M Enjoji

Kyushu University, Hukuoka, Fukuoka, Japan

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Publications (342)867.72 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the metabolic changes in skeletal muscle and/or adipose tissue in glucagon-like peptide-1-induced improvement of nonalcoholic fatty liver disease (NAFLD). Male Wistar rats were fed either a control diet (control group) or a high-fat diet (HFD). After 4 wk, the HFD-fed rats were subdivided into two groups; one group was injected with exenatide [HFD-Ex(+) group] and the other with saline [HFD-Ex(-) group] every day for 12 wk. The control group received saline and were fed a control diet. Changes in weight gain, energy intake, and oxygen consumption were analyzed. Glucose tolerance tests were performed after 8 wk of treatment. Histological assessments were performed in liver and adipose tissue. RNA expression levels of lipid metabolism related genes were evaluated in liver, skeletal muscle, and adipose tissue. Exenatide attenuated weight gain [HFD-Ex(-) vs HFD-Ex(+)] and reduced energy intake, which was accompanied by an increase in oxygen consumption and a decrease in the respiratory exchange ratio [HFD-Ex(-) vs HFD-Ex(+)]. However, exenatide did not affect glucose tolerance. Exenatide reduced lipid content in the liver and adipose tissue. Exenatide did not affect the expression of lipid metabolism-related genes in the liver or skeletal muscle. In adipose tissue, exenatide significantly upregulated lipolytic genes, including hormone-sensitive lipase, carnitine palmitoyltransferase-1, long-chain acyl-CoA dehydrogenase, and acyl-CoA oxidase 1 [HFD-Ex(-) vs HFD-Ex(+)]. Exenatide also upregulated catalase and superoxide dismutase 2 [HFD-Ex(-) vs HFD-Ex(+)]. In addition to reducing appetite, enhanced lipid use by exenatide in adipose tissue may reduce hepatic lipid content in NAFLD, most likely by decreasing lipid influx into the liver.
    World Journal of Gastroenterology 03/2014; 20(10):2653-63. · 2.55 Impact Factor
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    ABSTRACT: Background & AimsInjury to biliary epithelial cells caused by disorders in bile composition may be the initial step in the pathogenesis of primary biliary cirrhosis (PBC). We therefore examined choline/phospholipid metabolism in livers of patients with PBC. Methods Hepatic levels of mRNA encoded by choline metabolism-related genes in early stage PBC patients were quantified by real-time RT-PCR. Serum cholesterol and triglyceride concentrations in each lipoprotein compartment and serum/tissue choline levels were also measured. OCT1 expression was quantified by genotype (rs683369 and rs622342). ResultsSerum choline concentrations were significantly higher in PBC patients than in normal individuals, with the concentrations in the former lowered by treatment with fibrates. Hepatic choline levels were markedly lower in PBC patients than in controls. The levels of expression of genes associated with choline uptake (OCT1 and CTL1), phosphatidylcholine synthesis (PEMT and BHMT), and phosphatidylcholine transport (MDR3) were significantly upregulated in PBC compared with control livers. Serum cholesterol concentrations and the cholesterol/triglyceride ratio in serum VLDL were markedly higher in PBC patients than in controls. In PBC liver, OCT1 protein levels were lower in patients with minor (CG/GG at rs683369 and/or CC at rs622342) than major (CC at rs683369 and AA at rs622342) genotypes of the OCT1 gene. Conclusions During early stage PBC, hepatocellular choline uptake and PC synthesis become dysregulated. OCT1 genotypes may influence the pathogenesis of PBC.This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 03/2014; · 3.87 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of health problems in Western (industrialized) countries. Moreover, the incidence of infantile NAFLD is increasing, with some of these patients progressing to nonalcoholic steatohepatitis. These trends depend on dietary habits and life-style. In particular, overeating and its associated obesity affect the development of NAFLD. Nutritional problems in patients with NAFLD include excess intake of energy, carbohydrates, and lipids, and shortages of polyunsaturated fatty acids, vitamins, and minerals. Although nutritional therapeutic approaches are required for prophylaxis and treatment of NAFLD, continuous nutrition therapy is difficult for many patients because of their dietary habits and lifestyle, and because the motivation for treatment differs among patients. Thus, it is necessary to assess the nutritional background and to identify nutritional problems in each patient with NAFLD. When assessing dietary habits, it is important to individually evaluate those that are consumed excessively or insufficiently, as well as inappropriate eating behaviors. Successful nutrition therapy requires patient education, based on assessments of individual nutrients, and continuing the treatment. In this article, we update knowledge about NAFLD, review the important aspects of nutritional assessment targeting treatment success, and present some concrete nutritional care plans which can be applied generally.
    World Journal of Gastroenterology 02/2014; 20(7):1756-1767. · 2.55 Impact Factor
  • 02/2014; 105(2):42-7.
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    ABSTRACT: Although the mechanisms responsible for acute liver failure (ALF) have not yet been fully elucidated, studies have indicated that intrahepatic macrophage activation plays an important role in the pathogenesis of ALF through intrahepatic microcirculatory disorder and consequent parenchymal cell death. Intrahepatic microcirculatory disorder has been demonstrated in animal models using intravital microscopy; however, the limitations of this method include simultaneously evaluating blood flow and the surrounding pathological changes. Therefore, in this study, we devised a novel method involving tetramethylrhodamine isothiocyanate (TRITC)-dextran administration for the pathological assessment of hepatic microcirculation. In addition, we aimed to elucidate the mechanisms through which intrahepatic microcirculatory disorder progresses with relation to activated macrophages. ALF was induced in Wistar rats by exposure to lipopolysaccharide and D-galactosamine. Intrahepatic microcirculation and microcirculatory disorder in zone 3 (pericentral zone) of the livers of rats with ALF was observed. Immunohistochemical examinations in conjunction with TRITC-dextran images revealed that the macrophages were mainly distributed in zone 2 (intermediate zone), while cleaved caspase-3-positive hepatocytes, pimonidazole and hypoxia-inducible factor 1-α were abundant in zone 3. We also found that 4-hydroxy-2-nonenal and nicotinamide adenine dinucleotide phosphate oxidase (NOX)4-positive cells were predominantly located in the zone 3 parenchyma. The majority of apoptotic hepatocytes in zone 3 were co-localized with NOX4. Our results revealed that the apoptotic cells in zone 3 were a result of hypoxic conditions induced by intrahepatic microcirculatory disorder, and were not induced by activated macrophages. The increased levels of oxidative stress in zone 3 may contribute to the progression of hepatocyte apoptosis.
    International Journal of Molecular Medicine 12/2013; · 1.96 Impact Factor
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    ABSTRACT: To analyzed the association between inosine triphosphatase (ITPA) (rs1127354) genotypes and sustained virological response (SVR) rates in peginterferon (Peg-IFN)α + ribavirin (RBV) treatment. Patients who underwent Peg-IFNα + RBV combination therapy were enrolled (n = 120) and they had no history of other IFN-based treatments. Variation in hemoglobin levels during therapy, cumulative reduction of RBV dose, frequency of treatment withdrawal, and SVR rates were investigated in each ITPA genotype. In patients with ITPA CC genotype, hemoglobin decline was significantly greater and the percentage of patients in whom total RBV dose was < 60% of standard and/or treatment was withdrawn was significantly higher compared with CA/AA genotype. However, SVR rates were equivalent between CC and CA/AA genotypes, and within a subset of patients with Interleukin 28B (IL28B) (rs8099917) TT genotype, SVR rates tended to be higher in patients with ITPA CC genotype, although the difference was not significant. ITPA CC genotype was a disadvantageous factor for Peg-IFNα + RBV treatment in relation to completion rates and RBV dose. However, CC genotype was not inferior to CA/AA genotype for SVR rates. When full-length treatment is accomplished, it is plausible that more SVR is achieved in patients with ITPA CC variant, especially in a background of IL28B TT genotype.
    World journal of gastrointestinal pharmacology and therapeutics. 08/2013; 4(3):54-60.
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    ABSTRACT: The prognosis of patients with hepatocellular carcinoma (HCC) may be improved by novel treatments focusing on the characteristic metabolic changes of this disease. Therefore, we analyzed the biological interactions of metabolic features with the degree of tumor differentiation and the level of malignant potential in 41 patients with completely resectable HCC. The expression levels in resected samples of mRNAs encoded by genes related to tumor metabolism and metastasis were investigated, and the correlation between these expression levels and degrees of differentiation was analyzed. Of the 41 patients, 2 patients had grade I, 27 had grade II, and 12 had grade III tumors. Reductions in the levels of 3-hydroxyacyl-CoA dehydrogenase (HADHA) and acyl-CoA oxidase (ACOX)-2 mRNAs, and increases in pyruvate kinase isoenzyme type M2 (PKM2) mRNA were significantly correlated with the progression of de-differentiation. Analysis of partial correlation coefficients showed that the level of PKM2 mRNA expression was significantly correlated with those of pro-angiogenic genes, vascular endothelial growth factor (VEGF) and ETS-1. Moreover, the levels of VEGF-A and ETS-1 mRNA expression were independently correlated with that of the epithelial-mesenchymal transition (EMT)‑related gene SNAIL. These findings suggest that reductions in fatty acid oxidation and responses to hypoxia may affect the progression of malignant phenotypes in HCC.
    Molecular Medicine Reports 11/2012; · 1.17 Impact Factor
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    ABSTRACT: Despite the use of pegylated-interferon (peg-IFN) plus ribavirin combination therapy, many patients infected with hepatitis C virus (HCV)-1b remain HCV-positive. To determine whether addition of pitavastatin and eicosapentaenoic acid (EPA) is beneficial, the "add-on" therapy option (add-on group) was compared retrospectively with unmodified peg-IFN/ribavirin therapy (standard group). Association of host- or virus-related factors with sustained virological response was assessed. In HCV replicon cells, the effects of pitavastatin and/or EPA on HCV replication and expression of innate-immunity- and lipid-metabolism-associated genes were investigated. In patients infected with HCV-1b, sustained virological response rates were significantly higher in the add-on than standard group. In both groups, sustained virological response rates were significantly higher in patients with genotype TT of IL-28B (rs8099917) than in those with non-TT genotype. Among the patients with non-TT genotype, sustained virological response rates were markedly higher in the add-on than standard group. By multivariate analysis, genome variation of IL28B but not add-on therapy remained as a predictive factor of sustained virological response. In replicon cells, pitavastatin and EPA suppressed HCV replication. Activation of innate immunity was obvious in pitavastatin-treated cells and EPA suppressed the expression of sterol regulatory element binding protein-1c and low-density lipoprotein receptor. Addition of pitavastatin and EPA to peg-IFN/ribavirin treatment improved sustained virological response in patients infected with HCV-1b. Genotype variation of IL-28B is a strong predictive factor in add-on therapy. J. Med. Virol. © 2012 Wiley Periodicals, Inc.
    Journal of Medical Virology 11/2012; · 2.37 Impact Factor
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    ABSTRACT: Background and Aims:  Magnifying endoscopy (ME) with narrow-band imaging (NBI) revealed a white opaque substance (WOS) within the superficial part of the gastric neoplasia; however, its nature has remained obscure. A WOS noted within the duodenum was reported to comprise lipid droplets (LD) absorbed by the duodenal epithelium. We attempted to ascertain whether the WOS within gastric neoplasia could also comprise LD and whether the presence of this WOS could be correlated with a specific phenotype. Methods:  Forty-three patients with early gastric epithelial neoplasia underwent ME with NBI. The presence or absence of WOS in the neoplasias was recorded based on the findings of ME with NBI. One biopsy specimen was taken from each of the neoplasias. Cryostat sections underwent oil red O staining for LD. Serial sections were immunostained using the first antibody of CD10, MUC2, CDX2, human gastric mucin, MUC5AC and MUC6. The tissue phenotype was classified as intestinal (I), gastric (G) and gastrointestinal (GI) type based on the results of immunostaining. In total, 49 gastric neoplasias from 43 patients were investigated. Results:  Prevalence of LD in WOS-positive versus WOS-negative lesions was 96.2% (25/26) and 4.3% (1/23), respectively (P < 0.001, Fisher's exact test). WOS was present in GI- and I-type lesions, but not in G-type lesions. Conclusions:  WOS may be LD that have been accumulated in the superficial part of the gastric neoplasia of a certain intestinal phenotype.
    Digestive Endoscopy 11/2012; 24(6):419-25. · 1.61 Impact Factor
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    ABSTRACT: To investigate the effects of antithrombin III (AT III) injection via the portal vein in acute liver failure. Thirty rats were intraperitoneally challenged with lipopolysaccharide (LPS) and D-galactosamine (GalN) and divided into three groups: a control group; a group injected with AT III via the tail vein; and a group injected with AT III via the portal vein. AT III (50 U/kg body weight) was administrated 1 h after challenge with LPS and GalN. Serum levels of inflammatory cytokines and fibrin degradation products, hepatic fibrin deposition, and hepatic mRNA expression of hypoxia-related genes were analyzed. Serum levels of alanine aminotransferase, tumor necrosis factor-α and interleukin-6 decreased significantly following portal vein AT III injection compared with tail vein injection, and control rats. Portal vein AT III injection reduced liver cell destruction and decreased hepatic fibrin deposition. This treatment also significantly reduced hepatic mRNA expression of lactate dehydrogenase and heme oxygenase-1. A clinically acceptable dose of AT III injection into the portal vein suppressed liver damage, probably through its enhanced anticoagulant and anti-inflammatory activities.
    World Journal of Gastroenterology 04/2012; 18(16):1884-91. · 2.55 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that ranges in severity from simple steatosis to cirrhosis. NAFLD is considered to be associated with hepatic metabolic disorders, resulting in overaccumulation of fatty acids/triglycerides and cholesterol. The pathogenesis and progression of NAFLD are generally explained by the "two-hit theory." Most studies of lipid metabolism in the NAFLD liver have focused on the metabolism of fatty acids/triglycerides; therefore, the impact of cholesterol metabolism is still ambiguous. In this paper, we review recent studies on NAFLD from the viewpoint of hepatic lipid metabolism-associated factors and discuss the impact of disordered cholesterol metabolism in the etiology of NAFLD. The clinical significance of managing cholesterol metabolism, an option for the treatment of NAFLD, is also discussed.
    International journal of hepatology. 01/2012; 2012:925807.
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    ABSTRACT: Nutritional states of Japanese patients with liver cirrhosis have recently shown great diversity, some show protein energy malnutrition and others excessive nutrition and obesity. For there to be adequate guidance regarding dietary treatment, it is important that a patient's current nutritional state be clarified. We assessed nutritive intake in Japanese cirrhotic patients and determined their nutritional problems. Subjects were non-hospitalized patients with hepatitis C virus (HCV)-related cirrhosis in the compensated stage (n=47), chronic hepatitis C (n=46) or healthy volunteers (n=32). A brief self-administered diet history questionnaire was conducted with assistance from a registered dietitian. We categorized patients with cirrhosis according to daily intake of energy and protein; 10.6% had an energy and protein intake within a normal range, 72.4% showed excessive intake, and 17.0% showed insufficient intake of energy or protein. In cirrhotic patients with diabetic complications, the intake levels of energy, proteins, fat and carbohydrates were significantly higher than in patients without diabetes. Moreover, cirrhotic patients had significantly higher intake levels of energy, protein and fat than did chronic hepatitis C patients and healthy individuals. In patients with HCV-related liver cirrhosis, insufficient intake of energy and protein was shown in some, while many, especially those with diabetes, showed excessive intake. For nutritive management of cirrhotic patients, the intake of various nutrients should be appropriately assessed and effective nutritional education systems established.
    Asia Pacific Journal of Clinical Nutrition 01/2012; 21(3):400-5. · 1.06 Impact Factor
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    ABSTRACT: Residual hepatic functional reserve in cirrhotic patients is generally evaluated by a multivariate scoring system (Child-Pugh classification), which includes serum albumin levels as a variable. However, several patients show discrepancies between serum albumin levels and the progression of liver fibrosis, especially those with alcoholic cirrhosis. To assess whether hepatic capacity of protein synthesis varies with the etiology of cirrhosis, serum albumin and cholinesterase levels, and prothrombin time were compared between alcoholic cirrhosis and hepatitis C virus (HCV)-related cirrhosis. To minimize the influence of malnutrition and extrahepatic platelet destruction, patients with hepatocellular carcinoma, uncontrolled diabetes, appetite loss and/or splenal longitudinal size >15 cm were excluded. The patients with compensated liver cirrhosis were divided into three groups as follows: alcohol(+)/HCV(+) (alcohol + HCV group; n=31), alcohol(-)/HCV(+) (HCV group; n=31) and alcohol(+)/HCV(-) (alcohol group; n=27). These groups were adjusted with respect to age, gender, body mass index and platelet count. Serum albumin levels in the alcohol group were significantly higher than those in the HCV group, with a difference of approximately 0.5 g/dl in every class of platelet count. The correlation of the alcohol + HCV group was intermediate between the alcohol and HCV groups. On the other hand, the correlations between serum cholinesterase levels and platelet counts were similar among the three groups. The prothrombin time was also comparable among the groups. Accordingly, serum albumin levels were higher in patients with alcoholic cirrhosis and alcohol consumption should be carefully considered when evaluating hepatic functional reserve.
    Experimental and therapeutic medicine 01/2012; 3(1):72-75. · 0.34 Impact Factor
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    ABSTRACT: It has been reported that hepatitis C virus (HCV) infection is closely associated with hepatic metabolic disorders. Hepatic steatosis and insulin resistance are both relatively common in patients with chronic hepatitis C. Recent investigations suggest that HCV infection changes the expression profile of lipid-metabolism-associated factors in the liver, conferring advantages to the life cycle of HCV. Moreover, insulin resistance and steatosis are independent predictors of impaired response to antiviral treatment in chronic hepatitis C. In this paper, we summarize our current knowledge of hepatic metabolic disorders and describe how HCV leads to and exploits these hepatic disorders. We also discuss the clinical significance of insulin sensitizers used to improve insulin resistance and lipid modulators used to manage lipid metabolism as potential treatment options for chronic hepatitis C.
    International journal of hepatology. 01/2012; 2012:264017.
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    ABSTRACT: Am80, a synthetic retinoid, has been used in differentiation therapy for acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) as one of natural retinoid has been also used to treat APL. ATRA treatment causes neuronal differentiation by inducing tropomyosin-related kinase B (TrkB) expression and increasing the sensitivity to brain-derived neurotrophic factor (BDNF), a TrkB ligand. In the present study, we investigated the effects of Am80 on neuronal differentiation, BDNF sensitivity and TrkB expression in human neuroblastoma SH-SY5Y cells. Treatment with Am80 induced morphological differentiation of neurite outgrowth and increased the expression of GAP43 mRNA, a neuronal differentiation marker. Additionally, TrkB protein was also increased, and exogenous BDNF stimulation after treatment with Am80 induced greater neurite outgrowth than without BDNF treatment. These results suggest that Am80 induced neuronal differentiation by increasing TrkB expression and BDNF sensitivity.
    Biomedical Research 01/2012; 33(5):291-7. · 1.15 Impact Factor
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    ABSTRACT: The dietary intake of patients with nonalcoholic fatty liver disease (NAFLD) is generally characterized by high levels of carbohydrate, fat, and/or cholesterol, and these dietary patterns influence hepatic lipid metabolism in the patients. Therefore, careful investigation of dietary habits could lead to better nutrition therapy in NAFLD patients. The main treatment for chronic hepatitis C (CHC) is interferon-based antiviral therapy, which often causes a decrease in appetite and energy intake; hence, nutritional support is also required during therapy to prevent undernourishment, treatment interruption, and a reduction in quality of life. Moreover, addition of some nutrients that act to suppress viral proliferation is recommended. As a substitutive treatment, low-iron diet therapy, which is relatively safe and effective for preventing hepatocellular carcinoma, is also recommended for CHC patients. Some patients with liver cirrhosis (LC) have decreased dietary energy and protein intake, while the number of LC patients with overeating and obesity is increasing, indicating that the nutritional state of LC patients has a broad spectrum. Therefore, nutrition therapy for LC patients should be planned on an assessment of their complications, nutritional state, and dietary intake. Late evening snacks, branched-chain amino acids, zinc, and probiotics are considered for effective nutritional utilization.
    Gastroenterology Research and Practice 01/2012; 2012:859697. · 1.62 Impact Factor
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    ABSTRACT: Dipeptidyl peptidase-4 (DPP4) is a serine protease that degrades glucagon-like peptide-1 (GLP-1), an incretin hormone that stimulates insulin secretion from pancreatic β-cells. DPP4 is also involved in the regulation of T cell-mediated inflammatory processes. These properties of DPP4 suggest that it may play a role in the progression of non-alcoholic fatty liver disease (NAFLD). Hepatic DPP4 mRNA expression levels were analyzed by real-time PCR using liver biopsy samples from 17 NAFLD patients and 10 healthy subjects. In NAFLD patients, we also examined correlations between DPP4 expression levels and metabolic factors, including homeostasis model assessment-insulin resistance (HOMA-IR), body mass index (BMI), and serum cholesterol and triglyceride levels. To examine the potential effects of nutritional factors, DPP4 expression levels were analyzed in HepG2 cells subjected to various culture conditions. Hepatic DPP4 mRNA expression was significantly greater in NAFLD patients than in control subjects. DPP4 expression levels were negatively correlated with HOMA-IR and positively correlated with serum cholesterol levels. In HepG2 cells, high glucose significantly enhanced DPP4 expression, whereas insulin, fatty acids and cholesterol did not. Increased hepatic expression of DPP4 in NAFLD may be associated with metabolic factors, including insulin resistance, and may adversely affect glucose metabolism in this liver disease.
    Molecular Medicine Reports 12/2011; 5(3):729-33. · 1.17 Impact Factor
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    ABSTRACT: We aimed to assess differences in early viral dynamics following treatment with either peg-IFNalpha2a or peg-IFNalpha2b in combination with ribavirin in patients with chronic genotype 1b HCV infection. Sixty-one patients in the peg-IFNalpha2a + ribavirin treatment (group alpha2a) and 88 patients in the peg-IFNalpha2b + ribavirin treatment (group alpha2b) were retrospectively analyzed. The early dynamics of HCV RNA over 12 weeks were evaluated. Sustained virological response (SVR) was defined as undetectable HCV RNA at week 24 after end of therapy. First- (day 0-1) and second-phase (day 1-28) viral decline rates were calculated in accordance with theoretical formulae. Baseline HCV RNA concentrations were almost similar between the 2 groups. In group alpha2a, viral decline was significantly greater than in group alpha2b at weeks 4, 8, and 12. In group alpha2a, viral decline was significantly greater in SVR patients than in non-SVR patients at week 2, whereas significantly greater viral decline in SVR patients was found during weeks 1-12 in group alpha2b. The first-phase viral decline rate was significantly larger in group alpha2a than in group alpha2b (1.31 ± 0.84 vs. 0.70 ± 0.97 log IU/mL/day; p < 0.0001). Within SVR patients, first-phase viral decline rate was significantly larger in group α2a compared with group alpha2b (1.45 ± 0.85 vs. 0.78 ± 1.0 log IU/mL/day; p < 0.0001). Second-phase viral decline rate was comparable between the groups. Peg-IFNalpha2a showed earlier viral decline than peg-IFNalpha2b and the difference was obvious, especially in the first-phase viral decline.
    Medical science monitor: international medical journal of experimental and clinical research 12/2011; 17(12):CR687-91. · 1.22 Impact Factor
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    ABSTRACT: Pancreatic cancer (PC) has a poor clinical prognosis with a <10% 5-year survival rate. Because there are no specific biomarkers of PC, it is difficult to detect small PC tumors and most patients are diagnosed at an advanced stage. Specific biomarkers are useful tools for the early detection of cancer. However, PC-related biomarkers, such as CA19-9 lack specificity and sensitivity. In this study, we took an immunological approach to establish novel monoclonal antibodies (mAbs) specific for the pancreatic juice from PC patients, which would be potentially useful in the diagnosis of PC. Mice were immunized by subtractive immunization using mixed pancreatic juices from chronic pancreatitis and PC patients as the tolerogen and the immunogen, respectively. After screening by Western blotting, four mAbs were obtained: 2P-1-2-1, 2P-1-17-1, 6P-3-2-4 and 7P-9-11-6. The mAb 2P-1-2-1 showed reactivity against the tolerogen at 115 and 120 kDa, but only the 120-kDa antigen was also reactive to the immunogen. The mAb 2P-1-17-1 showed an intense smear reactivity at ~150 kDa against the immunogen. Finally, the mAbs 6P-3-2-4 and 7P-9-11-6 showed PC-specific reactivity to the immunogen at >250 kDa and at ~70 kDa, respectively. We propose that investigation of pancreatic juice samples with these mAbs may enable us to perform reliable differential diagnosis of benign and malignant diseases. Furthermore, we demonstrated that subtractive immunization is a useful method for producing mAbs specific for the pancreatic juice from PC patients.
    International Journal of Molecular Medicine 06/2011; 28(4):599-603. · 1.96 Impact Factor
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    ABSTRACT: Disturbances in hepatic microcirculation are believed to be involved in the mechanisms regulating the progression of acute liver injury (ALI). Evaluation of hepatic hemodynamics in patients with acute liver injury might be helpful in understanding the extent of the intrahepatic microcirculatory disturbances. Therefore, we investigated whether contrast-enhanced ultrasonography (CEUS) is useful to evaluate the changes in hepatic hemodynamics in patients with ALI. CEUS was performed in 21 patients with ALI and coagulopathy. Participants were injected with 0.0075 mL Sonazoid/kg body weight, and time-intensity curves were simultaneously recorded for the hepatic and portal veins. The data were compared with those of 10 healthy volunteers. The arrival time of Sonazoid in the hepatic vein was similar to that in the portal vein in the patients, whereas the arrival time in the hepatic vein was delayed relative to that in the portal vain in the controls (interval between the hepatic and portal vein arrival times, control vs patients 6.74 ± 3.07 s vs 1.13 ± 1.07 s, P < 0.001). Repeated examination revealed that the interval between the hepatic and portal vein arrival times was extended by improvements in hepatic function. The early arrival of Sonazoid in the hepatic vein in the patients is likely to reflect the formation of intrahepatic shunts as a result of hepatic microcirculatory disturbances. CEUS using Sonazoid is a useful method to estimate the changes in hepatic hemodynamics in patients with ALI.
    Journal of Gastroenterology and Hepatology 05/2011; 26(12):1749-56. · 3.33 Impact Factor

Publication Stats

6k Citations
867.72 Total Impact Points

Institutions

  • 1974–2013
    • Kyushu University
      • • Graduate School of Medical Sciences
      • • Medical Institute of Bioregulation - MIB Hospital
      • • Faculty of Medical Sciences
      • • Division of Pathobiology
      • • Division of Internal Medicine
      Hukuoka, Fukuoka, Japan
  • 2012
    • Kyoto Prefectural University of Medicine
      • Graduate School of Medical Science
      Kioto, Kyōto, Japan
  • 2008–2012
    • Kyushu Medical Center
      Hukuoka, Fukuoka, Japan
    • Fukuoka University
      • Faculty of Pharmaceutical Sciences
      Fukuoka-shi, Fukuoka-ken, Japan
  • 2009
    • Fukuoka City Hospital Organization
      Hukuoka, Fukuoka, Japan
  • 1997–2000
    • Baylor College of Medicine
      • Department of Medicine
      Houston, Texas, United States
  • 1993
    • University of Occupational and Environmental Health
      • School of Medicine
      Kitakyūshū, Fukuoka-ken, Japan
  • 1992
    • St.Mary's Hospital (Fukuoka - Japan)
      Hukuoka, Fukuoka, Japan