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On-treatment predictions of success in peg-interferon/ribavirin treatment using a novel formula

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World Journal of Gastroenterology 2010年第1期16卷 89-97页

作者： Hidetsugu Saito Hirotoshi Ebinuma Keisuke Ojiro Kanji Wakabayashi Mika Inoue Shinichiro Tada toshifumi hibi Department of Internal Medicine School of MedicineKeio University

AIM:To predict treatment success using only simple clinical data from peg-interferon plus ribavirin therapy for chronic hepatitis C. METHODS:We analyzed the clinical data of 176 patients with chronic hepatitis and hepatitis C virus genotype 1 who received 48 wk standard therapy, derived a predictive formula to assess a sustained virological response of the individual patient using a logistic regression model and confirmed the validity of this *** formula was constructed using data from the first 100 patients enrolled and validated using data from the remaining 76 patients. RESULTS:Sustained virological response was obtained in 83(47.2%)of the patients and we derived formulae to predict sustained virological response at pretreatment and weeks 4,12 and *** likelihood of sustained virological response could be predicted effectively bythe formulae at weeks 4,12 and 24(the area under the curve of the receiver operating characteristic:0.821, 0.802,and 0.891,respectively),but not at baseline (0.570).The formula at week 48 was also constructed and validation by test data achieved good prediction with 0.871 of the area under the curve of the receiver operating *** by this formula was always superior to that by viral kinetics. CONCLUSION:These results suggested that our formula combined with viral kinetics provides a clear direction of therapy for each patient and enables the best tailored treatment.

关键词： Logistic regression analysis Predictive formula Prolongation of the therapy Response-guided therapy Viral kinetics

High expressions of caveolins on the proliferating bile ductules in primary biliary cirrhosis

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World Journal of Gastroenterology 2005年第24期11卷 3710-3713页

作者： Hiroaki Yokomori Masaya Oda Go Wakabayashi Masaki Kitajima Kazunori Yoshimura Masahiko Nomura toshifumi hibi Department of Internal Medicine Organized Center of Clinical Medicine Department of Surgery Department of Physiology

AIM: An increase in bile ductular structures is observed in diverse human liver diseases, especially in primary biliary cirrhosis (PBC). These structures harbor the progenitor cell component of the liver. Caveolins are cholesterol-binding proteins involved in the regulation of several intracellular processes including cholesterol transport. This study aims to examine the role of caveolin in ***: Immunohistochemical and Western blottingstudies were performed on human liver specimens obtained from patients with PBC and normal liver samples. The expression of caveolin (CAV)-1 and -2 was determined using specific ***: In normal liver, scanty immunostaining for CAV1 and -2 was observed in bile ductules. In PBC liver samples, the expression levels of CAV-1 and -2 were increased on proliferating bile ductules especially in stage 3 cases, but was sparse on interlobular bile duct in stage 1 specimens. Especially, the regenerating bile ductules at the interface of portal tracts and necrotic areas were immunostained intensely for CAV-1 and -2. These phenomena were confirmed by Western ***: The present results demonstrate increased expression of caveolins in proliferating bile ductules in PBC, which may be related to the homeostasis of cholesterol transport in regenerating bile ductules in PBC liver.

关键词： Proliferating bile ductule Caveolin Immunohis tochemistry Primary biliary cirrhosis

Enhanced plasma ghrelin levels in Helicobacter py/ori-colonized, interleukin-1-receptortype 1-homozygous knockout (IL-1R1-/-) mice

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World Journal of Gastroenterology 2005年第27期11卷 4148-4153页

作者： Yuka Abiko Hidekazu Suzuki Tatsuhiro Masaoka Sachiko Nomura Kumiko Kurabayashi Hiroshi Hosoda Kenji Kangawa toshifumi hibi Department of Internal Medicine and Center for Integrated Medical Research Department of Biochemistry

AIM： Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor, and it plays a role in stimulating the growth hormone secretion, food intake,body weight gain and gastric motility. Eradication of Helicobacterpylori （H pylon） was shown to be associated with increase of the body weight. On the other hand, Hpylori infection evokes the release of gastric IL-1β. The present study was designed to investigate the involvement of the gastric IL-1 signal in the ghrelin dynamics in Hpyloricolonized ***： Twelve-week-old female IL-l-receptor type 1-homozygous-knockout mice （IL-1R1^-/-） and their wild-type littermates （WT） were orally inoculated with H pylori （Hp group）, while other cohorts received oral inoculation of culture medium （Cont group）. Thirteen weeks after the inoculation, the mice were examined. The plasma and stomach ghrelin levels and the gastric preproghrelin mRNA were ***： Although the WT mice with Hpyloriinfection showed a significantly decreased body weight as compared with that of the animals without HpyloriinfecUon,Hpyloriinfection did not influence the body weight of the IL-1Rl-knockout （IL-1R1^-/-） mice. In the Hpylori-infected IL-1R1＋ mice, the total and active ghrelin levels in the plasma were significantly increased, and the gastric ghrelin level was decreased. No significant differences were noted in the gastric preproghrelin mRNA ***： Ghrelin secretion triggered by H pylori infection might be suppressed by IL-1β, the release of which is also induced by the infection, resulting in the body weight loss of mice with Hpyloriinfection.

关键词： Ghrelin Hpylori IL-1 Body weight Myelo-peroxidase

Herbal cardiotonic pills prevent gut ischemia/reperfusion-induced hepatic microvascular dysfunction in rats fed ethanol chronically

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World Journal of Gastroenterology 2005年第4期11卷 511-515页

作者： Yoshinori Horie Shuka Mori Masahiro Konishi Mikio Kajihara Takehiko Kaneko Yoshiyuki Yamagishi Shinzo Kato Hiromasa Ishii toshifumi hibi Department of Internal Medicine School of Medicine Keio University Tokyo Japan

AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaettn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, Salviae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation. Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/ reperfusion (I/R) in rats fed ethanol chronically. METHODS: Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 min after the onset of superior mesenteric artery occlusion. Plasma tumor necrosis factor (TNF)-α and endotoxin levels were measured 1 h after the onset of reperfusion. Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia. RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-α and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats, the gut I/R-induced increases in the number of stationary leukocytes, plasma endotoxin levels and ALT activities were enhanced. Pretreatment with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption. CONCLUSION: These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular inju

关键词： Intestinal reperfusion injury Hepatic microvascular dysfunction Cardiotonic Pill Ethanol

Expression of adhesion molecules on mature cholangiocytes in canal of Hering and bile ductules in wedge biopsy samples of primary biliary cirrhosis

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World Journal of Gastroenterology 2005年第28期11卷 4382-4389页

作者： Hiroaki Yokomori Masaya Oda Mariko Ogi Go Wakabayashi Shigeyuki Kawachi Kazunori Yoshimura Toshihiro Nagai Masaki Kitajima Masahiko Nomura toshifumi hibi Department of Internal Medicine Kitasato Institute Medical Center Hospital Saitama 364-8501Japan Organized Center of Clinical Medicine International University of Health and Welfare Tokyo 107-0052Japan Laboratory of Pathology Kitasato Institute Medical Center Hospital Saitama 364-8501Japan Department of Surgery School of Medicine Keio UniversityTokyo 160-0016Japan Physiology Saitama Medical School Saitama 350-0495Japan Electron Microscopy Laboratory School of Medicine Keio UniversityTokyo 160-0016Japan Department of Internal Medicine School of Medicine Keio UniversityTokyo 160-0016Japan

AIM：To examine the expression of intercellular adhesion molecule-1 （ICAM-1） and lymphocyte function-associated antigen-1（LFA-1）expression on canals of Hering （COH）and bile ductules associated with the autoimmune process of bile duct destruction in primary biliary cirrhosis（PBC）．METHODS：Ten wedged liver biopsies of PBC（five cases each of stages 2 and 3）were studied. The liver specimens were processed for transmission electron microscopy. Immunohistochemistry was performed using anti-ICAM-1 and anti-LFA-1 mouse *** situ hybridization was done to examine the messenger RNA expression of ICAM-1 in ***-embedded sections using peptide nucleic acid probes and the catalyzed signal amplification （CSA）***-silver staining for electron microscopy was Derrormed using anti-ICAM and anti-LFA-1 mouse *** immunogold particles on epithelial cells of bileductules and cholangiocytes of CoH cells were counted and analyzed *** blotting was performed to confirm ICAM-1 protein expression．RESULTS：In liver tissues of PBC ***-stochemistry showed aberrant ICAM-1 expression on the plasma membrane of epithelial cells lining bile ductules，and also on mature cholangiocytes but not on hepatocytes in ***-1-positive lymphocytes were closely associated with epithelial cells in bile ***-1 expression at protein level was confirmed by Western *** situ hybridization demonstrated ICAM-1 mRNA expression in bile ductules and LFA-1 mRNA in lymphocytes infiltrating the *** immunoelectron microscopy，ICAM-1 was demonstrated on the basal suface of epithelial cells in bile ductules and on the luminal surfaces of cholangiocytes in damaged *** with intermediate morphology resembling progenitor cells in Coil were not labeled with ICAM-1 and LFA-1．CONCLUSION：De novo expression of ICAM-1 both on mature cholangiocytes in COH and epithelial cells in bile ductules in PBC implies that lymphocyte-indu

关键词： Primary biliary cirrhosis Canal of Hedng Small bile ductile ICAM-1 LFA-1 Immunohistochemistry Western blot Immunogold electron microscopyPrimary biliary cirrhosis Canal of Hedng Small bile ductile ICAM-1 LFA-1 Immunohistochemistry Western blot Immunogold electron microscopy

Method for Detecting NADPH-Cytochrome P450 Reductase in Liver Microsomal Fractions by Using Native Polyacrylamide Gel Electrophoresis and NADPH-Diaphorase Staining

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American Journal of Analytical Chemistry 2013年第6期4卷 301-305页

作者： Hirokazu Yokoyama Yukishige Okamura toshifumi hibi Department of Internal Medicine School of Medicine Keio University Shinanomachi Shinjukuku Tokyo Japan

By combining native polyacrylamide gel electrophoresis (PAGE) and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining, a simple method for detecting NADPH-cytochrome P450 reductase in tissue samples was established. When rat liver microsomal fractions were examined by this method, several bands with different mobility were visualized. Western blot analysis indicated that the band which appeared in the most anodal position among them represented NADPH-cytochrome P450 reductase. SDS-PAGE/Western blot analysis revealed that the molecular weight of the protein forming the band was around 80 kDa, which was identical to that of rat NADPH-cytochrome P450 reductase. The intensity level of NADPH-diaphorase staining assigned to this enzyme estimated by this method increased four times in microsomal fractions prepared from rat fed ethanol chronically compared to that from controls. When a dilution series of a rat liver microsomal fraction was examined by this method and SDS-PAGE/Western blot analysis, their staining intensities representing this enzyme were significantly correlated with each other. Using the naive PAGE/NADPH-diaphorase staining method, NADPH-cytochrome P450 reductase is detected in rat liver microsomes. This method is beneficial because compared with the conventional SDS-PAGE/Western blot analysis, the quantification of NADPH-cytochrome P450 reductase in tissue samples is allowed to be more easily done.

关键词： NADPH-Cytochrome p450 Reductase Native PAGE NADPH-Diaphorase Staining Chronic Ethanol Consumption

Surveillance using trimodal imaging endoscopy after endoscopic submucosal dissection for superficial gastric neoplasia

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World Journal of Gastroenterology 2014年第43期20卷 16311-16317页

作者： Hiroyuki Imaeda Naoki Hosoe Kazuhiro Kashiwagi Yosuke Ida Rieko Nakamura Hidekazu Suzuki Yoshimasa Saito Naohisa Yahagi Yasushi Iwao Yuko Kitagawa toshifumi hibi Haruhiko Ogata Takanori Kanai Department of General Internal Medicine Saitama Medical UniversitySaitama 350-0495Japan Center for Diagnostic and Therapeutic Endoscopy School of MedicineKeio UniversityTokyo 108-8345Japan Division of Gastroenterology Department of Internal MedicineSchool of MedicineKeio UniversityTokyo 108-8345Japan Cancer Center School of MedicineKeio UniversityTokyo 108-8345Japan Center for Preventive Medicine School of MedicineKeio UniversityTokyo 108-8345Japan Department of Surgery School of MedicineKeio UniversityTokyo 108-8345Japan

AIM: To evaluate the effectiveness of trimodal imaging endoscopy (TME) to detect another lesion after endoscopic submucosal dissection (ESD) for superficial gastric neoplasia (SGN).

关键词： Autofluorescence imaging Endoscopic submucosal dissection Superficial gastric neoplasia

Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction

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World Journal of Gastroenterology 2012年第21期18卷 2735-2738页

作者： Toshihiro Nishizawa Hidekazu Suzuki Takama Maekawa Naohiko Harada Tatsuya Toyokawa Toshio Kuwai Masanori Ohara Takahiro Suzuki Masahiro Kawanishi Kenji Noguchi Toshiyuki Yoshio Shinji Katsushima Hideo Tsuruta Eiji Masuda Munehiro Tanaka Shunsuke Katayama Norio Kawamura Yuko Nishizawa toshifumi hibi Masahiko Takahashi Division of Gastroenterology National Hospital Organization Tokyo Medical CenterTokyo 1528902 Japan Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of MedicineTokyo 1608582 Japan Division of Gastroenterology National Hospital Organization Kyoto Medical CenterKyoto 6128555 Japan Division of Gastroenterology National Kyushu Medical CenterFukuoka 8108563 Japan Division of Gastroenterology National Hospital Organization Fukuyama Medical CenterFukuyama 7208520 Japan Division of Gastroenterology National Hospital Organization Kure Medical CenterKure 7370023 Japan Division of Gastroenterology National Hospital Organization Hakodate Medical CenterHakodate 0418512 Japan Division of Gastroenterology National Hospital Organization Maizuru Medical CenterMaizuru 6258502 Japan Division of Gastroenterology National Hospital Organization Higashihiroshima Medical CenterHigashihiroshima 7390041 Japan Division of Gastroenterology National Hospital Organization Sendai Medical CenterSendai 9838520 Japan Division of Gastroenterology National Hospital Organization Osaka Medical CenterOsaka 5400006 Japan Division of Gastroenterology National Hospital Organization Ureshino Medical CenterUreshino 8430393 Japan Division of Gastroenterology National Hospital Organization Osaka Minami Medical CenterKawachinagano 5868521 Japan Division of Gastroenterology National Hospital Organization Fukuoka Higashi Medical CenterKoga 8113195 Japan Division of Gastroenterology National Hospital Organization Yonago Medical CenterYonago 6838518 Japan Division of Gastroenterology National Hospital Organization Disaster Medical CenterTachikawa 1900014 Japan Pharmaceutical Department National Center for Global Health and MedicineTokyo 1658655 Japan

We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)- AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the 13C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to followup. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%,respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.

关键词： Helicobacter pylori Amoxicillin Dual therapy Eradication Urea breath test

Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery

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World Journal of Gastroenterology 2007年第26期13卷 3581-3591页

作者： Jing-Yan Han Yoshinori Horie Soichiro Miura, Yasutada Akiba Jun Guo Dan Li Jing-Yu Fan Yu-Ying Liu Bai-He Hu Li-Hua An Xin Chang Man Xu De-An Guo Kai Sun Ji-Ying Yang Shu-Ping Fang Ming-Ji Xian Masahiro Kizaki Hiroshi Nagata toshifumi hibi Department of Integration of Chinese and Western Medicine School of Basic Medical Sciences Peking University Beijing 100083 China Department of Internal Medicine School of Medicine Keio University Tokyo 160-8582 Tokyo Japan Second Department of Internal Medicine National Defense Medical College Saitama 359-8513 Saitama Japan Tasly Microcirculation Research Center Peking University Health Science Center Beijing 100083 China

AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system. METHODS: LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation,such as diameters of arterioles and venules,velocity of RBCs in venules,leukocyte rolling,adhesion and emigration,free radicals released from post-capillary venules,FITC- albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile,the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils,and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro. RESULTS: The continuous infusion with LPS resulted in a number of responses in microcirculation,including a significant increase in the positive region of venulestained with Monastral blue B,rolling and adhesion of leukocytes,production of oxygen radical in venular wall,albumin efflux and enhanced mast cell degranulation in vivo,all of which,except for the leukocyte rolling,were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils,and the expression of ICAM-1 in HUVECs were increased by exposure to LPS,and they were attenuated by compound Danshen injection. CONCLUSION: These results suggest that compound Danshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance.

关键词： Compound Danshen Mesenteric microci-rculation Oxygen-free radical Adhesion molecules Lipopolysaccharide