PubMed Health⌕ Search

Biomedical subjects

Kiichi Satoh

Publications and source records attributed to Kiichi Satoh.

At least 19 recordsLinked to original sources
PubMed2006

Changes in plasma ghrelin levels, gastric ghrelin production, and body weight after Helicobacter pylori cure.

BACKGROUND: Ghrelin is a body weight-regulating peptide produced and secreted primarily by the gastric mucosa. Helicobacter pylori infection impairs gastric ghrelin production, leading to a lower plasma ghrelin concentration. However, the effect of H. pylori eradication on plasma ghrelin levels and its relation to body weight change after H. pylori cure are still uncertain. We examined the association of plasma ghrelin levels with gastric ghrelin production and body weight change before and after H. pylori eradication. METHODS: Plasma ghrelin concentrations, gastric ghrelin expression, and body weight were determined in a total of 134 consecutive individuals before and 12 weeks after successful H. pylori eradication. Gastric ghrelin expression was evaluated by determining mRNA expression levels and the number of ghrelin-producing cells in gastric mucosa biopsy specimens by real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. RESULTS: Plasma ghrelin concentration increased in 50 patients and decreased in 84 patients after H. pylori eradication. After H. pylori cure, however, gastric preproghrelin mRNA expression was increased nearly fourfold (P < 0.0001), and the number of ghrelin-positive cells was increased or unchanged. In contrast, plasma ghrelin changes after H. pylori cure were inversely correlated with both body weight change (P < 0.0001) and initial plasma ghrelin levels (P < 0.0001). CONCLUSIONS: Changes in plasma ghrelin concentrations before and after H. pylori cure were inversely correlated with body weight change and initial plasma ghrelin levels but not with gastric ghrelin production in Japanese patients.

Amoxicillin↗
PubMed2006

A close relationship between intestinal metaplasia and Cdx2 expression in human gallbladders with cholelithiasis.

We previously reported a case of a human gallbladder with cholelithiasis consisting of intestinal metaplasia with the expression of caudal-related homeobox transcription factor (Cdx2). However, it is unclear how often intestinal metaplasia and Cdx2 expression occur in human, nontumorous gallbladders with cholelithiasis. We studied the incidence of intestinal metaplasia and Cdx2 expression in human gallbladders with cholelithiasis. Gallbladders were resected under laparoscopy from 103 patients with cholelithiasis between September 2003 and March 2005. The mean age of the patients was 59.6 +/- 15.0 years (range, 22-92 years). We retrospectively reviewed these cases to look for the presence of intestinal metaplasia and the expression of Cdx2. In addition, the characteristics of intestinal metaplasia were examined by immunostaining for Muc2, chromogranin A, and serotonin. Intestinal metaplasia was found in 11.7% (12/103) of the gallbladders with cholelithiasis. The mean ages of patients with and without intestinal metaplasia were 60.8 +/- 15.4 and 59.4 +/- 14.9 years, respectively. Cdx2, Muc2, chromogranin A, and serotonin were expressed in 91.7% (11/12), 91.7% (11/12), 83.3% (10/12), and 50.0% (6/12) in intestinal metaplastic mucosa, respectively. Only one case (1.1%) that expressed Cdx2 without intestinal metaplasia did not express Muc2, chromogranin A, and serotonin. We found that 10.7% (11/103) of nontumorous gallbladders resected because of cholelithiasis under laparoscopy revealed intestinal metaplasia with Cdx2 expression.

Adult↗
PubMed2006

The intestine-specific homeobox gene Cdx2 induces expression of the basic helix-loop-helix transcription factor Math1.

The basic helix-loop-helix transcription factor Math1, which is transiently expressed in proliferating neural precursors in multiple domains of the developing nervous system, is also related to the cell fate decision of enteroendocrine, goblet, and Paneth cells in the intestine. On the other hand, the transcription factor Cdx2, which is normally confined to intestinal epithelial cells, is related to the differentiation of these cells. Therefore, we investigated the relationship between Math1 and Cdx2 in intestinal epithelial cells. The Math1 and Cdx2 expressions in normal intestinal mucosa and intestinal metaplastic mucosa from mouse and human stomachs, as well as an intestinal crypt-derived cell line, were analyzed by immunohistochemistry, reverse transcription-polymerase chain reaction and Northern blotting, and Math1 enhancer element was analyzed by luciferase reporter assays. Math1-positive epithelial cells co-expressing Cdx2 were found in normal intestinal mucosa from humans and mice. Furthermore, Math1-producing epithelial cells that showed positive immunostaining for Cdx2 were also observed in intestinal metaplastic mucosa from human and Cdx2 transgenic mouse stomachs, although they were not detected in normal gastric mucosa of humans and mice. Expression of Cdx2 stimulated endogenous Math1 mRNA expression in the intestinal crypt-derived cell line IEC-6, corroborating observations in Cdx2-expressing intestinal metaplastic mucosa. Furthermore, expression of Cdx2 in IEC-6 cells conferred the ability to express a Math1 reporter gene containing a Math1 enhancer. Based on these results, we hypothesize that Cdx2 is involved in activating Math1 expression in intestinal epithelial cells.

Animals↗
PubMed2005

Cdx2 specifies the differentiation of morphological as well as functional absorptive enterocytes of the small intestine.

Many transcription factors are involved in the molecular control of intestinal epithelial cell differentiation. We report in this study that the transcription factor Cdx2 functions to define absorptive enterocytes during intestinal epithelial differentiation. Cdx2 is expressed in the villi of the normal small intestine. Intestinal metaplasia, which expresses Cdx2, occurs as a pathological condition in gastric mucosa. We have previously established Cdx2 transgenic mice expressing Cdx2 exclusively in the gastric epithelium. In this study using Cdx2 transgenic mice, we show that Cdx2 plays a key role in the differentiation of intestinal absorptive enterocytes. The gastric mucosa of Cdx2 transgenic mice was morphologically completely changed into intestinal metaplastic mucosa. Absorptive enterocytes had microvilli which were observed by electron microscope. The intestinal metaplastic mucosa of Cdx2 transgenic mice expressed sucrase and peptide transporter PepT1. Disaccharidase and leucine aminopeptidase activities were observed in the intestinal metaplastic mucosa. Glucose and amino acids were absorbed from Cdx2 transgenic mouse stomach with intestinal metaplasia. Finally we generated mice whose intestine was extensively excised. Cdx2 transgenic mice with intestinal metaplasia survived even after extensive intestinal excision. We successfully demonstrated that Cdx2 induced not only morphological but also functional absorptive enterocytes in the intestinal metaplastic mucosa in vivo. Our results suggest that Cdx2 is necessary and sufficient by itself to specify the development of intestinal absorptive enterocytes, whereas other factors which are expressed in the small intestine are not always necessary for the differentiation of functional absorptive enterocytes.

Amino Acids↗
PubMed2004

Development of gastric carcinoma from intestinal metaplasia in Cdx2-transgenic mice.

In the progression of chronic gastritis, gastric mucosal cells deviate from the normal pathway of gastric differentiation to an intestinal phenotype. Many epidemiologic studies have found an association between the formation of intestinal metaplasia and the development of gastric carcinoma. However, there is no direct evidence that shows intestinal metaplasia is a precursor lesion of gastric carcinoma, to date. We periodically examined the intestinal metaplastic mucosa of Cdx2-transgenic mice we have previously generated. Gastric polyps developed from intestinal metaplastic mucosa in all stomachs of Cdx2-transgenic mice examined. These gastric polyps consisted of intestinal-type adenocarcinoma that invaded the submucosa and muscularis propria and occasionally spread into the subserosa. p53 and APC gene mutations were recognized in the adenocarcinomas. The participation of APC and p53 gene mutations in gastric carcinogenesis from the intestinal metaplasia was verified by the Cdx2-transgenic mice, carrying Apc(Min) mutation or p53 deficiency, that developed gastric polyps much earlier than Cdx2 alone. We successfully showed that long-term intestinal metaplasia induces invasive gastric carcinoma. These results indicate that intestinal metaplasia itself plays a significant role in the genesis and progression of gastric carcinoma.

Adenocarcinoma↗
PubMed2004

Impaired production of gastric ghrelin in chronic gastritis associated with Helicobacter pylori.

Ghrelin is primarily secreted from the stomach and has been implicated in the coordination of eating behavior and weight regulation. The effects of Helicobacter pylori infection on plasma ghrelin concentration and gastric ghrelin production still have not been well known. We determined plasma ghrelin concentration in a total of 160 consecutive individuals with normal body mass index including 110 H. pylori-infected and 50 H. pylori-negative subjects. The expression levels of ghrelin mRNA and ghrelin-producing cells in the gastric mucosa were quantified with real-time quantitative RT-PCR and immunohistochemistry, respectively. The severity of gastric atrophy was evaluated by serum pepsinogen concentrations. Plasma ghrelin concentration, gastric ghrelin mRNA, and ghrelin-positive cell numbers in gastric mucosa were significantly lower in H. pylori-infected subjects. The decrease in plasma ghrelin concentration in H. pylori-positive subjects was accompanied by an attenuation of ghrelin mRNA expression and a reduction of ghrelin-positive cell numbers in the gastric mucosa. Moreover, lower serum pepsinogen I concentrations and I/II ratio were significantly associated with lower plasma ghrelin concentrations in H. pylori-positive subjects. These findings suggest that impaired gastric ghrelin production in association with atrophic gastritis induced by H. pylori infection accounts for the decrease in plasma ghrelin concentration.

Chronic Disease↗
PubMed2004

Involvement of syntaxin 4 in the transport of membrane-type 1 matrix metalloproteinase to the plasma membrane in human gastric epithelial cells.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) localized on the plasma membrane plays a central role in various normal biological responses including tissue remodeling, wound heeling, and angiogenesis and in cancer cell invasion and metastasis, by functioning as a collagenase and activating other matrix metalloproteinases. In order to elucidate the molecular mechanism of the MT1-MMP targeted localization on the plasma membrane, we examined the participation of syntaxin proteins in MT1-MMP intracellular transport to the plasma membrane in human gastric epithelial AGS cells. Western blotting showed that syntaxin 3 and 4 proteins, which are known to function in intracellular transport towards the plasma membrane, were expressed in AGS cells. Immunocytochemistry revealed that transient transfection of AGS cells with dominant-negative mutant syntaxin 4 decreased plasma membrane MT1-MMP expression. In contrast, transient transfection with either dominant-negative mutant syntaxin 3 or 7 did not affect MT1-MMP localization on the plasma membrane. Cell surface biotinylation assay and Matrigel chamber assay demonstrated that stable transfection with dominant-negative mutant syntaxin 4 decreased the amount of MT1-MMP on the plasma membranes and inhibited the cell invasiveness. We suggest that syntaxin 4 is involved in the intracellular transport of MT1-MMP toward the plasma membrane.

Biological Transport↗
PubMed2004

Gastrointestinal angiodysplasia in a patient with type 2 von Willebrand's disease and analysis of exon 28 of the von Willebrand factor gene.

Although the association between gastrointestinal angiodysplasia and von Willebrand's disease has been suggested, molecular mechanisms involved in the formation of angiodysplasia in patients with von Willebrand's disease remained undetermined. We examined exon 28 of the von Willebrand factor gene in a patient with both von Willebrand's disease and recurrent bleeding from angiodysplasia in the duodenum as well as his father's, and found a point mutation, C 3916-->T (amino acid substitution; Arg 543-->Trp), in the A1 domain of the von Willebrand factor gene. This mutation was identical with a previously reported mutation in a patient with von Willebrand's disease complicated with gastrointestinal angiodysplasia.

Adult↗
PubMed2003

Aberrant expression of CDX2 in Barrett's epithelium and inflammatory esophageal mucosa.

BACKGROUND: There have been no detailed reports directly comparing the expression of CDX1 with that of CDX2 in the inflammatory esophageal mucosa and Barrett's epithelium. The present study was designed to examine the expression of CDX 1/2 in inflammatory esophageal mucosa with or without Barrett's epithelium. METHODS: The expression of CDX1/2 genes was analyzed using the reverse transcriptase-polymerase chain reaction (RT-PCR) in 34 human esophageal biopsy specimens, and CDX2 expression was also evaluated immunohistochemically, using anti-human CDX2 monoclonal antibody. The biopsy specimens for RNA extraction were taken endoscopically from esophageal mucosa with mucosal break due to gastroesophageal reflux disease (GERD), Barrett's epithelium, and normal epithelium. The expressions of mucin markers (MUC2) and intestine-specific genes (sucrase-isomal-tase, human defensin-5, alkaline phosphatase) were also comparatively analyzed. RESULTS: CDX1/2 expression was not found in the normal esophageal mucosa. The prevalence of CDX1/2 mRNA expression was significantly higher in the mucosa with Barrett's epithelium than in the mucosa without Barrett's epithelium. It is noteworthy, however, that the CDX2 mRNA expression was initiated at the stage of esophagitis, when neither CDX1 nor intestine-specific genes had emerged yet. In contrast to CDX2, CDX1 was expressed only in Barrett's epithelium. Immunohistochemical study demonstrated strong and extensive nuclear immunoreactivity for CDX2 in Barrett's epithelium. Furthermore, fine granular cytoplasmic staining was also observed in the cytoplasm in Barrett's epithelium, as well as in inflammatory esophageal mucosa. CONCLUSIONS: We report here, for the first time, that CDX2 is expressed in patients with Barrett's epithelium and inflammatory esophageal mucosa. These findings imply that the expression of CDX2 may be an early event leading to the development of Barrett's esophagus.

Adult↗
PubMed2003

Follow-up survey of a large-scale multicenter, double-blind study of triple therapy with lansoprazole, amoxicillin, and clarithromycin for eradication of Helicobacter pylori in Japanese peptic ulcer patients.

BACKGROUND: To evaluate histopathological changes and effects on inhibition of ulcer recurrence, a follow-up survey was performed in Japanese patients with Helicobacter pylori-positive active peptic ulcers. These patients had previously participated in a large-scale multicenter trial of triple therapy with lansoprazole (LPZ)/amoxicillin (AMPC)/clarithromycin (CAM) for eradication of H. pylori. METHODS: Patients who had been treated with LPZ only or a combination of LPZ, AMPC, and CAM for a period of 7 days and in whom ulcer healing had been confirmed after treatment were grouped according to successful or failed eradication of H. pylori. They were examined endoscopically to determine whether ulcers had recurred. The updated Sydney system was applied to study histological changes after H. pylori eradication therapy, compared with baseline. RESULTS: Twelve months after treatment for H. pylorieradication, gastric ulcers had recurred in 11.4% of those with successful H. pylorieradication and in 64.5% of those with unsuccessful H. pylori eradication. Duodenal ulcers had recurred in 6.8% of patients for whom H. pylori eradication was successful and in 85.3% of patients in whom eradication failed. These findings proved that H. pylori eradication significantly reduced ulcer recurrence ( P < 0.0001 for both types of ulcers). Histopathological findings of inflammation and activity grade in both gastric and duodenal ulcers were more favorable in patients with successful eradication than in those with unsuccessful eradication. CONCLUSIONS: H. pylori eradication significantly inhibited ulcer recurrence in Japanese peptic ulcer patients. Histopathological findings were also improved with regard to inflammation and activity (neutrophils) in patients in whom H. pylori eradication was successful.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

[New triple therapy for Helicobacter pylori infection in Japan].

In Japan, a phase 3 trial of 1-week triple therapy with lansoprazole(L), amoxicillin(A), and clarithromycin(C) was finished in March, 2000. Patients were randomized into three groups: L 30 mg bid and placebos, and L 30 mg bid, A 750 mg bid and C 200 mg bid or 400 mg bid. Eradication rates were high in group LAC200(88-91%) and group LAC400 (84-89%). Next, a phase 3 trial of 1-week triple therapy with omeplazole (O), A and C was finished in 2001. Eradication rates were 78.8% in the group of O 20 mg, A 750 mg and C 400 mg bid, and 83.0% in the group of O 20 mg, A 1,000 mg, and C 500 mg bid.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2002

Indications for Helicobacter pylori eradication therapy and first-line therapy regimen in Japan: recommendation by the Japanese Society for Helicobacter Research.

In November 2000, eradication therapy for Helicobacter pylori infection was approved under the present Japanese system of health insurance. Before the approval, the Japanese guideline of "Diagnosis and Treatment of H. pylori infection" was made by the guideline committee of the Japanese Society for Helicobacter Research. Indications for H. pylori eradication therapy were classified into three groups: (A) recommended: gastric and duodenal ulcers; (B) recommended and managed at a specialized institution: low-grade gastric mucosa-associated lymphoid tissue lymphoma; (C) current studies of the significance of the therapy: following endoscopic mucosal resection of early gastric cancer and gastric surgery for gastric cancers, hyperplastic gastric polyp, atrophic gastritis, and nonulcer dyspepsia. The first-line therapy regimen recommended is 1 week of triple therapy with a proton pump inhibitor standard dose twice a day, amoxicillin 750 mg bid, and clarithromycin 200 or 400 mg bid. The reasons for preferring this regimen are to avoid extensive use of metronidazole, which is allowed for treatment of Trichomonas infection in Japan, and the low rate of emergence of clarithromycin-resistant H. pylori with amoxicillin co-therapy. For second-line therapy patients should be referred to specialists, who can examine the susceptibility of H. pylori isolates against antibiotics and have much experience with this therapy.

Helicobacter Infections↗
PubMed2002

Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia.

BACKGROUND: The CDX1 and CDX2 genes are intestinal transcription factors that may be involved in the regulation of proliferation and differentiation of intestinal epithelial cells. There have been no detailed reports directly comparing the expression of CDX1 with that of CDX2 in chronic gastritis and intestinal metaplasia. Accordingly, we examined the expression of CDX1/2 and its association with the expression of other intestinal metaplasia-associated genes during the development of intestinal metaplasia. METHODS: The expression of CDX1/2 genes was analyzed, using the reverse transcriptase-polymerase chain reaction, in 44 human gastric tissue samples obtained endoscopically. The expressions of mucin markers (MUC2, MUC5AC), intestine-specific genes (sucrase-isomaltase, human defensin-5, alkaline phosphatase), a gene marker for fundic gland area (H+/K+ATPase beta subunit), and a gene for entire gastric glands (pepsinogen C) were also comparatively analyzed. RESULTS: There was no expression of CDX1/2 in gastric mucosa not infected by Helicobacter pylori. The prevalence of CDX1 mRNA expression was significantly higher in mucosa with intestinal metaplasia than in mucosa without intestinal metaplasia. It is noteworthy that CDX2 was expressed in the antral and fundic mucosa in the absence of the expression of CDX1 and gene markers for intestinal metaplasia. CONCLUSIONS: The expression of CDX2 precedes those of CDX1, sucrase-isomaltase, other intestine-specific genes (human defensin-5, alkaline phosphatase), and MUC2 during the progression of intestinal metaplasia. These findings imply that the expression of CDX2 may trigger the initiation and development of intestinal metaplasia.

Adult↗
PubMed2002

Aberrant expression of CDX2 in the gastric mucosa with and without intestinal metaplasia: effect of eradication of Helicobacter pylori.

BACKGROUND: The intestine-specific transcription factor CDX2 plays an important role in differentiation and maintenance of intestinal epithelial cells. Development and progression of intestinal metaplasia (IM) in the stomach is closely associated with Helicobacter pylori-gastritis. We investigated expression of CDX2 protein in the gastric mucosa with and without IM before and after eradication of H. pylori. MATERIALS AND METHODS: The subjects comprised five normal controls and 29 H. pylori-positive patients (15 with antral IM and 14 without IM), who were followed for 12 months after eradication of H. pylori. Biopsies were taken from the greater curvatures of the antrum and middle body. Expression of CDX2 was evaluated immunohistochemically using anti-CDX2 antibody. RESULTS: CDX2 expression was not found in controls. Strong nuclear staining was observed extensively in IM, but rarely in the gastric epithelium, except for the focal area in only four antral biopsies (three with and one without IM). Fine granular cytoplasmic staining was also observed in the perinuclear regions of IM and the gastric epithelial cells in half of the patients. In 13 of the 15 patients with IM, IM did not regress after eradication of H. pylori, and the extent of nuclear staining in IM did not change. The extent of cytoplasmic staining did not change either. CONCLUSIONS: Our results indicate that CDX2 expression in the gastric mucosa is found in patients with chronic gastritis and is closely associated with IM. CDX2 expression in IM or the gastric epithelial cells did not disappear after eradication of H. pylori.

Adult↗
PubMed2002

Success rate of curative endoscopic mucosal resection with circumferential mucosal incision assisted by submucosal injection of sodium hyaluronate.

BACKGROUND: Circumferential mucosal incision around a lesion is effective for reliable endoscopic mucosal resection. However, mucosal incision with a needle knife is difficult, even with submucosal injection of normal saline solution. To make needle-knife incision easier and safer, sodium hyaluronate has been used rather than normal saline solution. The aim of this study was to evaluate the clinical outcome of endoscopic mucosal resection with circumferential mucosal incision assisted by submucosal injection of sodium hyaluronate. METHODS: For 70 gastric lesions treated by submucosal injection of sodium hyaluronate, the size of the lesion and the resection specimen, the en bloc resection rate, complications, and local recurrence during follow-up were assessed. RESULTS: The mean size of the lesions and resection specimens were, respectively, 19.9 mm and 30.0 mm. The en bloc resection rates were 89% (42/47) for lesions up to 20 mm in diameter and 48% (11/23) for those greater than 20 mm (1-20 mm vs. >20 mm, p = 0.0004). Three patients underwent surgery because of invasive cancer in the EMR specimen. During follow-up (median 14 months, range 3-38 months), 2 recurrent lesions were found. No major complication occurred. CONCLUSIONS: Submucosal injection of sodium hyaluronate is a reliable method with a high success rate for en bloc resection of lesions up to 20 mm in diameter. Mucosal incision with a needle knife can be performed safely with submucosal injection of sodium hyaluronate.

Adenocarcinoma↗