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PubMed Central (PMC3 - NLM DTD) (2,708,190 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).

American Journal of Physiology - Gastrointestinal and Liver Physiology

Mostrando recursos 1 - 20 de 791

1. Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome - Ringel, Yehuda; Maharshak, Nitsan
The pathophysiology of irritable bowel syndrome (IBS) is believed to involve alterations in the brain-gut axis; however, the etiological triggers and mechanisms by which these changes lead to symptoms of IBS remain poorly understood. Although IBS is often considered a condition without an identified “organic” etiology, emerging evidence suggests that alterations in the gastrointestinal microbiota and altered immune function may play a role in the pathogenesis of the disorder. These recent data suggest a plausible model in which changes in the intestinal microbiota and activation of the enteric immune system may impinge upon the brain-gut axis, causing the alterations in...

2. Helicobacter hepaticus increases intestinal injury in a rat model of necrotizing enterocolitis - Dvorak, Katerina; Coursodon-Boyiddle, Christine F.; Snarrenberg, Chelsea L.; Kananurak, Anchasa; Underwood, Mark A.; Dvorak, Bohuslav
Enterohepatic helicobacter species (EHS) infect the intestinal tract and biliary tree, triggering intestinal and hepatic disorders. Helicobacter hepaticus, the prototypic murine EHS, is also associated with inflammation. Necrotizing enterocolitis (NEC) is a devastating disease of premature infants. The cause of NEC is not fully understood, but anomalies of bacterial colonization (dysbiosis) are thought to play an important role in disease onset. To evaluate the effect of H. hepaticus infection on the development of NEC, premature formula-fed rats were kept either in H. hepaticus-free conditions or colonized with H. hepaticus; both groups were exposed to asphyxia and cold stress. The incidence...

3. Irgm1-deficient mice exhibit Paneth cell abnormalities and increased susceptibility to acute intestinal inflammation - Liu, Bo; Gulati, Ajay S.; Cantillana, Viviana; Henry, Stanley C.; Schmidt, Elyse A.; Daniell, Xiaoju; Grossniklaus, Emily; Schoenborn, Alexi A.; Sartor, R. Balfour; Taylor, Gregory A.
Crohn's disease (CD) is a chronic, immune-mediated, inflammatory disorder of the intestine that has been linked to numerous susceptibility genes, including the immunity-related GTPase (IRG) M (IRGM). IRGs comprise a family of proteins known to confer resistance to intracellular infections through various mechanisms, including regulation of phagosome processing, cell motility, and autophagy. However, despite its association with CD, the role of IRGM and other IRGs in regulating intestinal inflammation is unclear. We investigated the involvement of Irgm1, an ortholog of IRGM, in the genesis of murine intestinal inflammation. After dextran sodium sulfate exposure, Irgm1-deficient [Irgm1 knockout (KO)] mice showed increased...

4. Epimorphin deletion inhibits polyposis in the Apcmin/+ mouse model of colon carcinogenesis via decreased myofibroblast HGF secretion - Swietlicki, Elzbieta A.; Bala, Shashi; Lu, Jianyun; Shaker, Anisa; Kularatna, Gowri; Levin, Marc S.; Rubin, Deborah C.
Interactions between the epithelium and surrounding mesenchyme/stroma play an important role in normal gut morphogenesis, the epithelial response to injury, and epithelial carcinogenesis. The tumor microenvironment, composed of stromal cells including myofibroblasts and immune cells, regulates tumor growth and the cancer stem cell niche. Deletion of epimorphin (Epim), a syntaxin family member expressed in myofibroblasts and macrophages, results in partial protection from colitis and from inflammation-induced colon cancer in mice. We sought to determine whether epimorphin deletion protects from polyposis in the Apcmin/+ mouse model of intestinal carcinogenesis. Epim−/− mice were crossed to Apcmin/+ mice; Apcmin/+ and Apcmin/+/Epim−/− mice were...

5. A multicenter study to standardize reporting and analyses of fluorescence-activated cell-sorted murine intestinal epithelial cells - Magness, Scott T.; Puthoff, Brent J.; Crissey, Mary Ann; Dunn, James; Henning, Susan J.; Houchen, Courtney; Kaddis, John S.; Kuo, Calvin J.; Li, Linheng; Lynch, John; Martin, Martin G.; May, Randal; Niland, Joyce C.; Olack, Barbara; Qian, Dajun; Stelzner, Matthias; Swain, John R.; Wang, Fengchao; Wang, Jiafang; Wang, Xinwei; Yan, Kelley; Yu, Jian; Wong, Melissa H.
Fluorescence-activated cell sorting (FACS) is an essential tool for studies requiring isolation of distinct intestinal epithelial cell populations. Inconsistent or lack of reporting of the critical parameters associated with FACS methodologies has complicated interpretation, comparison, and reproduction of important findings. To address this problem a comprehensive multicenter study was designed to develop guidelines that limit experimental and data reporting variability and provide a foundation for accurate comparison of data between studies. Common methodologies and data reporting protocols for tissue dissociation, cell yield, cell viability, FACS, and postsort purity were established. Seven centers tested the standardized methods by FACS-isolating a specific...

6. Adaptive regulation of human intestinal thiamine uptake by extracellular substrate level: a role for THTR-2 transcriptional regulation - Nabokina, Svetlana M.; Subramanian, Veedamali S.; Valle, Judith E.; Said, Hamid M.
The intestinal thiamine uptake process is adaptively regulated by the level of vitamin in the diet, but the molecular mechanism involved is not fully understood. Here we used the human intestinal epithelial Caco-2 cells exposed to different levels of extracellular thiamine to delineate the molecular mechanism involved. Our results showed that maintaining Caco-2 cells in a thiamine-deficient medium resulted in a specific and significant increase of [3H]thiamine uptake compared with cell exposure to a high level of thiamine (1 mM). This adaptive regulation was also associated with a higher level of mRNA expression of thiamine transporter-2 (THTR-2), but not thiamine...

7. Transcellular oxalate and Cl− absorption in mouse intestine is mediated by the DRA anion exchanger Slc26a3, and DRA deletion decreases urinary oxalate - Freel, Robert W.; Whittamore, Jonathan M.; Hatch, Marguerite
Active transcellular oxalate transport in the mammalian intestine contributes to the homeostasis of this important lithogenic anion. Several members of the Slc26a gene family of anion exchangers have a measurable oxalate affinity and are expressed along the gut, apically and basolaterally. Mouse Slc26a6 (PAT1) targets to the apical membrane of enterocytes in the small intestine, and its deletion results in net oxalate absorption and hyperoxaluria. Apical exchangers of the Slc26a family that mediate oxalate absorption have not been established, yet the Slc26a3 [downregulated in adenoma (DRA)] protein is a candidate mediator of oxalate uptake. We evaluated the role of DRA...

8. Cysteine 96 of Ntcp is responsible for NO-mediated inhibition of taurocholate uptake - Ramasamy, Umadevi; Anwer, M. Sawkat; Schonhoff, Christopher M.
The Na+ taurocholate (TC) cotransporting polypeptide Ntcp/NTCP mediates TC uptake across the sinusoidal membrane of hepatocytes. Previously, we demonstrated that nitric oxide (NO) inhibits TC uptake through S-nitrosylation of a cysteine residue. Our current aim was to determine which of the eight cysteine residues of Ntcp is responsible for NO-mediated S-nitrosylation and inhibition of TC uptake. Thus, we tested the effect of NO on TC uptake in HuH-7 cells transiently transfected with cysteine-to-alanine mutant Ntcp constructs. Of the eight mutants tested, only C44A Ntcp displayed decreased total and plasma membrane (PM) levels that were also reflected in decreased TC uptake....

9. Developmental origins of colon smooth muscle dysfunction in IBS-like rats - Li, Qingjie; Winston, John H.; Sarna, Sushil K.
Epidemiological studies show that subsets of adult and pediatric patients with irritable bowel syndrome (IBS) have prior exposures to psychological or inflammatory stress. We investigated the cellular mechanisms of colonic smooth muscle dysfunction in adult rats subjected to neonatal inflammation. Ten-day-old male rat pups received 2,4,6-trinitrobenzene sulfonic acid to induce colonic inflammation. Colonic circular smooth muscle strips were obtained 6 to 8 wk later. We found that about half of the neonate pups subjected to inflammatory insult showed a significant increase in expression of the pore-forming α1C-subunit of Cav1.2b channels in adult life. These were the same rats in whom...

10. Reduced thoracic fluid content in early-stage primary biliary cirrhosis that associates with impaired cardiac inotropy - Zalewski, Paweł; Jones, David; Lewis, Ieuan; Frith, James; Newton, Julia L.
Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by cholestasis. Recent MRI studies have confirmed the presence of cardiac abnormalities in noncirrhotic PBC patients. However, cardiorespiratory consequences of these abnormalities have not been explored. Thoracic fluid content (TFC) is a noninvasive bioelectrical impedance measure of the electrical conductivity of the chest cavity. We explored TFC and its relationship with cardiac contractility parameters in early-stage PBC patients, compared with chronic liver disease and community controls. TFC was measured in early-stage PBC (noncirrhotic; n = 78), nonalcoholic fatty liver disease (n = 23), and primary sclerosing cholangitis (n = 18)...

11. Characterization of CFTR High Expresser cells in the intestine - Jakab, Robert L.; Collaco, Anne M.; Ameen, Nadia A.
The CFTR High Expresser (CHE) cells express eightfold higher levels of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel compared with neighboring enterocytes and were first identified by our laboratory (Ameen et al., Gastroenterology 108: 1016, 1995). We used double-label immunofluorescence microscopy to further study these enigmatic epithelial cells in rat intestine in vivo or ex vivo. CHE cells were found in duodenum, most frequent in proximal jejunum, and absent in ileum and colon. CFTR abundance increased in CHE cells along the crypt-villus axis. The basolateral Na+K+Cl− cotransporter NKCC1, a key transporter involved in Cl− secretion, was detected at...

12. Tumor protein D52 controls trafficking of an apical endolysosomal secretory pathway in pancreatic acinar cells - Messenger, Scott W.; Thomas, Diana D. H.; Falkowski, Michelle A.; Byrne, Jennifer A.; Gorelick, Fred S.; Groblewski, Guy E.
Zymogen granule (ZG) formation in acinar cells involves zymogen cargo sorting from trans-Golgi into immature secretory granules (ISGs). ISG maturation progresses by removal of lysosomal membrane and select content proteins, which enter endosomal intermediates prior to their apical exocytosis. Constitutive and stimulated secretion through this mechanism is termed the constitutive-like and minor-regulated pathways, respectively. However, the molecular components that control membrane trafficking within these endosomal compartments are largely unknown. We show that tumor protein D52 is highly expressed in endosomal compartments following pancreatic acinar cell stimulation and regulates apical exocytosis of an apically directed endolysosomal compartment. Secretion from the endolysosomal...

13. Studies of mucus in mouse stomach, small intestine, and colon. II. Gastrointestinal mucus proteome reveals Muc2 and Muc5ac accompanied by a set of core proteins - Rodríguez-Piñeiro, Ana M.; Bergström, Joakim H.; Ermund, Anna; Gustafsson, Jenny K.; Schütte, André; Johansson, Malin E. V.; Hansson, Gunnar C.
The mucus that protects the surface of the gastrointestinal tract is rich in specialized O-glycoproteins called mucins, but little is known about other mucus proteins or their variability along the gastrointestinal tract. To ensure that only mucus was analyzed, we combined collection from explant tissues mounted in perfusion chambers, liquid sample preparation, single-shot mass spectrometry, and specific bioinformatics tools, to characterize the proteome of the murine mucus from stomach to distal colon. With our approach, we identified ∼1,300 proteins in the mucus. We found no differences in the protein composition or abundance between sexes, but there were clear differences in...

14. Genome-wide transcriptome analysis identifies novel gene signatures implicated in human chronic liver disease - Smalling, Rana L.; Delker, Don A.; Zhang, Yuxia; Nieto, Natalia; Mcguiness, Michael S.; Liu, Shuanghu; Friedman, Scott L.; Hagedorn, Curt H.; Wang, Li
The molecular mechanisms behind human liver disease progression to cirrhosis remain elusive. Nuclear receptor small heterodimer partner (SHP/Nr0b2) is a hepatic tumor suppressor and a critical regulator of liver function. SHP expression is diminished in human cirrhotic livers, suggesting a regulatory role in human liver diseases. The goal of this study was to identify novel SHP-regulated genes that are involved in the development and progression of chronic liver disease. To achieve this, we conducted the first comprehensive RNA sequencing (RNA-seq) analysis of Shp−/− mice, compared the results with human hepatitis C cirrhosis RNA-seq and nonalcoholic steatohepatitis (NASH) microarray datasets, and...

15. Studies of mucus in mouse stomach, small intestine, and colon. I. Gastrointestinal mucus layers have different properties depending on location as well as over the Peyer's patches - Ermund, Anna; Schütte, André; Johansson, Malin E. V.; Gustafsson, Jenny K.; Hansson, Gunnar C.
Colon has been shown to have a two-layered mucus system where the inner layer is devoid of bacteria. However, a complete overview of the mouse gastrointestinal mucus system is lacking. We now characterize mucus release, thickness, growth over time, adhesive properties, and penetrability to fluorescent beads from stomach to distal colon. Colon displayed spontaneous mucus release and all regions released mucus in response to carbachol and PGE2, except the distal colon and domes of Peyer's patches. Stomach and colon had an inner mucus layer that was adherent to the epithelium. In contrast, the small intestine and Peyer's patches had a...

16. Studies of mucus in mouse stomach, small intestine, and colon. III. Gastrointestinal Muc5ac and Muc2 mucin O-glycan patterns reveal a regiospecific distribution - Holmén Larsson, Jessica M.; Thomsson, Kristina A.; Rodríguez-Piñeiro, Ana M.; Karlsson, Hasse; Hansson, Gunnar C.
The mouse intestinal mucus is mainly made up by the gel-forming Muc2 mucin and the stomach surface mucus Muc5ac, both extensively O-glycosylated. The oligosaccharide diversity provides a vast library of potential recognition sites for both commensal and pathogenic organisms. The mucin glycans are thus likely very important for the selection and maintenance of a stable intestinal flora. Here we have explored the O-glycan patterns of the mouse gastrointestinal tract mucins. The mucins from the mucus of the distal and proximal colon, ileum, jejunum, duodenum, and stomach of conventionally raised wild-type (C57BL/6) mice were separated by composite gel electrophoresis. The O-linked...

17. CXCL12 induces hepatic stellate cell contraction through a calcium-independent pathway - Saiman, Yedidya; Agarwal, Ritu; Hickman, DaShawn A.; Fausther, Michel; El-Shamy, Ahmed; Dranoff, Jonathan A.; Friedman, Scott L.; Bansal, Meena B.
Liver fibrosis, with subsequent development of cirrhosis and ultimately portal hypertension, results in the death of patients with end-stage liver disease if liver transplantation is not performed. Hepatic stellate cells (HSCs), central mediators of liver fibrosis, resemble tissue pericytes and regulate intrahepatic blood flow by modulating pericapillary resistance. Therefore, HSCs can contribute to portal hypertension in patients with chronic liver disease (CLD). We have previously demonstrated that activated HSCs express functional chemokine receptor, CXCR4, and that receptor engagement by its ligand, CXCL12, which is increased in patients with CLD, leads to further stellate cell activation in a CXCR4-specific manner. We...

18. Glucagon-like peptide-2 induces rapid digestive adaptation following intestinal resection in preterm neonates - Vegge, Andreas; Thymann, Thomas; Lund, Pernille; Stoll, Barbara; Bering, Stine B.; Hartmann, Bolette; Jelsing, Jacob; Qvist, Niels; Burrin, Douglas G.; Jeppesen, Palle B.; Holst, Jens J.; Sangild, Per T.
Short bowel syndrome (SBS) is a frequent complication after intestinal resection in infants suffering from intestinal disease. We tested whether treatment with the intestinotrophic hormone glucagon-like peptide-2 (GLP-2) increases intestinal volume and function in the period immediately following intestinal resection in preterm pigs. Preterm pigs were fed enterally for 48 h before undergoing resection of 50% of the small intestine and establishment of a jejunostomy. Following resection, pigs were maintained on total parenteral nutrition (TPN) without (SBS, n = 8) or with GLP-2 treatment (3.5 μg/kg body wt per h, SBS+GLP-2, n = 7) and compared with a group of...

19. Paradoxical regulation of ChAT and nNOS expression in animal models of Crohn's colitis and ulcerative colitis - Winston, John H.; Li, Qingjie; Sarna, Sushil K.
Morphological and functional changes in the enteric nervous system (ENS) have been reported in inflammatory bowel disease. We examined the effects of inflammation on the expression of choline acetyltransferase (ChAT) and nNOS in the muscularis externae of two models of colonic inflammation, trinitrobenzene sulfonic acid (TNBS)-induced colitis, which models Crohn's disease-like inflammation, and DSS-induced colitis, which models ulcerative Colitis-like inflammation. In TNBS colitis, we observed significant decline in ChAT, nNOS, and protein gene product (PGP) 9.5 protein and mRNA levels. In DSS colitis, ChAT and PGP9.5 were significantly upregulated while nNOS levels did not change. The nNOS dimer-to-monomer ratio decreased...

20. Differential expression of multidrug resistance protein 5 and phosphodiesterase 5 and regulation of cGMP levels in phasic and tonic smooth muscle - Al-Shboul, Othman; Mahavadi, Sunila; Sriwai, Wimolpak; Grider, John R.; Murthy, Karnam S.
Previous studies have identified differences in the expression of proteins that regulate myosin light chain phosphorylation and contraction in tonic and phasic smooth muscle. cGMP plays a critical role in smooth muscle relaxation and is important for optimal function of phasic and tonic smooth muscle. The intracellular cGMP levels are regulated by its hydrolysis via phosphodiesterase 5 (PDE5) and efflux via novel multidrug resistance protein 5 (MRP5). In the present study we tested the hypothesis that the differences in the phasic and tonic behavior of smooth muscles may be related to differences in mechanisms that terminate cGMP signaling. Expression of...

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