Yo Aoyagi

Increased mucosal expression of GATA-3 and STAT-4 in pediatric ulcerative colitis

Background:  Serum pro‐inflammatory cytokine levels are frequently elevated in the acute phase of pediatric inflammatory bowel disease (IBD). Because the role of pro‐inflammatory cytokine in the acute phase of pediatric IBD has not been well investigated, the serum levels of pro‐inflammatory cytokines and the expression of Th1 and Th2 signaling molecules in mucosa from the acute phase of pediatric IBD were examined.

Neonatal transient eosinophilic colitis causes lower gastrointestinal bleeding in early infancy.

Background: Lower gastrointestinal bleeding (LGB), particularly in newborns, is of serious concern and requires urgent investigation and hospital care. Whereas allergic proctocolitis caused by food protein is a significant cause of LGB in infants with eosinophilia, there are several cases of diseases with symptoms similar to those of allergic proctocolitis but without an apparent allergic reaction influence. Patients and Methods: We examined 2 neonates using rectosigmoidoscopy who showed eosinophilia and experienced fresh LGB soon after birth and before their first feedings. Serum eosinic cationic protein (ECP) and platelet activating factor (PAF) levels were also examined in the second case to confirm the involvement of eosinophils for its pathogenesis. Results: Both patients were in a clinically stable condition, and their abdomens were soft. The results of their blood analyses, abdominal radiographs, and stool cultures were normal, but they had gross eosinophilia: the eosinophil counts were 9014/mm3 (patient 1) and 1955/mm3 (patient 2). Rectosigmoidoscopy with colonic mucosal biopsy revealed nodular lymphoid hyperplasia with a pale mucosal surface and massive oozing with diffuse eosinophilic infiltration in the lamina propria. In patient 2 the serum ECP and PAF levels were elevated to 123 μg/L (normal, <14.7) and 13.1 μmol/L/min (normal, <6). A few days after intravenous hydration therapy, LGB was no longer detected, and the serum ECP and PAF levels returned to normal. Conclusions: Inasmuch as these infants had LGB similar to allergic proctocolitis without any allergic reactions, we suggest that infiltrated eosinophils in the colonic mucosa could be involved in the pathogenesis of LGB in early infancy.

Peroxisome proliferator-activated receptor γ 2 mutation may cause a subset of ulcerative colitis

Aim:  Previous studies suggest the homeostasis between acquisition of tolerance to the indigenous microflora and protective immune responses appears to be disrupted in inflammatory bowel disease (IBD). Some experimental studies indicate peroxisome proliferator‐activated receptor γ (PPARγ) has been implicated as a regulator of intestinal inflammatory responses. In addition, the toll‐like receptor (TLR)‐4 can regulate expression of PPARγ in colonic epithelial cells. We attempted to demonstrate whether the functional imbalance between TLRs and PPARγ could lead to the onset and some polymorphisms of those genes could contribute to susceptibility to IBD.

Microarray analysis of mucosal biopsy specimens in neonates with rectal bleeding: is it really an allergic disease?

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Monitoring 6-thioguanine nucleotide concentrations in Japanese children and adolescents with inflammatory bowel disease.

Background and Aim:  6‐Mercaptopurine (6‐MP) and azathioprine (AZA) are widely used as maintenance therapy in children with inflammatory bowel disease (IBD). However, proper 6‐thioguanine nucleotide (6‐TGN) concentrations in Japanese children with IBD have not been reported.

Polarized production of T-helper cell type 1 cells in Peyer's patches in Crohn's disease.

Background/Aims: Although Peyer’s patches (PPs) serve as important antigen-sampling sites for the immune system, surprisingly little attention has been paid to their associations with the onset of Crohn’s disease (CD) as antigen entry sites. To examine the immunological events in PPs, we performed functional and phenotypical studies on PP cells, the lamina propria cells in the colonic mucosa and peripheral blood mononuclear cells (PBMC) in inflammatory bowel disease. Patients: The subjects were 9 children and adolescents with active CD, 9 with inactive CD, 11 with active ulcerative colitis (UC), and 22 normal controls. Methods: The cytokine profile in PPs and lamina propria was performed through Elispot assay and RT-PCR. PP mononuclear cells and PBMC from the subjects were analyzed by flow cytometry using monoclonal antibodies to interferon-γ and interleukin-4, and CC chemokine receptors (CCR) 4 and 5. Results: Th1 together with Tc1 cells were dominant in PPs in the active phase of CD, but not in inactive CD, UC, or normal controls. They did not actually produce interferon-γ, however they have abundant mRNA of the cytokine. Substantial levels of CCR5 ligands, MIP-1α and RANTES mRNA were found in the inflamed intestinal mucosa in CD. Conclusions: It is conceivable that PPs in the terminal ileum in CD may initially sample luminal antigens where Th1-type memory cells are activated which migrate to the peripheral intestinal mucosa. Those immunological changes may not be related to the etiology of UC.

Outcome of infants presenting rectal bleeding: a retrospective study in a single institution.

Although rectal bleeding in infancy (RBI) is not a rare phenomenon, the clinical course of RBI is not fully understood.

Comparison of Gene Expression Between Pediatric and Adult Gastric Mucosa with Helicobacter pylori Infection

Although Helicobacter pylori infection among adults is a major risk factor for the development of gastric cancer and initial infection with H. pylori may occur before 5 years of age, the direct effects of H. pylori infection since childhood on gastric mucosa are unknown. The aim of this study was to evaluate gene expression in the H. pylori‐infected gastric mucosa of children.

Microarray analysis of gastric mucosa among children with Helicobacter pylori infection.

Background:  Although initial infection with Helicobacter pylori may occur before 5 years of age, the pediatric mucosal immune response against H. pylori is not clear. The aim of the present study was to evaluate immune responses in the H. pylori‐infected gastric mucosa of children using microarray and real‐time polymerase chain reaction (PCR) analysis of pediatric gastric samples.

Analysis of inflammatory signals in Japanese children with Crohn's disease

Although it is recognized that the Th1 and Th17 cytokines are directly involved in the pathogenesis of Crohns disease (CD), the precise cause of pediatric CD in the Japanese population has not been well established. In the present study, we examined the expression of pro‐inflammatory cytokines and their signaling molecules in the intestinal mucosa of Japanese children with acute‐ and remission‐phase CD.