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Background: Apheresis therapy involves the selective removal of leukocytes and is used to induce remission in ulcerative colitis (UC) patients. The aim of this study was to demonstrate the efficacy and safety of apheresis therapy for maintaining UC remission.Methods: We conducted a multicenter, prospective, randomised-control trial of patients with remitting UC induced by granulocyte and monocyte adsorption apheresis or leukocytapheresis. Patients were randomly assigned to the apheresis group (twice per month for 12 months) or the control group (no apheresis treatment) using a 1:1 allocation ratio. The primary endpoint was the rate of cumulative clinical remission (Mayo score ≤ 2) at 12 months. The secondary endpoints were the rates of clinical remission, endoscopic remission, and complete endoscopic remission at 12 months.Results: Between March 2013 and March 2017, 164 patients were enrolled. The cumulative remission rate at 12 months was 46.6% in the apheresis group and 36.4% in the control group (p = 0.1621). The rate of endoscopic remission at 12 months was significantly higher in the apheresis group than in the control group (42.5% vs. 25.9%) p = 0.0480). The rate of clinical remission (47.5% vs.32.1%, p = 0.0540) and complete endoscopic remission (33.8% vs.19.8%, p = 0.0513) tended to be higher in the apheresis than in the control group; however, the difference was not significant. No severe adverse events were observed in either group.Conclusions: Apheresis was well tolerated as maintenance therapy for UC although the cumulative clinical remission rate at 12 months was comparable between the apheresis and control groups. [ABSTRACT FROM AUTHOR]

Background: The 52-week safety and efficacy of adalimumab in Japanese patients with moderately to severely active ulcerative colitis were demonstrated in a placebo-controlled phase 2/3 trial. Data from patients who enrolled in the open-label extension study are presented.Methods: Remission and response per the full Mayo score (FMS) and the partial Mayo score (PMS), remission per the Inflammatory Bowel Disease Questionnaire (IBDQ) score, corticosteroid-free remission, and mucosal healing were assessed up to week 196 (week 208 for remission/response per PMS) of adalimumab treatment in patients who received one or more doses of adalimumab with use of a hybrid nonresponder imputation (hNRI) method. Nonresponder imputation was used for missing data up to the latest possible follow-up date for each patient, followed by observed case. Adalimumab trough concentrations were reported from week 52 to week 196 of treatment. Treatment-emergent adverse events were reported for all adalimumab-treated patients.Results: Two hundred sixty-six patients received adalimumab. At week 196 of treatment, remission and response rates per FMS, remission and response rates per PMS, remission rate per IBDQ score, mucosal healing rate, and corticosteroid-free remission rate were 19.2%, 32.2%, 22.5%, 32.5%, 33.1%, 30.5% (hNRI), and 40.5% (17/42; as observed), respectively. Serum adalimumab concentrations remained constant in patients receiving 40 mg every other week but increased in patients who underwent dose escalation. The safety profile was consistent with that in the 52-week study.Conclusions: The efficacy of adalimumab in Japanese patients with moderately to severely active ulcerative colitis was maintained for up to 4 years of treatment. No new safety signals were observed. [ABSTRACT FROM AUTHOR]

Background: Osteopenia and osteoporosis are considered to be extra-intestinal manifestations of inflammatory bowel disease (IBD). Anti-tumor necrosis factor (TNF)-α biologics have been introduced as novel medications for an active IBD. However, it is still not well documented whether anti-TNF-α affects the frequency of bone loss or abnormality of bone mineral markers among patients with IBD.Aims: This study was to investigate the biochemical basis of low bone mineral density (BMD) and increased turnover in IBD during infliximab (IFX) therapy.Methods: Forty patients with Crohn's disease (CD), 80 patients with ulcerative colitis (UC), and 65 age- and gender-matched controls were included. BMD was measured with dual-energy X-ray absorptiometry, and vitamins K and D were measured as serum undercarboxylated osteocalcin (ucOC) and 1,25-(OH)2D, respectively. Bone formation and resorption were based on measuring bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx), respectively.Results: Significantly lower BMD was found in patients with UC and CD as compared to controls (P < 0.05). BAP, 1,25-(OH)2D, ucOC, and NTx were significantly higher in CD patients, but not in UC patients as compared to controls (P < 0.05). Further, serum NTx level was significantly higher in CD patients who were receiving IFX as compared to CD patients who were not receiving IFX (P < 0.01).Conclusions: A lower BMD and higher bone metabolism markers were found in CD patients as compared to controls or UC patients. A significant increased serum level of NTx, a biochemical marker of increased bone resorption, was observed in CD patients during IFX therapy. [ABSTRACT FROM AUTHOR]

Purpose: The value of enteral nutrition (EN) as maintenance therapy in patients with quiescent Crohn's disease (CD) has not been fully evaluated. The purpose of this study was to review the efficacy of EN for the maintenance of remission in patients with quiescent CD. Methods: Seven prospective cohort studies evaluating the efficacy of EN for the maintenance of remission in quiescent CD were included. Three of the seven studies were randomized-controlled trials (RCTs). In all studies, patients used EN as a supplement or as a nocturnal tube feeding in addition to their normal food. Results: One study compared the efficacy of elemental diet and polymeric diet. Elemental and polymeric diets were equally effective for the maintenance of clinical remission and for allowing tapering and cessation of steroid therapy. The other six studies compared the outcomes between patients treated with and without EN. The maintained clinical remission rate at 1 year was significantly higher in patients treated with EN in four of the six studies. Quantitative pooling of the studies was not feasible due to a small number of RCTs and a narrative account of the study characteristics. Conclusions: Our review suggests that EN is useful for the maintenance of remission in patients with quiescent CD. However, there are several limitations in the reviewed studies. There are few RCTs. Further, the sample size is small, and the duration of intervention and follow-up is short. Large and well-designed RCTs should be conducted to rigorously evaluate the efficacy of EN for maintaining remission. [ABSTRACT FROM AUTHOR]

Background: Adalimumab is a fully human, monoclonal antibody against tumor necrosis factor that is approved in Western countries for the treatment of moderately to severely active ulcerative colitis (UC). Methods: This 52-week, phase 2/3, randomized, double-blind study evaluated adalimumab for induction and maintenance treatment in 273 anti-TNF-naive Japanese patients with UC who were refractory to corticosteroids, immunomodulators, or both. Patients received placebo, adalimumab 80/40 (80 mg at week 0, then 40 mg every other week), or adalimumab 160/80 (160/80 mg at weeks 0/2, then 40 mg every other week) in addition to background UC therapy. Results: At week 8, remission rates were similar among treatment arms, but more patients treated with adalimumab 160/80 achieved response (placebo, 35 %; 80/40, 43 %; 160/80, 50 %; P = 0.044 for 160/80 vs placebo) and mucosal healing (placebo, 30 %; 80/40, 39 %; 160/80, 44 %; P = 0.045 for 160/80 vs placebo) compared with placebo. At week 52, more patients receiving adalimumab 40 mg every other week achieved response (18 vs 31 %; P = 0.021), remission (7 vs 23 %; P = 0.001), and mucosal healing (16 vs 29 %; P = 0.015) compared with placebo. Week 8 response to adalimumab was associated with greater rates of response (61 %), remission (46 %), and mucosal healing (57 %) at week 52 relative to the overall population. Rates of serious adverse events were similar between treatment arms. Conclusions: Induction with adalimumab 160/80 mg led to early response and mucosal healing. Maintenance adalimumab had greater rates of long-term response, remission, and mucosal healing compared with placebo. No new safety signals were identified. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: In human blood, two monocyte populations exist, CD14++CD16− classical monocytes and CD14+CD16+ proinflammatory monocytes, which account for about 10% of total monocytes, but can expand to promote inflammatory conditions. CD14+CD16+ monocytes produce large amounts of inflammatory cytokines including TNF-α and IL-1. Adacolumn adsorptive carriers adsorb from the blood in the column most of the monocytes/macrophages and granulocytes and this has been associated with clinical efficacy in patients with active inflammatory bowel disease (IBD). This study was to investigate the CD14+CD16+ monocyte profile in patients with IBD and the impact of Adacolumn on this proinflammatory phenotype. METHODS: A total of 58 patients with ulcerative colitis (UC, N = 37) or Crohn's disease (CD, N = 21) together with 11 healthy controls were included in this study. Peripheral blood CD14+CD16+ monocytes were determined by three-color immunofluorescence and flow cytometry. RESULTS: The percentage of CD14+CD16+ monocytes in patients with active CD was significantly ( P= 0.0089) higher than the level in the control group, in patients with quiescent CD ( P= 0.0419) or quiescent UC ( P= 0.0063). Further, the percentage of CD14+CD16+ monocytes in patients with active UC who were on prednisolone (PSL) was less than the level in those not on PSL ( P < 0.0001), thus PSL might have a suppressive effect on CD14+CD16+ monocytes. Patients with active IBD were each given up to 10 Adacolumn granulocye/monocyte adsorption (GMA) sessions over an 8-wk period. The percentage of CD14+CD16+ monocytes decreased dramatically ( P= 0.0077 in UC and P= 0.0117 in CD) compared with entry levels. CONCLUSIONS: A significant reduction in peripheral CD14+CD16+ monocytes by GMA should mitigate the inflammatory drive and contribute to the clinical efficacy of this procedure. Reduction of CD14+CD16+ monocytes by corticosteroids was also seen. Hence, corticosteroids should enhance the efficacy of GMA. This is the first report on CD14+CD16+ monocytes being decreased by Adacolumn GMA in patients with IBD. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a useful strategy for treating various cancers. Details of the mechanisms of PDT have not been made clear yet. We intended to study the efficacy of PDT in relation to the cell cycle. HeLa S3 cells were synchronized by the thymidine block method. Cells in different cell cycle phases after release were treated with the water-soluble photosensitizer, ATX-S10(Na). The cellular viability after PDT was determined by the MTT assay. Intracellular levels of ATX-S10(Na) in different cell cycle phases were also determined. We found that cells in the S and G(2)/M phases were hypersensitive to PDT with ATX-S10(Na) in comparison with those in the G(1) phase, and that cellular levels of ATX-S10(Na) were increased in cells in the S and G(2)/M phases compared to those in the G(1) phase. We conclude that cellular ATX-S10(Na) levels differ among the different cell cycle phases, which is associated with the cell-cycle-dependent efficacy of PDT with ATX-S10(Na). [ABSTRACT FROM AUTHOR]

Active ulcerative colitis (UC) is associated with elevated granulocytes and monocytes/macrophages (GM) which show activation behavior and increased survival time. Further, fecal calprotectin (a stable neutrophil protein) level parallels intestinal inflammation and can predict UC relapse. Since GM are major sources of inflammatory cytokines and chemokines, they are suspected to have roles in the initiation and perpetuation of UC. Our objective was to investigated relationships between peripheral blood (PB) neutrophils, calprotectin, and UC disease activity. Full PB and calprotectin were determined in 69 healthy controls and 31 patients with UC, then 7 randomly selected patients received GM adsorptive apheresis (GMA) with Adacolumn, 10 sessions of 60-min duration each. Patients with UC had higher neutrophil counts (P < 0.001), but lower lymphocyte counts (P < 0.001) compared with controls. Further, fecal calprotectin levels showed a correlation with UC clinical activity index (CAI; P < 0.001) and mucosal inflammation (P < 0.001). Following GMA, there were falls in neutrophils (P < 0.02), CAI (P < 0.02) and calprotectin (P < 0.02). In conclusion, GM appear to contribute to intestinal inflammation and UC activity and reduction of these cells by GMA should benefit patients with active UC. Further, the correlations among calprotectin, UC activities, and PB neutrophils should serve as the basis for preemptive actions to control this disease. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the mechanism of cell death by photodynamic therapy (PDT) in the gastric cancer cell line MKN45 with focus on the mechanism of apoptosis. Gastric cancer cells (MKN45) were incubated with Photofrin for up to 24 h before exposure to He-Cd laser (441 nm, 1 J/cm2). Cell viability was assessed by the methyl-tetra-zolium assay after exposure to light. A 95% cell death (LD95) was measured with 10 microg/ml of Photofrin. DNA ladder formation and chromatin condensation were seen within 60 min. Caspase-3-like and caspase-9-like activities increased from 15 min after exposure to light. Reduction of rhodamine 123 uptake started at 30 min. Caspase-inhibitor VAD-fmk (10 mM) inhibited apoptosis, but did not influence cell viability. In conclusion, Photofrin-mediated PDT in the gastric cancer cell line MKN45 induces apoptosis within 60 min, and mitochondrial damage is likely as the first event of apoptosis. [ABSTRACT FROM AUTHOR]

OBJECTIVES: TNF-α has a major role in inflammatory bowel disease via two receptors, p55 (RI) and p75 (RII) expressed on many cell types, in particular neutrophils and monocytes (GM). Upon activation of these leukocytes, RI and RII are shed into the medium and can neutralize TNF. Accordingly, soluble RI and RII (s-RI/RII) are believed to have potent antiinflammatory actions. Further, in active UC, GM are elevated with activation behavior and recently adsorptive GM apheresis (GMA) in patients with severe UC was associated with a dramatic efficacy. In this study, we investigated the effects of GMA on serum s-RI/RII.METHODS: Thirty-one patients with UC, clinical activity index (CAI) 11.1 were treated with GMA by using the Adacolumn. In the column, leukocytes which bear the FcγR and complement receptors adhere to the column apheresis carriers (neutrophils, monocytes, and a small fraction of lymphocytes). One GMA session was 60 min at 30 mL/min and each patient could receive up to 11 sessions over 8 wk. Serum s-RI/II were measured in the blood at the column inflow (peripheral blood, time 0 and 60 min) and outflow at 60 min.RESULTS: Serum s-RI/RII showed strong correlation with CAI, r= 0.849 (p<0.001) and r= 0.867 (p<0.001), respectively and were greater than when patients were in remission or the levels in controls (p<0.001). s-RI/RII at the column outflow were higher compared with inflow (p<0.05) suggesting that RI/RII were shed from leukocytes which adhere to the carriers. Similarly s-RI/RII were significantly increased in the peripheral blood at the end of the 60 min GMA session compared with time 0. After 11 GMA sessions, CAI fell to remission level in 26 of 31 patients accompanied by falls of s-RI/RII.CONCLUSIONS: The sources of s-RI/RII are believed to be activated monocytes and neutrophils with further release when these leukocytes adhere to the column carriers. s-RI/RII released during GMA should contribute to the clinical efficacy of this procedure. [ABSTRACT FROM AUTHOR]

Abstract Purpose. We have previously reported that EPHB2 is overexpressed in gastric cancer; however, the expression profiles of its ligands, EFNB1 and EFNB2, are unknown. This study was designed to investigate the expression of EPHB2 and its ligands, EFNB1 and EFNB2, in human gastric cancer. Methods. Semi-quantitative RT-PCR using 32P was performed on human gastric cancer tissues and corresponding normal tissues (29 gastric cancer patients). Results. EPHB2 was more highly expressed in tumor tissues than in normal tissues in 21 out of 29 (72.4%), in gastric cancer patients ( P = 0.01); EFNB1 and EFNB2 were highly expressed in 21 out of 29 (72.4%) ( P = 0.037) and 14 out of 29 (48.3%) patients, respectively. The overexpression of EPHB2 was frequently detected in both well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma [10/13 (76.9%) and 9/14 (64.3%), respectively]. On the other hand, the overexpression of EFNB1 was more frequently detected in poorly differentiated adenocarcinoma than in well-differentiated adenocarcinoma [12/14 (85.7%) and 7/13 (53.8%), respectively. P =0.027]. Elevated levels of EPHB2 and EFNB1 were detected in substantial subsets of early gastric cancers. Genomic alterations to these three genes in gastric cancer specimens were either not found or rarely found except for several rare variations of EPHB2. Conclusions. These findings suggest that not only the expression of EPHB2, but the expression of its ligand EFNB1 may have some relation with the oncogenesis of gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract: Intra-abdominal desmoplastic small round cell tumor (IDSRT) is a rare neoplasm that develops in the abdominal cavity in young people. We experienced a 27-year-old man who visited with ascites of unknown cause. Compression of the colon was found by barium enema examination. On colonoscopic examination, diffuse white elevated lesions, about 5 mm in diameter, surrounded by rubedo, so-called aphthoid lesions, were also observed. IDSRT was diagnosed by biopsy at laparotomy, and chemotherapy with cyclophosphamide, etoposide, doxorubicin, and cisplatin was performed. The tumors shrank temporarily (partial response), but subsequently grew in size again. The patient died during the second course of chemotherapy after relapse. We present one case report, together with a review of the literature. [ABSTRACT FROM AUTHOR]

We investigated possible impairment of the signal transduction system in gastric myocytes of streptozotocin-induced diabetic (STZ) and spontaneous diabetic WBN/Kob (WBN/Kob) rats. Gastric motility 10 weeks after the onset of diabetes mellitus was significantly reduced in both diabetic rats compared with control, and the decreased motility was not recovered by the administration of insulin to maintain normal blood glucose levels. There was no significant difference between both types of diabetic rats and control rats in total number of [3H]quinuclidinyl benzilate ([3H]QNB) binding sites (Bmmax: 545-587 fmol/mg protein) on gastric smooth muscle cell membranes or in the affinity of [3H]QNB for the binding sites (Kd: 0.06-0.07 nM). Immunoblot analysis using polyclonal anti-G-protein antibodies indicated increased expression of Gsalpha in gastric smooth muscle cell membranes, but no significant change in Gialpha or Gq/11alpha expression in STZ rats, and decreased expression of Gq/11alpha with no significant change in Gsalpha and Gialpha in WBN/Kob rats. The cAMP production in gastric smooth muscle cell membranes was augmented in the absence and presence of 100 microM isoproterenol, and 100 microM forskolin in STZ rats, whereas no significant change of cAMP production was observed in WBN/Kob rats irrespective of the presence of the stimulants. These findings suggest that long-standing diabetes may induce alterations in signal transduction at downstream receptors in gastric myocytes, resulting in the impairment of gastric motility, although the mechanism of reduced contractile activity may differ between STZ and WBN/Kob rats. [ABSTRACT FROM AUTHOR]

Gastrin producing ovarian tumor is a rare cause of the Zollinger-Ellison syndrome. We report the case of an ovarian carcinoma showing increased plasma gastrin concentration. A 60-yr-old woman presented with epigastric pain and diarrhea. Physical examination showed a large mass in the lower abdomen. Computed tomography revealed a large multilocular ovarian cyst. Upper gastrointestinal endoscopy examination showed multiple ulcerations of the stomach and duodenum. The plasma gastrin level was 1500 pg/ml. No tumors were found in the pancreas and duodenum, and salpingo-oophorectomy was performed. Histologic examination revealed a mucinous tumor of borderline malignant potential. Immunoperoxidase studies for gastrin showed many gastrin-producing cells within the epithelium of the tumor. There have been 11 cases (including our patient) of gastrin-producing ovarian tumor reported in the literature. We review here the relevant literature. Although ovarian gastrinoma is extremely rare, it should be considered as a possible cause of the Zollinger-Ellison syndrome in women. [ABSTRACT FROM AUTHOR]

Hemobilia is relatively rare among hemorrhages in the digestive tract, and hemobilia caused by tumors of the biliary tract is particularly rare. We treated a 74-year-old-man with undifferentiated carcinoma of the gallbladder presenting with hemobilia. During hospitalization for neurogenic bladder at the Department of Urology, he showed progressive anemia. Since hemorrhage in the digestive tract was suspected, endoscopy of the upper gastrointestinal tract was performed, and bleeding from the papilla of Vater was observed. On ultrasound examination, findings were indicative of cholecystic cancer, and hemorrhage from the cystic duct was found on percutaneous transhepatic cholangioscopy. On perioral cholecystoscopy, however, masses of coagulated blood were found only in the gallbladder. Abnormalities such as dense staining of tumors or extravasation were not found on angiography. The patient died of hepatic failure due to rapid invasion of the liver by the tumor, associated with biliary infection and disseminated intravascular coagulation. At autopsy, a nodal tumor was found in the gallbladder, and the cavity of the gallbladder was filled with coagulated masses of blood. Direct invasion of the tumor to the liver, diaphragm, and transverse colon was found. The histopathological diagnosis was undifferentiated carcinoma (pleomorphic large-cell type). [ABSTRACT FROM AUTHOR]

We report a patient who survived total colonic type ulcerative colitis (UC) complicated by toxic megacolon (TM), disseminated intravascular coagulation (DIC), methicillin-resistant Staphylococcus aureus infection, and phlebothrombosis. A 69-year-old man was treated for about 4 months under the diagnosis of ischemic colitis at another hospital, and was transferred to our hospital. Based on endoscopic and pathological findings, we strongly suspected UC, and administered salazosulfapyridine and methylprednisolone, but TM and DIC developed, necessitating urgent subtotal colectomy. Despite his elderly age and the severe complications, he recovered and was discharged from our hospital about 4 months after admission. The mortality rate of UC complicated by TM and DIC in elderly patients is high, necessitating rapid initiation of high-dose steroid administration or surgical treatment. [ABSTRACT FROM AUTHOR]

Intragastric hyperacidity occurs after abrupt withdrawal of histamine H2-receptor antagonists, and the prolonged administration of these agents induces tachyphylaxis of the inhibitory effects on gastric acid secretion. We examined the effect of the prolonged administration of H2-receptor antagonists on the H2-receptor signaling system in parietal cells isolated from rabbits that had received H2-receptor antagonists for 14 days. [125I]aminopotentidine (APT) binding sites to H2 receptors in parietal cell membranes were increased without any significant change in the affinity for [125I]APT. The expression of Gs(alpha), guanosine triphosphate (GTP)-binding protein coupled to H2 receptor, was slightly increased. Basal as well as GTP- or histamine-stimulated cAMP production was increased, but no significant change was observed in the presence of an H2-receptor antagonist. The up-regulation of the H2 receptor and adenylate cyclase appeared to cause hypersecretion of acid after withdrawal of H2-receptor blockade. [ABSTRACT FROM AUTHOR]

The effects of Helicobacter pylori infection on gastric acid secretion has not been clarified. The aim of this study was to elucidate the effects of H. pylori infection on gastric juice pH in relation to gene expression of interleukin-1β (IL-1β), which is reported to inhibit gastric acid secretion. Gastric juice pH and serum gastrin levels were measured in patients with peptic ulcer disease. The amount of IL-1β mRNA in gastric fundic gland mucosa was also measured by a competitive reverse transcription-polymerase chain reaction method. These parameters were determined before and after treatment with lansoprazole and amoxicillin. Before treatment a significant positive relation was observed between the amount of IL-1β mRNA in gastric fundic gland mucosa and gastric juice pH. After treatment significant decreases in the amount of IL-1β mRNA, gastric juice pH, and serum gastrin levels were observed in patients with eradication of H. pylori, whereas no significant changes were observed in patients without eradication. These results suggest that H. pylori infection induces IL-1β and suppresses acid secretion, resulting in increases in gastric juice pH and serum gastrin levels. Eradication of H. pylori decreases IL-1β induction, resulting in an increase in gastric juice acidity and normalization of serum gastrin levels. [ABSTRACT FROM AUTHOR]

We report a case of primary small cell carcinoma of the esophagus in a patient with achalasia in whom pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) levels were measured. Although chemotherapy markedly reduced the size of the primary tumor and lymph node metastases, it had no effect on liver metastases. The tumor marker levels decreased after chemotherapy as the primary tumor and lymph node metastases decreased in size, and they increased as the liver metastases enlarged. However, there was a discrepancy between the levels of ProGRP and NSE during the patient's clinical course. We demonstrate the usefulness of measuring ProGRP and NSE levels to assess the effect of chemotherapy in patients with esophageal small cell carcinoma. [ABSTRACT FROM AUTHOR]

Human gastric cancer cells were used to examine the trophic effect of the muscarinic m3 receptor subtype. Expression of the m3 receptor was detected in five of eight cell lines examined, MKN-1, 7, 28, 74, and TMK-1 cells. An increase in intracellular Ca2+ in response to carbachol was observed in more than 90% of TMK-1 cells, allowing us to use these cells in the following experiments. Western blot analysis showed that carbachol predominantly phosphorylated tyrosine in a 100-kDa protein. While mitogen-activated protein (MAP) kinase activity in the presence of 100 microM carbachol or 10 ng/ml transforming growth factor (TGF)alpha was augmented to 15- to 60-fold of the baseline level for 5min, the activation was transient. Pretreatment of the cells with 1 microM phorbol 12-myristate 13-acetate abolished carbacol-induced MAP kinase activation, whereas no suppression was observed in the presence of 500 nM Calphostin C (Kyowa Medex, Tokyo Japan), a specific protein kinase C inhibitor. No DNA synthesis or cell proliferation was observed in the presence of carbachol. These results indicate that stimulation of the m3 subtype leads to tyrosine phosphorylation and MAP kinase activation, but is unlikely to have trophic effects in gastric mucosal cells. [ABSTRACT FROM AUTHOR]

p21-activated kinase (PAK) is a common effector protein of the small GTPases Cdc42 and Rac, leading to the activation of downstream mitogen activated protein kinases. PAK also mediates polarized cytoskeletal changes induced by these GTPases. The recently identified PAK-interacting exchange factor (PIX) acts as a guanine nucleotide exchange factor on Rac, and colocalizes with PAK in a focal complex, but little is known about the associated signaling cascades, including upstream activators of PIX. In this study, we show that one of the isoforms of PIX, αPIX, is activated by signaling cascades from the platelet-derived growth factor (PDGF) receptor and EphB2 receptor, and from integrin-induced signaling through phosphatidylinositol 3-kinase (PI3-kinase). αPIX is activated by forming a complex with these receptors either via association with PAK and Nck, or direct association with the p85 regulatory subunit of PI3-kinase. Synthetic phosphoinositide and membrane targeted PI3-kinase augmented the αPIX activity in vivo. In Xenopus, aggregates of mesodermal cells derived from embryos microinjected with αPIX significantly increased the peripheral spreading on fibronectin substrate in response to PDGF through PI3-kinase. These results indicate that αPIX is activated by PI3-kinase, and is involved in the receptor mediated signaling leading to the activation of the kinase activity of PAK, and the migration of mesodermal cells on extracellular matrix. [ABSTRACT FROM AUTHOR]

Objective: Although cholesterolosis of the human gallbladder is a relatively common disease, its etiology has not been fully understood. The aim of this study was to determine this etiology. Methods: The lipid composition of the gallbladder mucosa and gallbladder bile and the enzyme activities (acylCoA-cholesterol ester acyltransferase [ACAT] and cholesterol ester hydrolase [CEH]) of the gallbladder mucosa were measured in control subjects, patients with cholesterolosis, and patients with cholesterol gallstone disease. Results: Levels of cholesterol ester in gallbladder mucosa in patients with cholesterolosis (n = 12) were higher than those in control subjects (n = 8). With regard to the lipid content in gallbladder bile, no differences were found in concentrations of cholesterol, phospholipids, and bile acids among control subjects (n = 11), patients with cholesterolosis (n = 13), and those with cholesterol gallstone disease (n = 15). In gallbladder mucosa, ACAT activity was significantly higher in patients with cholesterolosis (n = 10) than in control subjects (n = 8), whereas CEH activity did not differ between the two groups. As a result, the ACAT/CEH activity ratio was higher in patients with cholesterolosis than in control subjects. Conclusions: It would be suggested that cholesterol ester synthesis of gallbladder mucosa might play an etiological role in the development of cholesterolosis. [ABSTRACT FROM AUTHOR]

Expression of muscarinic receptor subtypes inrat gastric smooth muscle was examined with reversetranscriptase-polymerase chain reaction (RT-PCR). Underthe condition for detecting the messages of m1-m4 subtypes in brain, atrium, and gastric mucosa,only the fragments of m2 and m3 subtypes were amplifiedwith RNA prepared from rat gastric smooth muscles.Furthermore, the amplified fragments were digested by restriction enzymes, reconfirming that thepredicted size products of m2 and m3 contain the partialDNA sequences of m2 and m3 subtypes, respectively. Wemeasured gastric motility in rats with a pressure transducer system under the continuous venousinfusion of the muscarinic antagonists atropine andbutylscopolamine (nonselective), AF-DX 116 (M2),zamifenacine (M3), and glucagon. Heart rate wasmonitored simultaneously in the tail. Gastric motilitywas inhibited in the presence of glucagon andzamifenacine without alteration of heart rate, whereasthere was no inhibition in the presence of AF-DX 116even after the augmentation of heart rate wasobserved. Gastric emptying was also suppressed in thepresence of zamifenacine, which had an effect comparablewith that of atropine, butylscopolamine, and glucagon. These results indicate that the activation ofthe M3 subtype in gastric smooth muscle causes itscontraction, and the M3 selective antagonist could be apotentially useful drug without an adverse effect on the heart for radiological and endoscopicexamination in the upper gastrointestinaltract. [ABSTRACT FROM AUTHOR]

A 32-year-old woman with ulcerative colitis had a relapsed of pyoderma gangrenosum during puerperium. Both the pyoderma gangrenosum and ulcerative colitis had been well controlled with oral prednisolone, but ulcerative colitis relapsed in pregnancy, and pyoderma gangrenosum relapsed in the puerperium. The pyoderma gangrenosum responded to methylprednisolone pulse therapy initially, but relapsed when prednisolone was tapered. A second trial of pulse therapy combined with cyclosporine resulted in complete remission of the pyoderma gangrenosum, and no recurrence was recognized after prednisolone was tapered. This is a very rare case of successful treatment with methylprednisolone pulse therapy combined with cyclosporine for pyoderma gangrenosum complicating ulcerative colitis. [ABSTRACT FROM AUTHOR]

Familial adenomatous polyposis of the colon, or Gardner's syndrome, is often accompanied by adenomas of the stomach and duodenum. We experienced a rare case of Gardner's syndrome, with adenomas of the common bile duct, in a patient who presented with relapsing acute pancreatitis. Our findings indicate that adenoma in the common bile duct or pancreatic duct should be considered as a possible etiology when patients with familial polyposis or Gardner's syndrome present with pancreatitis, particularly relapsing acute pancreatitis. [ABSTRACT FROM AUTHOR]

Calcium transport systems of isolated ileal epithelial cells were investigated. The concentration of cytosolic free calcium ions, [Ca], was monitored with a fluorescent Ca dye, fura-2. The fluorescence intensity ratio ( I/ I) was used as an index of [Ca]. [Ca] of the cells suspended in the nominally Ca-free solution was estimated at 52±3 nM. Ca uptake was followed for as long as 5 min in the presence of 100-1000 μM added CaCl. Most of the experiments were performed at 200 μM CaCl. The Ca uptake was abolished by 0.8 mM Ni and 50 μM Mn and partitally antagonized by 50 μM verapamil and 50 μM diltiazem but not affected by 20 μM nifedipine. The Ca entry was reduced by increasing concentrations of extracellular K in the presence of valinomycin, suggesting a voltage-dependent nature of the uptake. On the other hand, the Ca transport doubled in the presence of Bay K8644 (8 μM), a Ca channel agonist. The Bay-K-8644-induced uptake was inhibited by either 10 μM nifedipine, 10 μM verapamil or 10 μM diltiazem and was relatively independent of extracellular K concentration. These results suggest that there are at least two distinct Ca transport systems in the rat ileal epithelial cells, one resistant to organic Ca channel blockers but relatively sensitive to membrane potential (basal uptake) and another inducible by Bay K 8644 and sensitive to the channel blockers but relatively independent of membrane potential. [ABSTRACT FROM AUTHOR]

Ulcerative colitis associated with immune-mediated thrombocytopenia is rare. It has been suggested that antigenic mimicry between platelet surface antigen and bacterial glycoprotein plays a role in this association. We present a case in which exacerbation of UC sequentially induced development of ITP associated with elevation of PAIgG. In the case, two episodes of ITP occurred, with each preceded by exacerbation of UC. After remission of UC, ITP remitted and PAIgG simultaneously decreased. In the first episode, the onset of ITP was about I month after the exacerbation of UC. However. in the second episode, the onset of ITP was much faster, 11 days after that of UC, and the magnitude of elevation of PAIgG was much higher in the second episode. This may provide further evidence that ITP is causally associated with UC, and is the result of immunostimulation from luminal antigens and altered immunoregulation. [ABSTRACT FROM AUTHOR]

A case of congenital subclavian steal caused by a previously unreported aortic arch anomaly was demonstrated by angiography. The patient was shown to have a right aortic arch with a retroesophageal segment, a stenotic proximal portion of the left subclavian artery, and a left descending aorta. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about the article "Changes in Seroepidemiological Pattern of Helicobacter pylori and Hepatitis A Virus Over the Last 20 Years in Japan," by Toru Fujisawa.

Reports a case of prevention of rebleeding from a duodenal intradiverticular ulcer after Helicobacter pylori eradication. Background of hemorrhage; Information on the case of a 75-year-old woman who was admitted to the hospital with complaints of tarry stool.

Presents a letter to the editor about the seroprevalences of Helicobacter pylori and hepatitis A virus.