A mathematical simulation model to determine the optimal endoscopic screening strategy for detection of H. pylori-naïve gastric neoplasms.

Background: The effectiveness of esophagogastroduodenoscopy (EGD) screening in cohorts with low Helicobacter pylori prevalence is unknown. This study aimed to develop an optimally efficient EGD screening strategy for detecting H. pylori-naïve gastric neoplasms (HpNGNs).

[Endoscopic variceal ligation and percutaneous transhepatic obliteration difficulty in esophageal variceal bleeding: a case report].

A 48-year-old male patient with a history of alcoholic cirrhosis was admitted to our hospital due to hematemesis with a 7-day history of melena. Emergency esophagogastroduodenoscopy revealed esophageal variceal bleeding. We attempted hemostasis with endoscopic variceal ligation (EVL).

[A case of refractory ascites due to splenic arteriovenous fistula appeared during the course of observation and cured by embolization therapy].

This is a case of a 61-year-old female who presented to our hospital with liver dysfunction without any symptoms. She was diagnosed with splenic arteriovenous fistula. About 8 months later, she visited the hospital again due to abdominal distention and diarrhea.

Gastric epithelial neoplasm of fundic-gland mucosa lineage: proposal for a new classification in association with gastric adenocarcinoma of fundic-gland type.

Background: Gastric adenocarcinoma of fundic-gland type (GA-FG) is a rare variant of gastric neoplasia. However, the etiology, classification, and clinicopathological features of gastric epithelial neoplasm of fundic-gland mucosa lineage (GEN-FGML; generic term of GA-FG related neoplasm) are not fully elucidated. We performed a large, multicenter, retrospective study to establish a new classification and clarify the clinicopathological features of GEN-FGML.

Russell body duodenitis in a patient with retroperitoneal metastasis of ureteral cancer.

Russell bodies are globular and eosinophilic inclusion bodies in the cytoplasm of mature plasma cells. Plasma cells whose cytoplasm is filled with Russell bodies are designated as Mott cells. Russell body duodenitis (RBD) is a unique form of chronic duodenitis that is characterized by infiltration of numerous Mott cells.

Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis.

Background: Crohn's disease (CD) is an inflammatory bowel disease that is associated with several changes in the immune system, including an increased number of infiltrating macrophages. These macrophages release a variety of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) which are critically involved in the onset and the development of CD. The present study was performed to explore the initial involvement of macrophages in the development of T-cell-mediated chronic colitis.

MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis.

Background: Gut commensal microbes affect the development and activation of the mucosal and systemic immune systems. However, the exact molecular mechanism of these microbes that is involved in the development of colitis remains unclear.

Methods: The present study was conducted to determine the distinct role of the innate immune system in the development of a dextran sulfate sodium (DSS) colitis model in MyD88(-/-) mice, because myeloid differentiation protein (MyD88) is a major adaptor molecule essential for signaling via Toll-like receptors (TLRs).

CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells.

It is well known that immune responses in the intestine remain in a state of controlled inflammation, suggesting that not only active suppression by regulatory T cells plays an important role in the normal intestinal homeostasis, but also its dysregulation leads to the development of inflammatory bowel disease. In this study, we demonstrate that the CD4(+)CD25(bright) T cells reside in the human intestinal lamina propria (LP) and functionally retain regulatory activities. All human LP CD4(+) T cells regardless of CD25 expression constitutively expressed CTLA-4, glucocorticoid-induced TNFR family-related protein, and Foxp3 and proliferate poorly.

Ectopic CD40 ligand expression on B cells triggers intestinal inflammation.

Several studies indicate that CD4(+) T cells, macrophages, and dendritic cells initially mediate intestinal inflammation in murine models of human inflammatory bowel disease. However, the initial role of B cells in the development of intestinal inflammation remains unclear. In this study we present evidence that B cells can trigger intestinal inflammation using transgenic (Tg) mice expressing CD40 ligand (CD40L) ectopically on B cells (CD40L/B Tg).

Hyperexpression of inducible costimulator on lamina propria mononuclear cells in rat dextran sulfate sodium colitis.

Background And Aims: The authors have previously shown that a third member of the CD28 family, inducible costimulator (ICOS), was increased in the inflamed intestinal mucosa of murine experimental colitis, and that the blockade of ICOS ameliorated the development of colitis. However, the role of ICOS in rat intestinal inflammation and its expression profile remains unclear. In the present study, the authors investigated the involvement of ICOS in the development of rat dextran sulfate sodium (DSS)-induced colitis, and the therapeutic potential of anti-ICOS monoclonal antibody (mAb) in colitis.

Macrophage-derived IL-18 targeting for the treatment of Crohn's disease.

Crohn's disease is an inflammatory bowel disease associated with several changes in the immune system, including an increased number of infiltrating macrophages. These macrophages release a variety of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha, macrophage infiltrating factor (MIF), interleukin (IL)-6, IL-12 and IL-18, which are critically involved in the onset and the development of Crohn's disease. We here focus on the role of macrophages, especially macrophage-derived IL-18 in both patients with Crohn's disease and a murine model of Crohn's disease.

Blockade of B7-H1 suppresses the development of chronic intestinal inflammation.

A newly identified costimulatory molecule, programmed death-1 (PD-1), provides a negative signal that is essential for immune homeostasis. However, it has been suggested that its ligands, B7-H1 (PD-L1) and B7-dendritic cells (B7-DC; PD-L2), could also costimulate T cell proliferation and cytokine secretion. Here we demonstrate the involvement of PD-1/B7-H1 and B7-DC interaction in the development of colitis.

Interleukin-18 overproduction exacerbates the development of colitis with markedly infiltrated macrophages in interleukin-18 transgenic mice.

Background And Aim: The authors have previously shown that production of interleukin (IL)-18 was increased in the inflamed mucosa of patients with Crohn's disease (CD) and blockade of IL-18 ameliorated the murine model of CD. This demonstrated that IL-18 plays a significant role during intestinal inflammation. However, the initial role of IL-18 during intestinal inflammation was unclear; therefore the susceptibility of IL-18 transgenic (Tg) mice to acute dextran sulfate sodium (DSS)-induced colitis was examined.

Regulation of murine inflammatory bowel disease by CD25+ and CD25- CD4+ glucocorticoid-induced TNF receptor family-related gene+ regulatory T cells.

CD4(+)CD25(+) regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance and prevention of autoimmune disease. However, accumulating evidence suggests that a fraction of the peripheral CD4(+)CD25(-) T cell population also possesses regulatory activity in vivo. Recently, it has been shown glucocorticoid-induced TNFR family-related gene (GITR) is predominantly expressed on CD4(+)CD25(+) regulatory T cells.

Role of the innate immune system in the development of chronic colitis.

Based on Pasteur's work on the microbial nature of fermentation, it was widely believed that the presence of bacteria in the intestine was essential for the life of the host. It has also been known for decades that gut commensal microbes effect the activation and development of the systemic immune system through gut-associated lymphoid tissues (GALT). Recent extensive studies have shown that recognition of microbes is mediated by a set of germline-encoded receptors, Toll-like receptors (TLRs), in mammals.

Ameliorating effect of anti-inducible costimulator monoclonal antibody in a murine model of chronic colitis.

Background & Aims: Inducible costimulator (ICOS)/B7RP-1 represents a newly described receptor/ligand pair involved in costimulation of T cells by antigen-presenting cells. We investigated the involvement of the ICOS/B7RP-1 interaction in the pathogenesis of colitis and the therapeutic potential of anti-ICOS monoclonal antibody (mAb) in experimental colitis

Methods: We administered anti-ICOS or anti-B7RP-1 mAb to mice with experimental colitis induced by transfer of CD4(+)CD45RB(high) T cells from normal mice into SCID mice. The ability of CD4(+)CD45RB(high) cells derived from ICOS-/- mice to induce colitis was assessed.