:00
abstract::We previously noted a region of amino acid sequence homology between A-gliadin, a major alpha-gliadin component known to activate coeliac disease, and the early region E1b protein of human adenovirus serotype 12 (Ad12), an adenovirus isolated from the human intestinal tract. In the present study sera from coeliac dise...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.28.8.995
更新日期:1987-08-01 00:00:00
abstract::The plasma clearance and the liver uptake of intravenously administered (64)Cu were significantly impaired in four patients with Wilson's disease. These defects were unlikely to be simply expressions of the high liver copper concentration as the plasma clearance and hepatic uptake of (64)Cu were normal in four patient...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.12.2.139
更新日期:1971-02-01 00:00:00
abstract:BACKGROUND AND AIMS:Interleukin-6 (IL-6) is a well-recognised mediator of liver disease and regeneration. However, the in vivo effects of IL-6 on enterocytes and the intestinal tract have not been elucidated. We sought to determine the in vivo effects of IL-6 on enterocytes. METHODS:Murine models of increased or absen...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.2008.151175
更新日期:2010-02-01 00:00:00
abstract::Studies in the rat jejunum in vivo have shown that 5-hydroxytryptamine (5-HT) causes secretion of fluid and luminal release of prostaglandin (PG) E2. These effects can be blocked by indomethacin and ketanserin, which suggests that PGE2 may be an important intermediate in the transduction mechanism leading to 5-HT indu...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.29.10.1337
更新日期:1988-10-01 00:00:00
abstract:BACKGROUND:An increasing number of patients with severe or refractory ulcerative colitis involving only the rectum and sigmoid colon are being offered restorative proctocolectomy with ileal reservoir but very few data are available concerning the outcome for these patients. AIM:This study was designed to compare the o...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.38.4.574
更新日期:1996-04-01 00:00:00
abstract::A group of 80 patients with diseases of the small intestine were given a standardized psychiatric assessment every time they attended the outpatients' department over a period of a year. Forty-six patients with idiopathic steatorrhoea, 23 patients with Crohn's disease, and 11 patients with alactasia were interviewed o...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.11.6.459
更新日期:1970-06-01 00:00:00
abstract::Hepatitis C virus (HCV) is a human pathogen responsible for acute and chronic liver disease, infecting an estimated 130-170 million persons worldwide. An intriguing feature of HCV infection is its peculiar relationship with lipids: (1) HCV virions circulate in serum bound to lipoproteins; (2) lipids have been shown to...
journal_title:Gut
pub_type: 杂志文章,评审
doi:10.1136/gut.2009.192732
更新日期:2010-09-01 00:00:00
abstract::The effects of the methyl ester analogue of prostaglandin E1, misoprostol, on gastric epithelial cell proliferation were investigated in six dogs given 300 micrograms/kg/day of misoprostol orally for 11 weeks and in six control dogs given placebo for 11 weeks. Misoprostol treatment resulted in a 36% increase in stomac...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.30.3.316
更新日期:1989-03-01 00:00:00
abstract::Evidence is presented of a higher than normal incidence both of clinical coeliac disease and of small-intestinal mucosal abnormalities in relatives of children with coeliac disease. In such relatives the incidence of mucosal abnormality may differ from the incidence of clinical coeliac disease. The data show an absenc...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.12.10.789
更新日期:1971-10-01 00:00:00
abstract::It has been reported that intestinal permeability to polyethylene glycol 400 is increased in patients with Crohn's disease and their apparently unaffected first degree relatives. Because of the implications that these findings have for the aetiology of Crohn's disease these studies were repeated. Patients with Crohn's...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.33.3.320
更新日期:1992-03-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Progression of a colorectal adenoma to invasive cancer occurs in a minority of adenomas and is the most crucial step in colorectal cancer pathogenesis. In the majority of cases, this is associated with gain of a substantial part of chromosome 20q, indicating that multiple genes on the 20q ampli...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gutjnl-2011-301153
更新日期:2012-11-01 00:00:00
abstract:OBJECTIVE:To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin. DESIGN:In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30) infection were randomly assig...
journal_title:Gut
pub_type: 杂志文章,随机对照试验
doi:10.1136/gutjnl-2014-307498
更新日期:2015-06-01 00:00:00
abstract:OBJECTIVE:Therapeutic strategies silencing and reducing the hepatitis B virus (HBV) reservoir, the covalently closed circular DNA (cccDNA), have the potential to cure chronic HBV infection. We aimed to investigate the impact of small interferring RNA (siRNA) targeting all HBV transcripts or pegylated interferon-α (peg-...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gutjnl-2020-322571
更新日期:2021-01-28 00:00:00
abstract:BACKGROUND:Motor disturbances are sometimes associated with diarrhoea by unknown mechanisms. AIM:To determine if there is a quantitative link between intestinal motility and epithelial secretion. SUBJECTS:Experiments were performed in 21 healthy volunteers and three patients with villus atrophy. METHODS:Duodenal and...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.46.3.376
更新日期:2000-03-01 00:00:00
abstract:OBJECTIVE:Liver fibrosis and cirrhosis resulting from chronic liver injury represent a major healthcare burden worldwide. Growth differentiation factor (GDF) 11 has been recently investigated for its role in rejuvenation of ageing organs, but its role in chronic liver diseases has remained unknown. Here, we investigate...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gutjnl-2019-318812
更新日期:2020-06-01 00:00:00
abstract::Glucosamine synthetase, the first enzyme in glycoprotein synthesis, has been measured in serial rectal biopsies in four patients with membranous colitis. In two of the patients the levels of the enzyme were very high initially and in the other two patients the enzyme levels rose to a peak above the normal range after ...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.18.3.229
更新日期:1977-03-01 00:00:00
abstract::Gastric secretion from 24 subjects was collected by continuous nasogastric aspiration during the plateau of secretion evoked by intravenous histamine diphosphate, 0.01 mg/kg/hr. Simultaneously, phenol red was instilled at a constant rate into the proximal part of the stomach. Concentrations of phenol red in 15-minute ...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.10.10.787
更新日期:1969-10-01 00:00:00
abstract::Evidence is presented which indicates a possible reduction in recognition capacity for tumour cell antigens (EB(2) Burkitt lymphoma cell line) by lymphocytes from some patients with longstanding but inactive Crohn's disease. Three out of seven patients tested also showed diminished or absent lymphocytotoxicity when th...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.13.8.614
更新日期:1972-08-01 00:00:00
abstract::Hydrogen breath tests are widely used to explore the pathophysiology of functional gastrointestinal disorders. Small intestinal bacterial overgrowth and carbohydrate malabsorption are disorders detected by these tests that have been proposed to be of great importance for symptoms in, for instance, irritable bowel synd...
journal_title:Gut
pub_type: 杂志文章,评审
doi:10.1136/gut.2005.075127
更新日期:2006-03-01 00:00:00