[Show abstract][Hide abstract] ABSTRACT: Background:
CD5+ B cells are a type of regulatory immune cells, though the involvement of this B cell subset in intestinal inflammation and immune regulation is not fully understood.
We examined the distribution of CD5+ B cells in various mouse organs. Expression levels of CD11b, IgM, and toll-like receptor (TLR)-4 and -9 in B cells were evaluated. In vitro, TLR-stimulated IL-10 production by colonic lamina propria (LP) CD5+ and CD5- B cells was measured. In vivo, mice with acute or chronic dextran sulfate sodium (DSS)-induced colonic injury were examined, and the frequency of colonic LP CD5+ B cells in those was assessed by flow cytometry.
The expression level of TLR9 was higher in colonic LP CD5+ B cells as compared to CD5- B cells. Colonic LP CD5+ B cells produced greater amounts of IL-10 following stimulation with TLR ligands, especially TLR9, as compared with the LP CD5- B cells. Acute intestinal inflammation transiently decreased the frequency of colonic LP CD5+ B cells, while chronic inflammation induced a persistent decrease in colonic LP CD5+ B cells and led to a CD5- B cell-dominant condition.
A persistent altered mucosal B cell population caused by chronic gut inflammation may be involved in the pathogenesis of inflammatory bowel diseases.
[Show abstract][Hide abstract] ABSTRACT: A 60-year-old woman was admitted to our hospital with upper abdominal pain and jaundice. Computed tomography showed a 9-cm mass that was penetrated by the common hepatic artery in the pancreatic head area. Endoscopic retrograde pancreatography revealed no stenosis or obstruction of the main pancreatic duct, and a cytologic examination of the patient’s pancreatic juice was negative. Next, endoscopic ultrasoundguided fine needle aspiration was performed. The immunohistological findings of the specimen revealed a diffuse large B-cell lymphoma. The size of the tumor was significantly reduced after 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone).
[Show abstract][Hide abstract] ABSTRACT: Background and aim:
The serotonin reuptake transporter (SERT) terminates serotonin (5-HT) activity by removing it from interstitial space. Down-regulated colonic SERT expression has been reported in irritable bowel disease (IBS) and symptoms resembling IBS occur in cases of inflammatory bowel disease (IBD) in remission, thus a common pathogenesis for IBS and IBD is possible. However, little is known regarding SERT expression in colonic mucosa of IBD patients during healing.
Twenty-two ulcerative colitis (UC) patients underwent colonoscopy examinations, during which inflamed mucosa was distinguished from that undergoing healing. Healing mucosa was classified into regular and irregular vessel patterns by narrow-band imaging (NBI) magnifying colonoscopy. Expressions of SERT and various inflammation-related genes in biopsy samples were assessed using a PCR array system and real-time PCR. Colitis model mice were established by administration of dextran sodium sulfate (DSS) or transfer of CD4(+) T cells isolated from SAMP1 mice, then time-course changes of SERT and inflammatory gene expressions were observed in colonic mucosa.
In UC patients, SERT expression in inflamed mucosa was significantly lower than in healing mucosa. SERT expression was decreased in healing mucosa with an irregular vessel pattern with mildly increased levels of inflammatory gene expression. In mice, SERT expression was suppressed in inflamed mucosa and continuously observed with low-grade mucosal inflammation during colitis healing.
SERT expression is down-regulated in healing colonic mucosa of UC patients. That suppression may be dependent on the presence of remaining low grade colonic inflammation.
No preview · Article · Dec 2015 · Journal of Gastroenterology and Hepatology
[Show abstract][Hide abstract] ABSTRACT: Milk fat globule-epidermal growth factor 8 (MFG-E8) promotes phagocytic clearance of apoptotic cells to maintain normal tissue homeostasis. However, its functions in intestinal inflammation and carcinogenesis are unknown.
Experimental colitis was induced in MFG-E8 knockout (KO) and wild-type (WT) mice by dextran sodium sulfate (DSS) administration. Colon tissues were used for assessments of colitis activity and epithelial proliferation. A mouse colitis-associated cancer (CAC) model was induced by intraperitoneal injection of azoxymethane (AOM) and then the animals were given a single administration of DSS. A sporadic colon cancer model was established by repeated intraperitoneal injections of AOM. The role of MFG-E8 in epithelial proliferation with or without treatment of siRNA targeting αv-integrin was examined in vitro using a WST-1 assay.
The severity of colitis in KO mice was greater than that in WT mice, while the proliferative potential of colonic epithelial cells in KO mice was lower during the regenerative phase. In both CAC and sporadic models, tumor size in KO was lower as compared to WT mice, while decreased tumor incidence was only found in the CAC model. In vitro findings showed that MFG-E8 promotes epithelial cell proliferation, and treatment with a siRNA targeting αv-integrin reduced the proliferation of Colon-26 cells stimulated with recombinant MFG-E8.
MFG-E8 promotes tumor growth regardless of the presence or absence of colonic inflammation, whereas colon tumor development is initiated by MFG-E8 under inflammatory conditions. These MFG-E8 functions may be dependent on integrin-mediated cellular signaling.
No preview · Article · Jan 2015 · Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: A 71-year-old woman with borderline resectable cancer of the head of the pancreas with involvement of the portal vein and splenic artery was referred to our hospital. Gastrointestinal endoscopy and contrast-enhanced CT scan demonstrated a large tumor in the head of the pancreas involving the duodenum, portal venous system, and splenic artery. ERCP showed an abrupt interruption of the main pancreatic duct in the head of the pancreas and subsequent pancreatic juice cytology demonstrated adenocarcinoma. The patient underwent pancreaticoduodenectomy with splenic artery reconstruction to avoid performing a total pancreatectomy, which resulted in the R0 resection. Histologically, the tumor was a well-differentiated invasive ductal adenocarcinoma of the pancreas with invasion to the portal vein, as well as the duodenum. The patient received adjuvant chemoradiotherapy and has been cancer-free for 91 months after surgery with favorable nutrition and quality of life. Our case suggests that a curative pancreatectomy with preservation of the pancreatic functional reserve, as much as possible, may allow the patient to receive an adequate postoperative adjuvant therapy and lead to a favorable outcome in patients with borderline resectable pancreatic head cancer.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Few reports have compared the clinical efficacy of a pH-dependent release formulation of mesalazine (pH-5-ASA) with a time-dependent release formulation (time-5-ASA). We examined whether pH-5-ASA is effective for active ulcerative colitis (UC) in patients resistant to time-5-ASA.
We retrospectively and prospectively analyzed the efficacy of pH-5-ASA in mildly to moderately active UC patients in whom time-5-ASA did not successfully induce or maintain remission. The clinical efficacy of pH-5-ASA was assessed by clinical activity index (CAI) before and after switching from time-5-ASA. In addition, the efficacy of pH-5-ASA on mucosal healing (MH) was evaluated in a prospective manner by measuring fecal calprotectin concentration.
Thirty patients were analyzed in a retrospective manner. CAI was significantly reduced at both 4 and 8 weeks after switching to pH-5-ASA. In the prospective study (n=14), administration of pH-5-ASA also significantly reduced CAI scores at 4 and 8 weeks in these patients who were resistant to time-5-ASA. In addition, fecal calprotectin concentration was significantly decreased along with improvement in CAI after switching to pH-5-ASA.
Our results suggest that pH-5-ASA has clinical efficacy for mildly to moderately active patients with UC in whom time-5-ASA did not successfully induce or maintain remission.
Preview · Article · Nov 2014 · BioMed Research International
[Show abstract][Hide abstract] ABSTRACT: A flat, elevated lesion measuring 5 mm in diameter was found in the gastric body of an 80-year-old man. A biopsy showed moderately differentiated adenocarcinoma, and endoscopic ultrasonography revealed a hypoechoic mass located in the submucosa. Endoscopic submucosal dissection was subsequently performed, and a pathological examination revealed a tumor composed of adenocarcinoma and neuroendocrine carcinoma with submucosal infiltration. The pathological diagnosis was gastric mixed adenoneuroendocrine carcinoma (MANEC). An additional gastrectomy procedure was performed, and no recurrence was noted for at least three years. This case is interesting with respect to the carcinogenesis of endocrine cell carcinoma and MANEC.
No preview · Article · Nov 2014 · Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: Objective:
Irritable bowel syndrome (IBS)-like symptoms are often found in ulcerative colitis (UC) patients in remission. However, the prevalence of those symptoms in UC patients with endoscopic evidence of remission shown by mucosal healing remains unknown.
Material and methods:
IBS diagnosis was evaluated by questionnaire results according to the Rome III criteria. Clinical remission was assessed by clinical activity index (CAI), whereas endoscopic remission was evaluated by endoscopic index (Matts grade).
We enrolled 172 patients in clinical remission (CAI ≤ 4), after excluding 36 for incomplete questionnaire results or nonremission findings, as well as 330 control subjects. Of the 172 UC patients, 46 (26.7%) met the Rome III criteria, which was a significantly higher rate as compared with the controls (4.8%). The prevalence rate of IBS-like symptoms in UC patients with endoscopic remission findings (Matts grade ≤2) was 25.6%, which was similar to that of those with clinical remission. When endoscopic remission was defined as Matts grade 1, the prevalence rate of IBS-like symptoms was decreased to 15.4%, although the prevalence rate remained higher than that of the control subjects.
The prevalence of IBS-like symptoms in UC patients with clinical and endoscopic remission findings was significantly higher than that of control subjects. Furthermore, the prevalence rate in patients with complete endoscopic remission was decreased. These findings suggest that residual low-grade inflammation may influence the presence of IBS-like symptoms in UC patients in remission.
No preview · Article · Mar 2014 · Scandinavian Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: : The role of regulatory B cells (Bregs) producing interleukin (IL)-10 in the pathogenesis of inflammatory bowel diseases remains unknown. We investigated IL-10 production in B cells from patients with inflammatory bowel diseases and immunoregulatory functions of Bregs in experimental colitis mouse models. CpG DNA-induced IL-10 production in peripheral blood B cells isolated from patients with inflammatory bowel diseases and control subjects was examined. CD19 and CD1d were used for evaluating possible cell surface markers of Bregs. Colitis models of severe combined immunodeficiency mice were established by adoptive transfer of whole CD4 T cells or regulatory T cell (Treg)-depleted T cells (CD4CD25) isolated from SAMP1/Yit mice and the function of Bregs in intestinal inflammation was elucidated by evaluating the effects of cotransfer of whole or Breg-depleted B cells. CpG DNA-induced IL-10 production was significantly decreased in B cells from patients with Crohn's disease (CD), as compared with those from healthy controls, whereas Bregs were found to be enriched in a population of CD19 and CD1d B cells isolated from both human and mouse samples. The severity of intestinal inflammation was significantly increased in the Breg-depleted mice, with similar results also found in adoptive transfer colitis model mice even after Treg depletion. Our findings show that Bregs, characterized by the cell surface markers CD19 and CD1d, significantly reduced experimental colitis regardless of the presence or absence of Tregs. These results suggest that a deficiency or decrease of Bregs function exacerbates intestinal inflammation, which may be associated with the pathogenesis of CD.
No preview · Article · Jan 2014 · Inflammatory Bowel Diseases
[Show abstract][Hide abstract] ABSTRACT: Here we report the cases of eight patients who developed small bowel obstruction and/or gastric ulcers after ingesting rice cake, the traditional Asian food, and were managed conservatively. This report adds to the existing literature on gastrointestinal disorders induced by rice cake ingestion, which are characterized by gastrointestinal obstruction, perforation, and ulceration and are occasionally accompanied by peritonism. These conditions tend to occur in 50-60-year-old males who wear dentures or eat rapidly. Therapeutically, hard rice cake remnants in the upper gastrointestinal tract can be broken up by endoscopic snaring and can be detected by computed tomography as homogeneous high-density material at approximately 145 (range:120-206) Hounsfield units.
No preview · Article · Oct 2013 · Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology
[Show abstract][Hide abstract] ABSTRACT: During intestinal inflammation, a variety of signaling events are activated to perform several cell functions. Although the distinct roles of these pathways have been elucidated, the effects of their crosstalk activities remain to be clarified. We evaluated the crosstalk between two evolutionary conserved cell signaling systems, toll-like-receptor (TLR) 5 and Notch1, in intestinal epithelial cells during inflammation. Significant induction of the expression of Notch1 and Jagged1 was observed in the distal part of the colon, together with abundant localization of Notch1 intracellular domain (N1ICD) in the surface epithelium of inflamed colonic mucosa. By targeting intestinal epithelial cells, it was shown that recombination-signal-binding-protein-Jκ (RBP-Jκ)-mediated Notch functions are dependent on a flagellin-TLR5-mediated pathway. Conversely, using a γ-secretase inhibitor, we demonstrated that Notch synergistically increases TLR5‑mediated NF-κB activation. In addition, the effects of Notch on the NF-κB target gene interleukin-6 (IL-6) expression were revealed by evaluating the RBP-Jκ responsive element in the IL-6 promoter in vitro. Modulation of TLR5 and Notch crosstalk by transient blocking of Notch during the acute phase of colitis was beneficial for ameliorating colonic inflammation as well as disease status. In conclusion, the results suggest the effectiveness of Notch-targeted drug strategy for the treatment of intestinal inflammation.
No preview · Article · Sep 2013 · International Journal of Molecular Medicine
[Show abstract][Hide abstract] ABSTRACT: Systemic AA amyloidosis is a complication of various inflammatory diseases including Crohn's disease (CD). Amyloid nephropathy is the most common clinical presentation of AA amyloidosis leading to renal failure, and affected patients often require hemodialysis and ultimately renal transplantation. We herein report the successful use of infliximab as maintenance therapy for amyloid nephropathy in a patient with CD. In the present patient, surgical treatment and infliximab infusion immediately induced a remission of CD, and scheduled infliximab therapy successfully maintained the patient's stable condition for three years, with a significant decrease in the serum creatinine level.
No preview · Article · Sep 2013 · Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: There is increasing evidence regarding the role of immune activation in the etiology of irritable bowel syndrome (IBS), which has been mainly been shown in studies investigating mechanisms of postinfectious IBS (PI-IBS). Exposure to intestinal infection induces persistent low-grade systemic and mucosal inflammation, which is characterized by an altered population of circulating cells, mucosal infiltration of immune cells and increased production of various cytokines in IBS patients. Recent studies have also indicated an increased innate immune response in these patients by evaluating expression and activation of Toll-like receptors (TLRs). These findings suggest that immune activation may play a crucial role in the pathogenesis of IBS. In addition, psychological stress has been reported to be one of the factors that induces immune activation. However, it remains unknown whether immune activation in IBS patients is largely dependent on infectious gastroenteritis and/or psychological stress. Additional studies are necessary to understand the precise mechanism of immune activation and its relationship to the development of IBS.