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Author

Haruhiko Inatsu

Bio: Haruhiko Inatsu is an academic researcher from University of Miyazaki. The author has contributed to research in topics: Adrenomedullin & Inflammatory bowel disease. The author has an hindex of 12, co-authored 27 publications receiving 441 citations.

Papers
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Journal ArticleDOI
TL;DR: The results demonstrate that among this CD patient cohort, EN combined with IFX maintenance treatment was clinically useful for maintaining remission.
Abstract: Background One of the problems associated with infliximab (IFX) treatment for Crohn’s disease (CD) is loss of response during maintenance therapy.

69 citations

Journal ArticleDOI
TL;DR: It is shown that the protective capability of AM is associated with suppression of inflammation and maintenance of the intestinal epithelial barrier function, and a potential therapeutic value of this treatment for IBD is suggested.
Abstract: Hyperactivation and hyperpermeability of the intestinal epithelium is a hallmark of IBD. AM has been shown to reduce the severity of colitis in the acetic acid and TNBS-induced colitis model, however the mechanism of the therapeutic effect of AM against the colitis has not been clarified. Here, we show that the protective capability of AM is associated with suppression of inflammation and maintenance of the intestinal epithelial barrier function. In the DSS-induced colitis model, intra-rectal AM-treated mice showed a reduction in loss of body weight and severity of colitis. AM-treatment suppressed phosphorylation of STAT1 and STAT3 in the colonic epithelium, and altered the cytokine balance in the intestinal T cells, with lower levels of IFN-gamma and TNF-alpha but higher levels of TGF-beta. Expression of the epithelial intercellular junctions such as tight and adherence junctions were sustained in the AM-treated mice. In contrast, the epithelial junctions were down-regulated in the control mice, leading to loss of epithelial barrier integrity and enhanced permeability. Collectively, these data indicate a broad spectrum of AM-induced effects with respect to protection against DSS-induced colitis, and suggest a potential therapeutic value of this treatment for IBD.

48 citations

Journal ArticleDOI
01 Dec 2005-Peptides
TL;DR: Adrenomedullin administered intracolonically ameliorated the severity of acetic acid-induced colonic ulceration in rats and reduced the size of the ulcerative lesions, the associated edema, and the infiltration of the affected area by inflammatory cells.

48 citations

Journal ArticleDOI
TL;DR: It is suggested that HAI-1/SPINT1 has a crucial role in suppressing intestinal tumorigenesis, which implies a novel link between epithelial cell surface serine protease inhibitors and protection from carcinogenic stimuli.
Abstract: Hepatocyte growth factor activator inhibitor type 1 (HAI-1/SPINT1) is a membrane-bound serine protease inhibitor expressed on the surface of epithelial cells. Although HAI-1/SPINT1 is abundantly expressed in the intestinal epithelium, its role in intestinal tumorigenesis is not known. In this study, we investigated the role of Hai-1/Spint1 in intestinal tumorigenesis using mouse models. The membranous Hai-1/Spint1 immunoreactivity was decreased in murine Apc(Min/+) tumors and also in carcinogen (azoxymethane treatment followed by dextran sodium sulfate administration)-induced colon tumors compared with the adjacent non-neoplastic epithelium. The decreased immunoreactivity appeared to be due to sheddase activity of membrane-type 1 matrix metalloprotease. Then, we examined the effect of intestine-specific deletion of Spint1 gene on Apc(Min/+) mice. The loss of Hai-1/Spint1 significantly accelerated tumor formation in Apc(Min/+) mice and shortened their survival periods. Activation of HGF was enhanced in Hai-1/Spint1-deficient Apc(Min/+) intestine. Gene expression profiling revealed upregulation of the Wnt/β-catenin signaling circuit, claudin-2 expression, and angiogenesis not only in tumor tissue but also in the background mucosa without macroscopic tumors in Hai-1/Spint1-deficient Apc(Min/+) intestine. Intestinal deletion of Spint1 also enhanced the susceptibility to carcinogen-induced colon tumorigenicity of wild-type Apc mice. Our findings suggest that HAI-1/SPINT1 has a crucial role in suppressing intestinal tumorigenesis, which implies a novel link between epithelial cell surface serine protease inhibitors and protection from carcinogenic stimuli.

43 citations

Journal ArticleDOI
TL;DR: The results suggest that adrenomedullin, through its potent vasodilating activity, may play some role, in the stomach including the regulation of the mucosal blood flow.
Abstract: The aim of this study was to investigate the regional distribution, molecular forms, and gene expression of adrenomedullin in the rat gastrointestinal tract and to examine physiological changes in gastric adrenomedullin after 24-h fasting. The tissue concentration was measured by radioimmunoassay. The molecular forms were analyzed by high performance liquid chromatography. mRNA levels were quantified by Northern blotting and cells positive for adrenomedullin immunoreactivity were localized by immunohistochemistry. A high concentration of adrenomedullin was found in stomach, cecum, and colon (450-520 fmol/g wet tissue). Adrenomedullin immunoreactivity was also detected in duodenum, jejunum, and ileum (200-250 fmol/g wet tissue). Transcripts of the adrenomedullin gene were widely expressed throughout the gastrointestinal tract. The major form of adrenomedullin immunoreactivity in stomach and colon corresponded precisely with authentic adrenomedullin peptide. Adrenomedullin immunoreactive cells were present in the gastrointestinal endocrine system. The concentration and mRNA level of gastric adrenomedullin after fasting were significantly increased compared with findings in controls. Adrenomedullin is ubiquitous in the gastrointestinal tract, and may be produced by endocrine cells. The results suggest that adrenomedullin, through its potent vasodilating activity, may play some role, in the stomach including the regulation of the mucosal blood flow.

37 citations


Cited by
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Journal ArticleDOI
TL;DR: Its actions on cellular growth, the cardiovascular system, the central nervous system, and the endocrine system are all considered and some unresolved issues are considered.
Abstract: Since the discovery of adrenomedullin in 1993 several hundred papers have been published regarding the regulation of its secretion and the multiplicity of its actions. It has been shown to be an almost ubiquitous peptide, with the number of tissues and cell types synthesizing adrenomedullin far exceeding those that do not. In Section II of this paper we give a comprehensive review both of tissues and cell lines secreting adrenomedullin and of the mechanisms regulating gene expression. The data on circulating adrenomedullin, obtained with the various assays available, are also reviewed, and the disease states in which plasma adrenomedullin is elevated are listed. In Section III the pharmacology and biochemistry of adrenomedullin binding sites, both specific sites and calcitonin gene-related peptide (CGRP) receptors, are discussed. In particular, the putative adrenomedullin receptor clones and signal transduction pathways are described. In Section IV the various actions of adrenomedullin are discussed: its actions on cellular growth, the cardiovascular system, the central nervous system, and the endocrine system are all considered. Finally, in Section V, we consider some unresolved issues and propose future areas for research.

780 citations

Journal ArticleDOI
TL;DR: The recommended perioperative management of patients with IBD undergoing surgery accords with general ESPEN guidance for patients having abdominal surgery, and primary therapy using nutrition to treat IBD is moderately well supported in Crohn's disease.

427 citations

Journal ArticleDOI
TL;DR: The biology of these receptors is provided with an emphasis on understanding the unique actions of glucagon-related peptides through studies of the biology of their cognate receptors.
Abstract: The glucagon-like peptides include glucagon, GLP-1, and GLP-2, and exert diverse actions on nutrient intake, gastrointestinal motility, islet hormone secretion, cell proliferation and apoptosis, nutrient absorption, and nutrient assimilation. GIP, a related member of the glucagon peptide superfamily, also regulates nutrient disposal via stimulation of insulin secretion. The actions of these peptides are mediated by distinct members of the glucagon receptor superfamily of G protein-coupled receptors. These receptors exhibit unique patterns of tissue-specific expression, exhibit considerable amino acid sequence identity, and share similar structural and functional properties with respect to ligand binding and signal transduction. This article provides an overview of the biology of these receptors with an emphasis on understanding the unique actions of glucagon-related peptides through studies of the biology of their cognate receptors.

174 citations

Journal ArticleDOI
TL;DR: The present guideline is the first of a new series of "practical guidelines" based on more detailed scientific guidelines produced by ESPEN, and includes flow charts that connect the individual recommendations to logical care pathways and allow rapid navigation through the guideline.

174 citations

Journal ArticleDOI
TL;DR: Data suggest that the loss of the expression of the human homolog is required for the carcinogenesis of gastric tissue and that the gene has an activity adverse to malignant transformation of cells.
Abstract: Amplification of proto-oncogenes associated with their over-expression is one of the critical carcinogenic events identified in human cancer cells. In many cases of human gastric cancer, a proto-oncogene ERBB-2 is co-amplified with CAB1 genes physically linked to ERBB-2, and both genes are over-expressed. The amplified region containing ERBB-2 and CAB1 was named 17q12 amplicon from its chromosomal location. The syntenic region corresponding to the 17q12 amplicon is well conserved in mouse. In this study we isolated and characterized a novel mouse gene that locates telomeric to the mouse syntenic region. Northern blot analysis using the mouse cDNA and a cloned partial cDNA of human homolog disclosed a unique expression pattern of the genes. They are expressed predominantly in the gastrointestinal (GI) tract and in the skin at a lower level. Moreover, in the GI tract, the expression is highly restricted to the esophagus and stomach. Thus, we named the mouse gene Gasdermin (Gsdm). This is the first report of a mammalian gene whose expression is restricted to both upper GI tract and skin. Interestingly, in spite of its expression in normal stomach, no transcript was detected by Northern blot analysis in human gastric cancer cells. These data suggest that the loss of the expression of the human homolog is required for the carcinogenesis of gastric tissue and that the gene has an activity adverse to malignant transformation of cells.

174 citations