Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis.


BACKGROUND:Neutrophil elastase (NE) is a major secretory product from activated neutrophils and a major contributor to tissue destruction. However, little is known about the pathogenic contribution of NE to ulcerative colitis (UC). This study was designed to investigate the contribution of NE by measuring NE activity in plasma and colonic mucosal tissue from UC patients and a murine acute colitis model, and to elucidate the therapeutic effect of the NE-specific inhibitor ONO-5046. METHODS:The NE enzyme activities in plasma and colonic mucosal tissue from UC patients were directly measured using an enzyme-substrate reaction. Acute colitis was induced in mice by administration of 1.5% dextran sulfate sodium (DSS) for 5 days. DSS-induced colitis mice were then treated with ONO-5046 (50 mg/kg body weight) intraperitoneally twice a day. RESULTS:In UC patients, the NE enzyme activity was significantly elevated in both the plasma and colonic mucosal tissue compared with healthy controls. In DSS-induced colitis mice, the NE enzyme activity increased in parallel with the disease development. ONO-5046 showed therapeutic effects in DSS-treated mice by significantly reducing weight loss and histological score. ONO-5046 suppressed the NE enzyme activities in both plasma and culture supernatant of colonic mucosa from DSS-induced colitis mice. CONCLUSIONS:ONO-5046, a specific NE inhibitor, prevented the development of DSS-induced colitis in mice. NE therefore represents a promising target for the treatment of UC patients.


J Gastroenterol


Morohoshi Y,Matsuoka K,Chinen H,Kamada N,Sato T,Hisamatsu T,Okamoto S,Inoue N,Takaishi H,Ogata H,Iwao Y,Hibi T




Has Abstract


2006-04-01 00:00:00












  • Prognostic impact of primary tumor location in Stage III colorectal cancer-right-sided colon versus left-sided colon versus rectum: a nationwide multicenter retrospective study.

    abstract:BACKGROUND:Previous studies investigating the impact of tumor location on colorectal cancer prognosis only compared two groups by location, e.g., 'right-sided colon vs. left-sided colon,' 'colon vs. rectum,' and 'right-sided (right-sided colon) vs. left-sided (left-sided colon and rectum).' This nationwide multicenter ...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Shida D,Inoue M,Tanabe T,Moritani K,Tsukamoto S,Yamauchi S,Sugihara K,Kanemitsu Y

    更新日期:2020-10-01 00:00:00

  • Ciliated foregut cyst in cirrhotic liver.

    abstract::We encountered a patient with a ciliated hepatic foregut cyst with accompanying liver cirrhosis, which was hard to distinguish from well-differentiated hepatocellular carcinoma. A lesion 2 cm in diameter was found in the subcapsular region of the medial segment of the liver. It was slightly hypoechoic on ultrasonograp...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Murakami T,Imai A,Nakamura H,Tsuda K,Kanai T,Wakasa K

    更新日期:1996-06-01 00:00:00

  • Evolution of and obstacles in surgical treatment for hepatocellular carcinoma over the last 25 years: differences over four treatment eras.

    abstract::This study was designed to clarify what differences the last 25 years have made in surgical results for patients with hepatocellular carcinoma (HCC). We examined results for 716 hepatectomized patients in four treatment eras: first era (1973-1980; n = 58), second era (1981-1985; n = 155), third era (1986-1990; n = 243...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Yamanaka N,Takata M,Tanaka T,Yamanaka J,Yasui C,Ando T,Kuroda N,Maeda S,Okamoto E

    更新日期:2000-01-01 00:00:00

  • Elevation of ratio of urinary N-acetylneuraminlactose to free sialic acid in some advanced cancer patients.

    abstract::We estimated the levels of free sialic acid and sialylated oligosaccharides excreted in the urine of normal donors (n = 10) and patients with gastric cancer (n = 6) and colorectal cancer (n = 4). The total sialic acid level in cancer patients was similar to that in normal donors. However, the ratios of glycosidically ...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Shimada I,Shoji M,Futatsuya R,Katoh T,Kominato Y,Sakamoto T,Fujikura T

    更新日期:1995-02-01 00:00:00

  • Fibrogenesis serum markers in patients with chronic hepatitis C treated with alpha-IFN.

    abstract::The correlation between therapeutic response and liver fibrogenesis was studied in serum and liver specimens taken from 31 patients treated with alpha-interferon (IFN) (14 sustained responders and 17 non-responders) for chronic hepatitis C. Serum samples, collected before therapy, and at further 6-month intervals over...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Fabris P,Marranconi F,Bozzola L,Biasin MR,De Lazzari F,Plebani M,Benedetti P,Tositti G,Pellizzer G,Stecca C,de Lalla F

    更新日期:1999-06-01 00:00:00

  • The genetic classification of pancreatic neoplasia.

    abstract::Cancer is caused by the accumulation of inherited and/or acquired alterations in specific genes. The recent decline in the cost of DNA sequencing has allowed tumor sequencing to be conducted on a large scale, which, in turn, has led to an unprecedented understanding of the genetic events that drive neoplasia. This und...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,评审


    authors: Matthaei H,Semaan A,Hruban RH

    更新日期:2015-05-01 00:00:00

  • A patient with hepatitis C-related cirrhosis and hepatocellular carcinoma who was cured with an orthotopic liver transplantation and interferon therapy.

    abstract::A patient with hepatitis C virus (HCV)-related liver cirrhosis and hepatocellular carcinoma (HCC) was treated successfully with an orthotopic liver transplantation (OLT) followed by interferon therapy. The 36-year-old Japanese man was diagnosed as having liver cirrhosis in 1983. HCC was detected in 1991, and by 1994, ...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,评审


    authors: Shibata M,Yanaga K,Morizane T,Yanagawa T,Hirakawa M,Ueno Y,Esquivel CO,Mitamura K

    更新日期:2003-01-01 00:00:00

  • Clinical significance of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric cancer.

    abstract:BACKGROUND:Matrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis, being inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). In this study, we examined the expression of MMP-2, MMP-9, membrane-type 1 (MT1)-MMP, TIMP-1,...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Shim KN,Jung SA,Joo YH,Yoo K

    更新日期:2007-02-01 00:00:00

  • Epidemiology and clinical characteristics of GERD in the Japanese population.

    abstract::We reviewed articles on the epidemiology and clinical characteristics of gastroesophageal reflux disease (GERD) in Japan to clarify these features of GERD in this country. Although the definition of GERD depends on the individual study, the prevalence of GERD has been increasing since the end of the 1990s. The reasons...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,评审


    authors: Fujiwara Y,Arakawa T

    更新日期:2009-01-01 00:00:00

  • Possible involvement of Toll-like receptor 7 in the development of type 1 autoimmune pancreatitis.

    abstract:BACKGROUND:High serum immunoglobulin G4 (IgG4) levels and IgG4-positive plasma cell infiltration are characteristic of type 1 autoimmune pancreatitis (AIP). It is unclear whether innate immunity is a cause of type 1 AIP; the possible involvement of microbial infection has been suggested in its pathogenesis. To clarify ...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Fukui Y,Uchida K,Sakaguchi Y,Fukui T,Nishio A,Shikata N,Sakaida N,Uemura Y,Satoi S,Okazaki K

    更新日期:2015-04-01 00:00:00

  • Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-naive Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase III study.

    abstract:BACKGROUND:Vaniprevir is a potent macrocyclic hepatitis C virus (HCV) nonstructural protein 3/4A protease inhibitor. This phase III study evaluated the safety and efficacy of vaniprevir in combination with peginterferon alfa-2b and ribavirin (PR) for 24 weeks compared with PR alone for 48 weeks in treatment-naive Japan...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Hayashi N,Nakamuta M,Takehara T,Kumada H,Takase A,Howe AY,Ludmerer SW,Mobashery N

    更新日期:2016-04-01 00:00:00

  • Musashi-1 suppresses expression of Paneth cell-specific genes in human intestinal epithelial cells.

    abstract:BACKGROUND:Musashi-1 (Msi-1) is a RNA-binding protein, known as a putative marker of intestinal stem cells (ISCs). However, little is known about the function of Msi-1 within human intestinal epithelial cells (IECs). Thus, the present study aimed to clarify the role of Msi-1 in differentiation and proliferation of IECs...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Murayama M,Okamoto R,Tsuchiya K,Akiyama J,Nakamura T,Sakamoto N,Kanai T,Watanabe M

    更新日期:2009-01-01 00:00:00

  • Noninvasive diagnostic criteria for nonalcoholic steatohepatitis based on gene expression levels in peripheral blood mononuclear cells.

    abstract:BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) consists of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH); the latter progresses to liver cirrhosis and hepatocellular carcinoma. Discriminating NASH from NAFL typically involves liver biopsy. The mechanism of NASH progression is unclear but ...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Kado A,Tsutsumi T,Enooku K,Fujinaga H,Ikeuchi K,Okushin K,Moriya K,Yotsuyanagi H,Koike K

    更新日期:2019-08-01 00:00:00

  • Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan.

    abstract:BACKGROUND:There have been few epidemiological studies on gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in Japan. METHODS:We examined the epidemiology of GEP-NETs [pancreatic endocrine tumors (PETs) and gastrointestinal neuroendocrine tumors (GI-NETs)] in Japan in 2005 using a nationwide stratified random sa...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Ito T,Sasano H,Tanaka M,Osamura RY,Sasaki I,Kimura W,Takano K,Obara T,Ishibashi M,Nakao K,Doi R,Shimatsu A,Nishida T,Komoto I,Hirata Y,Nakamura K,Igarashi H,Jensen RT,Wiedenmann B,Imamura M

    更新日期:2010-02-01 00:00:00

  • Matrix metalloproteinase-3 secretion from human colonic subepithelial myofibroblasts: role of interleukin-17.

    abstract:BACKGROUND:Subepithelial myofibroblasts (SEMFs) play a role in extracellular matrix (ECM) metabolism in the colon. In this study, we investigated the effects of interleukin (IL)-17, IL-1beta, and tumor necrosis factor (TNF)-alpha on matrix metalloproteinase (MMP)-3 secretion in colonic SEMFs. METHODS:MMP-3 secretion a...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Bamba S,Andoh A,Yasui H,Araki Y,Bamba T,Fujiyama Y

    更新日期:2003-01-01 00:00:00

  • A case of AIDS-related hepatic Kaposi's sarcoma.

    abstract::In Japan, Kaposi's sarcoma (KS) is a very rare neoplasm. However, it does occur as one of the complications in patients with acquired immunodeficiency syndrome (AIDS). AIDS-related KS commonly involves the skin, lymph nodes, and gastrointestinal tract. Hepatic KS is sometimes observed in AIDS patients at autopsy, but ...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Tanaka T,Masuda G,Takechi A,Kobayashi H,Tanaka S,Koike M,Hattori N

    更新日期:1995-04-01 00:00:00

  • Effects of intravenous infusion of amino acids on cholecystokinin release and gallbladder contraction in humans.

    abstract::We investigated the effect of intravenous infusions of the therapeutically available amino acid solutions Moripron and Morihepamin (Roussel Morishita, Osaka, Japan) on gallbladder contraction and cholecystokinin (CCK) release in healthy male volunteers. Plasma CCK levels were measured by radioimmunoassay, using the an...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Shirohara H,Tabaru A,Otsuki M

    更新日期:1996-08-01 00:00:00

  • Cyclooxygenase, NSAIDs, and colorectal cancer.

    abstract::Prevention of human diseases has become a major focus of biomedical investigators around the world. Our current screening and treatment regimens for colorectal cancer are not effective, as indicated by the fact that this disease is the second leading cause of death from cancer in the United States. Recently published ...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,评审


    authors: DuBois RN,Smalley WE

    更新日期:1996-12-01 00:00:00

  • Factors affecting in-hospital mortality in patients with lower gastrointestinal tract bleeding: a retrospective study using a national database in Japan.

    abstract:BACKGROUND:Bleeding of the lower gastrointestinal tract requires hospitalization and can cause in-hospital death in the most serious cases; however, only a few studies have evaluated in-hospital death from bleeding of the lower gastrointestinal tract. The aim of this study was to investigate the in-hospital mortality o...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章,多中心研究


    authors: Niikura R,Yasunaga H,Yamaji Y,Horiguchi H,Fushimi K,Yamada A,Hirata Y,Koike K

    更新日期:2015-05-01 00:00:00

  • Mortality rate of patients with asymptomatic primary biliary cirrhosis diagnosed at age 55 years or older is similar to that of the general population.

    abstract:PURPOSE:Recent routine testing for liver function and anti-mitochondrial antibodies has increased the number of newly diagnosed patients with primary biliary cirrhosis (PBC). This study investigated the prognosis of asymptomatic PBC patients, focusing on age difference, to clarify its effect on the prognosis of PBC pat...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Kubota J,Ikeda F,Terada R,Kobashi H,Fujioka S,Okamoto R,Baba S,Morimoto Y,Ando M,Makino Y,Taniguchi H,Yasunaka T,Miyake Y,Iwasaki Y,Yamamoto K

    更新日期:2009-01-01 00:00:00

  • Anorectal malignant melanoma: preoperative usefulness of magnetic resonance imaging.

    abstract::Magnetic resonance imaging (MRI) findings in three patients with primary anorectal malignant melanoma are described. Two patients had melanotic and one had amelanotic anorectal melanoma. The findings of MRI with a pelvic coil and an endorectal coil were consistent with pathologic findings. MRI with a pelvic coil demon...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Matsuoka H,Nakamura A,Iwamoto K,Sugiyama M,Hachiya J,Atomi Y,Masaki T

    更新日期:2005-08-01 00:00:00

  • Estimation of glycogen levels in human colorectal cancer tissue: relationship with cell cycle and tumor outgrowth.

    abstract::In this study, we quantitatively measured glycogen levels in tissue samples obtained from tumors, regions adjacent to tumor, and regions of normal colorectum to determine whether the levels were related to cell cycle and cancer growth. Glycogen levels were analyzed in relation to histopathological factors, (tumor size...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Takahashi S,Satomi A,Yano K,Kawase H,Tanimizu T,Tuji Y,Murakami S,Hirayama R

    更新日期:1999-08-01 00:00:00

  • Images of Sonazoid-enhanced ultrasonography in multistep hepatocarcinogenesis: comparison with Gd-EOB-DTPA-enhanced MRI.

    abstract:BACKGROUND:Little is known about the difference in enhancement patterns of hepatocellular carcinoma (HCC) during multistep hepatocarcinogenesis between the post-vascular phase of Sonazoid-enhanced ultrasonography (SEUS) and hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine (Gd-EOB-DTPA)-enhanced MRI, as...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Ohama H,Imai Y,Nakashima O,Kogita S,Takamura M,Hori M,Seki Y,Sawai Y,Igura T,Fukuda K,Makino Y,Morimoto O,Ohsawa M,Sakamoto M,Murakami T

    更新日期:2014-06-01 00:00:00

  • Photodynamic therapy for human hepatoma-cell-line tumors utilizing biliary excretion properties of indocyanine green.

    abstract:BACKGROUND:Photodynamic therapy (PDT) has not been reported for human hepatoma, because cancer cells only weakly take up the photosensitizer. Indocyanine green (ICG) is a photosensitizer normally excreted into the bile, and bile excretion is impaired in human hepatomas. We examined whether human hepatoma cell lines pre...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Kaneko J,Inagaki Y,Ishizawa T,Gao J,Tang W,Aoki T,Sakamoto Y,Hasegawa K,Sugawara Y,Kokudo N

    更新日期:2014-01-01 00:00:00

  • Elevated urokinase-type plasminogen activator plasma levels are associated with deterioration of liver function but not with hepatocellular carcinoma.

    abstract::We measured urokinase-type plasminogen activator (u-PA) plasma levels in patients with various chronic liver diseases, including hepatocellular carcinoma (HCC), also measuring these levels in healthy volunteers. Plasma u-PA levels in the group of patients with decompensated liver cirrhosis (mean modified Pugh score of...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Sato S,Higashi T,Ouguchi S,Hino N,Tsuji T

    更新日期:1994-12-01 00:00:00

  • Serum leptin level can be a negative marker of hepatocyte damage in nonalcoholic fatty liver.

    abstract:BACKGROUND:The aim of this study was to determine whether leptin and insulin resistance (IR) showed differences between steatotic patients with and without elevated serum transaminases. METHODS:The study included 32 patients with fatty liver and high serum transaminase level (group I), 31 patients with fatty liver and...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Serin E,Ozer B,Gümürdülü Y,Kayaselçuk F,Kul K,Boyacioğlu S

    更新日期:2003-01-01 00:00:00

  • A proposed severity classification system for hepatolithiasis based on an analysis of prognostic factors in a Japanese patient cohort.

    abstract:BACKGROUND:Hepatolithiasis frequently results in severe complications. We conducted a cohort study to identify prognostic factors and to establish a hepatolithiasis severity classification system. METHODS:The study cohort comprised 396 patients who were identified through a 1998 nationwide survey and followed up for 1...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Suzuki Y,Mori T,Yokoyama M,Kim S,Momose H,Matsuki R,Kogure M,Abe N,Isayama H,Nakazawa T,Notohara K,Tanaka A,Tsuyuguchi T,Tazuma S,Takikawa H,Sugiyama M

    更新日期:2018-07-01 00:00:00

  • A case of triple synchronous cancers occurring in the gallbladder, common bile duct, and pancreas.

    abstract::We report a 74-year-old man with triple synchronous cancers occurring in the gallbladder, common bile duct, and pancreas. The patient had consulted a nearby physician because of epigastralgia and icterus. On September 30, 1997, the patient was admitted to our department for further evaluation and treatment. Abdominal ...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Sato K,Maekawa T,Yabuki K,Tamasaki Y,Maekawa H,Kudo K,Sengoku H,Kawa I,Wada R,Matsumoto M

    更新日期:2003-01-01 00:00:00

  • Ursodeoxycholic acid stabilizes the bile salt export pump in the apical membrane in MDCK II cells.

    abstract:BACKGROUND:Ursodeoxycholic acid (UDCA) partly exerts choleretic effects by modifying the function of the bile salt export pump (Bsep, ABCB11). UDCA induces insertion of Bsep into the canalicular membrane of hepatocytes; however, underlying mechanisms remain unknown. We aimed to elucidate molecular mechanisms behind UDC...

    journal_title:Journal of gastroenterology

    pub_type: 杂志文章


    authors: Kagawa T,Orii R,Hirose S,Arase Y,Shiraishi K,Mizutani A,Tsukamoto H,Mine T

    更新日期:2014-05-01 00:00:00

  • Influence of anti-ulcer drugs used in Japan on the result of (13)C-urea breath test for the diagnosis of Helicobacter pylori infection.

    abstract:BACKGROUND:The (13)C-urea breath test (UBT) is a simple breath test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the antiulcer drugs used in Japan on the results of UBT were determined. METHODS:The subjects ...

    journal_title:Journal of gastroenterology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Murakami K,Sato R,Okimoto T,Watanabe K,Nasu M,Fujioka T,Kodama M,Kagawa J

    更新日期:2003-01-01 00:00:00