Factors Involved in the Degeneration of Lymphoid Tissue in the Appendix.

INTRODUCTION: Studies evaluating the age-related alteration of human appendix have been reported. Although the appendix shows a degeneration of lymphoid tissues with aging, the mechanism of action remains unclear. MATERIAL AND METHODS: Surgically resected appendix tissues from patients with colon cancer, intestinal malrotation and ulcerative colitis (UC) were utilized for histological and flow cytometric analysis. RESULTS: Histological analysis showed that aging may induce steatotic changes in the appendix. However, there was no clear association between appendiceal fibrosis and aging. Lymphoid follicles in the appendix may start to develop before 5 days of age, gradually mature, and eventually disappear with aging. Flow cytometric analysis clearly identified a lymphocyte population in the appendix at 5 days, 45 and 75 years of age, and lymphoid follicles were also confirmed histologically. In contrast, lymphoid population was rarely detectable in the appendix at 79 and 80 years of age, and no lymphoid follicles were present histologically. Interestingly, cytograms from a case at 5 days of age suggested the existence of immature immune cells, as forward scatter showed an increase in cell size of the lymphocyte population. Histological analysis in UC patients found submucosal fat in the appendix of a case 66 years of age. Lymphoid follicular formation and mucosal structure were disrupted in cases of 70 and 72 years of age. UC patients may be more susceptible to steatotic change. Cytograms from appendices of UC patients also supported these histological findings. Our study confirms previous results that lymphoid tissues in the appendix degenerate over time, and proposes that inflammatory insult may facilitate the degenerative process in patients with UC.

Prediction of acute encephalopathy with biphasic seizures and late reduced diffusion in patients with febrile status epilepticus.

INTRODUCTION: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of acute encephalopathy among children in Japan. The pathogenesis of AESD is mostly delayed cerebral edema caused by excitotoxic injury. It is difficult to discriminate AESD and complex febrile seizure in the early phase. Many cases have neurologic sequelae because early intervention is difficult. METHODS: To establish an early diagnostic method, we assessed 213 hospitalized cases of febrile status epilepticus (FSE) between January 2004 and August 2014. We categorized FSE cases into an AESD group and a non-AESD group and compared their clinical courses, laboratory data and cranial computed tomography (CT) findings. RESULTS: Of 213 hospitalized FSE cases, 19 (9%) were AESD. Univariate analysis showed that the AESD group took a significantly longer time to wake after FSE, had a higher degree of respiratory acidemia, and higher levels of serum AST, ALT, LD, hyperglycemia and hyperammonemia than the non-AESD group. We developed a scoring model that predicts AESD based on multivariate analysis. Using cut-off points of 4 and more with this scoring model, we could identify the AESD cases with 93% sensitivity and 91% specificity. These scores also had a positive correlation with prognosis. DISCUSSION: Our scoring model enables early diagnosis of AESD. Patients with high scores should be observed carefully and early intervention should be considered.

Genetically engineered mouse models for studying inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that is mediated by very complex mechanisms controlled by genetic, immune, and environmental factors. More than 74 kinds of genetically engineered mouse strains have been established since 1993 for studying IBD. Although mouse models cannot fully reflect human IBD, they have provided significant contributions for not only understanding the mechanism, but also developing new therapeutic means for IBD. Indeed, 20 kinds of genetically engineered mouse models carry the susceptibility genes identified in human IBD, and the functions of some other IBD susceptibility genes have also been dissected out using mouse models. Cutting-edge technologies such as cell-specific and inducible knockout systems, which were recently employed to mouse IBD models, have further enhanced the ability of investigators to provide important and unexpected rationales for developing new therapeutic strategies for IBD. In this review article, we briefly introduce 74 kinds of genetically engineered mouse models that spontaneously develop intestinal inflammation.