Effect of Helicobacter pylori eradication on gastroesophageal function.

BACKGROUND: To elucidate the cause of possible occurrence of reflux esophagitis after Helicobacter pylori eradication, gastric and esophageal function among H. pylori infected Japanese patients were evaluated both before and after eradication therapy. METHODS: Nine H. pylori-positive patients were studied before and 6 months after successful H. pylori eradication. Studies included gastric emptying, esophageal manometry, gastric and esophageal pH monitoring as well as measuring serum levels of gastrin, pepsinogen I and pepsinogen II. RESULTS: Helicobacter pylori eradication was associated with a significant change in serum gastrin and pepsinogen levels, consistent with the improvement in mucosal inflammation. There was no significant change in gastric emptying, fasting or postprandial lower esophageal sphincter (LES) pressure, esophageal primary peristaltic contractions, frequency of transient LES relaxation, or gastroesophageal reflux, as assessed by 24 h pH monitoring. The percent time of the gastric pH>4 at night decreased significantly. A 41-year-old male developed erosive gastroesophageal reflux disease (GERD) (Los Angeles Classification Grade A) after eradication. Physiological studies showed he had abnormal esophageal motility prior to H. pylori eradication. CONCLUSIONS: With the exception of gastric pH at night, most patients did not experience a significant change in gastric or esophageal function after H. pylori eradication. Development of GERD post H. pylori eradication likely reflects an increase in the acidity of the refluxate superimposed on pre-existing abnormalities in gastroesophageal motility.

Expression of Musashi-1 in human normal colon crypt cells: a possible stem cell marker of human colon epithelium.

Musashi has been identified as an RNA-binding protein thought to be involved in asymmetric divisions during Drosophila neural development. To analyze expression patterns of mammalian Musashi homolog Musashi-1 in human normal colon crypt, 155 colon crypts separated from biopsy specimens of normal colonic mucosa were evaluated. Specimens were fixed, microdissected to isolate a few crypts, immunostained with anti-Musashi-1 antibody (14H1), and examined under confocal laser scan microscopy. The number of Musashi-1-positive cells in each crypt was 19.0 +/- 7.53 (mean +/- SD). Most Musashi-1 positive cells were located at the crypt base, between cell positions 1 and 10. Distribution of Musashi-1-positive cells corresponded with that of stem cells, as outlined in previous reports, implying that Musashi-1 is a key control element of asymmetrical division within the colon crypt. This is the first report outlining expression of Musashi-1 in human colon crypt cells.

Ciliated hepatic foregut cyst. A report of one case and a review of the literature.

We encountered a patient with a ciliated hepatic foregut cyst (CHFC), which is an uncommon cystic lesion of the liver and hard to distinguish from malignant tumor in imaging features. Cases of CHFC are very rare, five cases were reported in the 19th century and 53 cases in the 20th century. The histogenesis of CHFC is still unclear, but most authors consider that it could arise from the embryonic foregut. A few cases of CHFC mimicking neoplasm were reported. When the diagnosis of CHFC was obtained by fine needle aspiration, close follow-up is necessary in order to find early malignant change.

Antimicrobial activity of essential oils against Helicobacter pylori.

BACKGROUND: Helicobacter pylori is an important pathogen responsible for gastroduodenal diseases in humans. Although the eradication of H. pylori using antibiotics often improves gastroduodenal diseases, resistance to the antibiotics is emerging. MATERIALS AND METHODS: The antimicrobial effect of essential oils and the development of resistance to the essential oils were evaluated in vitro and in vivo. RESULTS: Thirteen essential oils used in this study completely inhibited the growth of H. pylori in vitro at a concentration of 0.1% (v/v). Cymbopogon citratus (lemongrass) and Lippia citriodora (lemon verbena) were bactericidal against H. pylori at 0.01% at pH 4.0 and 5.0. Resistance to lemongrass did not develop even after 10 sequential passages, whereas resistance to clarithromycin developed under the same conditions. In in vivo studies, the density of H. pylori in the stomach of mice treated with lemongrass was significantly reduced compared with untreated mice. CONCLUSIONS: These results demonstrate that the essential oils are bactericidal against H. pylori without the development of acquired resistance, suggesting that essential oils may have potential as new and safe agents for inclusion in anti-H. pylori regimens.

Successful treatment of intractable esophagothoracic fistula using covered self-expandable stent.

This report concerns the successful treatment with a covered self-expandable stent of an intractable thoracoesophageal fistula after total esophagectomy for esophageal cancer. Total esophagectomy was performed on a 68-year-old man who presented with a huge esophageal cancer in the lower esophagus. Massive leakage was observed on the 5th day postoperatively. Since high fever and coughing continued, he was diagnosed as having esophagothoracic fistula and pyothorax, after which fenestration of the right chest wall was performed. Although the patient's general condition was getting better, stenosis near the anastomosis (esophagogastrostomy) and the esophagothoracic fistula were resistant to treatment with balloon dilatation and repeated endoscopic mucotomy. Further treatment, consisting of glue or fibrin sealant injection was not effective. After a covered self-expandable stent had been placed endoscopically, however, the fistel was completely cured in 2 months. This new endoscopic approach thus represents a promising option for the treatment of intractable esophagothoracic fistula.

Serum thioredoxin levels as a predictor of steatohepatitis in patients with nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Thioredoxin (TRX) is a stress-inducible thiol-containing protein. The aim of this study was to evaluate the clinical significance of serum TRX in patients with nonalcoholic steatohepatitis (NASH) or simple steatosis. METHODS: Serum TRX levels were determined using an enzyme-linked immunosorbent assay kit in 25 patients with NASH, 15 patients with simple steatosis, and 17 healthy volunteers. RESULTS: Serum TRX levels (medians and (ranges), ng/ml) were significantly elevated in patients with NASH (60.3 (17.6-104.7)), compared to those in patients with simple steatosis (24.6 (16.6-69.7), P=0.0009) and in healthy controls (23.5 (1.3-50.7), P<0.0001). Serum ferritin levels in patients with NASH were also significantly higher than the levels in patients with simple steatosis. The receiver operating characteristic curve confirmed that serum TRX and ferritin levels were predictors for distinguishing NASH from simple steatosis. Higher grades of histological iron staining were observed in NASH than in simple steatosis. Serum TRX tended to increase in accordance with hepatic iron accumulation and the histological severity in patients with NASH. CONCLUSIONS: The pathogenesis of NASH may be associated with iron-related oxidative stress. The serum TRX level is a parameter for discriminating NASH from simple steatosis as well as a predictor of the severity of NASH.

Effects of etodolac, a selective cyclooxygenase-2 inhibitor, on the expression of E-cadherin-catenin complexes in gastrointestinal cell lines.

BACKGROUND: Recent studies have shown that cyclooxygenase-2 (COX-2) inhibitors may participate in the proliferation of cancer cells. Because the cadherin-catenin complex is not only a key component of the adherens junction but also has been suggested to regulate cell proliferation, modulation of these molecules may be a mechanism by which COX-2 activity affects cell proliferation. In this study, we evaluated the effect of a COX-2 inhibitor on the proliferation and expression of E-cadherin-complexes in gastrointestinal cancer cell lines. METHODS: The gastrointestinal cancer cell lines Caco2, HT29, and MKN45 were grown for 24 h in the presence and absence of a selective COX-2 inhibitor, etodolac (10(-5), 10(-4), and 10(-3) M). Cell proliferation was assessed by (3)H-thymidine incorporation, and the expression of E-cadherin and catenins was assessed by Western blotting, Northern blotting, and immunofluorescence. RESULTS: Etodolac induced a significant reduction in cell proliferation in Caco2 and MKN45 cells. E-cadherin expression was upregulated after stimulation with etodolac in Caco2 cells, whereas the expression of alpha-, beta-, gamma- and p120-catenins was not modified. The expression of E-cadherin mRNA was also upregulated in Caco2 cells, and was upregulated also in MKN45 cells, which did not express normal E-cadherin protein by the use of a mouse monoclonal antibody against human E-cadherin, HECD-1 antibody. Immunofluorescence revealed that the increased E-cadherin was localized at the cytoplasmic membrane. CONCLUSIONS: The inhibition of cell growth by etodolac in Caco-2 cells was associated with a dose-dependent upregulation and intense cytoplasmic localization of E-cadherin. No quantitative change in catenin expression was found in this phenomenon. These findings suggest that the COX-2 inhibitor affects the transcription of E-cadherin, or that there may be some homeostatic link between the cell cycle and E-cadherin transcription.

Development and use of a new staging system for severe acute pancreatitis based on a nationwide survey in Japan.

METHODOLOGY: In 1997, a cooperative nationwide survey of 192 patients diagnosed with severe acute pancreatitis in 1996 was carried out. RESULTS: Alcoholic pancreatitis was the major etiology (46%), and the male-to-female ratio was 2.6:1. Overall, the mortality rate was 27%, which was similar to the rate (30%) in the first nationwide survey of 1,219 patients diagnosed between 1982 and 1986 that was performed in 1987. A marked difference between the surveys was the early mortality rate within 2 weeks: 52% in the 1987 survey and 29% in the current survey. We devised a new stage classification system for acute pancreatitis. Stages 0 and 1 are equivalent to mild and moderate conditions, respectively, in the conventional classification, and stages 2 and higher correspond to severe acute pancreatitis. Severity scores of 2-8 are regarded as stage 2, scores of 9-14, as stage 3, and scores of > or =15, as stage 4. The mortality rates were as follows: 0, stages 0 and 1 at hospitalization; approximately 10%, stage 2; approximately 30-40%, stage 3; and approximately 70-100%, stage 4. CONCLUSION: We found that stage at hospitalization reflected the prognosis of acute pancreatitis.

Macroscopic and microscopic findings of livers in malignant hematologic disorders, biopsied under peritoneoscopy.

It is important to detect liver involvement in extranodal lesions in malignant hematologic disorders to make accurate diagnoses and estimate their clinical stage. We report seven cases of malignant lymphoma and a case of histiocytosis X. All patients expressed positive C-reactive protein and a high erythrocyte sedimentation rate, and a high serum value of alkaline phosphatase or lactic dehydrogenase was seen. Image analyses revealed enlarged livers without any space-occupying lesions. Peritoneoscopy with liver biopsy showed a diffuse presence of white maculae or peliosis hepatis on the liver surface among all the patients, and granulomas with or without malignant cells were observed histologically and congestion was seen in the lobules. Thus, peritoneoscopy with liver biopsy appears to be a useful tool not only to detect early liver involvement in malignant hematologic disorders but also to make their accurate diagnosis.

Involvement of Kupffer cells in the interaction between neutrophils and sinusoidal endothelial cells in rats.

During endotoxic liver injury, large numbers of neutrophils infiltrate the liver, and serum levels of tumor necrosis factor-alpha (TNF-alpha) become elevated. The object of this study was to assess the roles of TNF-alpha secreted by Kupffer cells in the interaction between neutrophils and sinusoidal endothelial cells (SECs). Rat neutrophils were perfused onto SECs that were stimulated with either TNF-alpha or supernatant from lipopolysaccharide (LPS)-stimulated Kupffer cells using an in vitro flow system. Numbers of adhered or migrated neutrophils were counted, and the effect of an antibody against intercellular adhesion molecule-1 (ICAM-1) was studied. Compared with controls (200 +/- 21 cells/mm2), neutrophil adhesion to SECs was significantly increased by both TNF-alpha (342 +/- 26 cells/mm2; P < 0.05) and LPS-stimulated Kupffer cell supernatant (331 +/- 29 cells/mm2; P < 0.05). Anti-ICAM-1 significantly inhibited neutrophil adhesion (139 +/- 10 cells/mm2; P < 0.05) and decreased the migration rate of neutrophils on SECs treated with LPS-stimulated Kupffer cell supernatant (P < 0.05). LPS-stimulated Kupffer cells secreted TNF-alpha in an LPS dose-dependent manner, and they significantly enhanced ICAM-1 expression on SECs (P < 0.05 vs. control). In addition, dexamethasone suppressed TNF-alpha production by LPS-stimulated Kupffer cells and decreased ICAM-1 expression and neutrophil adhesion on SECs. These findings suggest that Kupffer cells are involved in neutrophil adhesion and migration in hepatic sinusoids via TNF-alpha production and induction of ICAM-1 expression on SECs during liver injury associated with endotoxemia.

Suicide gene therapy of human hepatoma and its peritonitis carcinomatosis by a vector of replicative-deficient herpes simplex virus.

Herpes simplex virus type 1 (HSV-1) deleted for the immediate-early gene was applied for treatment of hepatoma cells of SKHep 1 and Huh-7. Hepatoma cells were cultured in medium containing HSV1 expressing GFP gene (QOZ/HG) to determine its transfection rate, and both cell lines infected by MOI 1 of QOZ/HG were found to have high expression of GFP without cytotoxicity. Subcutaneous growth of SKHep 1 cell tumor in nude mice was significantly reduced by injection of replicative-deficient herpes virus (TOZ.1) containing Tk-gene with administration of GCV, in comparison with that of noninjected tumor. SCID mice of peritonitis carcinomatosis due to Huh-7 hepatoma cells infected with TOZ.1 could survive longer under administration of GCV than those without TOZ.1. Therefore replicative-deficient HSV1 is a useful vector for treatment of human hepatoma cells, and TOZ.1 with GCV may be applied to suicide gene therapy for hepatoma and peritonitis carcinomatosis of hepatoma cells.

Polyethylenimine-mediated suicide gene transfer induces a therapeutic effect for hepatocellular carcinoma in vivo by using an Epstein-Barr virus-based plasmid vector.

The present study aimed to establish a novel efficient nonviral strategy for suicide gene transfer in hepatocellular carcinoma (HCC) in vivo. We employed branched polyethylenimine (PEI) and combined it with Epstein-Barr virus (EBV)-based plasmid vectors. The HCC cells transfected with an EBV-based plasmid carrying the herpes simplex virus-1 thymidine kinase (HSV-1 Tk) gene (pSES.Tk) showed up to 30-fold higher susceptibilities to ganciclovir (GCV) than those transfected with a conventional plasmid vector carrying the HSV-1 Tk gene (pS.Tk). The therapeutic effect in vivo was tested by intratumoral injection of the plasmids into HuH-7 hepatomas transplanted into C.B-17 scid/scid mutant (SCID) mice and subsequent GCV administrations. Treatment with pSES.Tk, but not pS.Tk, markedly suppressed growth of hepatomas in vivo, resulting in a significantly prolonged survival period of the mice. These findings suggest that PEI-mediated gene transfer system can confer efficient expression of the suicide gene in HCC cells in vivo by using EBV-based plasmid vectors.