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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 42 (1997), S. 1003-1012 
    ISSN: 1573-2568
    Keywords: ESOPHAGITIS ; PEPSIN ; ADAPTATION ; EPIDERMAL GROWTH FACTOR ; NITRIC OXIDE
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To study whether the esophageal mucosa was ableto elicit mucosal adaptation, we induced esophagealdamage by perfusing acidified pepsin in rabbits. Mucosaladaptation was induced by preexposing the esophageal mucosa to a mild irritant (acidified saline)for 60 min prior to acidified pepsin (strong irritant).Macroscopic and microscopic esophageal injury, cellproliferation, and mucosal barrier function(H+, K+, hemoglobin flux rates)were studied. Preexposure of the esophageal mucosa toacidified saline significantly decreased both themucosal damage and the mucosal barrier dysfunctioninduced by acidified pepsin. The development of this phenomenon wasnondependent on cell proliferation. Concomitanttreatment with either the nitric oxide synthaseinhibitor, NG-nitro-L-arginine, or theperfusion of immunospecific EGF-receptor antibodies or tyrphostin-25, aninhibitor of the tyrosine kinase activities ligated tothe intracytoplasmatic domain of the EGF receptor,during the preexposure period completely reversed the protection induced by acid. We conclude thatthe rabbit esophageal mucosa shows mucosal adaptation toacid and pepsin. The development of this phenomenon isfast, not dependent on cell proliferation, and dependent, at least in part, on nitric oxideand EGF-receptor-mediated mechanisms.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 45 (2000), S. 1802-1809 
    ISSN: 1573-2568
    Keywords: superoxide anion ; nitric oxide ; esophagitis ; superoxide dismutase ; sodium nitroprusside ; nitric oxide synthase inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been suggested that free radicals are involved in esophagitis. To study the role and potential interaction of superoxide anion and nitric oxide (NO) in low-grade esophagitis, we perfused acidified pepsin (30 min every 12 hr) for seven days in rabbits treated with different agents to modulate the generation of these radicals. Measurements included macroscopic and microscopic damage, superoxide anion generation, mucosal nitric oxide synthase activity, and peroxynitrite formation. Low-grade esophagitis was associated with increased nitric oxide synthase mucosal activity and mucosal damage was dose-dependently increased by treatment with the NO synthase inhibitor N G-nitro-l-arginine. Superoxide anion was scarcely generated in the mucosa, but this was not accompanied by any change in the activity of mucosal superoxide dismutase. Treatment with superoxide dismutase did not improve mucosal damage. Generation of peroxynitrites was not detected. In conclusion, nitric oxide is involved in the mucosal defense of the esophagus against acid- and pepsin-induced damage. Superoxide anion generation seems irrelevant in the induction of low-grade esophagitis and not sufficient to interact with nitric oxide to generate measurable mucosal peroxynitrite radicals.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cancer causes & control 3 (1992), S. 137-143 
    ISSN: 1573-7225
    Keywords: Alcohol ; case-control studies ; coffee ; gastric cancer ; Spain ; tobacco smoking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: A case-control study on gastric cancer was carried out between 1987 and 1989 in four regions of Spain. Three hundred and fifty-four cases of histologically confirmed adenocarcinoma were included (235 men and 119 women). For each case, a control was selected, matched by sex, age, and area of residence, from the same hospital as the case. No association was observed with smoking, nor with the consumption of coffee or tea. The usual consumption of alcohol was associated with gastric cancer in men (odds ratio = 1.54, 95 percent confidence interval = 1.03–2.31), but there was no dose-response relationship. No association was observed in women. All estimations were carried out taking into account the effect of the dietary factors associated with gastric cancer. In accordance with previous evidence, the association observed between gastric cancer and alcohol appears not to be causal.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 66 (1996), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The ocular ciliary epithelium, the site of aqueous humor secretion in the mammalian eye, is believed to play a key function in signaling mechanisms that regulate the rate of secretion, and thus intraocular pressure. One possible way of mediating these signaling functions is through neuropeptides and hormones secreted into the aqueous humor and acting on target tissues. We recently identified a cDNA clone sharing 100% identity with carboxypeptidase E (CPE), a neuropeptide-processing enzyme. Utilizing polymerase chain reaction, we further identified and characterized another processing enzyme, the peptidylglycine α-amidating monooxygenase (PAM), and the neuropeptide secretogranin II, a molecular marker restricted to neuroendocrine tissues. Using specific probes, we found that the nonpigmented ciliary epithelial cells express CPE, PAM, and secretogranin II mRNA, and protein. We also found that CPE and secretogranin II are abundant in aqueous humor. Treatment of cultured ciliary epithelial cells with veratridine and phorbol ester up-regulates CPE and PAM. Secretogranin II was found to be induced by veratridine, whereas phorbol ester had little effect, suggesting different mechanisms for secretion. The results demonstrate that secretogranin II, CPE, and PAM represent a specialized group of neuropeptide and neuropeptide-processing enzymes secreted by the ciliary epithelial cells which may confer to them neuroendocrine functions in cell-cell communication or cell signaling.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 69 (1997), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The ocular ciliary epithelium is a bilayer of neuroepithelial cells specialized in the secretion of aqueous humor fluid and the regulation of intraocular pressure. In this study, we report on the expression of the regulatory peptide neurotensin (NT) and a set of differentiated neuroendocrine markers including neurotensin receptors (NTrs), the prohormone convertases furin, PC1, and PC2, and the neuroendocrine polypeptide 7B2 in the ciliary epithelium. Using a human cell line, ODM-2, derived from the nonpigmented ciliary epithelium, we demonstrate that (1) NT expression is highly activated by nerve growth factor, glucocorticoid, and activators of adenylate cyclase; (2) NTr expression is up-regulated by selective ligand-activated β2-adrenergic receptor; and (3) PC1 and PC2 expression are up-regulated via distinct signaling transduction pathways. PC1 gene expression is activated by phorbol ester, and PC2 by the same inducers as those of NT expression. A radioimmunoassay for NT detected an NT-like immunoreactivity in human ciliary epithelium and ODM-2 cell extracts, in aqueous humor, and in conditioned culture medium. The results support the view that the entire ciliary epithelium functions as a neuroendocrine tissue, synthesizing, processing, and releasing NT into the aqueous humor where it may exert important physiological functions through autocrine and/or paracrine mechanisms.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 71 (1998), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Here we report the coexpression of the neuropeptide galanin and GalR-1 galanin receptors in the human ciliary epithelium, a bilayer of neuroepithelial cells [nonpigmented (NPE) and pigmented (PE)] with neuroendocrine functions, and in a cell line (ODM-2) derived from the NPE cells. Stimulation of ODM-2 cells with phorbol ester [phorbol 12-myristate 13-acetate (PMA)] or forskolin resulted in an up-regulation (two- to threefold) of galanin mRNA expression. Procaterol, a selective β2-adrenergic agonist, and the catecholamine isoproterenol exerted a long-term down-regulation on galanin mRNA expression when added alone or in combination with PMA or forskolin. These actions exerted by procaterol or isoproterenol were abolished in the presence of ICI 118,551, a selective β2-adrenergic antagonist. A radioimmunoassay for galanin peptide indicated that galanin or a galanin-like product is present in the human aqueous humor fluid and is accumulated with time in the culture medium of ODM-2 cells. It is interesting that norepinephrine, which exhibited no effect on galanin mRNA expression, induced a down-regulation in the level of galanin or galanin-like product accumulated in the medium of cultured ODM-2 cells to levels even lower than those induced by β2-adrenergic agonists. This effect is best explained by the concomitant up-regulation (four- to fivefold) of GalR-1 galanin receptor transcripts induced through the activation of α2-adrenergic receptors. These findings support the view that pathways elicited by the activation of α2- and β2-adrenergic receptors influence the expression of galanin and GalR-1 galanin receptors in ciliary epithelial cells.
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