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Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited disorder characterized by extensively vascularized tumors and cysts in specific organs. Angiogenesis is a striking future of VHL disease with its characteristic cysts and well-vascularized tumors. The hypervascular nature of VHL lesions has been linked to the overproduciton of vascular endothelial growth factor (VEGF) through increased expression of hypoxia inducible factor-1alpha (HIF-1alpha). Here we describe a rare case of VHL disease with esophageal and gastric varices due to arterioportal shunt in a serous cystadenoma of the pancreas, which, upon immunohistochemical examination, exhibited HIF-1alpha and VEGF expression. Rupture of esophageal varices was successfully treated with endoscopic injection sclerotherapy.

Elevation of the serum anti-Saccharomyces cerevisiae antibody (ASCA) level has been reported in patients with Crohn's disease. This study investigated the antigenic distribution of S. cerevisiae in human colon and peripheral leukocytes. ASCA was isolated from sera from patients with Crohn's disease using immuno-affinity chromatography and then biotinylated and assayed immunohistologically and immunocytologically to determine the distribution of antigens recognized by ASCA in human colon and peripheral leukocytes. Immunoblot analysis of yeast extract and human peripheral leukocytes was performed. Immunohistological study using biotinylated ASCA revealed the presence of yeast-like particles in the granulation tissue of inflamed colonic mucosa. Biotinylated ASCA also stained lymphocytes and polymorphonuclear cells infiltrating inflamed intestine. Monocytes in epithelioid granulomas of colon with Crohn's disease were also stained. Polymorphonuclear leukocytes in peripheral blood were also stained with biotinylated ASCA. The antigens reactive to ASCA among heat-extracted, non-heat-extracted yeast antigens, and human leukocyte extract differed. The findings of cross-reactivity of polymorphonuclear leukocytes with S. cerevisiae antigen and the presence of S. cerevisiae antigen in Crohn's disease granulomas suggest the possibility of involvement of S. cerevisiae in the pathogenesis of Crohn's disease.

Pulsed steroid therapy may induce rapid remission in patients with moderately severe ulcerative colitis in outpatient clinics. A total of 19 patients with moderately severe active ulcerative colitis who refused hospitalization were treated between October 1999 and September 2001 in the outpatient clinic. Patients were treated with either conventional oral steroid therapy or intravenous pulsed steroid therapy followed by conventional oral steroid therapy. Eight patients received conventional steroid therapy and 11 patients received pulsed steroid therapy followed by conventional steroid therapy. The efficacies of the two types of steroid therapy were equal, but patients with active colitis responded more quickly to pulsed steroid therapy than to conventional steroid therapy. No serious adverse effects were observed. Moderately severe colitis can be safely treated with either conventional or pulsed steroid therapy in the outpatient clinic, but pulsed steroid therapy may induce clinical remission more quickly than conventional steroid therapy.

Small intestinal tuberculosis is a rare disorder of the small intestine. We report the development of deep small bowel tuberculosis in a rheumatoid arthritis patient who was taking methotrexate. The diagnosis of small bowel tuberculosis was ascertained by typical endoscopic findings and production of interferon gamma in the peripheral blood. The patient was successfully treated with antituberculous chemotherapy combined with an antifibrotic agent, tranilast, to suppress the progression of intestinal stenosis toward symptomatic stricture.

Summary Background : In Helicobacter pylori infection, the effect of short-term triple therapy with proton pump inhibitor plus two antibiotics on gastric ulcer healing is not well known. Aim : To compare 1-week triple therapy with 8-week proton pump inhibitor therapy on gastric ulcer healing in infected patients. Patients and methods : We randomly assigned 120 patients with H. pylori and gastric ulcers to proton pump inhibitor plus amoxicillin and clarithromycin for 1 week (n = 61) or proton pump inhibitor alone for 8 weeks (n = 59), with endoscopic assessment of ulcer healing 8 weeks after the start of treatment. Results : Triple therapy eradicated H. pylori in 51 patients [intention-to-treat, 84%; 95% confidence interval (CI), 75–93%]. At 8 weeks, gastric ulcers were healed in 30 patients given triple therapy (49%; 95% CI, 37–62%) and in 49 patients given proton pump inhibitor (83%; 95% CI, 73–93%, P

Background: Ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine biosynthesis, mediates epithelial cell proliferation and plays a critical role in the optimal repair of gastric mucosal damage. Several studies have shown that Helicobacter pylori inhibits the growth and proliferation of gastric cells in vitro. Aim: To test whether H. pylori extract affects ODC mRNA expression and its enzyme activity in gastric cells and to examine the partial characterization of the molecule responsible for this effect. Methods: Human gastric cells (MKN-45) were used. Bacterial extracts from various E. coli or H. pylori strains, namely (1) cagA+, vacA+, CagA+, VacA+; (2) cagA+, vacA+, CagA+ VacA–; or (3) cagA–, vacA+, CagA–, VacA– were added to the cells. Cell proliferation was assessed by [3H]-thymidine incorporation, viability by MTT assay and LDH release test, ODC enzyme activity by 14CO2 counts from L-[114C]ornithine, and ODC mRNA by Northern blotting. Results: H. pylori and E. coli extract did not affect viability of gastric cells. H. pylori extract, especially extracts containing a protein greater than 50 kDa, significantly inhibited proliferation and ODC activity of gastric cells while E. coli extract had no effect. Inhibition of ODC activity was found in extracts of all H. pylori strains, irrespective of CagA and VacA protein expression. Serum stimulation induces an increase in ODC mRNA while H. pylori extract did not affect ODC mRNA expression. Conclusion: High molecular weight (greater than 50 kDa) proteins of H. pylori extract without CagA or VacA protein inhibited proliferation and ODC activity of human gastric cells, but did not affect ODC mRNA expression, suggesting that inhibition of ODC activity is regulated at the post-transcriptional level.

Background: Epidermal growth factor (EGF), which binds to EGF receptors (EGF-R), stimulates oesophageal epithelial cell proliferation, enabling rapid repair after mucosal injury. In the normal human oesophageal epithelium, EGF-R expression is present and confined to the basal layer. Aim: To examine histological changes in and dynamics of EGF-R expression during healing after acid reflux oesophagitis in a rat model. Methods: Gastric acid reflux oesophagitis was induced in Wistar rats by ligation of the pylorus and the transitional region between the forestomach and the grandular portion for 5 h, followed by release of both ligations. Rats were killed 7 and 14 days after production of oesophagitis to examine macroscopic and histological changes as well as dynamics of EGF-R expression. Epithelial cell proliferation was assessed by bromodeoxyuridine (BrdU) uptake, and expression of EGF-R mRNA and protein by RT–PCR and Western blotting or immunohistochemistry. Results: Gastric acid reflux induced erosive and ulcerative mucosal lesions in the lower and middle part of the oesophagus. These lesions were healed by 14 days and histologically showed thickening of the oesophageal epithelium from 41.11 ± 3.09 μm in controls to 142.73 ± 11.59 μm (P

Phlebosclerosis of the mesenteric vein is a rare condition causing chronic intestinal ischemia, it has only been reported in Japan. A 56-year-old man with liver cirrhosis and hepatic tumor presented with phlebosclerosis of mesenteric vein without any abdominal symptoms. He was admitted for examination of suspected hepatic tumor. Abdominal plain x-ray films and computed tomography revealed calcification of the mesenteric vein. Barium enema revealed narrowing and thumbprinting from the cecum to transverse colon. On colonoscopic examination, blue-black vessels were visible in the terminal ileum, and hyperemic nodular mucosa with small irregular ulcers surrounded by dark purple mucosa was found from the cecum to transverse colon. The etiology of mesenteric vein phlebosclerosis is unknown, although a physical mechanism rather than inflammatory changes appear to be involved in this rare and usually progressive condition of chronic intestinal ischemia.

A 32-year-old woman was admitted to our hospital for intractable Crohn’s disease. Crohn’s colitis was diagnosed at another hospital in August 1999. She had been successfully treated with oral mesalazine and an elemental diet. In March 2000, she had been admitted to the previous hospital for her third flare up of symptoms. She responded to oral mesalazine administration and total parenteral nutrition, but bowel symptoms were exacerbated and C-reactive protein level was elevated after a polymeric diet was started. Prednisolone 30 mg/day was started in addition to total parenteral nutrition, but hematochezia and elevated serum C-reactive protein level persisted, and she was referred to our hospital. She had about four bowel movements per day with fresh bleeding at the time of admission. Total parenteral nutrition and oral mesalazine were continued. The dose of oral prednisolone was increased from 15 mg/day to 40 mg/day. However, the frequency of bowel movements did not decrease and C-reactive protein level continued to exceed 1.5 mg/day. Mesalazine enemas were begun on 23 January 2001, and were effective in improving hematochezia and serum C-reactive protein. Both radiologic and endoscopic examinations revealed remarkable improvement.

Loss of response (LOR) to infliximab (IFX) has become an important clinical issue for patients with Crohn's disease (CD). Elemental diet (ED) therapy has been established as a nutrition therapy for CD in Japan. ED therapy can reduce antigen exposure and is both efficacious and safe.To evaluate the efficacy of concomitant ED therapy in maintaining regular IFX infusion in patients with CD.We retrospectively studied 125 patients with luminal CD treated with scheduled IFX maintenance therapy with a regular dosage. Patients were classified into two groups: the ED group with intake ≥ 900 kcal/day and the non-ED group with intake900 kcal/day. When clinical LOR was detected on the basis of disease activity, laboratory parameters, or endoscopic findings, the physician discontinued the infusion schedule of IFX. We investigated the efficacy of ED therapy for sustaining the scheduled IFX maintenance therapy.With the exception of ED intake, no significant differences were found in patient characteristics between the ED group and the non-ED group. The ED group was significantly superior to the non-ED group (p = 0.049) in sustaining scheduled IFX maintenance therapy. It is well known that ED therapy is more effective for small bowel lesions than colonic lesions in CD. When comparing ileitis and ileocolitis patients with CD, the ED group was significantly superior to the non-ED group (p = 0.015).Concomitant ED therapy is effective in maintaining scheduled IFX maintenance therapy in patients with luminal CD in order to prevent LOR.

Elevation of serum anti Saccharomyces cerevisiae antibody (ASCA) has been reported in patients with Crohn's disease. We analysed the subclasses of Immunoglobulin (Ig) G reaction in ASCA in sera from patients with inflammatory bowel disease, healthy controls, and patients with intestinal Behcet's disease. Serum samples were obtained from 29 patients with Crohn's disease, 30 patients with ulcerative colitis, 7 patients with intestinal Behcet's disease, and 12 healthy controls. Serum IgG subclasses IgG1, IgG2, IgG3, and IgG4 of ASCA were analysed using ELISA. IgG4 ASCA was significantly increased in patients with inflammatory bowel disease. In patients with intestinal Behcet's disease, IgG1, IgG3, and IgG4 ASCA were increased. Differential responses, in terms of subclasses in ASCA, were found in patients with inflammatory bowel disease and patients with intestinal Behcet's disease, which may represent different pathophysiologies of these intestinal inflammatory diseases.

SUMMARY 1. Production of nitric oxide (NO) is implicated in the pathogenesis of inflammatory bowel disease. However, the cells responsible for the production of NO in situ in the human colon remain unknown. 2. Surgical samples from 12 patients with ulcerative colitis, eight patients with Crohn’s disease and 10 controls were studied. Possible generation of NO was visualized by reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity in human colon. Immunohistological staining for various NO synthase (NOS) isoforms (endothelial, neuronal and inducible), nitrotyrosine and interleukin-2 was also performed. 3. Reduced NADPH diaphorase activity was not found in lamina propria mononuclear cells, but was found in colonic epithelium, endothelium and myenteric neurons and their processes. 4. The NADPH-diaphorase activity positive processes were significantly less common in colon from patients with Crohn’s disease compared with control colon. 5. Endothelial NOS was constitutively expressed on colonic endothelium. 6. Neuronal NOS was constitutively expressed on myenteric neurons. 7. Expression of inducible NOS (iNOS) was increased in the epithelium and endothelium of the colon of patients with ulcerative colitis. 8. No correlation was found between expression of iNOS and NADPH diaphorase activity. 9. Nitrotyrosine was expressed by lamina propria leucocytes, but not by epithelium. 10. Interleukin-2 was expressed on both leucocytes and myenteric neurons. 11. Colonic epithelium, endothelium and myenteric neurons synthesize NO. Myenteric neurons were principally responsible for NO production and NO may act as a neurotransmitter in the enteric nervous system.

Inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) are chronic long-lasting inflammatory diseases with yet unknown etiology. Recent advancement revealed that both diseases are associated with genetic predisposition and environmental factors such as luminal microorganisms and antigens. Crohn’s disease is associated with histopathologic features such as granuloma formation and longitudinal ulceration. In this article we describe the role of granuloma in the immunopathogenesis of Crohn’s disease. Granuloma of Crohn’s disease may play crucial roles as antigen-presenting cites to memory type T cells, which leads to activation and proliferation of T cells. Antigens presented at granuloma may be closely related to the disease.

当科にて現在まで経験した腸管ベーチェット病9例および単純性潰瘍4例について臨床的に検討した. 性別は男性11例, 女性2例である. 初発年齢は11歳から58歳, 平均36歳である. 診断の内訳は完全型ベーチェット病1例, 不全型ベーチェット病3例, ベーチェット病疑いが9例であり, 疑い症例のうち消化管病変以外のべーチェット病症状を認めない症例は4例である. 初期診断はクローン病4例 (うち1例は虫垂炎, 他の1例は腸結核も疑われる), ベーチェット病3例, 大腸癌2例, 若年性関節リウマチ1例, 膠原病1例, 単純性潰瘍1例, 不明1例である. 完全型および不全型ベーチェット病では2例で腸管切除が行われ, 頻回の入院歴がある. ベーチェット病疑い5例のうち2例で腸管切除が行われているが, 単純性潰瘍4例では1例が大腸癌の疑いにて腸管切除が行われているほか手術および入院の既往はなく, 臨床的に腸管ベーチェット病と異なる経過であった.

We report results of a retrospective chart review to evaluate factors predicting short-term outcome of patients with ulcerative colitis treated by corticosteroids. Between January 1992 and December 1997, we treated 71 patients with ulcerative colitis (44 with severe and 27 with moderately severe disease). Forty-nine patients were treated by conventional prednisolone therapy and 22 patients by steroid pulse therapy. There were no differences in clinical or endoscopic improvement between the two treatments. Clinical examination showed that 41 patients entered remission, 17 patients improved, and 13 patients did not respond. Endoscopically, 26 patients entered remission, 30 patients improved, and 15 patients did not respond. Extent of disease, type of disease (first attack, relapsing, or chronic active type), and endoscopic findings were factors useful in predicting short-term outcome of medical treatment.

患者は51歳の女性で, 主訴は突然の腹痛と水様便. 小腸造影で回腸末端に全周性の狭窄と縦走潰瘍を認め, Crohn病の疑いにてIVH・栄養療法を開始した. しかし, 症状は軽快せず, 蛋白漏出性胃腸症とイレウス症状が持続したため, ステロイド投与と絶食による治療を開始し, 蛋白の漏出と腹部症状は寛解したが, イレウス症状は持続した. 腹部血管造影を施行したところ上腸間膜動脈の末梢側での閉塞と側副血行路の発達を認め, 上腸間膜動脈閉塞症と診断, 側副血行の存在を確認し, 狭窄部を含めた小腸部分切除術を施行した. 組織学的には狭窄部にUL-IIIの潰瘍を認め, 潰瘍底の肉芽化が著しく壁の肥厚を認めた. 鉄染色ではヘモジデリンを貪食したマクロファージを認めた. 合併切除した腸間膜の動脈は内膜が肥厚し内腔が狭窄していた. 腹部血管造影検査にて, 上腸間膜動脈閉塞症と診断した1例を経験したので報告する.

The aim of the present paper was to determine the efficacy and potential of autofluorescence imaging (AFI) colonoscopy for patients with ulcerative colitis. Fifteen biopsy specimens were taken from endoscopic remission colonic mucosa. Eight specimens were AFI positive and seven specimens were AFI negative. While most of the histological activity findings for AFI-positive samples were moderate active (6/8, 75.0%), most of the findings for AFI-negative specimens were mild active (6/7, 85.7%). AFI findings for colitis-associated cancer or dysplasia are still unclear. Further prospective studies are needed to investigate the relationship of autofluorescence findings and recurrence rate.

We recently treated a patient with intractable ulcerative colitis complicated with Pneumocystis carinii pneumonia in whom sulfamethoxazole/trimethoprim caused pneumonitis. The pneumonitis was difficult to differentiate from worsening of the infection or the appearance of another opportunistic infection. The patient's history of sulfasalazine (sulfonamide)-induced pneumonitis made diagnosis possible. The CD4/CD8 ratio of lymphocyte subsets in bronchoalveolar lavage fluid was decreased at the diagnosis of Pneumocystis carinii pneumonia and this ratio had increased when drug-induced pneumonitis was diagnosed. Topical administration of beclomethasone dipropionate by enema was a safe and effective for the treatment of such a compromised patient with active colitis.

外来にて経過観察中に再燃をきたした潰瘍性大腸炎中等症6例に対して,ステロイド・パルス療法を行った.対象は男性5例,女性1例であり.左側大腸炎型4例,全大腸炎型2例である,年齢は25歳から49歳で,平均34歳である.パルス療法としては,1日量としてmethyl-prednisolonelgを補液に混じて点滴静注した.3日間連日点滴した後4日間休薬し,上記7日間を1コースとして,3例に1コース,3例に2コースのステロイド・パルス療法を行った.その結果,臨床的に緩解3例,有効1例,無効2例であり,有効および緩解例4例において入院が回避された.

SUMMARY 1. Phenotypical heterogeneity of macrophages infiltrating the colonic mucosa of patients with ulcerative colitis has been shown in many reports. The functional diversity of macrophages in inflamed colonic mucosa remains unclear. 2. Intestinal macrophages have been characterized by immunohistochemical staining and their ability to generate free oxygen radicals in inflamed and non-inflamed mucosa. 3. No correlation was found between RFD1 (activated dendritic cells), RFD7 (tissue macrophages) or RFD9 (epithelioid cells, giant cells in association with granuloma) positivity and either CD68 or human histocompatibility complex class II antigen (HLA-DR) positivity. The proportions of RFD7- and RFD9-positive cells were significantly increased in inflamed colonic mucosa. Nitroblue tetrazolium-reducing mononuclear cells were CD68 or RFD7 positive but they were rarely positive for HLA-DR and RFD1. 4. These results suggest that nitroblue tetrazolium-reducing macrophages are (scavenger) macrophages.

Infiltrating leucocytes are activated to generate reactive oxygen species or to produce several molecules in inflamed colonic mucosa. To clarify the phenotypical and functional properties of activating cells in colitic mucosa, 23 patients with ulcerative colitis and 13 controls were studied using a combined method for determining in situ nitroblue tetrazolium reducing activity and immunohistochemical characterization. Antibodies 25F9 (anti-macrophage), EG2 (anti-eosinophil cationic protein), MAC387 (anti-calprotectin, expressed by activated myeloid-histiocytes lineage), and MAC-1 (anti-CD11b) were used. The proportion of EG2, calprotectin, and CD11b-positive cells were significantly increased in inflamed mucosa. The proportion of EG2, calprotectin, and CD11b-positive cells significantly correlated with the histological degree of inflammation. Proportion of EG2-positive cells but not calprotectin nor CD11b-positive cells was significantly correlated with nitroblue tetrazolium reducing activity. Aggregated cells reducing nitroblue tetrazolium seen in severely inflamed mucosa were found to be EG2 positive. Most of the calprotectin-positive cells were 25F9 negative. In addition to activation of neutrophils and macrophages, eosinophil activation has been shown to be involved in inflamed colonic mucosa.

クローン病の実験モデルである2,4,6-trinitrobenzene sulfonic acid(TNBS)大腸炎を作成し,塩酸Azelastine(AZ)を投与して病変粘膜局所における免疫担当細胞の動態を免疫組織化学的に検討した.TNBS大腸炎群の潰瘍形成部ではICAM-1,Mac-1陽性の単核球の強い浸潤があり,隣接した粘膜固有層にはICAM-1陽性の血管内皮細胞とLFA-1,Mac-1陽性の単核球の増加がみられた.AZ投与群では,潰瘍形成を示したのは5例中1例のみであった.肉眼的に炎症のない粘膜においては,TNBS大腸炎群に比べICAM-1の発現とLFA-1,Mac-1陽性細胞は軽度に認められるのみであった.IgG,IgE含有細胞および好酸球数も有意に低下していた(p

1. A controlled-release preparation of mesalazine microgranules (PentasaR; Ferring AS, Vanlose, Denmark) releases the active ingredient over a wide area from the small intestine to the rectum and is consequently expected to bring about therapeutic benefits to patients with ulcerative colitis and Crohn's disease. 2. Mesalazine microgranules (50 or 150 mg/kg per day) were administered orally to each rabbit with carrageenan-induced colitis for six weeks. Its inhibitory effect on colonic mucosal damage was assessed in terms of the microscopic damage scores, leukotriene B4 concentrations and concentrations of mesalazine derivatives. 3. At the end of the experiment, the mesalazine 150 mg group had gained a significantly greater bodyweight than the control group. Microscopic damage was significantly lower in the 150 mg group than in the untreated control group. Tissue concentrations of 5-aminosalicylic acid and acetyl-5-amino-salicylic acid in the small and large intestine were higher in the 150 mg group than in the 50 mg group. Mucosal leukotriene B4 levels tended to be lower in rabbits receiving the larger dose of mesalazine. 4. The present study indicates that slow release 5-amino-salicylic acid at the larger dose reaches the large bowel in sufficiently high concentrations following oral administration and significantly reduces carrageenan-induced colitis in the rabbit.

クローン病に対する内科的緩解維持療法の有用性についてretrospectiveに検討した.対象は緩解期クローン病60例であり, 男性39例, 女性21例である.罹患範囲別には大腸型11例, 小腸型20例, 小腸大腸型29例である.栄養療法, 薬物療法およびこれらの併用療法による緩解維持効果に関して検討した.観察期間は214日から3,365日であり, 平均2,873日である.性別および罹患範囲別に有意な累積緩解率の差はみられなかった.合併症を有する症例では, 有意に累積緩解率が低下した.治療法別の累積緩解率では有意差は認められなかったが, 罹患範囲別に小腸大腸型においては併用療法が栄養療法に比して有効である傾向が認められた.

Objective Eosinophilic esophagitis (EoE) is diagnosed by the presence of dysphagia and intraepithelial eosinophilic infiltration of ≥15 per high-power field (HPF). EoE should be distinguished from proton pump inhibitor-responsive esophageal eosinophilic infiltration (PPI-R EEI) in patients that are responsive to PPI treatment. The aim of this study was to determine the prevalence of EoE and PPI-R EEI in Japanese patients in a multicenter study. Methods Ten hospitals participated in this study. Esophageal biopsy was performed when the patients had typical EoE symptoms or when endoscopic findings revealed a typical EoE appearance. EEI was defined as the intraepithelial eosinophilic infiltration of ≥15 per HPF. Patients with EEI received rabeprazole for 8 weeks to distinguish EoE from PPI-R EEI. Results A total of 13,634 subjects that underwent upper gastrointestinal endoscopy because of further examination or as a routine checkup were enrolled. Seventy-one (0.5%) patients suspected with EoE were examined by biopsy. A histological examination of 7 (9.9%) cases revealed EEI. Two of these 7 patients showed no symptoms and the other 5 were treated with PPI. Two (0.01%) patients were diagnosed with EoE and 3 (0.02%) with PPI-R EEI. Conclusion EoE and PPI-R EEI were rare in Japanese patients that underwent upper gastrointestinal endoscopy.

The traditional Japanese medicine rikkunshito ameliorates the nitric oxide-associated delay in gastric emptying. Whether rikkunshito affects gastric motility associated with 5-hydroxytryptamine (serotonin: 5-HT) receptors or dopamine receptors is unknown. We examined the effects of rikkunshito on the delay in gastric emptying induced by 5-HT or dopamine using the phenol red method in male Wistar rats. 5-HT (0.01–1.0 mg kg−1, i.p.) dose dependently delayed gastric emptying, similar to the effect of the 5-HT3receptor agonist 1-(3-chlorophenyl) biguanide (0.01–1.0 mg kg−1, i.p.). Dopamine also dose dependently delayed gastric emptying. The 5-HT3receptor antagonist ondansetron (0.04–4.0 mg kg−1) and rikkunshito (125–500 mg kg−1) significantly suppressed the delay in gastric emptying caused by 5-HT or 1-(3-chlorophenyl) biguanide. Hesperidin (the most active ingredient in rikkunshito) suppressed the 5-HT-induced delayed gastric emptying in a dose-dependent manner, the maximum effect of which was similar to that of ondansetron (0.4 mg kg−1). The improvement obtained by rikkunshito or ondansetron in delaying gastric emptying was completely blocked by pretreatment with atropine. Rikkunshito appears to improve delay in gastric emptying via the antagonistic action of the 5-HT3receptor pathway.

SUMMARY In this study the effect of K-76. a sesquiterpcne compound with anticomplementary activity isolated from a fungus culture, on carrageenan-induced colitis was studied from biochemical, histological and immunohistopathological aspects. K-76 suppressed epithelial cell loss, crypt abscess formation, inflammatory cell infiltration, mucosal atrophy, and ulceration. Immunohistochcmical examination of the colonic mucosa showed that the number of IgG- and IgM-positive plasma cells and the staining intensity for IgG and C3 were increased in carrageenan-induced colitis, but these changes were inhibited by K-76. Besides, serum mucoprotcin concentrations and CH50 levels were lower in the animals treated with carrageenan alone. K-76 exerted multifunctional activity, although its mechanisms of action remain obscure.

虚血性大腸炎は,血管側因子に起因する大腸の血流低下および腸管側因子に起因する腸管内圧の亢進などが複雑に関連し,腸管壁の傷害をひきおこす症候群である.近年,本邦において増加しており,まれな疾患ではなくなっているが,なお,その病因に関しては不明な点が少なくない.また,大腸内視鏡検査の普及に伴い,軽症例の診断が可能となり,このために若年発症例が少なくないことが判明した.臨床的に重要なことは,腸管壊死の発生を早期に診断し,適切な治療法を選択することにある.

Various different clinical indices (CI) and endoscopic indices (El) have been used to evaluate the clinical disease activity of ulcerative colitis (UC). However, no standardized CI or El of UC has been established. The aim of the present study was to determine whether or not any of the CI and/or EI for assessing the disease activity of UC could be established as a standard.The most frequently used CI and EI were identified from 100 published clinical trials dealing with UC, and representative CI and El were selected. Seventy-four patients were enrolled in this study and their CI and El were assessed prior to treatment and at 2, 4 and 8 weeks after treatment. Furthermore, changes over time and relationships among the indices were analyzed. In this study, the clinical activity index (CAI), the disease activity index (DAI), the Lichtiger index (LI) and the Seo index were selected as the representative CI, and the Baron score and the Rachmilewitz endoscopic index (REI) were selected as the representative EI.A significant decrease in all the CI and El was observed after treatment, as compared with the baseline values. Moreover, there were positive relationships among the CI and between the CI and El.Our results demonstrated that all the CI and El examined were almost equally useful for evaluating disease activity in UC patients. Further studies may help to determine which of the indices is the most suitable for use in UC clinical trials.

The complement inhibitor K-76 (Otsuka Pharmaceutical Co., Osaka, Japan) was clinically evaluated as a new drug for treatment of active stage ulcerative colitis (UC). As monotherapy, K-76 proved effective in four of five cases. Furthermore, in patients with active stage UC that continued despite administration of corticosteroid hormone and salicylazosulphapyridine (so-called refractory UC), concomitant administration of K-76 was effective in seven of 21 cases. Thus, we believe that the multifunctional agent K-76 will provide clinicians with a new therapeutic approach to inflammatory bowel diseases, including UC and Crohn's disease.

Crohn病102症例中肛門病変合併は30例(29.4%)にみられた.本症における消化管,あるいは全身的症状の出現以前における肛門病変の出現は7例(23.3%)であり,このうち大腸型Crohn病の5例中4例は肛門周囲膿瘍・痔瘻に至っている.肛門病変の種類別頻度は,肛門周囲膿瘍23例(76.6%),skin tag 6例(20%),直腸腔瘻3例(10%)である.Crohn病の腸管病変別の頻度は小腸型14例(47%),小腸・大腸型6例(20%),大腸型10例(33%)であり,これらのうち大腸病変を含有する場合においては肛門病変は53.3%を占めた.内科的治療と肛門病変との関連性は認められないが,Crohn病発症の早期の段階のdisease activityの高い時期に出現する傾向が強く,初期の治療の重要性が示唆された.

Prostaglandin (PG) E2 promotes gastrointestinal carcinogenesis and tumor progression. We determined the correlations between pattern of expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a catabolic enzyme for biological inactivation of PGE2, in gastric adenocarcinoma and various clinicopathological factors and patient outcome in an attempt to elucidate its biological significance. In 35 of 71 cases of gastric adenocarcinoma, expression of 15-PGDH protein was reduced in tumor tissues. Multivariate analysis revealed reduction of 15-PGDH expression to be an independent predictor of poor survival. The proportion of Ki67-positive cells in 15-PGDH-negative adenocarcinoma was higher than that in 15-PGDH-positive adenocarcinoma. No differences were found in clinicopathological parameters between patients with cyclooxygenase-2 (COX-2)-positive tumors and those with COX-2 negative tumors. In an in vitro study, use of specific siRNA to silence 15-PGDH or a specific inhibitor of 15-PGDH enhanced cell proliferation in the gastric cancer cell line AGS, which expresses 15-PGDH. These findings suggest that reduction of 15-PGDH is an independent predictor of poor survival associated with enhancement of cell proliferation in gastric adenocarcinoma. (Cancer Sci 2009)

Crohn's disease is associated with increased permeability of the intestine even in quiescent patients. Increased intestinal permeability may cause dysregulated immunological responses in the intestinal mucosa that leads to chronic intestinal inflammation. Tight junction proteins contribute to intestinal permeability, and functional abnormality and dislocation of such proteins may cause increased intestinal permeability. We studied the expression of tight junction proteins Rab13, vasodilator-stimulated phosphoprotein (VASP), zonula occludin-1 (ZO-1), and F-actin in the intestinal epithelium of patients with inactive inflammatory bowel disease. Surgical samples were obtained from 10 controls (without inflammatory bowel disease), 10 patients with Crohn's disease and 7 patients with ulcerative colitis. F-actin was visualized with fluorescent phalloidin. Tight junction proteins were visualized by an immunofluorescence method. Rab13, VASP, and ZO-1 were found in apical tight junctions in normal epithelium but were dislocated to the basolateral position in patients with inactive Crohn's disease, whereas the structure of F-actin was maintained in inactive mucosa. In patients with ulcerative colitis, these tight junction proteins were not dislocated. Latent dislocation of tight junction proteins in the inactive mucosa of patients with Crohn's disease may permit the invasion of gut antigens to initiate and perpetuate altered immune response.

We investigated the efficacy of surveillance colonoscopy using narrowband imaging as a handy method of optical pancolonic chromoendoscopy, and the potential of autofluorescence imaging colonoscopy for patients with ulcerative colitis.

Helicobacter pylori-induced immune responses are skewed toward a T helper (Th) 1 phenotype. IL-17-producing Th17 cells have recently been discovered, and we examined the role of IL-17A in H. pylori-induced gastritis. Six months after inoculation with H. pylori, the mice received an intraperitoneal injection of recombinant IL-17A, anti-IL-17A antibody or irrelevant IgG(2a) for 3days. H. pylori infection markedly increased mRNA for IL-17A. Double immunofluorescence studies showed that IL-17A proteins were expressed on CD4(+) T cells, macrophages, and dendritic cells. H. pylori infection elevated mRNAs for IL-12, IFN-gamma, and TNF-alpha with increase in myeloperoxidase activity, whereas it did not affect mRNAs for IL-4 and IL-5. Neutralization of IL-17A elevated mRNAs for IFN-gamma and TNF-alpha, and myeloperoxidase activity, whereas recombinant IL-17A had a tendency to reduce these parameters. In conclusion, IL-17A exerts anti-inflammatory effects on H. pylori-induced gastritis through suppression of Th1 differentiation.

Leukocytapheresis (LCAP) has been advocated as a treatment for moderate to severe active ulcerative colitis (UC) in Japan. To clarify the predictive factors for a rapid response to LCAP treatment, we conducted a multicenter prospective open-label study. A total of 105 patients with UC were analyzed. LCAP was performed using a Cellsorba EX column once a week for 5-10 sessions. The response was evaluated by the clinical activity index (CAI). When the CAI score decreased to less than half the pretreatment value or to less than 5 points within 3 weeks, the patient was considered to be a rapid responder. The average CAI significantly decreased from 11.7 to 4.2 (P < 0.01). Seventy-four percent of the patients responded to the therapy, and 53% of these patients were rapid responders. The following significant factors correlated with the rapid LCAP response: (i) steroid resistance (P < 0.05), (ii) severe disease indicated by a CAI score greater than 11 (P = 0.05), (iii) disease duration of less than 1 year (P < 0.05), and (iv) C-reactive protein levels before treatment (P < 0.01). These results suggest that the early initiation of LCAP is beneficial in patients with steroid-resistant UC.

One hundred and twenty-one ulcerative colitis patients diagnosed during the period of 1984 to 1988 were examined endoscopically on repeated occasions. Forty-six patients had total colitis, 56 had left-sided colitis, 15 had proctitis, and 4 were postoperative patients. When classified according to their macroscopic findings, 28 of the patients had the polyposis type of this disease, 88 had the atrophic type, and 5 had the mixed type. Longitudinal ulcers were found in 9 patients, occuring usually in the sigmoid colon. There was no pathological evidence of ischemic changes in these 9 patients. Mucosal bridges were found in 13 of the patients with total colitis, occurring somewhere from the cecum to the rectum. The mucosal bridges tended to be present during the mildly active stage of the disease. Red spots, which sometimes looked like vascular spiders, were found in 10 patients. The spots tended to appear before the disease went into the inactive stage. Histological observation showed regenerating vessels, sometimes with intramucosal bleeding; therefore the spots seemed to be intractable changes.

患者の受容性を向上させるためPEGの服用量を2Lよりもさらに減量するための改良を試みた.すなわち,PEG併用法においてPEG服用開始後の排便回数が4回あった時点で服用を中止するという方法(PEG変法)をretrospective studyより設定し,100人の患者に本方法を行いPEG併用法を行った100人と比較検討した.その結果,服用量はPEG併用法の2000mlに対して1710±280ml(1000-2000m1)と有意(p

Pathogenic bacterial components play critical roles in initiation of gastrointestinal inflammation via activation of intracellular signaling pathways which induce proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta. Lansoprazole (LANSO), a proton pump inhibitor, has been widely used for the treatment of peptic ulcers and reflux esophagitis due to its potent acid-suppressive effect. It has also been reported to have anti-inflammatory effects. In this study we investigated the effects of LANSO on the production of TNF-alpha and IL-1beta induced by lipopolysaccharide (LPS) and Helicobacter pylori water-soluble extract (HpWE) in the human monocytic cell line (THP-1). LANSO (100 microM) significantly reduced mRNA expression and production of TNF-alpha and IL-1beta by THP-1 cells stimulated by LPS and HpWE. LANSO inhibited phosphorylation and degradation of inhibitory factor kappaB-alpha (IkappaB-alpha) and phosphorylation of extracellular signal-regulated kinase (ERK) induced by LPS and HpWE in THP-1 cells. These findings suggest that LANSO exerts anti-inflammatory effects by suppressing induction of TNF-alpha and IL-1beta via inhibition of nuclear factor (NF)-kappaB and ERK activation.