Ken Kihira

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 Barretts epithelium. The present study was designed to examine the expression of CDX 1/2 in inflammatory esophageal mucosa with or without Barretts 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), Barretts 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 Barretts epithelium than in the mucosa without Barretts 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 Barretts epithelium. Immunohistochemical study demonstrated strong and extensive nuclear immunoreactivity for CDX2 in Barretts epithelium. Furthermore, fine granular cytoplasmic staining was also observed in the cytoplasm in Barretts epithelium, as well as in inflammatory esophageal mucosa. Conclusions: We report here, for the first time, that CDX2 is expressed in patients with Barretts epithelium and inflammatory esophageal mucosa. These findings imply that the expression of CDX2 may be an early event leading to the development of Barretts esophagus.

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 β 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 intes-tinal 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.

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.

Assessment of Atrophic Gastritis Using the OLGA System

Background:  An international group of gastroenterologists and pathologists (Operative Link for Gastritis Assessment (OLGA)) proposed the staging system of atrophy. The aim of this study was to assess the severity of atrophic gastritis using the OLGA system.

p53 expression in the gastric mucosa before and after eradication of Helicobacter pylori.

Accumulation of p53 has been recognized in the gastric mucosa infected with Helicobacter pylori. We investigated the prevalence of p53‐positive cells in the gastric mucosa before and one month after eradication of H. pylori and the relationship between p53 positivity and inflammation and cell proliferation.

The Efficacy and Safety of One-Week Triple Therapy with Lansoprazole, Clarithromycin, and Metronidazole for the Treatment of Helicobacter pylori Infection in Japanese Patients

The aim of this study was to evaluate the efficacy and tolerability of 1‐week, low‐dose triple therapy with lansoprazole, clarithromycin, and metronidazole (LCM) for the cure of H. pylori infection and to establish the adequate dosage of a new triple therapy for Japanese patients.

Efficacy of lansoprazole in eradication of Helicobacter pylori.

Fifty-eight Helicobacter pylori-positive ulcer patients received omeprazole 20 mg (n = 15), or lansoprazole 30 mg (n = 23), lansoprazole 60 mg (n = 13), or E3810 20 mg (n = 7) q.d. Another 63 H. pylori-positive ulcer patients received lansoprazole and clarithromycin for 2 weeks. Patients received lansoprazole 30 mg and clarithromycin 400 mg (group 1, n = 22), lansoprazole 30 mg and clarithromycin 800 mg (group 2, n = 12), or lansoprazole 60 mg and clarithromycin 800 mg (group 3, n = 29). Neither proton pump inhibitor (PPI) was capable of eradication by monotherapy, but the clearance rates in the lansoprazole group were 60.9 and 69.2%, which were higher than those for omeprazole (p < 0.05). In the dual therapy, eradication rates were 50, 50, and 72.4% in groups 1, 2, and 3, respectively. Minor side effects were observed in one case each in groups 1 and 3. Lansoprazole monotherapy proved more efficacious than omeprazole monotherapy, but it was unable to eradicate H. pylori. Dual therapy with lansoprazole 60 mg and clarithromycin 800 mg was an efficacious and safe regimen for H. pylori eradication in this study.

CagA and cytotoxicity of Helicobacter pylori are not markers of peptic ulcer in Japanese patients.

The infection with cagA‐positive Helicobacter pylori strains is reported to be associated with peptic ulcer disease in developed countries, but it is controversial in Asia. To investigate the relationship between the virulence factors of H. pylori and peptic ulcer disease in Japan, we compared these between ulcer and nonulcer patients.

An endoscopic topical therapy for the treatment of Helicobacter pylori infection

We modified a novel topical therapeutic method for the treatment of Helicobacter pylori infection to increase its effectiveness and tolerability. Sixty-six patients (with nonulcer dyspepsia, inactive ulcer, or active ulcer) were given lansoprazole (30 mg, h.s.) and pronase (18,000 tyrosine units, b.i.d.) orally for 2 days before the topical therapy. One hundred milliliters of 7% sodium bicarbonate solution containing bismuth subnitrate, amoxicillin, metronidazole (at two different regimens), and pronase was instilled into the stomach through an endoscope. A double-lumen tube with a balloon at the tip was inserted into the duodenum along with the endoscope. The balloon was inflated with 25 ml of air and was lodged postbulbarly. The solution was kept in the stomach for 2 h, and the patients position was changed every 15 min from the sitting to the supine, prone, and right lateral position, each position being maintained twice, to expose the entire gastric mucosa. The solution was aspirated at the end of the procedure. H. pylori infection was cured in 16/22 (72.7%) of patients with nonulcer dyspepsia, in 21/26 (80.7%) of patients with inactive ulcer, and in 1/18 (5.6%) patients with active ulcer. H. pylori eradication was confirmed 4 weeks after the therapeutic procedure by smear, culture, and histology of antral and corpus biopsy specimens. Side effects (loose stools) were observed in two patients only, and one patient had loss of appetite. These effects were transient. This endoscopic topical therapy for H. pylori infection is a safe, effective, and well tolerated procedure. With further modifications of the drug regimens and the method itself, this procedure could be of interest as anti-H. pylori therapy.

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 Willebrands disease has been suggested, molecular mechanisms involved in the formation of angiodysplasia in patients with von Willebrands disease remained undetermined. We examined exon 28 of the von Willebrand factor gene in a patient with both von Willebrands disease and recurrent bleeding from angiodysplasia in the duodenum as well as his fathers, 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 Willebrands disease complicated with gastrointestinal angiodysplasia.