Kazuo Ohba

Fatty liver in non-alcoholic non-overweight Japanese adults: Incidence and clinical characteristics

Background and Aims: Fatty liver is not uncommon in many countries, including Japan, and is mainly caused by alcohol usage and obesity. The aim of this study was to determine the incidence and causative factors of fatty liver in Japanese adults.

Ghrelin enhances gastric motility through direct stimulation of intrinsic neural pathways and capsaicin-sensitive afferent neurones in rats

Background: Ghrelin may stimulate gastric motility via the vagal nerve pathway. However, the mechanism of ghrelin-induced changes in gastrointestinal motility has not yet been clearly defined. The present study was designed to investigate whether ghrelin accelerates gastric emptying via capsaicin-sensitive afferent neurones and directly affects the enteric neuromuscular function. Methods: Gastric emptying of nutrient solids was assessed after intravenous administration of saline or ghrelin in conscious rats. The effects of ghrelin on gastric emptying were also examined in rats pretreated with capsaicin. Gastric emptying and intestinal transit of non-caloric liquids were evaluated using [Formula: See Text]Cr solution. The effects of ghrelin on spontaneous contractile activities of isolated strips from stomach and jejunum were also investigated and the influence of ghrelin on motor responses to carbachol and electrical field stimulation was examined. Results: Ghrelin significantly accelerated gastric emptying of both nutrient solids and non-caloric liquids in conscious rats. The intestinal transit of non-caloric liquids was also enhanced by ghrelin. Pretreatment with capsaicin prevented the ghrelin-induced acceleration of gastric emptying of nutrient solids. Ghrelin did not modulate spontaneous and carbachol-induced contractions of strips of gastric body, gastric antrum and jejunum. However, electrical field stimulation-induced contractions were significantly enhanced by ghrelin in the gastric body. Conclusions: The results suggest that the stimulatory effects of ghrelin on gastric motility are mediated by direct stimulation of the enteric neural pathway and capsaicin-sensitive afferent neurones.

Elevated levels of chemokines in esophageal mucosa of patients with reflux esophagitis.

Abstract Objective Chemokines play a key role in the pathogenesis of various inflammatory conditions. However, there is little information on their profile in reflux esophagitis (RE). We sought to study esophageal mucosa levels of chemokines in RE. Methods A total of 32 outpatients with RE and 13 normal controls were studied. Endoscopic severity of RE was classified according to the Los Angeles grading system. Paired biopsy specimens were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap frozen for measurement of mucosal levels of interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES), and IL-1β by enzyme linked immunosorbent assays, while the other was formalin-fixed for histopathological evaluation. Results IL-8, MCP-1, and RANTES levels were significantly higher in esophageal mucosa of RE patients than those of the controls. IL-8 levels correlated significantly with the endoscopic severity of RE. Basal zone hyperplasia and papillary elongation, histopathological hallmarks of RE, were both associated with higher levels of IL-8 and MCP-1. The presence of intraepithelial neutrophils and eosinophils, which also indicate RE, was associated with high levels of IL-8 and RANTES, respectively. There were no significant differences in IL-1β levels between the RE and control groups, but IL-1β levels correlated significantly with the IL-8 production. Again, the IL-8 levels were significantly decreased after lansoprazole treatment. Conclusion Our results indicate that chemokines produced locally in the esophageal mucosa may be involved in the development and progression of RE.

Clinicopathological study of nonalcoholic fatty liver disease in Japan: the risk factors for fibrosis.

Background/Aims: We evaluated patients with nonalcoholic fatty liver disease (NAFLD) and compared the clinical and pathological features to identify the risk factors for NAFLD with severe fibrosis.

Relation among plasma ghrelin level, gastric emptying, and psychologic condition in patients with functional dyspepsia.

Background and Goals Neurohormonal factors might play a role in the pathogenesis of functional dyspepsia (FD). However, the role of ghrelin, a gastrointestinal hormone that stimulates gastric motility, in FD is not yet clearly defined. The present study was designed to investigate plasma ghrelin levels and their relation with gastric emptying and psychologic status in FD. Methods Sixteen patients with FD of the dysmotility type and 19 healthy controls were enrolled in the study. Plasma active and desacyl ghrelin concentrations before and after test meal were measured by enzyme-linked immunosorbent assay. Gastric emptying and psychologic condition were studied using 13C acetate breath test and questionnaires, respectively. Results Gastric emptying was significantly prolonged in patients with FD compared with controls. Fasting desacyl and total ghrelin levels were significantly lower in FD patients than in controls, but fasting active ghrelin levels and postprandial levels of ghrelin in both forms were similar between the 2 groups. Fasting total ghrelin levels in FD patients did not differ from the postprandial levels, in contrast to what was found for controls. There was no significant association among gastric emptying, plasma ghrelin levels, and psychologic factors in FD patients. Conclusions Total secretory ability or metabolic condition of ghrelin may be altered in patients with FD. This seems to play a role in the pathophysiology of dysmotility type FD, independent of delayed gastric emptying or psychologic disorders.

Baseline Serum Cholesterol Is Associated with a Response to Pegylated Interferon Alfa-2b and Ribavirin Therapy for Chronic Hepatitis C Genotype 2

Background. HCV infection is associated with lipid disorders because this virus utilizes the host lipid metabolism to sustain its life cycle. Several studies have indicated that higher concentrations of serum cholesterol and LDL before treatment are important predictors of higher rates of sustained virological response (SVR). However, most of these studies involved patients infected with HCV genotype 1. Thus, we performed a multi-institutional clinical study to evaluate the impact of lipid profiles on SVR rates in patients with HCV genotype 2. Methods. A total of 100 chronic hepatitis C patients with HCV genotype 2 who received peg-IFN alfa-2b and ribavirin therapy were consecutively enrolled. The significance of age, sex, BMI, AST level, ALT level, WBC, hemoglobin, platelet count, gamma-glutamyltransferase, total cholesterol level (TC), LDL level, HCV RNA, and histological evaluation was examined for SVR using logistic regression analysis. Results. The 100 patients infected with HCV genotype 2 were divided into 2 groups, an SVR group and a non-SVR group. Characteristics of each group were subsequently compared. There was no significant difference in the level of HCV RNA, BMI, platelet, TG, or stage of fibrosis between the groups. However, there were significant differences in the levels of TC and LDL-C. In multivariate logistic regression analysis using baseline characteristics, high TC level was an independent and significant risk factor (relative risk 18.59, P = 0.015) for SVR. Conclusion. Baseline serum total cholesterol levels should be considered when assessing the likelihood of sustained treatment response following the course of peg-IFN and ribavirin therapy in patients with chronic HCV genotype 2 infection.

High plasma osteopontin levels in patients with inflammatory bowel disease.

Background Osteopontin (OPN) plays a key role in the progression of TH1-immune-mediated disease in models of multiple sclerosis and rheumatoid arthritis. Aim To determine whether plasma OPN levels in patients with inflammatory bowel disease are associated with disease activity. Methods Plasma samples were obtained from patients with ulcerative colitis (UC, n=30), Crohns disease (CD, n=30), and healthy volunteers (controls, n=30) and enzyme immunoassay was performed. Results Plasma OPN concentrations were significantly higher in patients with Crohns disease than in controls (951.9±538.5 ng/mL and 659.0±163.7 ng/mL, respectively). OPN concentrations in patients with UC were also higher than in the controls (1149.6±791.0 and 659.0±163.7, respectively). There was a significant difference in plasma OPN level between active UC and inactive UC (2102.0±552.8 and 649.4±313.0, respectively). Moreover, a significant correlation was observed between plasma OPN concentration and disease activity, as determined by the clinical activity index in patients with UC. Conclusions Our results indicate that the plasma concentrations of OPN are elevated in patients with UC and that OPN expression is correlated with clinical activity. These results provide insight into UC pathogenesis and suggest that OPN may be a useful tool for assessing disease activity.

Pseudomyxoma peritonei accompanied by intraductal papillary mucinous neoplasm of the pancreas

We describe a case ofpseudomyxoma peritonei (PMP) successfully managed with intraperitoneal hyperthermic chemoperfusion. This case is unique due to the concurrent presence of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The patient presented with abdominal fullness. Abdominal computed tomography revealed massive ascites, thickened peritoneum, and a cystic lesion of the pancreas. Cytological examination of ascitic fluid sample showed mucin-rich atypical cells. Endoscopic retrograde pancreatography revealed a cystic lesion with the defect probably due to mural nodule and mucin, communicating with the pancreatic duct. At exploratory laparotomy, massive ascites and multiple nodules were identified within the peritoneal cavity. No primary tumour, including mucinous neoplasm of the appendix, was found. Histopathological examination of the omentum showed mucinous adenocarcinoma in pools of mucoid material, consistent with PMP. The relation between PMP and IPMN of the pancreas was possible, but not conclusive. The patient received intraperitoneal perfusion of saline heated to 42°C containing cisplatin, etoposide, and mitomycin C, followed by 24 courses of postoperative chemotherapy with gemcitabine. The patient remains in good general condition with no signs of progression of PMP for 2 years, but with a gradual and progressive enlargement of the pancreatic cystic lesion.

Primary biliary cirrhosis among atomic bomb survivors in Nagasaki, Japan

Despite rapid progress in methods for analyzing radiation effects, much remains to be learned about the mechanisms and processes of radiation-induced immunological dysfunction. Among 17,899 sera obtained from atomic bomb survivors in Nagasaki, Japan, sera from 484 participants who complied with a reexamination for alkaline phosphatase (ALP) were tested for antimitochondrial antibody (AMA) by indirect immunofluorescence, and autoantibodies against 2-oxo-acid dehydrogenase complex (2-OADC) by immunoblotting to investigate the prevalence of primary biliary cirrhosis (PBC). Of these 484 sera, 28 (5.8%) were seropositive for AMA. The 484 participants were divided into three groups according to distance from the hypocenter: 72 who were exposed within 1999 m (closest group), 368 from 2000 to 5999 m (intermediate distant group), and 44 outside 6000 m (distant group). The positivity rates for AMA in these three groups were 6/72 (8.3%), 22/368 (6.0%), and 0/44 (0%), respectively (P =.08). Furthermore, high titers ( > 1:320) of AMA were observed in 3/6 (50%) AMA-positive sera from the closest group, in contrast to 4/22 (18%) from the intermediate distant group, although there was no significant correlation between AMA titer and distance from the hypocenter (P =.07). Of these 28 AMA-positive sera, 11 (39%) were from participants who had already been diagnosed with PBC, and 25 (89%) contained antibodies against at least one component of 2-OADC enzymes by immunoblotting. Therefore, the prevalence of PBC was estimated to be at least 615 cases per million (792 per million women). Our results suggest that the prevalence of PBC in atomic bomb survivors in Nagasaki is higher than that reported for the general population in Japan, and a further survey of the environmental factors, including radiation exposure, that predispose to PBC would be needed for understanding this disease of unknown etiology.

Correlation between histopathological findings of the liver and IgA class antibodies to 2-oxo-acid dehydrogenase complex in primary biliary cirrhosis

Although anti-mitochondrial antibody (AMA) is the characteristic serological feature of primary biliary cirrhosis (PBC), its pathogenetic role remains unclear. We tested sera from 72 Japanese patients with histologically confirmed PBC for AMA by indirect immunofluorescence, anti-pyruvate dehydrogenase complex (PDC) by enzyme inhibition assay, immunoglobulin (Ig) G class anti-PDC by ELISA, and IgG, IgM, and IgA class anti-2-oxo-acid dehydrogenase complex (2-OADC) by immunoblotting. Of the 72 sera, 60 (83%), 50 (69%), 42 (58%), and 71 (99%) were positive for AMA by immunofluorescence, enzyme inhibition assay, ELISA, and immunoblotting, respectively. There was no significant correlation between histological stages and AMA by immunofluorescence, PDC inhibitory antibodies by enzyme inhibition assay, IgG class anti-PDC antibodies by ELISA, or IgG and IgM class anti-2-OADC by immunoblotting. IgA class anti-2-OADC by immunoblotting was more frequent in stages 2–4 than in stage 1 (P = 0.0083). Of the IgA class anti-2-OADC, anti-PDC-E2 (74 kDa) and anti-E3BP (52 kDa) were more frequent in stages 2–4 than in stage 1 (P = 0.0253 and 0.0042, respectively). Further examination of histopathological findings in 53 of 72 liver biopsy specimens showed that IgA class anti-PDC-E2 and IgA class anti-E3BP were associated with bile duct loss, and IgA class anti-PDC-E2 was also associated with interface hepatitis and atypical ductular proliferation. IgA is known to be secreted into the bile through biliary epithelial cells, implying that IgA class anti-PDC-E2 and E3BP may have a specific pathogenetic role during their transport into the bile by binding to their target antigen(s) in biliary epithelial cells, and this may be followed by dysfunction and finally destruction of biliary epithelial cells. Our present results suggest that these autoantibodies against 2-OADC detected by immunoblotting may be associated with the pathogenesis and pathologic progression of PBC.