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Background Rikkunshito, a standardized Japanese herbal medicine, is thought to accelerate gastric emptying and relieve dyspepsia, although no large-scale, randomized, placebo-controlled trials of rikkunshito have been conducted. This study aimed to determine the efficacy and safety of rikkunshito for treating functional dyspepsia (FD). Methods FD patients received 2.5 g rikkunshito or placebo three times a day for 8 weeks in this multicenter, randomized, placebo-controlled, parallel-group trial. The primary end point was the proportion of responders at 8 weeks after starting test drug, determined by global patient assessment (GPA). The improvement in four major dyspepsia symptoms severity scale was also evaluated. In addition, plasma ghrelin levels were investigated before and after treatment. Key Results Two hundred forty-seven patients were randomly assigned. In the eighth week, the rikkunshito group had more GPA responders (33.6%) than the placebo (23.8%), although this did not reach statistical significance (p = 0.09). Epigastric pain was significantly improved (p = 0.04) and postprandial fullness tended to improve (p = 0.06) in the rikkunshito group at week 8. Rikkunshito was relatively more effective among Helicobacter pylori-infected participants (rikkunshito: 40.0% vs placebo: 20.5%, p = 0.07), and seemed less effective among H. pylori-uninfected participants (rikkunshito: 29.3% vs placebo: 25.6%, p = 0.72). Among H. pylori-positive individuals, acyl ghrelin levels were improved just in rikkunshito group. There were no severe adverse events in both groups. Conclusions & Inferences Administration of rikkunshito for 8 weeks reduced dyspepsia, particularly symptoms of epigastric pain and postprandial fullness. (UMIN Clinical Trials Registry, Number UMIN000003954).

Background and study aims: Colonoscopy is one of the most reliable methods for the detection of colorectal neoplasms. However, colonic peristalsis during colonoscopy results in some neoplastic lesions being hidden from view and commonly requires an intravenous or intramuscular injection of antispasmodic agents, which may sometimes causes unexpected adverse reactions. The aim of this study was to evaluate the efficacy of L-menthol spray as an antiperistaltic agent and its effect on adenoma detection. Patients and methods: This was a prospective, randomized, single-blind placebo-controlled trial. A total of 226 patients who were scheduled to undergo colonoscopy were randomly assigned to receive either 20 mL of 1.6 % L-menthol (n = 118) or placebo (n = 108). Both treatments were sprayed locally onto the colonic mucosa via an endoscope. The adenoma detection rate (ADR) and the proportion of patients with no peristalsis were the primary and secondary outcomes, respectively. Results: The ADR was significantly higher in the L-menthol group than in the placebo group (60.2 % vs. 42.6 %; P = 0.0083). The proportion of patients with no peristalsis after treatment with L-menthol was significantly higher than in the placebo group (71.2 % vs. 30.9 %; P Conclusions: The results suggest that the suppression of colonic peristalsis by L-menthol sprayed directly onto the colonic mucosa improves the ADR. Clinical trial registration: ID: UMIN 000007972.

There are more than 70 proteins in chicken egg white, most of which have a role in host defense. We isolated a novel protein from chicken egg white which we termed EW135 by means of polyethylene glycol precipitation and ionexchange chromatography, and an amino acid sequence analysis of its tryptic peptides showed it to be a member of the group B scavenger receptor cysteine-rich domain superfamily. EW135 was speculated to be complexed with a substance (s) in egg white in a Ca 2+ -dependent manner. From a structural point of view, EW135 may play a role in host defense.

We present a case of systemic sarcoidosis. A 72-year-old Japanese woman, who was diagnosed with asymptomatic enlarged abdominal para-aortic lymph nodes in April 2000, was admitted to our hospital in December 2003 because of multiple mass lesions of the liver and spleen. She had hepatosplenomegaly and asymptomatic pulmonary fibrosis. Blood examination revealed cholestasis and progressing liver synthetic dysfunction. In laparoscopic photographs, various sizes of whitish flat lesions were scattered on the surface of the liver. Liver biopsy showed non-caseating epithelioid cell granulomas. These lesions of the spleen disappeared on contrast-enhanced computed tomography imaging, and serum liver dysfunction was improved rapidly after steroid therapy. Laparoscopy may be useful for the diagnosis of granulomatous liver disease, such as hepatobiliary sarcoidosis.

It is well established that prostaglandins (PGs) exert potent pharmacological actions on vascular and nonvascular smooth muscle, although their effects on the sphincter of Oddi (SO) remain to be elucidated. The aim of this study was to investigate the effect of PGE1 on motility of the human SO. Twenty patients appearing for routine endoscopic retrograde cholangiopancreatography (ERCP) examination were studied. Each patient was randomly allocated to receive an intravenous infusion of normal saline (six patients), or alprostadil alfadex, a synthetic PGE1 analog, at a dose of either 0.05 or 0.1 μg/kg/min (seven patients for each condition). Endoscopic biliary manometry was done with a recording of basal SO pressure, amplitude of SO phasic contractions, and phasic contractile frequency before and 5 min after intravenous infusions, using a 4-French microtransducer catheter. There was no significant change in SO motor variables following application of normal saline. Alprostadil alfadex significantly decreased basal SO pressure at a dose of 0.05 μg/kg/min, and significantly decreased all parameters at a dose of 0.1 μg/kg/min. A synthetic PGE1 analog, alprostadil alfadex, effectively inhibits motility of the human SO. This drug may be of clinical application as a SO-relaxing agent.

Cytokine oncostatin M (OM) exerts growth-inhibitory and differentiative effects on breast cancer cells. Previously we showed that the transcription from the p53 gene in breast cancer cells was down regulated by OM. To elucidate the molecular mechanisms underlying the OM effect on p53 transcription, in this study, we dissected the p53 promoter region and analysed the p53 promoter activity in breast tumor cells. We showed that treatment of MCF-7 cells with OM induced a dose- and time-dependent suppression of p53 promoter activity. The p53 promoter activity was decreased to 35% of control at 24 h and further decreased to 20% at 48 h by OM at concentrations of 5 ng/ml and higher. Deletion of the 5'-flanking region of the p53 promoter from -426 to -97 did not affect the OM effect. However, further deletion to -40 completely abolished the repressive effect of OM. The p53 promoter region -96 to -41 contains NF-kappaB and c-myc binding sites, and a newly identified UV-inducible element PE21. Mutations to disrupt NF-kappaB binding or c-myc binding to the p53 promoter decreased the basal promoter activity without affecting the OM-mediated suppression, whereas mutation at the PE21 motif totally abolished the OM effect. We further demonstrated that insertion of PE21 element upstream of the thymidine kinase minimal promoter generated an OM response analogous to that of the p53 promoter. Finally, we detected the specific binding of a nuclear protein with a molecular mass of 87 kDa to the PE21 motif. Taken together, we demonstrate that OM inhibits the transcription of the p53 gene through the PE21 element. Thus, the PE21 element is functionally involved in p53 transcription regulated by UV-induction and OM suppression.

A 63-year-old woman was referred to our hospital for further examination because of an incidental finding of early gastric cancer. Endoscopic submucosal dissection (ESD) was successfully performed for complete resection of the tumor. On the first post-ESD day, the patient suddenly complained of abdominal pain after an episode of vomiting. Abdominal computed tomography (CT) showed delayed perforation after ESD. The patient was conservatively treated with an intravenous proton pump inhibitor and antibiotics. On the fifth post-ESD day, CT revealed a gastric wall abscess in the gastric body. Gastroscopy revealed a gastric fistula at the edge of the post-ESD ulcer, and pus was found flowing into the stomach. An intradrainage stent and an extradrainage nasocystic catheter were successfully inserted into the abscess for endoscopic transgastric drainage. After the procedure, the clinical symptoms and laboratory test results improved quickly. Two months later, a follow-up CT scan showed no collection of pus. Consequently, the intradrainage stent was removed. Although the gastric wall abscess recurred 2 wk after stent removal, it recovered soon after endoscopic transgastric drainage. Finally, after stent removal and oral antibiotic treatment for 1 mo, no recurrence of the gastric wall abscess was found.

The mutant gene coding for a proline-activating domain (grs2-pro) was cloned and sequenced from Bacillus brevis Nagano, BII-3 strain, which produces gramicidin S synthetase 2 defective in proline-activation. By comparison of the nucleotide sequence with the wild-type sequence, a single point mutation was found at the 2609th guanine, which was replaced with adenine, resulting in the change of the 870th glycine to glutamic acid. Homology search for the deduced amino acid sequence of grs2-pro gene revealed that the 870th glycine was conserved in adenylate-forming enzymes, and its flanking sequence was highly conserved among the aminoacyl adenylate-forming enzymes, such as antibiotic peptide synthetases: gramicidin S synthetase 1 and 2 (GS1, GS2), tyrocidine synthetase 1 (TS1), and delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS); and other aminoacyl adenylation enzymes: alpha-aminoadipate reductase (LYS2), EntF, and AngR. On the other hand, this flanking sequence was not conserved in the other adenylate-forming enzymes lacking amino acid activation, such as acetyl-CoA synthetase, long-chain acyl-CoA synthetase, luciferase, and 4-coumarate CoA ligase. Single base substitutions at the 870th GGG codon were carried out by oligonucleotide site-directed mutagenesis. Four mutagenized clones were isolated, containing grs2-pro genes which exchange 870-Gly for alanine, valine, arginine, and tryptophan. The translated products from these clones could scarcely catalyze proline-dependent ATP-32PPi exchange reaction. The coil structure of 870-Gly region was lost in the mutants. These results suggest that the 870-Gly residue of grs2-pro protein is essential for aminoacyl-adenylation in the antibiotic peptide synthetase family.

A case of a 60-year-old Japanese woman with small cell lung cancer involving skin and stomach is reported. She was diagnosed as primary small cell lung cancer accompanied by extensive cutaneous metastases. Three months after the last chemotherapy, she complained of nausea and vomiting. Brain CT scan showed no evidence of central nervous system involvement. Upper gastrointestinal study and upper gastrointestinal fiberscopy revealed multiple metastatic gastric tumors. Skin and stomach are uncommon metastatic sites for any malignancy. Furthermore, only a few cases with gastric metastasis could be diagnosed during their lifetime.

A fragment encoding proline-activating domain (grs 2-pro) of gramicidin S synthetase 2 (GS 2) was found in an 8.1-kilobase pairs (kb) DNA fragment of Bacillus brevis Nagano, which contained the full length of GS 1 gene (grs 1). The clones designated GS719 and GS708, which expressed gramicidin S synthetase 1, were elucidated to express immunoreactive proteins to GS 2 antibodies with approximate molecular weights of 115,000, 105,000 (GS719), and 110,000 (GS708). The partial purification of the gene products of these clones was carried out using DEAE-Sepharose CL-6B column chromatography. The immunoreactive proteins to GS 2 antibodies were separated from gramicidin S synthetase 1 protein and had specific proline-dependent ATP-32PPi exchange activity. The nucleotide sequence for the proline-activating domain in the 8.1-kb insert was determined. This fragment was 2,879 base pairs long, and encoded 959 amino acids. The calculated molecular weight of 111,671 was consistent with the apparent molecular weight of 115,000 found in SDS-PAGE of the immunoreactive products to GS 2 antibodies. The open reading frame for this protein followed grs 1 gene, though two were separated by a 73-base pair noncoding sequence, and remained open to the end.(ABSTRACT TRUNCATED AT 250 WORDS)

An infrared ray electronic video-endoscope with a laser diode light source was used to obtain information on the submucosal area. As contrast medium we employed indocyanine green, which has a light absorption peak in the infrared range. The wavelength of the laser diode was set to 810 nm as suggested by the results of the spectrophotometric study on the reflected light at fingertips after injection of ICG (3 mg/kg). Using this system we inspected the stomach under visible light and then continuously under infrared light before and after intravenous injection of ICG (2 mg/kg). A dendritic figure with fine ramifications emerged in the early stage after intravenous injection of indocyanine green, which was not seen under visible light. These features of the figure visualized by the infrared endoscope suggest that they have a close relationship with blood vessels and blood circulation beneath the mucosal surface. This infrared electronic endoscope system provides submucosal information more readily and at a lower cost than ever before, and also the infrared lighting method of this system could be applied to almost all available electronic endoscopes by modulating infrared cutting filters, so it could become a valuable clinical tool.

比較的稀とされる原発性縦隔精上皮腫の一症例を経験したので報告した.患者は52歳の男性で, 縦隔悪性奇形腫の疑いにて本院胸部外科入院.放射線療法後, 腫瘍摘出術施行したが, 非治癒的切除に終わった.手術標本にて精上皮腫と診断された為, 術後Cis-platinum等による化学療法と放射線療法を受けた.しかし4カ月後, 左癌性胸膜炎再燃し当科入院された.CPA, ACTM-D, VCRによる化学療法を施行したが肺炎にて死亡された.

Bromodeoxyuridine (BrdU) immunohistochemistry has recently been introduced for the visualization of DNA-synthesizing nuclei. To determine the optimal conditions for detecting BrdU-incorporated nuclear DNA in formalin- or ethanol-fixed, paraffin-embedded human gastric tissues, we tested several different pretreatment procedures of hydrolysis with HCl and enzymatic digestion with actinase before the immunohistochemical staining. Three cases of surgically resected stomachs were perfused with artificial blood containing BrdU and fixed in formalin, ethanol or with their combination for different durations. The results of BrdU-immunohistochemical stainings were checked and the labeling indices were compared. As for hydrolysis, treatment with 2N HCl at 25°C for 90min was sufficient to detect the immunoreactivity in the stomach irrespective of fixative conditions tested. However, to obtain the most suitable stainings an additional enzymatic digestion was needed, and the optimal condition with actinase was different according to the fixation time in formalin- and/or ethanol-fixed tissues. There are also a few differences in the demonstrability of nuclear BrdU among various kinds of cells, i.e. normal epithelial cells, immunoblasts in the lymphoid follicle and cancer cells. Our method could extend the range of application of BrdU immunohistochemistry for cell kinetic studies using human surgically resected organs.

A 69-year-old man was referred to our hospital for epigastralgia. He was found to have elevation of serum amylase and CA19-9. Ultrasonography, abdominal CT, MRCP, ERCP and EUS showed the cystic lesion and a possibility of an other tumor. There was a stenosis of the main pancreatic duct (MPD) at the pancreas head and dilatation of the MPD from the body to the tail. Intraductal papillary mucinous neoplasm (IPMN) of the branch pancreatic duct was diagnosed, and there was a likelihood of ductal carcinoma of the pancreas. We therefore performed pancreatoduodenectomy. Pathological finding showed invasive carcinoma from an intraductal papillary mucinous neoplasm with invasive ductal carcinoma of the pancreas.

Angiodysplasia has been recognized as one of the main causes of gastrointestinal bleeding, but few such lesions have been found, or treated by an endoscopic procedure, in the ileum. We endoscopically identified angiodysplasia in the ileum of an 85-year-old female who had tarry stools. Because she had severe aortic stenosis, we treated the lesion endoscopically by combining polidocanol injection and electrocoagulation with hot biopsy forceps. This method was considered to be safe and efficient, especially for lesions in the thin walled intestine.

It is well established that prostaglandins (PGs) exert potent pharmacological actions on vascular and nonvascular smooth muscle, although their effects on the sphincter of Oddi (SO) remain to be elucidated. The aim of this study was to investigate the effect of PGE1 on motility of the human SO. Twenty patients appearing for routine endoscopic retrograde cholangiopancreatography (ERCP) examination were studied. Each patient was randomly allocated to receive an intravenous infusion of normal saline (six patients), or alprostadil alfadex, a synthetic PGE1 analog, at a dose of either 0.05 or 0.1 microg/kg/min (seven patients for each condition). Endoscopic biliary manometry was done with a recording of basal SO pressure, amplitude of SO phasic contractions, and phasic contractile frequency before and 5 min after intravenous infusions, using a 4-French microtransducer catheter. There was no significant change in SO motor variables following application of normal saline. Alprostadil alfadex significantly decreased basal SO pressure at a dose of 0.05 microg/kg/min, and significantly decreased all parameters at a dose of 0.1 microg/kg/min. A synthetic PGE1 analog, alprostadil alfadex, effectively inhibits motility of the human SO. This drug may be of clinical application as a SO-relaxing agent.

A 66-year-old man with chronic obstructive lung disease was admitted to our hospital, presenting with mesenteric volvulus and mild liver injury. A superior mesenteric angiogram revealed that the arteries supplying the small intestine were twisted in the arterial phase, while the portal vein was not visualized in the late phase. A celiac angiogram demonstrated that portal blood flow from the splenic venous return was maintained. The patient's symptoms had almost resolved the day after admission, and his serum transaminases level had gradually decreased to normal with conservative therapy. A superior mesenteric angiogram on the 13th hospital day showed a normal arteriogram and the portal vein demonstrated blood flow from the superior mesenteric vein. Liver biopsy revealed hemorrhagic necrosis around the central veins, which was compatible with ischemic hepatitis. Since the patient's O2 saturation level on admission was not low enough to have caused ischemic hepatitis by itself, we suspect that a sudden decrease in portal blood flow was the additional factor that allowed the threshold for the initiation of ischemic liver damage to be reached.

Mutant grs1 genes were cloned and sequenced from the Bacillus brevis Nagano BI-4, C-3, E-1, and E-2 strains, which produce defective gramicidin S synthetase 1 (GS1), lacking racemase activity. Surprisingly, these mutant genes had entirely the same sequence as that of the wild type gene. These mutant strains also produce defective gramicidin S synthetase 2 (GS2), lacking 4'-phosphopantetheine, a prosthetic group of this enzyme. The participation of this group in phenylalanine racemization is suggested.

Background/Aim: Prostaglandins (PGs), widely distributed in the human and animal gastrointestinal tract, play important roles in cytoprotection, secretion and absorbtion, and motility of the digestive tract. However, their effects on the biliary tract are not well studied. The aim of the present study is to investigate effects of PGs E1 and F2a on motility of the human sphincter of Oddi (SO). Methods: Twenty-seven patients appearing for routine endoscopic retrograde cholangiopancreatography (ERCP) were studied. Each patient was randomly allocated to receive an intravenous infusion of normal saline (six patients), alprostadil alfadex, a synthetic PGE1 analogue, at a dose of either 0.05 or 0.1 μg/kg/min (seven patients for each condition), or dinoprost, a synthetic PGF2α analogue, at a dose of 1.0 μg/kg/min (seven patients). Endoscopic biliary manometry was done with a recording of basal SO pressure (mmHg), SO phasic wave amplitude (mmHg) and frequency (/min) before and 5 min after intravenous infusions, using a 4 Fr microtransducer catheter (Galtec Ltd). Values are reported as the mean±SEM. Paired Student's t tests were used to compare variables before and after injection. Differences with p values of less than 0.05 were considered significant. Results: There was no significant change in SO motor variables following application of normal saline. Alprostadil alfadex significantly decreased basal SO pressure and SO phasic wave frequency at a dose of 0.05 μg/kg/min and significantly decreased all parameters at a dose of 0.1 μg/kg/min, while dinoprost significantly increased only SO phasic wave frequency. Conclusion: A synthetic PGE1 analogue, alprostadil alfadex, has an inhibitory effect on motility of the human SO.This drug may be applicable to clinical use as a SO relaxing agent.