Kimitomo Morise

Elevation of interleukin-6 in inflammatory bowel disease is macrophage- and epithelial cell-dependent

Local interleukin-6 (IL-6) activity was studied using colonic mucosal tissues in inflammatory bowel disease (IBD) and inflammatory control patients. Active IBD specimens exhibited significantly higher IL-6 activity than control specimens in both cultures of isolated lamina propria mononuclear cells (LPMC) and mucosal tissues with an increased number of IL-6-producing cells. However, the activity in inactive IBD or inflammatory controls did not differ from controls. Northern blot analysis demonstrated IL-6 messenger RNA in LPMC and colonic epithelial cells isolated from active IBD specimens but not in control cells. Furthermore, immunofluorescent microscopic study of active IBD specimens showed more conspicuous staining of IL-6 in infiltrating LPMC (mostly CD68+ cells) and colonic epithelial cells. These results suggest that elevation of local IL-6 activity may be a characteristic feature of active IBD and both macrophages and colonic epithelial cells are the major cell types responsible for this phenomenon.

Helicobacter pylori infection induces a decrease in immunoreactive-somatostatin concentrations of human stomach

Immunoreactive-somatostatin (ir-somatostatin) concentrations of the gastric mucosa and gastric juice withHelicobacter pylori infection were measured in the human stomach. One hundred seventy-one patients (106 males, 65 females;, mean age, 52.0; range, 19–84 years) were registered. Gastric juice and mucosa were obtained with the usual endoscopy procedure. Somatostatin concentration was measured by radioimmunoassay. The irsomatostatin concentrations in theH. pylori-negative group were significantly higher than in the positive group gastric mucosa, whereas its levels in gastric juice tended to decrease withH. pylori infection. There was an inverse correlation between luminal ammonia levels and ir-somatostatin concentrations of the gastric mucosa. On the other hand, ir-somatostatin concentrations of the gastric mucosa significantly decreased with chronic and active inflammatory change. This decrease was not correlated with the grade of active inflammation, which was in close relation, toH. pylori infection, but with the grade of chronic inflammation. These results indicate thatH. pylori may reduce ir-somatostatin concentrations of the human stomach and that its effect is partly mediated via luminal ammonia produced byH. pylori.

Abnormal neuropeptide concentration in rectal mucosa of patients with inflammatory bowel disease

Regulatory neuropeptides are widely distributed in the gastrointestinal tract, where they play an important role in motility, secretion, and immune and inflammatory responses. In this study, the rectal mucosal content of somatostatin (SOM), substance P (SP), β-endorphin (BE), and thyrotropin-releasing hormone (TRH) was measured by radioimmunoassay in 56 patients with ulcerative colitis (UC), 15 patients with Crohns disease (CD), 15 patients with acute infectious colitis (AIC), and 11 controls, who showed no inflammation of the rectal mucosa, nor abnormal bowel movements. The content of immunoreactive (ir)-SOM was decreased in UC patients, especially in those with persistent disease activity, while the levels of ir-SP, BE, and TRH were increased in such patients. Some changes of ir-peptide levels were also observed in CD and AIC patients. The changes in neuropeptide levels were analyzed in relation to histological grades of inflammation in UC patients, grades 4–5 showing the most significant changes. The levels of ir-SOM, SP, BE, and TRH showed no significant change in chronic persistent UC when measured 6–12 months after the initial examination. In contrast, in patients with remitting intermittent UC, the levels of SP and BE decreased during remission. Abnormal intestinal neuropeptide content may be implicated in the continued mucosal immune and inflammatory responses that are manifested in patients with inflammatory bowel disease.

Endoscopic injection sclerotherapy for esophageal varices during pregnancy

Pregnancy is uncommon in patients with portal hypertension, and the correct treatment for pregnant women with esophageal varices has not yet been established. There have been only a few reports on endoscopic injection sclerotherapy (EIS) during pregnancy for the control of variceal bleeding. Here we report two women with esophageal varices who underwent EIS. One was a pregnant woman with variceal hemorrhage who was saved by emergency EIS and was delivered safely. The second woman underwent prophylactic EIS for esophageal varices before becoming pregnant. This woman later gave birth uneventfully. Thus EIS appears to be a useful treatment for pregnant women with esophageal varices.

Expression of adhesion molecules and HLA-DR by macrophages and dendritic cells in aphthoid lesions of Crohn's disease: An immunocytochemical study

The phenotypes and ultrastructure of macrophages and dendritic cells in aphthoid lesions of the colon were immunocytochemically observed in patients with Crohns disease. Biopsy specimens were endoscopically obtained from both aphthoid and advanced lesions in Crohns disease patients. Biopsy specimens obtained from patients with infectious colitis and from normal individuals served as controls. Aphthoid lesions contained densely aggregated CD68+ macrophages, which were surrounded by numerous ID-1+ dendritic cells. In the normal controls and infectious colitis patients, however, a few scattered CD68+ macrophages and ID-1+ dendritic cells were noted beneath the surface epithelium. CD3+ lymphocytes were significantly increased in both aphthoid and advanced lesions of Crohns disease, but the CD4/CD8 ratio was similar in all groups studied. The double immunoperoxidase staining method revealed that both CD68+ macrophages and ID-1+ dendritic cells in the aphthoid lesions simultaneously expressed ICAM-1 and HLA-DR antigens. Electronmicroscopic observation revealed that CD68+ macrophages had numerous vesicles and lysosomal granules and few projections, and that ID-1+ dendritic cells had appreciable cytoplasmic protrusions with a few vacuoles. These findings suggested that the colonic mucosa in Crohns disease contained two types of macrophage/dendritic cells in the same lineage that expressed intercellular adhesion molecules and class-II MHC antigens. It also appeared that the aphthoid lesions of Crohns disease featured an increase in macrophages and dendritic cells consistent with immunological activation.

Endoscopic ultrasonography with color Doppler function in the diagnosis of rectal variceal bleeding.

Extraesophagogastric variceal bleeding in patients with portal hypertension is rare, but has been reported after endoscopic injection sclerotherapy (EIS) for esophageal varices. Here, we report rectal variceal hemorrhage following EIS. Endoscopic ultrasonography with color Doppler function (EUSCD) was useful for the diagnosis of rectal varices and complete hemostasis was obtained with EIS. A review of the literature since 1980 revealed a total of 15 patients, including ours, with extraesophagogastric variceal bleeding following EIS. This suggests EIS is the principal emergency treatment for bleeding rectal varices.

Phenotypic and functional characterization of T-cell lines generated from colonoscopic biopsy specimens in patients with ulcerative colitis

Intestinal T-cell lines were generated from lamina propria mononuclear cells isolated from colonoscopic biopsies in ulcerative colitis patients and controls. In both ulcerative colitis and controls, expanded cells were constituted largely by T-cell receptor αβ+, CD4+, CD45RA− (helper), and CD8+, CD11b− (cytotoxic) phenotypes. T-cell receptor Vβ gene usage was not significantly changed after cell expansion and no difference was observed between ulcerative colitis and controls. Ulcerative colitis cells, especially those derived from the patients with long-standing disease, showed significantly higher levels of cytotoxicity against the target cells, including those of colonic epithelial origin, and enhanced production of tumor necrosis factor-α and interferon-γ after short incubation with anti-CD3 antibody. Generation of T-cell lines from colonoscopic biopsy specimens may be useful for detailed functional characterization of locally infiltrating T cells in ulcerative colitis patients.

Immunoreactive-somatostatin concentrations of the human stomach and mood state in patients with functional dyspepsia : a preliminary case-control study

Immunoreactive‐somatostatin (ir‐SS) concentrations of the gastric mucosa and mood state in patients with functional dyspepsia were examined. The subjects were 12 patients with upper abdominal discomfort, nausea and/or vomiting (motility disorder group) and 14 patients complaining of upper abdominal pain (ulcer‐like disorder group) for more than a month without any organic upper‐gastrointestinal tract disease proven by endoscopy. These patients were compared with either an age‐ and sex‐matched group of asymptomatic outpatients without any organic disease (control group: n= 26) or to a group of patients with peptic ulcer (n= 19). Somatostatin concentrations of the stomach were measured by radio‐immunoassay, and the mood state of each subject was assessed by Manifest Anxiety Scale (MAS) and Self‐rating Depression Scale test. Immunoreactive‐somatostatin concentrations of the gastric mucosa were significantly higher in the ulcer‐like disorder group than in the peptic ulcer, motility disorder or control group, and gastric juice levels were higher in the ulcer‐like disorder group. The psychometric tests showed that the motility disorder group was more depressive than the ulcer‐like disorder group, but there were no differences between the motility disorder, ulcer‐like disorder and peptic ulcer group in MAS scores or environmental factors. These results indicate that there may be two different subgroups in functional dyspepsia influenced by both ir‐SS concentration of the stomach and/or mood state.

Effect of luminal administration of thyrotropin-releasing hormone or somatostatin on gastric pH and interaction of these peptides in rats

SummaryThe effect of intraluminal administration of thyrotropin-releasing hormone (TRH) on gastric pH and release of luminal somatostatin, and a possible interrelationship between TRH and somatostatin in the rat stomach were studied. TRH was administered into the stomach via an intragastric tube at various doses (50 pg/kg-10 μg/kg) and gastric pH was measured after 15 min. The intraluminal administration of TRH significantly decreased gastric pH at doses over 1.0 ng/kg. Time-course studies at a dose of 100 ng/kg TRH exhibited a significant decrease in gastric pH at 15, 30 and 60 min. Furthermore, TRH administration caused a significant increase in immunoreactive-somatostatin (ir-somatostatin) concentrations in the gastric wall and a significant decrease in ir-somatostatin concentrations in the gastric juice. On the other hand, intraluminal administration of somatostatin caused a significant increase in ir-TRH concentrations in the gastric wall and a significant decrease in ir-TRH concentrations in the gastric juice, and significantly raised gastric pH at 5 min. These findings suggest that luminal TRH may exert a regulatory effect on gastric acid secretion, and that TRH may have a possible interaction with somatostatin in the modulation of gastric acid secretion.

Effect of cold-restraint stress on immunoreactive thyrotropin-releasing hormone and immunoreactive somatostatin in the rat stomach

The effects of cold-restraint stress on immunoreactive thyrotropin-releasing hormone (ir-TRH) and immunoreactive somatostatin (ir-SOM) concentrations in the rat stomach were investigated. Rats immobilized with a spring-loaded metallic plate were placed in a room maintained at 4°C for 1–3 h and then decapitated serially for investigation. Gastric ir-TRH and ir-SOM concentrations were measured by individual radioimmunoassays. Cold-restraint stress induced gastric mucosal lesions as well as a decrease of the ir-TRH concentration in the glandular stomach, an increase of the ir-TRH concentration in the gastric juice, and a decrease in gastric pH. In contrast, this stress caused an increase of ir-SOM in the glandular stomach and a decrease of ir-SOM in the gastric juice. However, cold or restraint stress alone did not induce gastric mucosal lesions or changes in gastric ir-TRH and ir-SOM concentrations or the gastric pH. To clarify the endocrine influence of peripheral TRH, pretreatment with thyroid hormone was performed to inhibit elevation of the serum TRH level during cold-restraint stress. Despite this pretreatment, cold-restraint stress still induced ulcer formation, along with changes in gastric ir-TRH and ir-SOM concentrations and gastric pH. These findings suggest that changes in gastric ir-TRH and ir-SOM concentrations may be closely related to ulcer formation due to cold-restraint, and that TRH may act in a paracrine manner in the stomach.