Absent X-linked inhibitor of apoptosis protein expression in T cell blasts and causal mutations including non-coding deletion.

BACKGROUND: X-linked inhibitor of apoptosis protein (XIAP) deficiency is one of inborn errors of immunity characterized by recurrent hemophagocytic lymphohistiocytosis and refractory inflammatory bowel disease (IBD), mimicking Crohn's disease. The aim of this study is to make an accurate diagnosis of XIAP deficiency based on genetic and XIAP expression studies and to investigate endoscopic findings shared by patients with this disease. METHODS: Four male patients with recurrent hemophagocytic lymphohistiocytosis and long-term refractory IBD were studied for the diagnosis of XIAP deficiency. Endoscopic findings of the four patients were also studied in parallel. RESULTS: These four patients were diagnosed with XIAP deficiency based on the absent XIAP expression in cultured T-cell blasts. Sequence analysis of the responsible gene, XIAP, demonstrated two novel nonsense mutations of p.Gln114X and p.Glu25X, and a previously reported nonsense mutation of p.Arg381X. Although no mutations in the coding region were detected in the fourth patient, further studies demonstrated a novel 2,199 bp deletion encompassing non-coding exon 1, presumably affecting transcription and stability of XIAP mRNA. All of the patients eventually underwent hematopoietic stem cell transplantation, leading to a complete or partial remission of IBD. These four patients shared an endoscopic finding of multiple wide and longitudinal ulcers with straight and non-raised edge in the colon. CONCLUSIONS: X-linked inhibitor of apoptosis protein expression in T-cell blasts could facilitate the diagnosis of this disease, especially with causal mutations in non-coding regions.

Effectiveness and Persistency of Ustekinumab Treatment for Ulcerative Colitis: A Phoenix retrospective Cohort Study.

Background: Real-world data regarding ustekinumab (UST) for ulcerative colitis (UC) particularly in biologics-naïve patients is currently limited. This study aimed to elucidate the real-world effectiveness and safety of UST for UC. Methods: Overall, 150 patients with UC treated with UST from March 2020 to January 2023 were enrolled across 7 referral hospitals. To assess the clinical efficacy and persistence of UST, retrospective analyses were conducted from weeks 8 to 56. Predictive factors concerning the response and persistence of UST were examined through univariate and multivariate analyses. Results: Of the 150 patients, 125 received UST for remission induction, including 36% biologics-naïve. The response and remission rates were 72.8% and 56.0% at week 8 and 73.2% and 63.4% at week 56, respectively. Biologics-naïve patients represented higher response and remission rates at week 8 (84.4% and 73.3%) than those with biologics exposure (66.2% and 46.2%). Patients with prior antitumor necrosis factor (anti-TNF) and vedolizumab (VDZ) exposure had relatively lower response and remission rates (34.5% and 24.1%, respectively). The 1-year cumulative persistence rate was 84.0%. Multivariate analysis revealed that the chronic continuous type and prior anti-TNF and VDZ exposure were negative predictive factors for week 8 responsiveness. Clinical response at week 8 was a predictor of 1-year persistence. Adverse event incidence remained notably low at 6.4%. Conclusions: This study highlights the safety and effectiveness of UST as an induction and maintenance therapy for UC. Chronic continuous type and previous anti-TNF and VDZ exposure negatively contributed to short-term effectiveness, whereas short-term effectiveness provided good persistency.

[Clinicopathological study of acute esophageal mucosal lesion].

Acute esophageal mucosal lesion (AEML) is a comprehensive disease that includes necrotizing esophagitis and acute erosive esophagitis, which result in upper gastrointestinal bleeding. However, little is known about AEML. We examined the clinicopathological features of 57 AEML cases. AEML presented as acute diffuse esophagitis showing an endoscopically erosive mucosa. The disease did not include corrosive injury, radiation-induced damage, infectious esophagitis, or acute exacerbation of chronic gastroesophageal reflux disease. AEML predominantly affected elderly men, and upper gastrointestinal bleeding was the frequent presenting symptom. Severe underlying diseases such as cranial nerve disease or pneumonia were observed in 98% of the patients. Esophageal sliding hernia and gastroduodenal ulcers were endoscopically observed in 67% and 63% of the patients, respectively. Deaths due to exacerbation of the underlying diseases accounted for 16%. Most cases rapidly improved with conservative management using a proton pump inhibitor or an H2 blocker. Therefore, AEML should be considered a disease having characteristics different from those of common gastroesophageal reflux disease.

Effectiveness and Factors Associated with Response to Golimumab in Japanese Patients with Ulcerative Colitis in Real Clinical Practice: The Phoenix Study.

Introduction: There have been limited reports on the clinical efficacy of golimumab (GLM) in Japanese patients with ulcerative colitis (UC) in real clinical practice. This study aimed to explore the real-life effectiveness and factors associated with response to GLM in Japanese patients with UC. Methods: This observational, retrospective, multicenter study was conducted in hospitals with expertise in inflammatory bowel disease treatment. Sixty-three patients treated with GLM and active UC were included in the analysis. Clinical remission (CR) (partial Mayo (pMayo) score ≤2) in the induction and maintenance phases after GLM treatment and associated factors were evaluated. Results: The proportion of patients achieving CR in the induction and maintenance phases was 41.3% (26/63) and 46.0% (29/63, the last observation carried forward method was used for patients who discontinued treatment for reasons other than inadequate response), respectively. The median pMayo score was 5 (interquartile range (IQR): 4-6) at baseline, 3 (IQR: 1-5) in the induction phase, and 1 (IQR: 0-3) in the maintenance phase. Hemoglobin, platelet, and C-reactive protein levels changed, consistent with the pMayo score. Multivariate logistic analysis revealed that biologic-naive status was an independent factor associated with CR in the induction (p = 0.0200) and maintenance (p = 0.0459) phases, and a disease duration of >60 months until GLM initiation was associated with CR in the induction phase (p = 0.0427). Conclusions: The effectiveness of GLM in daily clinical practice has been confirmed in Japanese patients with active UC. Biologic-naive patients responded more to GLM in the induction and maintenance phases, and patients with disease duration of >60 months until initiation of GLM were more responsive in the induction phase.

Paneth cells regulate both chemotaxis of immature dendritic cells and cytokine production from epithelial cells.

Paneth cells in the small intestine are able to sense luminal bacteria and secrete granules that contain antibacterial peptides. Human defensin (HD)-5 and -6 are antimicrobial peptides found in human Paneth cell granules, and are major bactericidal components. We investigated whether any constituents in the Paneth cell secretions showed chemotactic activity or stimulated cytokine secretion from intestinal epithelial cells, and assessed to what extent HD-5 and -6 were responsible for these activities. The secretions from human Paneth cells and recombinant HD-5 and -6 were evaluated to elucidate their effects on the chemotaxis of dendritic cells (DCs) in a migration assay. The Paneth cell secretions were chemotactic for immature DCs at concentrations ranging from 10 to 1,000 µg/ml. HD-6 was active at 100 ng/ml, but HD-5 was not. Next, the stimulation of cytokine production by the T84 intestinal cell line was assessed using ELISA and/or an antibody array. The secretions more strongly stimulated interleukin (IL)-8 production than did the defensin peptides, and induced production of various cytokines by the antibody array. The secretions were also analyzed by high performance liquid chromatography (HPLC) and mass spectrometry (MS) in order to determine the components. A large number of molecules was found in the secretions, and HD-5 was identified as an immature propeptide. In conclusion, some constituents other than defensin in human Paneth cell secretions activated the migration of DCs and induced the production of inflammatory cytokines. Therefore, Paneth cells may play a role in the innate immunity associated with adaptive immune responses.

A new antimesenteric functional end-to-end handsewn anastomosis: surgical prevention of anastomotic recurrence in Crohn's disease.

BACKGROUND: Recurrence of Crohn's disease usually occurs at anastomotic sites. OBJECTIVE: A new anastomosis technique (Kono-S anastomosis) designed to minimize anastomotic restenosis was compared with conventional anastomoses. DESIGN AND SETTINGS: The Kono-S anastomosis technique was first used for Crohn's disease in 2003 at the Asahikawa Medical University Hospital. The resection is accomplished by transecting the bowel with a linear cutter so that the mesentery side is located in the center of the stump. Both stumps are sutured to create a supporting column to maintain the diameter and dimension of the anastomosis. Longitudinal enterotomies are made at the antimesenteric sides of the 2 segments of intestine. The side-to-side antimesenteric anastomosis is then performed in transverse fashion. The medical records and follow-up details of all patients undergoing this procedure were reviewed. PATIENTS: : From 2003 to 2009, 69 patients with Crohn's disease who underwent Kono-S anastomosis (group S) were compared with 73 historical patients with Crohn's disease who underwent conventional anastomosis (group C) from 1993 to 2003. MAIN OUTCOME MEASURES: A Kaplan-Meier analysis of the follow-up data on surgical recurrence at the anastomosis was performed. The endoscopic recurrence score at the anastomosis was calculated. RESULTS: The median endoscopic recurrence score in group S was significantly lower than that in group C (2.6 vs 3.4; P = .008). The Kaplan-Meier analysis showed a lesser probability of anastomotic surgical recurrence in the S group at 5 years (0% vs 15%; P = .0013). The absence of postoperative infliximab did not affect the restenosis rate in group S. LIMITATIONS: This study was limited by its historical retrospective nature. CONCLUSION: The Kono-S anastomosis appears to be effective in preventing anastomotic surgical recurrence in Crohn's disease.

Endosopic autofluorescence imaging is useful for the differential diagnosis of intestinal lymphomas resembling lymphoid hyperplasia.

BACKGROUND: A method for the differential diagnosis of intestinal lymphomas resembling lymphoid hyperplasia (LH) by endoscopy remains to be clearly established. OBJECTIVE: To evaluate the usefulness of autofluorescence imaging (AFI) in diagnosing intestinal lymphoma. SETTING: Single-center study. DESIGN: Prospective study. PATIENTS: One hundred forty-three samples obtained from the intestinal tissues of 21 patients with malignant lymphoma were included in the study. INTERVENTIONS: The terminal ileum and entire colon were observed using conventional endoscopy equipped with AFI. The AFI images were taken by 3 endoscopists and then were evaluated by 3 predominant color intensities; green, magenta, and blended. To quantify the strength of fluorescence captured by AFI, the area of the obtained biopsy specimens on images was manually traced, the signal density of either magenta or green was measured, and then the ratio of the reverse gamma value of green divided by that of magenta was defined as the Fluorescence index (F index). MAIN OUTCOME MEASUREMENTS: The ability to use AFI to distinguish intestinal lymphoma from normal or LH. RESULTS: The cell density is inversely proportional to the F index. The F index of lymphoma was significantly lower than that of normal mucosa or LH. The visual classification of AFI showed the overall accuracy in diagnosing lymphoma was 91.5%, and was well correlated with the F index. LIMITATIONS: Single-center study. CONCLUSIONS: AFI-embossed lymphoma lesions seemed as magenta and could be discriminated from LH or normal mucosa with a high overall accuracy through perception of the cell density of the lesion. Therefore, AFI is considered to be an effective procedure for determining the accurate stage and appropriate therapy in intestinal lymphoma.

A multicenter study of the efficacy and safety of leukocytapheresis therapy without concomitant systemic steroid treatment in patients with active ulcerative colitis.

We conducted a multicenter study to investigate the efficacy of leukocytapheresis (LCAP) without concomitant steroid therapy in active ulcerative colitis (UC) patients. Twenty patients were enrolled. LCAP was performed twice a week for 3 weeks. The results revealed a significant decrease of the Lichtiger's clinical activity index (CAI) from 11.7±2.6 at baseline to 6.6±4.1 after the therapy. The endoscopic index and serum C-reactive protein levels also decreased significantly after the therapy. Of the 20 patients, 15 (75%) were assessed as responders (CAI≤4 or ΔCAI≥3), and 7 (35%) achieved complete remission (CAI≤4). No serious adverse reactions were encountered. The results suggest that LCAP is an effective and safe option for patients with active UC who had not received systemic steroid treatment.

Efficacy and safety of a new vedolizumab subcutaneous formulation in Japanese patients with moderately to severely active ulcerative colitis.

BACKGROUND/AIMS: A subgroup analysis was conducted in Japanese patients with moderate to severe ulcerative colitis (UC) enrolled in the phase 3 VISIBLE 1 study, which evaluated the safety and efficacy of a new vedolizumab subcutaneous (SC) formulation. METHODS: Eligible patients received open-label infusions of vedolizumab 300 mg intravenous (IV) at weeks 0 and 2 in the induction phase. Patients with clinical response by complete Mayo score at week 6 entered the double-blind maintenance phase and were randomized to vedolizumab 108 mg SC every 2 weeks, placebo, or vedolizumab 300 mg IV every 8 weeks. The primary endpoint was clinical remission (complete Mayo score ≤ 2 points; no individual subscore > 1 point) at week 52. RESULTS: Of 49 patients who entered the induction phase, 22 out of 49 patients (45%) had clinical response at week 6 and were randomized to vedolizumab 108 mg SC (n = 10), placebo (n = 10), or vedolizumab 300 mg IV (n = 2). At week 52, 4 out of 10 patients (40%) who received vedolizumab SC had clinical remission versus 2 out of 10 patients (20%) who received placebo (difference: 20% [95% confidence interval, -27.9 to 61.8]). Two patients (2/10, 20%) who received vedolizumab SC experienced an injection-site reaction versus none who received placebo. CONCLUSIONS: Our results indicate that the efficacy of vedolizumab SC in a subgroup of Japanese patients with UC are similar with those in the overall VISIBLE 1 study population, and with those established with vedolizumab IV. The safety and tolerability of vedolizumab SC were generally similar to that established for vedolizumab IV. (ClinicalTrials.gov ID NCT02611830; EudraCT 2015-000480-14).

Long-Term Clinical Effectiveness of Ustekinumab in Patients With Crohn's Disease: A Retrospective Cohort Study.

Background: This study clarifies the long-term effectiveness of ustekinumab based on real-life data from Japanese Crohn's disease (CD) patients. Methods: A total of 137 patients were included, and 124 patients (90.5%) were exposed to anti-tumor necrosis factor-α agents. Results: The clinical remission rate at week 52 was 32.4% in moderate to severely active CD patients. The achievement of clinical remission for 8 weeks after ustekinumab therapy induction was associated with clinical remission at week 52. Ustekinumab persistence rate at week 104 was 81.4%. Conclusion: Ustekinumab is effective and persistent in CD patients with the previous treatment history of several biologics.

Effects of Helicobacter pylori infection on genetic instability, the aberrant CpG island methylation status and the cellular phenotype in Barrett's esophagus in a Japanese population.

Genetic or epigenetic alterations in Barrett's esophagus (BE) with/without Helicobacter pylori (H. pylori) infection remain unclear. We examined the effects of H. pylori infection on genetic instability (GIN), the CpG island methylation status and a biomarker related to BE carcinogenesis. We analyzed 113 Japanese individuals with endoscopically suspected BE. The patients included, Group CLE (n = 25): no specialized intestinal metaplasia (SIM) in a columnar lined epithelium (control); Group BE (n = 88): all had SIM. Microsatellite instability and a loss of heterozygosity as GIN, the methylation status at hMLH1, E-cadherin, p16 and APC, and immunoreactivity using a monoclonal antibody (mAb) Das-1, which specifically reacts with BE, were evaluated. Nine additional patients with BE were prospectively followed up for 2 years after successful H. pylori eradication. The frequency of GIN, methylation at E-cadherin and APC, and mAb Das-1 reactivity in Group BE was significantly higher than that in Group CLE (p < 0.0001, p < 0.0001 and p < 0.005, and p < 0.0001, respectively). Furthermore, GIN, E-cadherin methylation and mAb Das-1 reactivity showed a significantly higher incidence in patients with H.pylori infection than in those without H. pylori infection (p < 0.01, p < 0.005, and p < 0.01, respectively). Interestingly, the patients from Group BE were observed to change to a stable state of molecular alterations in 60% for GIN, 42.9% for E-cadherin methylation and 55.6% for APC methylation, or a reduction of mAb Das-1 reactivity was noted in 25% following eradication. H. pylori infection may therefore affect these molecular alterations associated with the pathogenesis of BE, to some degree, in the Japanese population.

An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment.

OBJECTIVES: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active ulcerative colitis (UC). However, with routine weekly treatment, it may take several weeks to achieve remission, and to date, the efficacy of a more frequent treatment schedule remains unknown. The aim of this study was to assess the clinical efficacy and safety of intensive GMA treatment in patients with active UC. METHODS: This was an open-label, prospective, randomized multicenter study to compare an intensive, two GMA sessions per week, with the routine, one GMA session per week. A total of 163 patients with mild-to-moderately active UC were randomly assigned to routine weekly treatment or intensive treatment. The maximum number of sessions of GMA permitted was 10. However, when patients achieved remission, GMA was discontinued. Remission rate at the end of the study, time to remission, and adverse events were assessed in both groups. RESULTS: Of the 163 patients, 149 were available for efficacy analysis as per protocol, 76 were in weekly GMA, and 73 were in intensive GMA. At the end of the study period, clinical remission was achieved in 41 of 76 patients (54.0%) in weekly GMA and in 52 of 73 patients (71.2%) in intensive GMA (P=0.029). The mean time to remission was 28.1+/-16.9 days in the weekly GMA treatment group and 14.9+/-9.5 days in the intensive GMA group (P<0.0001). Intensive GMA was well tolerated without GMA-related serious adverse side effects. CONCLUSIONS: Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients' morbidity time without increasing the incidence of side effects.

Efficacy and safety of abrilumab, an α4ß7 integrin inhibitor, in Japanese patients with moderate-to-severe ulcerative colitis: a phase II study.

BACKGROUND/AIMS: Inhibition of α4ß7 integrin has been shown to be effective for induction and maintenance therapy in patients with ulcerative colitis (UC). We investigated the effects of varying doses of the α4ß7 inhibitor abrilumab in Japanese patients with moderate-to-severe UC despite conventional treatments. METHODS: In this randomized, double-blind, placebocontrolled study, 45 UC patients were randomized to abrilumab 21 mg (n=11), 70 mg (n=12), 210 mg (n=9), or placebo (n=13) via subcutaneous (SC) injection for 12 weeks. The double-blind period was followed by a 36-week open-label period, in which all patients received abrilumab 210 mg SC every 12 weeks, and a 28-week safety follow-up period. The primary efficacy variable was clinical remission at week 8 (total Mayo score ≤2 points with no individual subscore >1 point). RESULTS: Clinical remission at week 8 was 4 out of 31 (12.9%) overall in the abrilumab groups versus 0 out of 13 in the placebo group (abrilumab 21 mg, 1/10 [10.0%]; 70 mg, 2/12 [16.7%]; 210 mg, 1/9 [11.1%]). In both the double-blind and open-label periods, fewer patients in the abrilumab groups experienced ≥1 adverse event compared with those in the placebo group. There were no cases of progressive multifocal leukoencephalopathy and no deaths. CONCLUSIONS: Abrilumab 70 mg and 210 mg yielded numerically better results in terms of clinical remission rate at Week 8 than placebo, with the 210 mg dose showing more consistent treatment effects. Abrilumab was well tolerated in Japanese patients with UC.

Sonic hedgehog derived from human pancreatic cancer cells augments angiogenic function of endothelial progenitor cells.

Hedgehog signaling is important in the pathogenesis of pancreatic cancer. Several recent observations suggest the involvement of sonic hedgehog (SHH) in postnatal neovascularization. We identified a novel role for SHH in tumor-associated angiogenesis in pancreatic cancer. Immunohistochemical analysis revealed that patched homolog 1 (PTCH1), both a receptor for and transcriptional target of hedgehog signaling, was expressed in a small fraction of endothelial cells within pancreatic cancer, but not in normal pancreatic tissue. When endothelial progenitor cells (EPC) isolated from human peripheral blood were cultured with supernatant from SHH-transfected 293 cells or pancreatic cancer cells, mRNA levels of vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 and angiopoietin-1 were significantly increased, whereas no such induction was observed in human umbilical vein endothelial cell (HUVEC) and human dermal microvascular endothelial cell (HMVEC). HUVEC tube formation was stimulated when cocultured with EPC, and preconditioning EPC with supernatant from KP-1 N pancreatic cancer cells highly expressing SHH significantly enhanced the effect. The effect was partially attenuated by specific inhibition of SHH with cyclopamine or a neutralizing antibody. These findings suggest that tumor-derived SHH can induce angiogenesis, and this is mediated by its effects on EPC specifically. Targeting SHH would be a novel therapeutic approach that can inhibit not only proliferation of cancer cells but also EPC-mediated angiogenesis.

Oral spherical adsorptive carbon for the treatment of intractable anal fistulas in Crohn's disease: a multicenter, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Anal fistulas are common in individuals with Crohn's disease (CD). We sought to evaluate the efficacy of oral spherical adsorptive carbon (AST-120) (Kremezin; Kureha Corporation, Tokyo, Japan) for the treatment of intractable anal fistulas in patients with CD. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, patients with CD and at least one active anal fistula under treatment were assigned to receive either AST-120 or placebo for 8 wk. Improvement was defined as a reduction of 50% or more from baseline in the number of draining fistulas observed at both 4 and 8 wk. Remission was defined by closure of all draining fistulas at both 4 and 8 wk. The Perianal Disease Activity Index (PDAI) and Crohn's Disease Activity Index (CDAI) were also assessed. RESULTS: In total, 62 patients were randomized, of whom 57 received AST-120 (N = 27) or placebo (N = 30). The improvement rate in the AST-120 group (37.0%) was significantly greater than that in the placebo group (10.0%) (P= 0.025). The corresponding remission rates were 29.6% and 6.7%, respectively (P= 0.035). PDAI significantly improved at both 4 and 8 wk with AST-120, compared to placebo (P= 0.004 and P= 0.005, respectively). CDAI was also significantly improved at both 4 and 8 wk in the AST-120 group, compared to the placebo group (P= 0.007 and P= 0.001, respectively). AST-120 treatment was well tolerated and no life-threatening adverse events were observed. CONCLUSION: AST-120 is useful for the control of intractable anal fistulas in CD patients.

Clinicopathologic implications of genetic instability in intestinal-type gastric cancer and intestinal metaplasia as a precancerous lesion: proof of field cancerization in the stomach.

To clarify field cancerization in the stomach by genetic alterations, we studied 83 cases of intestinal-type gastric cancer (GC) and paired intestinal metaplasia (IM) distant from GC and 39 cases of chronic gastritis with IM (CG-IM) for genetic instability (GIN). Microsatellite instability (MSI) and loss of heterozygosity (LOH) were evaluated at 5 microsatellite loci. The incidence of GIN was 21% (8/39) in CG-IM, 48% (40/83) in GC-IM, and 65% (54/83) in GC and showed a significant difference among these 3 categories. By tumor location, MSI showed the highest incidence in GC and GC-IM with the tumor located in the upper third of the stomach. GIN in GC and GC-IM significantly increased with the progression of tumor invasion from mucosal to advanced cancer. GIN, especially LOH, was more frequently detected in cases with vs without lymphatic or vascular invasion and lymph node involvement in GC and GC-IM. The GIN of GC and GC-IM was significantly similar in relation to clinicopathologic features. Biologic detection of GIN in IM may be a surrogate marker for GC risk and for clinical evaluation of malignant potential. The condition is consistent with the hypothesis of field cancerization in the stomach.

Functional role of metaplastic paneth cell defensins in Helicobacter pylori-infected stomach.

BACKGROUND AND AIMS: Chronic gastritis is caused by Helicobacter pylori infection, and gastritis is classified as inflammation, atrophy, and intestinal metaplasia. Detailed pathologic studies have shown that H. pylori settles on the surface of gastric mucosa, and that it is eliminated from metaplastic mucosa. However, its mechanism of natural protection is not well known. METHODS: Antimicrobial human enteric defensin expression was determined in the RNA and protein levels. Recombinant enteric defensins were produced with a bacterial expression system and their anti-H. pylori activities were assessed by bactericidal assay. RESULTS: Human enteric defensin (HD)-5 and HD-6 were detected in Paneth cells, which are observed in the gastric metaplastic mucosa as well as small intestinal epithelia. HD-5 protein was coexpressed with trypsin, which is considered to be an activating enzyme of HD-5. Less H. pylori was observed in the intestinal metaplasia with HD-5 expressing Paneth cells. The recombinant defensins showed killing activity against H. pylori at a low concentration in vitro. CONCLUSIONS: The human defensins that are expressed in the metaplastic Paneth cells eliminate H. pylori. Metaplastic change may be a purposive development of the human stomach.

[Inflammatory bowel disease--the role and issue of glucocorticoid].

We herein reviewed the clinical applications of glucocorticoid (GC) hormones to inflammatory bowel disease (IBD). In the therapeutic strategy for active ulcerative colitis, topical/systemic GC administration is still central during these fifty years. However, non -responders to GC are present at 30-40% of the active UC patients. We analyzed the expression of GC receptor isoform, namely hGRbeta, in peripheral blood mononuclear cells, and suggest the possibility that expression of hGRbeta, induced by proinflammatory cytokine IL-18, is closely related GC resistance in UC.

Psoriasiform and pustular eruption induced by infliximab.

Although antitumor necrosis factor (anti-TNF)-alpha therapy provides beneficial effects on various chronic inflammatory skin diseases including psoriasis, cutaneous side-effects have also been reported. We describe four patients who showed psoriasiform eruption following anti-TNF-alpha therapy (infliximab) for Crohn's disease. In all patients, Crohn's disease had responded well to infliximab. Three patients developed plaque-type psoriasiform eruption on the trunk and four extremities, while one patient showed pustular eruption on the palms and soles accompanied with plaque-type psoriasis. In all these patients, skin lesions subsided with topical application of corticosteroid ointment or psoralen plus ultraviolet A treatment.