記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Non-invasive imaging techniques have greatly advanced the assessment of liver fibrosis and steatosis but are not fully evaluated in overweight patients. We evaluated the diagnostic performance of vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE) to assess fibrosis and controlled attenuation parameter (CAP) and MR imaging (MRI)-proton density fat fraction (MRI-PDFF) to assess steatosis in overweight and obese patients with non-alcoholic fatty liver disease (NAFLD). We included 163 biopsy-proven patients with NAFLD who underwent VCTE, MRE/MRI-PDFF, and liver biopsy (years 2014-2020) who were classified according to their body mass index (BMI) as normal (BMI < 25 kg/m2, n = 38), overweight (25 ≤ BMI < 30 kg/m2, n = 68), and obese (BMI ≥ 30 kg/m2, n = 57). VCTE and MRE detected fibrosis of stages ≥ 2, ≥ 3, and 4 with an area under the receiver operating curve (AUROC) of 0.83-0.94 (VCTE) and 0.85-0.95 (MRE) in all groups, without considerable differences. MRI-PDFF detected steatosis of grades ≥ 2 and 3 with high AUROC in all groups (0.81-1.00). CAP's diagnostic ability (0.63-0.95) was lower than that of MRI-PDFF and decreased with increasing BMI compared to MRI-PDFF. VCTE and MRE similarly accurately assess fibrosis, although MRI-PDFF is more accurate than CAP in detecting steatosis in overweight and obese patients with NAFLD.

DOI： 10.1038/s41598-022-25843-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: SmartExam is a novel computational method compatible with FibroScan that uses a software called SmartDepth and continuous controlled attenuation parameter measurements to evaluate liver fibrosis and steatosis. This retrospective study compared the diagnostic accuracy of conventional and SmartExam-equipped FibroScans for liver stiffness measurement (LSM). METHODS: The liver stiffness and the associated controlled attenuation parameters of 167 patients were measured using conventional and SmartExam-Equipped FibroScan as well as reference methods like magnetic resonance elastography (MRE) and magnetic resonance imaging-based proton density fat fraction measurements (MRI-PDFF) to assess its diagnostic performance. M or XL probes were selected based on the probe-to-liver capsule distance for all FibroScan examinations. RESULTS: The liver stiffness and controlled attenuation parameter (CAP) correlation coefficients calculated from conventional and SmartExam-equipped FibroScan were 0.97 and 0.82, respectively. Using MRE/MRI-PDFF as a reference and the DeLong test for analysis, LSM and the area under the receiver operating characteristic curve for CAP measured by conventional and SmartExam-equipped FibroScan showed no significant difference. However, the SmartExam-equipped FibroScan measurement (33.6 seconds) took 1.4 times longer than conventional FibroScan (23.2 seconds). CONCLUSIONS: SmartExam has a high diagnostic performance comparable to that of conventional FibroScan. Since the results of the conventional and SmartExam-equipped FibroScan were strongly correlated, it can be considered useful for assessing the fibrosis stage and steatosis grade of the liver in clinical practice, with less variability but little longer measurement time compared to the conventional FibroScan.

DOI： 10.1111/jgh.16076

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND & AIMS: As alternatives to the expensive liver biopsy for assessing liver fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD), we directly compared the diagnostic abilities of magnetic resonance elastography (MRE), vibration-controlled transient elastography (VCTE), and two-dimensional shear wave elastography (2D-SWE). METHODS: Overall, 231 patients with biopsy-proven NAFLD were included. Intra- and inter-observer reproducibility was analyzed using intraclass correlation coefficient in a sub-group of 70 participants, in whom liver stiffness measurement (LSM) was performed by an elastography expert and an ultrasound expert who was an elastography trainee on the same day. RESULTS: Valid LSMs were obtained for 227, 220, 204, and 201 patients using MRE, VCTE, 2D-SWE, and all three modalities combined, respectively. Although the area under the curve did not differ between the modalities for detecting stage ≥1, ≥2, and ≥3 liver fibrosis, it was higher for MRE than VCTE and 2D-SWE for stage 4. Sex was a significant predictor of discordance between VCTE and liver fibrosis stage. Skin-capsule distance and the ratio of the interquartile range of liver stiffness to the median were significantly associated with discordance between 2D-SWE and liver fibrosis stage. However, no factors were associated with discordance between MRE and liver fibrosis stage. Intra- and inter-observer reproducibility in detecting liver fibrosis was higher for MRE than VCTE and 2D-SWE. CONCLUSIONS: MRE, VCTE, and 2D-SWE demonstrated excellent diagnostic accuracy in detecting liver fibrosis in patients with NAFLD. MRE demonstrated the highest diagnostic accuracy for stage 4 detection and intra- and inter-observer reproducibility. UMIN Clinical Trials Registry No. UMIN000031491.

DOI： 10.1016/j.cgh.2020.12.016

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: Liver stiffness measurement (LSM) and spleen stiffness measurement (SSM@50 Hz) using standard vibration-controlled transient elastography (VCTE) have been studied as a noninvasive test for screening of gastroesophageal varices (GEV) in chronic liver disease (CLD). Recently, a novel spleen-dedicated VCTE (SSM@100 Hz) has been developed. We evaluated the diagnostic performance of SSM@100 Hz, SSM@50 Hz, LSM, and other noninvasive tests using esophagogastroduodenoscopy (EGD) as the reference as well as the correlation with hepatic venous pressure gradient (HVPG). METHODS: A total of 123 patients with CLD enrolled in this cross-sectional study. SSM@100 Hz, SSM@50 Hz, and LSM were determined by VCTE. EGD and HVPG were performed within 12 weeks before or after VCTE. RESULTS: GEV were present in 60 patients. Failure or suboptimal SSM were fewer at 100 Hz (4.0%) than at 50 Hz (17.7%). All SSM values obtained at 100 Hz were lower than the 100 kPa ceiling threshold, but 10 patients reached the 75 kPa ceiling threshold for SSM@50 Hz. SSM@100 Hz was most accurate (area under the receiver operating characteristic [AUROC] = 0.944) for the diagnosis of GEV compared to SSM@50 Hz, LSM, and scoring systems. AUROC of SSM@100 Hz for diagnosis of high-bleeding risk varices (HRV) was 0.941, which was significantly higher than that of SSM@50 Hz (AUROC = 0.842, P = 0.002). SSM@100 Hz showed higher specificity (82.0%) for diagnosis of HRV than SSM@50 Hz (specificity = 67.1%). SSM@100 Hz was significantly correlated with HVPG (r = 0.71, P < 0.001). CONCLUSIONS: The novel spleen-dedicated VCTE examination can be used for noninvasive assessment of GEV and HVPG in CLD. Japan Registry of Clinical Trials Registry No. jRCTs032200119.

DOI： 10.1002/jgh3.12689

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The role of hepatic iron overload (HIO) in nonalcoholic fatty liver disease (NAFLD) pathogenesis has not been fully elucidated. PURPOSE: This study aimed to investigate the effect of HIO and examine the diagnostic usefulness of magnetic resonance imaging (MRI)-based R2* quantification in evaluating hepatic iron content (HIC) and pathological findings in NAFLD. STUDY TYPE: Prospective and retrospective. POPULATION: A prospective study of 168 patients (age, 57.2 ± 15.0; male/female, 80/88) and a retrospective validation study of 202 patients (age, 57.0 ± 14.4; male/female, 113/89) with liver-biopsy-confirmed NAFLD were performed. FIELD STRENGTH/SEQUENCE: 3 T; chemical-shift encoded multi-echo gradient echo. ASSESSMENT: Using liver tissues obtained by liver biopsy, HIC was prospectively evaluated in 168 patients by atomic absorption spectrometry. Diagnostic accuracies of HIC and R2* for grading hepatic inflammation plus ballooning (HIB) as an indicator of NAFLD activity were assessed. STATISTICAL TESTS: Student's t-test and analysis of variance (ANOVA) with Scheffe's multiple testing correction for univariate comparisons; multivariate logistic analysis. P-value less than 0.05 is statistically significant. RESULTS: HIC was significantly correlated with HIB grades (r = 0.407). R2* was significantly correlated with HIC (r = 0.557) and HIB grades (r = 0.569). R2* mapped an area under the receiver operating characteristic (AUROC; 0.774) for HIC ≥808 ng/mL (median value) with cutoff value of 62.5 s-1 . In addition, R2* mapped AUROC of HIB for grades ≥3 was 0.799 with cutoff value of 58.5 s-1 . When R2* was <62.5 s-1 , R2* correlated weakly with HIC (r = 0.372) as it was affected by fat deposition and did not correlate with HIB grades (P = 0.052). Conversely, when R2* was ≥62.5 s-1 , a significant correlation of R2* with HIC (r = 0.556) and with HIB grades was observed (P < 0.0001) with being less affected by fat deposition. DATA CONCLUSION: R2*  ≥ 62.5 s-1 is a promising modality for non-invasive diagnosis of clinically important high grades (≥3) of HIB associated with increased HIC. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

DOI： 10.1002/jmri.27810

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The treatment of diabetes has a significant impact on the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We compared the effectiveness of tofogliflozin, a selective sodium-glucose cotransporter 2 inhibitor, and pioglitazone for the treatment of NAFLD patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: This open-label, prospective, single-center, randomized clinical trial recruited NAFLD patients with type 2 diabetes mellitus and a hepatic fat fraction of at least 10% as assessed based on the MRI-proton density fat fraction (MRI-PDFF). Eligible patients were stratified according to hemoglobin A1c (HbA1c), alanine transaminase, and MRI-PDFF levels and randomly assigned (1:1) to receive either 20 mg tofogliflozin or 15-30 mg pioglitazone, orally, once daily for 24 weeks. The primary endpoint was an absolute change in MRI-PDFF at 24 weeks. Efficacy and safety was assessed in all treated patients. This trial was registered in the Japan Registry of Clinical Trials. RESULTS: Overall, 40 eligible patients were randomly assigned to receive tofogliflozin (n=21) or pioglitazone (n=19). Changes in hepatic steatosis after 24 weeks of treatment were evaluated by MRI-PDFF, which showed a significant decrease in both groups (-7.54% (p<0.0001) and -4.12% (p=0.0042) in the pioglitazone and tofogliflozin groups, respectively). Compared with baseline, the body weight decreased by 2.83±2.86 kg (-3.6%, p=0.0443) in the tofogliflozin group and increased by 1.39±2.62 kg (1.7%, p=0.0002) in the pioglitazone group after 24 weeks. No life-threatening events or treatment-related deaths occurred. CONCLUSIONS: Tofogliflozin was well tolerated, and it reduced the MRI-PDFF levels in NAFLD patients with type 2 diabetes mellitus. TRIAL REGISTRATION NUMBER: jRCTs031180159.

DOI： 10.1136/bmjdrc-2020-001990

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most common chronic liver disease worldwide, along with the concurrent epidemics of metabolic syndrome and obesity. Patients with NAFLD have increased risks of end-stage liver disease, hepatocellular carcinoma, and liver-related mortality. However, the largest cause of death among patients with NAFLD is cardiovascular disease followed by extrahepatic malignancies, whereas liver-related mortality is only the third cause of death. Extrahepatic complications of NAFLD include chronic kidney disease, extrahepatic malignancies (such as colorectal cancer), psychological dysfunction, gastroesophageal reflux disease, obstructive sleep apnea syndrome, periodontitis, hypothyroidism, growth hormone deficiency, and polycystic ovarian syndrome. The objective of this narrative review was to summarize recent evidences about extrahepatic complications of NAFLD, with focus on the prevalent/incident risk of such diseases in patients with NAFLD. To date, an appropriate screening method for extrahepatic complications has not yet been determined. Collaborative care with respective experts seems to be necessary for patient management because extrahepatic complications can occur across multiple organs. Further studies are needed to reveal risk profiles at baseline and to determine an appropriate screening method for extrahepatic diseases.

DOI： 10.3390/diagnostics10110912

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Japan Society of Hepatology  

DOI： 10.2957/kanzo.61.504

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

症例は45歳女性。急性骨髄性白血病に対して同種骨髄移植が行われ、移植後はタクロリムス、ステロイドによる免疫抑制療法を18ヵ月継続した。移植前はHBV既往感染の状態であったが、移植から38ヵ月後に肝機能障害、HBs抗原陽転化、HBV-DNA量上昇を認め、HBV再活性化と診断した。同種骨髄移植前後に赤血球濃厚液の頻回の輸血によりヘモクロマトーシスを合併していた影響もあり、血清フェリチン値は著明高値であった。肝生検では過剰な鉄沈着と急性肝炎の所見を認めた。ラミブジンにより治療を開始し、その後テノホビルアラフェナミドへ切り替えた。HBV再活性化とヘモクロマトーシスの関連性は不明であったが、HBV治療と鉄キレート剤により血清フェリチン値も漸減した。HBV既往感染状態での同種骨髄移植では、長期間にわたりHBV再活性化への注意が必要である。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The laxative drug lubiprostone improves intestinal permeability in healthy volunteers. We aimed to assess efficacy and safety of lubiprostone in patients with non-alcoholic fatty liver disease (NAFLD) with constipation via attenuation of intestinal permeability. METHODS: This randomised, double-blind, placebo-controlled, phase 2a study in Yokohama City University Hospital, Japan, recruited patients (aged 20-85 years) with NAFLD and constipation, alanine aminotransferase (ALT) at least 40 U/L, liver stiffness (≤6·7 kPa), and hepatic fat fraction at least 5·2% when assessed by MRI-proton density fat fraction. Eligible patients were randomly assigned (11:10:9) by a computer-based system and stratified by age and sex to receive 24 μg lubiprostone, 12 μg lubiprostone, or placebo, orally, once per day for 12 weeks. The primary endpoint was the absolute changes in ALT at 12 weeks. Efficacy analysis was done by intention to treat. Safety was assessed in all treated patients. This trial was registered with University Hospital Medical Information Network Clinical Trials Registry (UMIN000026635). FINDINGS: Between March 24, 2017, and April 3, 2018, we screened 288 patients, of whom 150 (52%) were randomly assigned to treatment: 55 patients were assigned to receive 24 μg lubiprostone, 50 to receive 12 μg lubiprostone, and 45 to receive placebo. A greater decrease in the absolute ALT levels from baseline to 12 weeks was seen in the 24 μg lubiprostone group (mean -13 U/L [SD 19]) than in the placebo group (1 U/L [24]; mean difference -15 U/L [95% CI -23 to -6], p=0·0007) and in the 12 μg lubiprostone group (-12 U/L [21]) than in the placebo group (mean difference -13 U/L [-22 to -5], p=0·0023). 18 (33%) of 55 patients in the 24 μg group had at least one adverse event, as did three (6%) of 47 patients in the 12 μg group and three (7%) of 43 in the placebo group. The most common adverse event was diarrhoea (17 [31%] of patients in the 24 μg group, three [6%] in the 12 μg group, none in the placebo group). No life-threatening events or treatment-related deaths occurred. INTERPRETATION: Lubiprostone was well tolerated and reduced the levels of liver enzymes in patients with NAFLD and constipation. Further studies are necessary to better define the efficacy and tolerability of lubiprostone in patients with NAFLD without constipation. FUNDING: Mylan EPD G.K.

DOI： 10.1016/S2468-1253(20)30216-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Non-alcoholic fatty liver disease (NAFLD) is associated with a higher risk of atherosclerotic disease. However, the relationships between the severity of coronary atherosclerosis and pathologic findings in patients with NAFLD remain unknown. We aimed to characterize the coronary artery lesions in patients with NAFLD using coronary computed tomography angiography (CCTA). Overall, 101 patients with liver biopsy-proven NAFLD who had chest pain or electrocardiographic abnormalities underwent CCTA. Coronary artery lesions, including coronary artery stenosis (CAS), calcium score (CACS, Agatston score), and coronary artery non-calcified plaque were assessed using multi-slice CT. Multivariate analysis showed that age, smoking status, prevalence of dyslipidemia (DLP) and non-alcoholic steatohepatitis (NASH), and stage of fibrosis were independent risk factors for CAS. Age, and the prevalence of DM and DLP, were independent risk factors for CACS, and the prevalence of NASH tended to be an independent risk factor. In addition, the prevalence of DLP and NASH were independent risk factors for non-calcified plaques. Coronary artery lesions are more common in patients with NASH than in those with non-alcoholic fatty liver, suggesting a higher risk in patients with NASH. Therefore, patients with NASH should be closely followed, with particular vigilance for coronary artery diseases.

DOI： 10.3390/diagnostics10030129

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/hepr.13349

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Publishing  

Background and Aim: In the condition of high prevalence of non-alcoholic fatty liver disease (NAFLD), a new diagnostic algorithm to efficiently identify NAFLD patients with significant fibrosis is urgently required. We evaluated the predictive ability of the fibrosis-4 index (FIB-4 index) for significant liver fibrosis (F ≥ 2) in a cohort of Japanese patients with NAFLD. Methods: We prospectively calculated the FIB-4 index in patients who were incidentally diagnosed as fatty liver in medical checkups and then conducted liver stiffness measurement by vibration-controlled transient elastography (VCTE) only in patients in whom the FIB-4 index was more than the low cut-off index (&gt
 1.45). Results: Of the 5929 people who underwent medical checkups, a total of 1374 people were identified as having fatty liver. Among these, we performed VCTE in 106 patients in whom the FIB-4 index was higher than 1.45. The distribution of the fibrosis stage as estimated by VCTE in the patients was as follows: F0, 52.8%
F1, 10.3%
F2, 21.6%
F3, 11.3%
and F4, 3.7%. The positive predictive value of the FIB-4 index for detecting NAFLD with significant fibrosis was 36.6%. The minimum value of the FIB-4 index was constant for each estimated fibrosis stage. Conclusions: This is the first prospective study to evaluate the usefulness of the FIB-4 index as the first step to screen NAFLD patients with significant fibrosis. In Japan, addition of one further step that combined with the FIB-4 index is necessary to meaningfully reduce the number of patients needing liver stiffness measurement or liver biopsy.

DOI： 10.1111/jgh.14559

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jgh.14559

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jgh.14294

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: This paper reports the protocol of a randomised, double-blind, placebo-controlled study to test the efficacy, safety, and tolerability of lubiprostone (LUB) vs. placebo on suppressing gut permeability in non-alcoholic fatty liver disease (NAFLD) patients with constipation. NAFLD, including non-alcoholic steatohepatitis (NASH), is a common chronic liver disorder. Progression is associated with increased gut permeability and gut-derived endotoxins. Most NAFLD/NASH clinical trial drugs aim to improve liver function or systemic metabolism. LUB is a type 2 chloride channel activator used as a laxative for the treatment of patients with constipation. LUB suppresses gut permeability induced by non-steroidal anti-inflammatory drugs in healthy volunteers and lowers blood endotoxin levels. There have been no clinical studies of LUB for NAFLD/NASH patients. METHODS: The study plans to enrol adult patients (20-85 years, planned enrolment, n = 150; planned sample size, n = 120) with NAFLD and constipation, alanine aminotransferase ≥40 IU/L, equivalent steatosis grade ≥1, and equivalent fibrosis stage <4 measured using non-invasive vibration-controlled transient elastography and magnetic resonance imaging. Participants will be randomly allocated into three groups: LUB 12 μg, LUB 24 μg, and a placebo group. RESULTS: The primary endpoint will be changes in alanine aminotransferase from baseline at 12 weeks. The main secondary endpoint will be changes in intestinal permeability from baseline at 12 weeks using the lactulose mannitol ratio. CONCLUSIONS: This study will determine whether LUB improves gut permeability in NAFLD patients with constipation. TRIAL REGISTRATION: This trial is registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000026635).

DOI： 10.1016/j.cct.2018.04.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jgh.14156

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with increased risks of atherosclerotic diseases, including cardiovascular disease. However, the difference in risk between patients with non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) has not yet been determined. Accumulating evidence has shown that high amounts of small dense low-density lipoprotein (sdLDL) are closely associated with atherosclerotic diseases. This study investigated differences in risk factors for atherosclerotic diseases, especially LDL-migration index (LDL-MI), an indicator of sdLDL, between patients with NAFL and NASH.
Methods: LDL-MI was analyzed in a primary cohort of 156 patients with NAFLD, including 53 with NAFL and 103 with NASH, and a validation cohort of 69 patients with NAFLD, including 25 with NAFL and 44 with NASH.
Results: In the primary cohort, NASH was associated with elevated LDL-MI (p=0.039). Multiple regression analysis showed that NASH and the non-use of lipid lowering medications were independently correlated with higher LDL-MI in all patients with NAFLD. Among patients not on lipid lowering medications, those with NASH had significantly higher LDL-MI than those with NAFL (p=0.001). These findings were confirmed in a validation cohort, in that LDL-MI was significantly higher in patients with NASH than with NAFL (p=0.043).
Conclusion:This study is the first to show that LDL-MI, an indicator of sdLDL, was higher in patients with NASH than with NAFL, suggesting that the risk of atherosclerotic diseases may be higher in NASH than NAFL. Patients with NASH should be followed closely, especially for the progression of liver pathology and atherosclerotic diseases.

DOI： 10.1371/journal.pone.0115403

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Although therapeutic intervention for nonalcoholic steatohepatitis (NASH) at an early stage is important owing to the progressive nature of the disease, diagnosis using noninvasive methods remains difficult. We previously demonstrated NASH specific impairment of choline metabolism and the use of fasting plasma free choline (fCh) levels for NASH diagnosis. Here, we investigated the utility of an oral choline tolerance test (OCTT), based on disordered choline metabolism, as a novel noninvasive method for NASH diagnosis.
Sixty-five patients with biopsy proven nonalcoholic fatty liver disease (NAFLD) and 17 healthy controls were enrolled. Blood samples were obtained from all subjects five times during the OCTT (before and 1, 2, 3, and 4 h after oral loading with 260 mg choline).
Four-hour fCh levels after oral loading choline were markedly increased in NASH patients, compared with non-NASH subjects. For detecting NASH, compared with non-NASH subjects, the area under the curve for 4-h fCh levels was 0.829 on receiver operating characteristic (ROC) analysis. The cut-off level for NASH diagnosis was a parts per thousand yen0.16 mg/dL, and the sensitivity, specificity, positive predictive value, and negative predictive value were 80.1, 82.6, 78.4, and 84.4 %, respectively. Moreover, 4-h fCh levels were significantly associated with the disease activity based on NAFLD activity score in patients with NAFLD.
Four-hour fCh levels obtained by an OCTT reflect a NASH specific disorder of choline metabolism, suggesting that the OCTT is a novel and useful noninvasive method for diagnosing NASH at an early stage with sufficient accuracy for clinical practice.

DOI： 10.1007/s00535-013-0776-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

AimRecently, several studies have shown the existence of associations between lipoprotein profiles and hepatitis C virus (HCV), although only a limited amount of information is available about the mechanisms underlying the changes in the lipoprotein profiles associated with HCV. In this study, we investigated the association between lipoprotein profile, classified according to the particle size, and lipoprotein metabolism.
MethodsWe used four kinds of cells for this experiment; full-length genome HCV RNA replicon cells (OR6), sub-genomic HCV RNA replicon cells (sO), and OR6c cells and sOc cells, which were the same cell lines treated with interferon-. The triglyceride (TG) levels in the lipoprotein subclasses of the culture medium were measured by high-performance liquid chromatography. The mRNA expression levels of several molecules associated with lipoprotein metabolism were measured in the OR6, OR6c, sO and sOc cells. To confirm some of the results obtained using the in vitro system, liver biopsy samples obtained from the patients were also examined.
ResultsThe content of TG in the large low-density lipoprotein (LDL) and medium LDL in the culture medium was increased only in the OR6 cells. The hepatic triglyceride lipase (HTGL) mRNA expression levels were lower in the OR6 cells than in the OR6c cells (P&lt;0.01). Examination of the HTGL expression levels in the patients' livers revealed a decrease in HTGL expression in the chronic hepatitis C liver as compared with that in the chronic hepatitis B or non-alcoholic steatohepatitis liver (P&lt;0.01).
ConclusionWe showed that HCV inhibits HTGL production in hepatocytes, inducing a change of the lipoprotein profile.

DOI： 10.1111/hepr.12072

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: There have been some reports on the use of paired biopsies for monitoring disease progression in non-alcoholic fatty liver disease (NAFLD) patients. Recently, transient elastography has been developed as a non-invasive method for predicting the severity of liver fibrosis. We investigated 4-year disease progression in NAFLD patients by evaluating liver stiffness measurements (LSM) obtained using transient elastography. Methods: Of 97 biopsy-proven NAFLD patients whose LSM were obtained 4 years prior, we revaluated 36 who were available for follow up and compared their current stage of fibrosis with that at initial assessment. Fibrosis stage was diagnosed according to the cut-off values previously reported by our institution. We also investigated correlations between changes in LSM and changes in non-invasive fibrosis markers obtained by performing biochemical tests and clinical data. Results: A total of nine (25%) patients had fibrosis progression, 17 (47.2%) had static disease and 10 (27.8%) had fibrosis remission. Among patients with stage 0 fibrosis as per initial LSM (n=16), 11 had static disease and five had fibrosis progression according to LSM obtained 4 years later. Changes in LSM correlated with changes in the FIB4 index (R=0.519, P=0.0011) and aspartate aminotransferase-to-platelet ratio index (R=0.346, P=0.0412), but not with changes in other non-invasive markers. Conclusion: Transient elastography is non-invasive and easy to use
therefore, it can be a useful tool for monitoring the severity of hepatic fibrosis in NAFLD patients. © 2013 The Japan Society of Hepatology.

DOI： 10.1111/hepr.12039

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Aim A rapid and non-invasive method of detecting fibrosis in patients with chronic liver diseases is of major clinical interest. The purpose of this study was to comparatively investigate the effectiveness of the Liver Fibrosis Index (LF Index) calculated using real-time tissue elastography (RTE) in patients with non-alcoholic fatty liver disease (NAFLD) and patients with chronic hepatitis C (CHC). Methods Twenty-seven patients with biopsy-proven NAFLD and 93 patients with biopsy-proven CHC were included. They underwent transient elastography (TE), serum liver fibrosis marker testing and RTE to calculate the LF Index. Results The LF Index showed a stepwise increase with increasing histological severity of fibrosis in CHC patients (P = 0.0102), whereas no significant correlation of the LF Index with the histological severity of liver fibrosis in NAFLD patients (P = 0.852). There was a significant correlation between the LF Index and liver stiffness measured by TE in CHC patients (r = 0.319, P = 0.0009). On the other hand, no such correlation was observed in NAFLD patients. While in CHC patients, the LF Index was correlated with the FIB-4 index, no such correlation was observed in NAFLD patients. Conclusion The LF Index calculated by RTE is effective for assessment of liver fibrosis in patients with CHC. On the other hand, it is not useful in patients with NAFLD. This is the first study to compare the clinical usefulness of RTE as non-invasive assessment of liver fibrosis between CHC and NAFLD. Further investigations are required to refine statistical assessment of RTE.

DOI： 10.1111/hepr.12023

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Ampullary early stage cancer (early CA) potentially harbors lymphovascular invasion; there are few data on markers that could differentiate adenoma and early CA.
To investigate those markers, we compared the tumor diameter and Ki-67 expression in endoscopy biopsy specimens of adenoma with those of early CA.
Patients on whom endoscopic papillectomy (EP) was performed (n = 35) with histopathologically proven adenomas and with low/high grade dysplasia and early CA were studied. We made pre-procedure evaluations of ampullary tumors by using endoscopic ultrasonography (EUS) and transpapillary intraductal ultrasonography. Tumor diameter was measured by EUS. Endoscopic biopsy using immunostaining of Ki-67 labeling index (LI) prior to EP were evaluated.
The areas under the receiver-operating characteristic (AUROC) curves for tumor diameter and Ki-67 expression were 0.824 and 0.873, respectively. Cut-off values calculated based on AUROC data were 15 mm in tumor diameter and 32 cells/high-power field (HPF) in Ki-67. Early CA (n = 11) was diagnosed by using a cut-off value for tumor diameter in 8 out of 11 patients (sensitivity 72.7 %, specificity 66.7 %, accuracy 68.6 %). Significant infiltration of the major duodenal papilla by Ki-67 positive tumor cells (&gt; 31/HPF) was recognized in 8 of the 11 patients with early CA (sensitivity 100 %, specificity 54.2 %, accuracy 62.9 %).
Observation of tumor diameter and Ki-67 LI would be helpful for safety EP. EP should not be indicated for ampullary tumors more than 15 mm in diameter and/or Ki-67 LI 31/HPF.

DOI： 10.1007/s00534-013-0594-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Background: Hepatitis C virus (HCV) induces endoplasmic reticulum (ER) stress which, in turn, activates the unfolding protein response (UPR). UPR activates three distinct signalling pathways. Additionally, UPR induces autophagy (UPR-autophagy pathways). On the other hand, it has become clear that some positive-single-strand RNA viruses utilize autophagy. Some groups have used the siRNA silencing approach to show that autophagy is required for HCV RNA replication. However, the mechanism of induction of the UPR-autophagy pathways remain unclear in the cells with HCV.
Background: Method and results: we used a genome-length HCV RNA (strain 0 of genotype 1b) replication system (OR6) in hepatoma cells (HuH-7-derived OR6 cells). As control, we used OR6c cells from which the HCV genome had been removed by treatment with interferon-alpha. The UPR-autophagy pathways were activated to a greater degree in the 0R6 cells as compared to the OR6c cells. Rapamycin, mTOR-independent autophagy inducer, activated HCV replication in the 0R6 cells. On the other hand, HCV replication in the cells was inhibited by 3-methyladenine (3-MA), which is an inhibitor of autophagy. Salubrinal (Eukaryotic Initiation Factor 2(eIF2)-alpha phosphatase inhibitor), 3-ethoxy-5, 6-dibromosalicylaldehyde (X-box binding protein-1 (XBP-1) splicing inhibitor) and sp600125 (c-Jun N-terminal kinases UNK) inhibitor) inhibited HCV replication and autophagy. Additionally, HCV replication and autophagy were inhibited more strongly by combination of these inhibitors.
Conclusion: Our results suggest that UPR-autophagy pathways exert an influence on HCV replication. Therefore, control these pathways may serve as a novel therapeutic strategy against replication of HCV. (C) 2013 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2013.01.103

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AIMS: Liver inflammation is a risk factor for the progression of nonalcoholic fatty liver disease (NAFLD). However, the diagnosis of liver inflammation is very difficult and invasive liver biopsy is still the only method to reliably detect liver inflammation. We previously reported that overexpression of CD14 in Kupffer cells may trigger the progression to nonalcoholic steatohepatitis (NASH) via liver inflammation following hyper-reactivity to low-dose lipopolysaccharide. Therefore, the aim of this study was to investigate the relationship between soluble type of CD14 (sCD14) and histological features in patients with NAFLD. METHODS: Our cohort consisted of 113 patients with liver biopsy-confirmed NAFLD and 21 age-matched healthy controls. Serum sCD14 levels were measured by an enzyme-linked immunosorbent assay. RESULTS: Serum sCD14 levels were significantly associated with diagnosis of NASH and the area under the receiver operator characteristic curve (AUROC) to distinguish between not NASH and NASH was 0.802. Moreover, serum sCD14 levels were significantly associated with the disease activity based on NAFLD activity score and hepatic CD14 mRNA expression, which is correlated with membrane CD14 (mCD14) expression, in patients with NAFLD. In multiple regression analysis, the serum sCD14 levels were independently associated with liver inflammation. The AUROC to distinguish between mild and severe liver inflammation in patients with NAFLD was 0.752. CONCLUSIONS: We found that serum sCD14 levels increased significantly with increasing liver inflammation grade in patients with NAFLD, reflecting increased hepatic CD14 expression. Serum sCD14 is a promising tool to predict the worsening of liver inflammation, and may offer a potential biomarker for evaluation of therapeutic effects in NAFLD.

DOI： 10.1371/journal.pone.0065211

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Aim: Choline is a dietary component that is crucial for normal cellular function. Choline is predominantly absorbed from the small intestine and completely metabolized in the liver. We recently demonstrated that free choline (fCh) levels in blood reflect the level of phosphatidylcholine synthesis in the liver and is correlated with the onset of non-alcoholic steatohepatitis (NASH). Our aim here was to validate the utility of this biomarker for NASH diagnosis. Methods: Our cohort consisted of 110 patients with biopsy proven non-alcoholic fatty liver disease (NAFLD) from four centers across Japan and 25 age-matched healthy controls. Plasma fCh levels were measured using high-performance liquid chromatography. Results: Patients with diagnosed or borderline NASH had significantly increased plasma fCh levels when compared with control subjects, or patients not diagnosed with NASH. Interestingly, an association between plasma fCh levels and expression of microsomal triglyceride transfer protein, which catalyzes the transfer of triglyceride, was reflected in the markedly negative correlation between these two variables in patients with NAFLD. Moreover, the grade of liver steatosis and fibrosis stage increased with increasing plasma fCh levels (P &lt; 0.05). The area under the receiver-operating characteristic (ROC) curves for NASH, including borderline diagnosis, was 0.811. Additionally, the areas under the ROC for fibrosis stage were 0.816 for &gt;stage 1, 0.805 for &gt;stage 2, 0.809 for &gt;stage 3 and 0.818 for &gt;stage 4. Conclusion: Plasma fCh levels are closely related to the grade of liver steatosis and fibrosis, and predict NASH severity. Plasma fCh levels are therefore a potential diagnostic marker for early-stage NASH in clinical practice.

DOI： 10.1111/j.1872-034X.2012.00976.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CELL PRESS  

Although bacterial endotoxin, such as lipopolysaccharide (LPS), plays a key role in the pathogenesis of nonalcoholic steatohepatitis (NASH), detailed mechanisms of this pathogenesis remain unclear. Here, we demonstrate that upregulation of CD14 by leptin-mediated signaling is critical to hyperreactivity against endotoxin during NASH progression. Upregulation of CD14 in Kupffer cells and hyperreactivity against low-dose LPS were observed in high-fat diet (HFD)-induced steatosis mice, but not chow-fed-control mice. Hyperresponsivity against low-dose LPS led to accelerated NASH progression, including liver inflammation and fibrosis. Administering leptin in chow-fed mice caused increased hepatic expression of CD14 via STAT3 signaling, resulting in hyperreactivity against low-dose LPS without steatosis. In contrast, a marked decrease in hepatic CD14 expression was observed in leptin-deficient ob/ob mice, despite severe steatosis. Our results indicate that obesity-induced leptin plays a crucial role in NASH progression via enhanced responsivity to endotoxin, and we propose a mechanism of bacteria-mediated progression of NASH.

DOI： 10.1016/j.cmet.2012.05.012

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記述言語：英語   出版者・発行元：SPRINGER TOKYO  

DOI： 10.1007/s00535-012-0556-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BAISHIDENG PUBL GRP CO LTD  

AIM: To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) resistant to transarterial chemoembolization (TACE).
METHODS: This study was conducted on 42 patients who received HAIC for advanced HCC between 2001 and 2010 at our hospital. 5-fluorouracil (5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir. Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU. The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010 (written in Japanese); one group of patients who did not fulfill the criteria for TACE resistance (group A, n = 23), and another group who fulfilled the criteria for TACE resistance (group B, n = 19). We compared the outcomes in terms of the response and survival rates between the two groups.
RESULTS: Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B (response rate: 48% vs 16%, P = 0.028, tumor suppression rate: 87% vs 53%, P = 0.014). Furthermore, both the progression-free survival rate and survival time were significantly superior in group A than in group B (3-, 6-, 12-, and 24-mo = 83%, 70%, 29% and 20% vs 63%, 42%, 16% and 0%, respectively, P = 0.040, and 9.8 nno vs 6.2 mo, P = 0.040). A multivariate analysis (Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival (P = 0.007).
CONCLUSION: HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE. Other tools for treatment, i.e., molecular-targeting agents may be considered for these cases. (C) 2012 Baishideng. All rights reserved.

DOI： 10.3748/wjg.v18.i16.1933

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

DOI： 10.1016/j.jhep.2011.07.021

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: The ideal medication for acid-related diseases should have a rapid onset of action to promote hemostasis and cause efficient resolution of symptoms. The aim of our study was to comparatively investigate the inhibitory effect on gastric acid secretion of a single oral administration of omeprazole plus mosapride with that of omeprazole alone.
Methods: Ten Helicobacter pylori-negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 6 hours after a single oral administration of omeprazole 20 mg or that of omeprazole 20 mg plus mosapride 5 mg (the omeprazole being administered one hour after the mosapride). Each administration was separated by a 7-days washout period.
Results: The average pH during the 6-hour period after administration of omeprazole 20 mg plus mosapride 5 mg was higher than that after administration of omeprazole 20 mg alone (median: 3.22 versus 4.21, respectively; p = 0.0247).
Conclusions: In H. pylori -negative healthy male subjects, an oral dose of omeprazole 20 mg plus mosapride 5 mg increased the intragastric pH more rapidly than omeprazole 20 mg alone.

DOI： 10.1186/1471-230X-12-25

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Objectives The aim of this study was to characterize the pancreatic cystic lesions in von Hippel-Lindau (VHL) disease and to document the changes that occur in the pancreas.
Methods We retrospectively analyzed the medical records and the computed tomography (CT) and magnetic resonance imaging (MRI) findings of 20 VHL patients who were diagnosed between 1996 and 2010 at our hospital. The clinical findings, family history and type of tumors and/or cysts were reviewed for each patient. We also analyzed the imaging findings for the pancreas in detail.
Results Pancreatic involvement was noted in 16 of the 20 patients (80%). Eleven patients had multiple cysts diffusely distributed in the pancreas, and one patient had a single cyst in the pancreas head. Two patients had serous cystic neoplasms (SCNs) with multiple cysts, and another two patients had neuroendocrine tumors (NETs) which were conventional radiological findings. The largest cysts of four patients (26.7%) increased in size and that of three patients (20%) decreased in size during the follow-up period. We performed surgical resections for the pancreatic tumors (one NET and one SCN) and also performed endoscopic treatment for a pancreatic cyst in one VHL patient with obstructive jaundice. None of the patients died as a result of pancreatic disease.
Conclusion The most common type of pancreatic lesions was multiple cysts. SCNs were present in only 10% of the VHL patients. Pancreatic cysts showed positive and/or negative growth according to the CT and MRI findings. The pancreatic cystic lesions did not influence the outcome of the VHL patients.

DOI： 10.2169/internalmedicine.51.7194

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Peroxisome proliferator-activated receptor-γ (PPARγ) has been reported to reduce inflammation and attenuate fibrosis in the liver. In this study, we investigated the effects of PPARγ on the liver injury induced by 20 mg/kg Concanavalin A (Con A). The mice were administered one of the three types of PPARγ ligands (pioglitazone, ciglitazone, and troglitazone) for 1 week, and the serum alanine aminotransferase (ALT) levels at 20 h after Con A injection were significantly elevated in the PPARγ ligand-treated mice. Furthermore, the serum ALT levels after Con A injection in the PPARγ hetero-knock-out mice (PPARγ +/- mice) were lower than those in the wild-type mice (WT mice). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) revealed extensive liver damage induced by Con A in the pioglitazone-treated mice. Electrophoresis mobility shift assay (EMSA) revealed that activation of translocation of nuclear factor- (NF-κ) B, which is a suppressor of apoptosis, in the nucleus of the hepatocytes was suppressed in the pioglitazone-treated mice after Con A injection. In this study, we showed that PPARγ exacerbated Con A-induced liver injury via suppressing the translocation of NF-κB into the nucleus, thereby inhibiting the suppression of liver cell apoptosis. © 2012 Yuji Ogawa et al.

DOI： 10.1155/2012/940384

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Background Relapse and spontaneous remission (SR) are characteristic features of autoimmune pancreatitis (AIP).
Aim and methods We conducted a study to determine if the predictive factors might be potentially related to the relapse in 70 consecutive AIP patients. Regarding SR, we studied the data of patients without corticosteroid treatment (CST).
Results CST was administered to 60% (42/70) of the patients; however, relapse was noted in 45.2% (19/42) of these patients. In 95% (18/19) of the AIP patients developing relapse, the relapse occurred within 3 years. The relapse rate was 80% (12/15) in the AIP patients administered CST for less than 12 months and 25.9% (7/27) in those administered CST for over 12 months (p &lt; 0.01). The results of univariate analysis revealed significant association of relapse with the presence of jaundice, IgG4 seropositivity, presence of diffuse pancreas swelling, duodenal papillitis (DP), history of initial CST, and history of supportive treatment (p &lt; 0.05), whereas multivariate analysis revealed that IgG4 seropositivity (OR 10.506, p = 0.0422) and the presence of jaundice (OR 6.945, p = 0.0174) are significant independent factors predictive of relapse in AIP patients. SR was recognized in 65.0% (13/20) of AIP patients without CST. The results of univariate analysis revealed that SR was associated with IgG4 seropositivity (p &lt; 0.05), and multivariate analysis identified IgG4 seropositivity (OR 0.032, p = 0.0092) as a significant independent factor predictive of SR in these cases.
Conclusion AIP patients with IgG4 seropositivity and jaundice are at a higher risk of relapse and they could therefore be candidates for over 3 years of maintenance CST. AIP patients with IgG4 seronegativity have a high likelihood of SR.

DOI： 10.1007/s00535-011-0393-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Expression of the forkhead/winged helix family of transcription factor P3+ regulatory T cells (FOXP3(+) Treg), a master gene of regulatory T cells (Treg) is observed in patients with autoimmune pancreatitis (AIP). We investigated the usefulness of detection of FOXP3(+) Treg in the main duodenal papilla for differential diagnosis between AIP and pancreatic cancer (Pca).
Firstly, we determined the cut-off value of FOXP3 expression in duodenal papilla taken from the patients with AIP (n = 22) and chronic pancreatitis (n = 21). Data from 32 patients with AIP and 30 patients with Pca who had undergone endoscopic biopsy were then studied. The numbers of FOXP3(+) Treg-positive lymphocytes and IgG4-positive plasma cells per high-power field (HPF) were counted in all the histopathological specimens.
The areas under the receiver-operating characteristic (AUROC) curves for FOXP3(+) and IgG4 expression were 0.934 and 0.953, respectively. Cut-off values calculated based on AUROC data were 14/HPF in FOXP3 and 10/HPF in IgG4. Seropositivity for IgG4 was observed in 22 out of the 31 patients with AIP (sensitivity 71.0%, specificity 84.6%, accuracy 75.0%). Significant infiltration of the major duodenal papilla by FOXP3(+) lymphocytes (a parts per thousand yen14/HPF) was recognized in 18 of the 32 patients with AIP (sensitivity 56.3%, specificity 100%, accuracy 77.4%). Significant infiltration of the major duodenal papilla by IgG4-positive plasma cells (a parts per thousand yen10/HPF) was recognized in 27 of the 32 patients with AIP (sensitivity 84.4%, specificity 80.0%, accuracy 82.3%).
Observation of FOXP3(+) cells in the main duodenal papilla may be useful in the differential diagnosis between AIP and Pca.

DOI： 10.1007/s00534-010-0359-0

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記述言語：英語   出版者・発行元：SPRINGER TOKYO  

DOI： 10.1007/s00535-010-0356-8

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記述言語：英語   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

The factors involved in the progression of non-alcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) are not fully understood and thus it is urgently needed to elucidate these factors. Steatosis is not causal in the development of NASH, but rather it sensitizes the liver to the damaging effects of second hits such that stressors innocuous to a healthy liver lead to the development of NASH in the steatotic liver. In the previous study, most of the hepatic lipid metabolite profiles were similar in the NAFL and NASH groups. However, very-low-density lipoprotein (VLDL) synthesis, especially hepatic microsomal triglyceride transfer protein (MTP) mRNA expression, was impaired in the NASH group. Moreover, NASH showed significantly higher incidence of minor alley appearance compared with NAFL, indicating the possibility of association between NASH pathogenesis and decreased congenital MTP activity. MTP is one of the enzymes that transfer triglycerides to nascent apolipoprotein B, producing VLDL and removing lipid from the hepatocyte. A growing body of literature suggests that the measurement of hepatic MTP expression may be helpful for diagnosis; and moreover, hepatic MTP activator may be a possible therapeutic agent for the treatment of NASH.

DOI： 10.1254/jphs.10R14FM

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Liver abscess is recognized as a life-threatening disease. However, even in recent years, approximately 50% of liver abscess cases are considered to be cryptogenic. Here, we report a case of liver abscess associated with periodontal bacterial infection by Fusobacterium necrophorum, which is commonly found in the oropharyngeal flora. A 36-year-old man presented with fever and contrast-enhanced abdominal computed tomography revealed multiple liver abscesses. F.necrophorum was isolated from oral smears, liver aspirates and blood samples. Liver abscesses caused by periodontal bacterial infection are rare, however, the incidence is expected to increase in the future, as periodontitis is extremely common and is on the rise as one of the most common chronic infections in the world. A systemic survey including periodontitis may be required for the exact diagnosis of the source of infection.

DOI： 10.1111/j.1872-034X.2010.00748.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

Background and Aim:
Differentiation of sclerosing cholangitis-associated autoimmune pancreatitis (SC-AIP), primary sclerosing cholangitis (PSC) and cancer of the hilar part of the bile duct (CHB) has been challenging. The aim of the present study was to evaluate characteristic intraductal ultrasonography (IDUS) features that could be used to discriminate SC-AIP from PSC and CHB.
Methods:
Six patients with SC-AIP, 10 patients with PSC and 12 patients with CHB were identified. We reviewed the following bile duct features observed using IDUS to determine their usefulness for differentiating SC-AIP from PSC and CHB: presence of symmetrical wall thickness, wall thickness, presence of homogeneous internal foci and presence of lateral mucosal lesions continuous to the hilar.
Results:
IDUS results (SC-AIP, PSC, CHB) were as follows: wall thickness (mm), 3.7 +/- 0.9, 2.6 +/- 0.9, 2.8 +/- 0.0.6; presence of symmetrical wall thickness, 100% (6/6), 20% (2/10), 8.3% (1/12); presence of homogeneous internal foci, 100% (6/6), 10% (1/10), 8.3% (1/12); and presence of lateral mucosal lesions continuous to the hilar, 83.3% (5/6), 40%(4/10), 25% (3/12). Symmetrical wall thickness of the bile duct, homogeneous internal foci and lateral mucosal lesions continuous to the hilar were detected significantly more often among the patients with SC-PSC than among the patients with PSC or CHB (P &lt; 0.05).
Conclusions:
IDUS findings, such as symmetrical wall thickness, presence of homogeneous internal foci and presence of lateral mucosal lesions continuous to the hilar can facilitate the differential diagnosis of SC-AIP from PSC and CHB.

DOI： 10.1111/j.1443-1661.2010.01039.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: ideally, medications for the treatment of acid-related diseases should have a rapid onset of action to promote hemostasis and the resolution of symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral administration of lafutidine alone or combined with peppermint oil.
Methodology: Ten Helicobacter pylori-negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 4 hours after a single oral administration of lafutidine (10mg) or the administration of lafutidine (10mg) with peppermint oil (0.64mL). Each administration was separated by a 7-day washout period.
Results: No significant difference in the average pH was observed during the 4-hour period after the combined administration of lafutidine and peppermint oil and after the administration of lafutidine alone (median gastric pH: 5.09 versus 5.29; p=0.3122).
Conclusions: In H. pylori-negative healthy male subjects, an oral dose of lafutidine combined with peppermint oil did not increase the intragastric pH faster than lafutidine alone.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Scientific Literature Inc.  

Background: A visceral fat area of more than 100 cm2 as measured by computed tomography (CT) at the umbilical level has been included as a criterion for obesity in all the proposed criteria for metabolic syndrome. However, CT cannot be used frequently because of radiation exposure. We evaluated the usefulness of measurement of the serum levels of nitric oxide (NO), instead of CT and the waist circumference, as a marker of abdominal visceral fat accumulation. Material/Methods: The study was carried out in 80 subjects. The serum levels of NO metabolites (nitrate/nitrite) were measured using the Griess reagent. Results: Simple and multiple regression analysis revealed that the serum levels of NO metabolites showed the greatest degree of correlation with the visceral fat area (r=0.743, p&lt
0.0001), and corresponded to a visceral fat area of 100 cm2, as determined using the ROC curve, was 21.0 μmol/ml (sensitivity 88%, specificity 82%)
this method was more sensitive than the waist circumference for evaluation of the visceral fat accumulation. Conclusions: Measurement of the serum levels of NO metabolites may be a simple, safe, convenient and reliable method for the evaluation of visceral fat accumulation in clinical diagnostic screening. © Med Sci Monit.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Scientific Literature Inc.  

Background: A visceral fat area of more than 100 cm2 as measured by computed tomography (CT) at the umbilical level has been included as a criterion for obesity in all the proposed criteria for metabolic syndrome. However, CT cannot be used frequently because of radiation exposure. We evaluated the usefulness of measurement of the serum levels of nitric oxide (NO), instead of CT and the waist circumference, as a marker of abdominal visceral fat accumulation. Material/Methods: The study was carried out in 80 subjects. The serum levels of NO metabolites (nitrate/nitrite) were measured using the Griess reagent. Results: Simple and multiple regression analysis revealed that the serum levels of NO metabolites showed the greatest degree of correlation with the visceral fat area (r=0.743, p&lt
0.0001), and corresponded to a visceral fat area of 100 cm2, as determined using the ROC curve, was 21.0 μmol/ml (sensitivity 88%, specificity 82%)
this method was more sensitive than the waist circumference for evaluation of the visceral fat accumulation. Conclusions: Measurement of the serum levels of NO metabolites may be a simple, safe, convenient and reliable method for the evaluation of visceral fat accumulation in clinical diagnostic screening. © Med Sci Monit.

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The liver is the first organ to receive nutrients that enter the body via the intestines after a meal, and this organ plays a pivotal role in energy metabolism. Nonalcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease in the world and is now considered to be a component of metabolic syndrome. A wide spectrum of histological changes has been observed in NAFLD, ranging from simple steatosis, which is generally non-progressive, to nonalcoholic steatohepatitis (NASH), liver cirrhosis, liver failure, and sometimes even hepatocellular carcinoma. Histologically, the condition is characterized by macrovesicular hepatic steatosis, and diagnoses are only made in patients who do not have a history of alcohol consumption in amounts sufficient to be considered harmful to the liver. Insulin resistance is nearly universal in patients with NAFLD and nonalcoholic steatohepatitis (NASH). Although the pivotal cause of the development of NAFLD/NASH is still unknown, insulin resistance is strongly suspected of playing an important role in the development of these lesions. Type 2 diabetes, glucose intolerance and insulin resistance occur at a high frequency in patients with NAFLD, and these conditions have been shown to be of prognostic significance. Regarding the molecular mechanisms underlying insulin resistance in patients with NAFLD/NASH, cytokine-adipokine interactions are believed to be intricately involved. Insulin resistance is thought to be regulated by proinflammatory cytokines, adipokines (TNF-α, adiponectin, leptin), and peroxisome proliferator-activator receptors (PPARs). Recent reports have described the involvement of genetic factors as well as environmental factors in the development of insulin resistance. Genetic factors are also thought to be important in the development ofNAFLD/NASH, and genetic polymorphisms of genes encoding TNF-α, adiponectin, and PPARs are reportedly associated with the development of NAFLD/NASH. Most therapeutic modalities that are already in use or under development target major pathways that are believed to be essential to the pathogenesis of NAFLD/NASH, and these therapies are often directed at improving insulin resistance via pharmacologic (thiazolidinediones, metformin), surgical, or dietary approaches. Here, we review recent evidence concerning insulin resistance and NAFLD/NASH as a step towards a comprehensive understanding of the pathophysiology and treatment of NAFLD/NASH. © 2010 Nova Science Publishers, Inc. All rights reserved.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Pegylated interferon and ribavirin combination therapy is the standard treatment for patients with chronic hepatitis C (CHC), but treatment failure can be difficult to predict. We and others have reported a relation between lipid values and sustained viral responses in patients with CHC. However, the relationship between lipid values and treatment failure has not been previously reported. The present study investigated the association between the profiles of phospholipids and free cholesterol (FC), the main constitutive ingredients of the surface of lipoprotein, classified according to particle size and hepatitis C treatment, and determined the usefulness of these parameters for predicting the outcome of treatment. Fifty-five patients with CHC (33 men and 22 women) were included in the study. The serum total cholesterol, triglyceride, phospholipids, and FC levels in the lipoprotein subclasses were determined using high-performance liquid chromatography with gel permeation columns, enabling the lipoproteins to be classified into 13 subclasses according to particle size. According to a univariate analysis, the treatment failure group had a significantly higher serum phospholipid level overall in the high-density lipoprotein (HDL) and medium HDL fractions as well as a higher serum FC level in the HDL fraction and all HDL subclass fractions compared with the corresponding values in the non-nonvirological response group. Higher serum phospholipid and FC concentrations in the HDL subclasses were predictive of a failure to respond in patients with genotype 1b.

DOI： 10.1111/j.1365-2893.2009.01253.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: The aim of this study was to evaluate the correlation between gastrointestinal symptoms and diet therapy.
Methodology: The subjects comprised of 8 patients who attended the diabetes division at Fujisawa City Hospital between April and June 2007. The subjects were diagnosed as having diabetes mellitus based on the results of a blood analysis. The body weight of the subjects was measured, and the subjects were asked to score their gastrointestinal symptoms according to the Frequency Scale for the Symptoms of GERD (FSSG) before and after diet therapy for 9 to 14 days.
Results: Diet therapy for diabetic subjects was effective for weight reduction. The total FSSG score was decreased, and the reduction in dysmotility-like symptoms was greater than the reduction in acid-reflux-related symptoms.
Conclusions: Diet therapy for mild diabetic patients also improves gastrointestinal symptoms.

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記述言語：日本語   出版者・発行元：一般社団法人 日本消化器内視鏡学会  

AIM: We evaluated the characteristic endoscopic ultrasonography (EUS) findings of early autoimmune pancreatitis (AIP). Methods: Nineteen patients with AIP who underwent EUS and endoscopic retrograde cholangiopancreatography (ERCP) were identified from our database. We reviewed the following features of EUS as being potentially characteristic of early AIP: hyperechoic foci, hyperechoic strands, lobularity, hyperechoic duct margins and reduced echogenicity. According to the Cambridge classification for chronic pancreatitis, we classified AIP into early AIP (Cambridge Grade 0-2) and advanced AIP (Grade 3-5) and examined the histopathological findings in each stage of AIP. Results: Here were 9 cases of early AIP and 10 cases of advanced AIP. Five of the 9 early cases of AIP showed spontaneous remission without corticosteroid therapy (p&lt;0.05). The EUS findings were as follows (early vs. advanced); hyperechoic foci, 100% (9/9) vs. 100% (10/10); hyperechoic strands, 66.7% (6/9) vs. 70% (7/10); lobularity, 77.8% (7/9) vs. 20% (2/10); hyperechoic duct margin, 90% (8/9) vs. 30% (3/10); and reduced echogenicity, 88.9% (8/9) vs. 90% (9/10). Lobularity and hyperechoic duct margins were detected at a significantly higher frequency in the early AIP than in advanced AIP patients (p&lt;0.05). In relation to the histopathologic findings, acinar cells were preserved to a better extent in the cases of early AIP, whereas the acinar cells were reduced in number and replaced by massive fibrosis in the patients with advanced AIP. Conclusions: Lobularity and hyperechoic duct margin are characteristic EUS features of early AIP, which has a more favorable prognosis, showing a higher frequency of spontaneous remission and preservation of acinar cells, than advanced AIP.

DOI： 10.11280/gee.52.2745

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記述言語：英語   出版者・発行元：GEORG THIEME VERLAG KG  

DOI： 10.1055/s-0029-1214857

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Hepatocellular carcinoma (HCC) is one of the most common neoplasms worldwide. Portal vein tumor thrombosis (PVTT) is a common complication of advanced HCC, and the prognosis of advanced HCC with PVTT is extremely poor. We report a case of HCC with PVTT evaluated by contrast-enhanced ultrasonography (CEUS) before and after hepatic arterial infusion chemotherapy (HAIC). A 59-year-old man with chronic hepatitis C was admitted to our hospital. CEUS clearly showed the thread and streaks sign in a solid lesion that occupied the right main branch of the portal vein. HAIC was performed, and CEUS after HAIC clearly showed disappearance of the thread and streaks sign. CEUS was very useful in diagnosing PVTT and in evaluating the effectiveness of HAIC in this case.

DOI： 10.1007/s10396-010-0259-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Aim: Although non-alcoholic fatty liver disease (NAFLD) is now a common cause of chronic liver disease, discriminating between simple steatosis and non-alcoholic steatohepatitis (NASH), especially early-stage NASH, remains difficult. We investigated the clinical usefulness of measuring the spleen volume as a marker of early-stage NASH.
Methods: We evaluated computed tomography (CT) images obtained in 84 patients with histologically diagnosed NAFLD (22 with simple steatosis, 62 with NASH with mild fibrosis [stages 1-2]). We defined the data obtained by the following formula as a spleen-body index (SBI): SBI = maximal CT axial section area of the spleen (cm(2))/body surface area (BSA) (cm(2)) x 10(4). We compared the SBI between patients with simple steatosis and those with NASH with mild fibrosis.
Results: The mean SBI of the simple steatosis group was 15.8 +/- 3.9, while that of the NASH with mild fibrosis group was 18.7 +/- 5.7. This difference between the two groups was significant (P = 0.0314). A multiple logistic regression analysis showed that the SBI was significantly correlated with the discrimination of simple steatosis and NASH with mild fibrosis. The area under the receiver-operator curve was 0.661 for distinguishing between simple steatosis and NASH with mild fibrosis (P = 0.026, 95% confidence interval = 0.532-0.789).
Conclusion: Spleen enlargement may be a distinct feature of NASH, especially early-stage NASH. SBI might be a non-invasive and simple method of differentiating NASH and simple steatosis.

DOI： 10.1111/j.1872-034X.2010.00643.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Aim:
Non-alcoholic steatohepatitis (NASH) is considered a hepatic manifestation of metabolic syndrome. However, effective drug therapy for NASH has not been established yet. In the present study, we evaluated the efficacy of 6 months of ezetimibe treatment for NASH patients with dyslipidemia for the comparison of improvement of the clinical parameters and histological alterations.
Methods:
We prospectively evaluated 10 consecutive NASH patients with dyslipidemia who agreed to participate in this study. The patients were given ezetimibe (10 mg/day) for 6 months, and clinical parameters and histological alterations were comparatively evaluated before and after treatment. All the patients were given standard calorie diet (30 kcal/kg per day, carbohydrate 50-60%, fat 20-30%, protein 15-20%) and exercise counseling from 3 months before the ezetimibe treatment.
Results:
The serum aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein and type IV collagen 7 s levels were significantly improved by the treatment with ezetimibe for 6 months. In histological observations, follow-up liver biopsies revealed that the NAS score and steatosis grade were also significantly improved. The fibrosis stage did not change significantly, but six of the 10 patients exhibited an improvement in their fibrosis stage.
Conclusion:
Major clinical parameters and histological observations were significantly improved by the treatment with ezetimibe. Our pilot study demonstrated the efficacy of ezetimibe for drug therapy of NASH and may lead to a large-scale clinical trial in the future.

DOI： 10.1111/j.1872-034X.2010.00644.x

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記述言語：英語   出版者・発行元：MOSBY-ELSEVIER  

DOI： 10.1016/j.gie.2010.01.033

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Aim:
Congenital extrahepatic portosystemic shunt (CEPS) is a rare anomaly in which the enteric blood bypasses the liver and drains into the systemic veins through various venous shunts. Patients with CEPS often have liver tumors and complications such as cardiac or other anomalies, but portosystemic encephalopathy and gastrointestinal bleeding occur only occasionally. The clinical problems differ for each individual with CEPS, and establishing a prognosis can be very difficult.
Methods:
We reviewed the clinical features of 136 reported cases of CEPS and classified these cases according to their portosystemic shunts.
Results:
We classified portal blood flow directly into the inferior vena cava (IVC) as type A (88 cases), portal blood flow into the renal vein as type B (36 cases), and portal blood flow into the iliac vein via an inferior mesenteric vein as type C (12 cases). Type A patients were complicated with cardiac anomalies at a higher rate than other types. Type C patients had lower prevalences of cardiac anomalies and portosystemic encephalopathy than the other types, but the prevalence of gastrointestinal bleeding was significantly higher (P &lt; 0.0001). The prognosis of CEPS has improved, and only six deaths have been previously reported, all of which occurred in type A patients.
Conclusions:
We reviewed the previously reported cases of CEPS. Classification according to the portosystemic shunt system might be useful for investigating the clinical features of CEPS.

DOI： 10.1111/j.1872-034X.2010.00667.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

Paraganglioma, a sporadically occurring rare tumor should be included in the differential diagnosis of retroperitoneal tumors, such as malignant lymphomas, gastrointestinal stromal tumors, sarcoma and carcinoma of unknown primary site. A 58-year-old Japanese woman presented with a large retroperitoneal tumor detected by ultrasonography (US). She had no medical history of hypertension. Computed tomography showed a mass, 7 cm in diameter, located between the pancreas and the inferior vena cava. It was unclear whether the mass originated from the duodenum or the mesentery. Endoscopic ultrasonography (EUS) demonstrated a large solid paraduodenal mass. Doppler US revealed sparse vascularity in the tumor. With the differential diagnosis of retroperitoneal tumor, we carried out EUS-FNA. At the time of the third needle puncture, transient severe hypertension was noted, with a blood pressure measurement of 269/130 mmHg. Data obtained from urine and blood examinations after EUS-fine-needle aspiration indicated a diagnosis of paraganglioma.

DOI： 10.1111/j.1443-1661.2010.00939.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

Pegylated interferon and ribavirin combination therapy is the standard treatment for patients with chronic hepatitis C (CHC). Some groups have reported a relation between lipid values and response while others have reported that microsomal triglyceride transfer protein, a key enzyme in the assembly and secretion of lipoproteins, was related to hepatitis C virus (HCV). The aim of this study was to investigate the association between the lipoprotein profiles, classified according to size, and hepatitis C treatment and the usefulness for predicting the outcome of treatment. Forty-four patients with CHC (27 men and 17 women) were included in the study. The serum cholesterol and triglyceride (TG) levels in the lipoprotein subclasses were determined using high-performance liquid chromatography with gel permeation columns, which classified lipoproteins into 20 subfractions based on particle size. According to a univariate analysis, those who achieved an sustained viral response (SVR) had a significantly higher serum total cholesterol level, higher cholesterol levels in the low-density lipoprotein subfraction (25.5 nm in diameter) and the very low-density lipoprotein (VLDL) subfraction (44.5 and 36.8 nm), and a higher serum TG level in the VLDL subfraction (44.5 nm), compared with the corresponding values in the non-SVR group. Higher serum cholesterol and TG concentrations in the lipoprotein subfractions were predictive of an SVR to therapy for HCV infection with genotype 1b prior to the start of interferon treatment.

DOI： 10.1111/j.1365-2893.2009.01179.x

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   出版者・発行元：GEORG THIEME VERLAG KG  

DOI： 10.1055/s-0029-1215119

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. The spectrum of NAFLD is broad, extending from simple steatosis through nonalcoholic steatohepatitis (NASH). Iron is regarded as a putative element that interacts with oxygen radicals, and high rates of hyperferritinemia and increased hepatic iron stores have been demonstrated in NASH. We investigated serum ferritin concentrations, HFE gene mutations, and insulin resistance in Japanese NASH patients and the diagnostic utility of serum ferritin concentrations as a means of distinguishing NASH. Serum ferritin concentrations were measured in 86 patients with histopathologically verified NAFLD (24 with steatosis and 62 with NASH) and 20 control subjects, they were tested for HFE gene mutations and their insulin resistance was measured. The serum ferritin concentration was significantly higher in the NASH patients than in the patients with simple steatosis (P = 0.006). There was no significant difference between the groups in HFE gene mutation (C282Y, H63D, and S65C), and the serum ferritin level was related with insulin resistance. The area under the ROC curve was 0.732 for distinguishing NASH from simple steatosis (P = 0.005; 95% CI, 0.596-0.856). In conclusion high serum ferritin concentrations are a distinguishing feature of Japanese NASH patients independent of HFE gene mutations.

DOI： 10.1007/s10620-009-0771-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Background. The pathogenesis of nonalcoholic steatohepatitis (NASH) is still unclear. Recently, the 2-hit hypothesis was proposed, in which nitric oxide production, representing oxidative stress, was proposed as a very important candidate for the second hit.
Methods. The total study period was 10 weeks. A total of 20 rats were randomly divided into 2 groups. Group 1 was administered the Choline-Deficient, l-Amino Acid-Defined diet to produce a NASH model, and Group 2 as control received the Choline-Sufficient, l-Amino Acid-defined diet. The blood and tissue concentrations of nitrate + nitrite were measured using the Griess reagent and the expression levels of inducible nitric oxide synthase (iNOS) proteins and mRNA was determined by Western blotting.
Results. In regard to nitric oxide (NO) and NO metabolites, there were significant differences in the blood (especially portal venous blood) as well as tissue (liver and visceral fat) concentrations between the 2 animal groups; the amounts of NO metabolites in the tissues were much higher in the NASH models. The level of nitrotyrosine was much markedly higher in the NASH models than in the controls. In regard to the tissue expression of iNOS a significant difference between the 2 groups was found in the visceral fat, especially in the mesenterium.
Conclusions. Based on these results, we hypothesize that the iNOS expression and NO levels in the visceral fat increase, with increased diffusion of NO and its metabolites into the liver, resulting in increased nitrotyrosine formation in the liver; this, in turn, induces inflammation, apoptosis, and fibrosis in the liver, which are one of the characteristic features of NASH.

DOI： 10.1111/j.1530-0277.2008.00756.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Objective: Patients with autoimmune pancreatitis (AIP) sometimes present with Mikulicz disease (MD); however, the clinical features regarding these AIP patients with MD have not yet been fully elucidated. Our aim is to study the clinical differences between AIP with and without MD.
Methods: Twenty-eight AIP patients were divided into 2 groups, one with MD and one without it. The following factors having a possible association with the presence or absence of MD were investigated: sex; serum IgG and IgG4 levels; the presence or absence of antinuclear auto-antibodies, jaundice, diabetes mellitus, swollen duodenal papilla, diffuse pancreatic swelling, spontaneous remission, and relapse.
Results: The MD and non-MD groups consisted of 5 AIP and 23 AIP patients, respectively. The results of univariate analysis revealed that AIP patients presenting with MD were significantly associated with a younger onset, female predominance, high serum IgG4 titer, and diffuse pancreatic swelling (P &lt; 0.05). In 4 of the MD patients, onset preceded pancreatitis.
Conclusions: Autoimmune pancreatitis patients presenting with MD tended to have different clinical features from the non-MD AIP patients, such as having an earlier onset, female tendency, and diffuse pancreatic swelling with a high titer of serum IgG4. Autoimmune pancreatitis with MD tended to precede gastroenterological events.

DOI： 10.1097/MPA.0b013e3181bc119d

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background and Aims: FOXP3+ regulatory T cells (Tregs) play a central role in self-tolerance and suppress the effective antitumor immune response. A recent study revealed that indoleamine 2,3-dioxygenase (IDO)-mediated tryptophan depletion was able to affect local tumor-infiltrating lymphocytes. The aim of this study was to investigate the clinical significance of the tumor-infiltrating Tregs and tumoral IDO expression during the progression of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Methods: We investigated the prevalence and localization of FOXP3+ Tregs, CD8+ lymphocytes, and IDO expression in IPMNs by immunohistochemistry. We recruited 39 cases with IPMNs (IPMA: adenoma, n = 11; IPMB: borderline malignancy, n = 9; IPMC: noninvasive carcinoma, n = 7; I-IPMC: invasive IPMC, n = 12). Results: The prevalence of Tregs increased step by step during the carcinogenesis of IPMNs (Kruskal-Wallis test: p &lt; 0.0001). IDO expression in the tumor was observed in 5 cases with IPMNs (IPMC, n = 1; I-IPMC, n = 4). IDO expression in the tumor was positively correlated with the prevalence of Tregs in IPMNs. Conclusions: FOXP3+ Tregs play a role in controlling the immune surveillance against IPMNs at the premalignant stage. IDO expression in the tumor is one of the late-stage phenomena of multistage carcinogenesis of IPMNs. Copyright (C) 2010 S. Karger AG, Basel and IAP

DOI： 10.1159/000308966

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記述言語：英語   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.49.3233

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hindawi Limited  

Extrahepatic portal vein aneurysm is a rare disorder. From 1956 to 2008, we found only 43 published English-language reports, including 67 cases, using PubMed. We report a case of a 77-year-old woman who had complaints of lower abdominal fullness and residual urine. We performed ultrasonography (US), which demonstrated a congenital extrahepatic portal vein aneurysm. She had no obvious symptoms of the extrahepatic portal vein aneurysm. She had undergone gastrectomy without blood transfusion for gastric ulcer more than 20 years ago. Physical examination revealed no abnormal findings. US revealed a 2.2 × 1.8 cm, round shaped hypoechogenic lesion at the hepatic hilum. Color Doppler US showed bidirectional colors due to circular flow within this lesion. 3D-CT and CT angiography demonstrated that the saccular aneurysm at the hepatic hilum was 3.0 cm in diameter and was enhanced equal to that of portal vein. Twenty-six months after the diagnosis, the aneurysm had not grown in size. Since our patient had no serious complaints or liver disease, surgical procedures had not been employed. US and 3D-CT are noninvasive diagnostic techniques and are helpful in the diagnosis and follow-up of extrahepatic portal vein aneurysms. Copyright © 2010 Norio Yukawa et al.

DOI： 10.1155/2010/560495

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記述言語：英語   出版者・発行元：GEORG THIEME VERLAG KG  

DOI： 10.1055/s-0029-1214690

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

Aim:
Genetic factors as well as environmental factors play an important role in the development of non-alcoholic fatty liver disease (NAFLD). Recently, inducible nitric oxide synthase (iNOS) was significantly higher in the severest form of non-alcoholic steatohepatitis (NASH), and nitric oxide (NO) has been determined to play an important role in the process of fibrosis in NASH. In this study, we investigated iNOS gene polymorphisms for associations with NAFLD.
Methods:
A total of 115 NAFLD patients, consisting of 65 patients with NASH and 50 patients with simple steatosis, in whom a positive diagnosis had been made by liver biopsy, and 435 healthy control subjects, were recruited into this study.
Results:
We investigated 10 single nucleotide polymorphisms (SNP) of the iNOS gene, one of which, rs1060822, had the lowest P-value in the allele frequency model (P = 0.00078) with an odds ratio (95% confidence interval) of 0.49 (0.32-0.75). Four SNP, rs2297510, rs2297511, rs2797512 and rs1060822, were significantly associated with NAFLD, even when the most conservative Bonferroni&apos;s correction was applied. Linkage disequilibrium analysis revealed that SNP rs1060822 and three other SNP, rs2297510, rs2297511 and rs2797512, were in the same block. We also investigated associations between rs1060822 genotypes and the fibrosis index, and the results of the analysis revealed an additive increase in the fibrosis index and intrahepatic iNOS mRNA expression in the patients with the T allele of rs1060822.
Conclusion:
This is the first study to identify genetic variations in iNOS that may influence the risk of NAFLD and liver fibrosis in NAFLD.

DOI： 10.1111/j.1872-034X.2009.00539.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JOHN WILEY & SONS INC  

The specific mechanisms of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) pathogenesis remain unknown. In the present study we investigated the differences between NAFL and NASH in terms of liver lipid metabolites and serum lipoprotein. In all, 104 Japanese subjects (50 men and 54 postmenopausal women) with histologically verified NAFL disease (NAFLD) (51 with NAFL, 53 with NASH) were evaluated; all diagnoses were based on liver biopsy findings and the proposed diagnostic criteria. To investigate the differences between NAFL and NASH in humans, we carefully examined (1) lipid inflow in the liver, (2) lipid outflow from the liver, (3) very-low-density lipoprotein (VLDL) synthesis in the liver, (4) triglyceride (TG) metabolites in the liver, and (5) lipid changes and oxidative DNA damage. Most of the hepatic lipid metabolite profiles were similar in the NAFL and NASH groups. However, VLDL synthesis and lipid outflow from the liver were impaired, and surplus TGs might have been produced as a result of lipid oxidation and oxidative DNA damage in the NASH group. Conclusion: A growing body of literature suggests that a deterioration in fatty acid oxidation and VLDL secretion from the liver, caused by the impediment of VLDL synthesis, might induce serious lipid oxidation and DNA oxidative damage, impacting the degree of liver injury and thereby contributing to the progression of NASH. Therefore, dysfunctional VLDL synthesis and release may be a key factor in progression to NASH. (HEPATOLOGY 2009;50:772-780.)

DOI： 10.1002/hep.23094

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia, type 2 diabetes mellitus and hypertension, making it difficult to treat NAFLD effectively using any monotherapy available to date. In this study, we propose a novel combination therapy for NAFLD comprising ezetimibe (EZ), a cholesterol absorption inhibitor, and acarbose (AC), an alpha-glucosidase inhibitor.
Methods: C57BL/6J mice were divided into five treatment groups as follows: basal diet (1113), high-fat diet (HFD) only, HFD with EZ (5 mg/kg/day), HFD with AC (100 mg/kg/day), and HFD with both EZ and AC for 24 weeks.
Results: Long-term combination therapy with EZ and AC significantly reduced steatosis, inflammation and fibrosis in the liver, compared with long-term monotherapy with either drug, in an HFD-induced NAFLD mouse model; the combination therapy also significantly increased the expression of microsomal triglyceride transfer protein (MTP) and peroxisome proliferators-activated receptor-alpha 1 (PPAR-alpha 1) in the liver, compared with either monotherapy, which may have led to the improvement in lipid metabolic disorder seen in this model.
Conclusions: Combination therapy with EZ and AC for 24 weeks improved the histopathological findings in a mouse model of NAFLD. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jhep.2009.05.017

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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Background
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver injury in many countries. Genetic factors are important for the development of NAFLD, as well as environmental factors. Recently an angiotensin II type 1 receptor (AGTR1) has been recognized as important in the aetiology of fibrosis in the liver.
Objective
In this study we investigated the association between angiotensin II type 1 receptor gene polymorphism (ATGR1) and NAFLD.
Methods
One hundred and sixty-seven NAFLD patients [106 with nonalcoholic steatohepatitis (NASH) and 61 with simple steatosis] with a positive diagnosis by liver biopsy and 435 healthy control subjects were recruited in this study.
Results:
We investigated 12 single nucleotide polymorphisms (SNPs) of the ATGR1 gene, among which rs3772622 showed the lowest P-value of allele frequency model (P=0.0000012) with an odds ratio (95% confidence interval) of 1.95 (1.49-2.55). Five SNPs (rs3772622, rs3772633, rs2276736, rs3772630 and rs3772627) were significantly associated with NAFLD, even when the most conservative Bonferroni&apos;s correction was applied. Linkage disequilibrium analysis revealed that SNP rs3772622 and another four SNPs (rs3772633, rs2276736, rs3772630 and rs3772627) were in the same block. We investigated the association between rs3772622 genotypes and the fibrosis index. The results of the analysis revealed an additive increase of the fibrosis index in the patients with the A allele of rs3772622.
Conclusions
This is the first report to demonstrate the genetic variations in ATGR1 that may influence the risk of NAFLD and liver fibrosis in NAFLD.

DOI： 10.1111/j.1478-3231.2009.01988.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Purpose To determine the prevalence and progression of Barrett's epithelium and associated risk factors in Japan. Methods The study population comprised 869 cases. Endoscopic Barrett's epithelium was diagnosed based on the Prague C & M Criteria. The correlations of clinical factors with the prevalence and progression of endoscopic Barrett's epithelium were examined. Results Endoscopic Barrett's epithelium was diagnosed in 374 cases (43%), in the majority of which the diagnosis was short-segment Barrett's esophagus. The progression of Barrett's epithelium was identified in 47 cases. In univariate and multiple logistic regression analyses, aging, smoking habit, and erosive esophagitis were significantly associated with the prevalence of Barrett's epithelium, whereas aging and erosive esophagitis, especially severe erosive esophagitis, were significant contributing factors to the progression of Barrett's epithelium. Conclusions Forty-three percent of the total study population was diagnosed as having endoscopic Barrett's epithelium. During the follow-up period, 12.6% of the cases with Barrett's epithelium exhibited progression which was associated with aging and severe erosive esophagitis.

DOI： 10.1007/s10620-008-0537-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

Aim:
We evaluated the characteristic endoscopic ultrasonography (EUS) findings of early autoimmune pancreatitis (AIP).
Methods:
Nineteen patients with AIP were identified from our database. We reviewed the following features of EUS as being potentially characteristic of early AIP: hyperechoic foci, hyperechoic strands, lobularity, hyperechoic pancreatic duct margins and reduced echogenicity. According to the Cambridge classification for chronic pancreatitis, we classified AIP into early AIP (Grades 0-2) and advanced AIP (Grades 3-5) and examined the histopathological findings in each stage of AIP.
Results:
There were nine cases of early AIP and 10 cases of advanced AIP. Five of the nine early cases of AIP showed spontaneous remission without corticosteroid therapy (P &lt; 0.05). The EUS findings were as follows (early vs advanced): hyperechoic foci, 100% (9/9) vs 100% (10/10); hyperechoic strands, 66.7% (6/9) vs 70% (7/10); lobularity, 77.8% (7/9) vs 20% (2/10); hyperechoic pancreatic duct margin, 88.9% (8/9) vs 30% (3/10); reduced echogenicity, 88.9% (8/9) vs 90% (9/10). Lobularity and hyperechoic pancreatic duct margin were detected at a significantly higher frequency in early AIP than in the advanced AIP patients (P &lt; 0.05). Regarding the histopathological findings, acinar cells were better preserved in the cases of early AIP, whereas acinar cells were reduced in number and replaced by massive fibrosis in the patients with advanced AIP.
Conclusions:
Lobularity and hyperechoic pancreatic duct margin are characteristic EUS features of early AIP, which has a more favorable prognosis, and shows a higher frequency of spontaneous remission and preservation of acinar cells, than advanced AIP.

DOI： 10.1111/j.1443-1661.2009.00879.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: The association between obesity and the risk of Barrett&apos;s esophagus (BE) is unclear. Furthermore, the association between visceral obesity and the risk of BE is entirely unknown.
Methods: We conducted a retrospective study in 163 patients with non-alcoholic fatty liver disease (NAFLD) who underwent both endoscopy and abdominal CT at an interval of less than a year at our institution. BE was endoscopically diagnosed based on the Prague C & M Criteria. The surface areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated from CT images at the level of the umbilicus. The correlations between the BMI, VAT, and SAT and the risk of BE were examined by univariate and multivariate analyses.
Results: Sixty-nine of the 163 study participants (42.3%) were diagnosed to have endoscopic BE, which was classified as short-segment BE (SSBE) in almost all of the cases. There were no significant differences in the age or gender distribution between the groups with and without BE. According to the results of the univariate analysis, VAT was significantly associated with the risk of BE; the BMI tended to be higher in the group with BE than in the group without BE, but this relation did not reach statistical significance. VAT was independently associated with the risk of BE even after adjustment for the BMI.
Conclusion: In Japanese patients with NAFLD, obesity tended to be associated with the risk of BE, and this risk appeared to be mediated for the most part by abdominal visceral adiposity.

DOI： 10.1186/1471-230X-9-56

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

Hepatocellular carcinoma (HCC) is one of the most commonly occurring malignances worldwide. Curative therapies such as resection, percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) have been applied to patients with early-stage HCC. Patients with more advanced cancers require local or systemic therapies. We present the results of our retrospective review conducted to evaluate whether transarterial chemoembolization (TACE) alone and combined TACE with percutaneous ablation for HCC exhibited superior efficacy to palliative treatment.
The effects of TACE and of the combined therapies (TACE + PEI or TACE + RFA) on the long-term survival rates were evaluated in 268 untreated HCC patients by various statistical analyses.
The cumulative survival rates in the TACE alone group were significantly superior to those in the palliative treatment group. Further, the cumulative survival rates in the combined TACE + PEI/RFA group were significantly superior to those in the TACE alone group. When the comparison among the groups was restricted to patients with two or three tumors fulfilling the Milan criteria, significantly greater prolongation of survival was observed in the combined TACE + PEI/RFA group than in the PEI/RFA alone group.
The aforementioned treatment modalities yielded greater improvements of the survival rate and survival duration as compared to palliative treatment in HCC patients. Furthermore, in terms of the effect on the survival period, combined TACE + PEI/RFA therapy was more effective than TACE monotherapy, and also more effective than PEI or RFA monotherapy in cases with multiple tumors fulfilling the Milan criteria.

DOI： 10.1111/j.1872-034X.2009.00490.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

The antithrombotic effects of low-dose aspirin (LDA) are well established, and it is used for primary and secondary prevention of cardiovascular events. However, the small intestinal toxicity of LDA remains unclear. The aim of this study was to review the characteristics of small bowel injury in long-term LDA users with capsule endoscopy (CE).
We retrospectively reviewed all chronic LDA users (&gt; 3 months) who underwent CE for suspected small bowel diseases from May 2004 to May 2008 at two medical centers.
At our institutions, a total of 22 patients (13 males and 9 females, mean age 66.3 years) taking LDA underwent a CE examination. The indications for CE were obscure gastrointestinal bleeding in 21 patients and 1 patient who had abdominal pain. Twenty-one patients (95.5%) had some small bowel mucosal injury. Small bowel erosions were identified in 14 patients (63.6%). This enteropathy was characterized by multiple petechiae, loss of villi, erosions, and ulcers with round, irregular, and punched-out shapes. Two patients had circumferential ulcers with stricture. In most patients, small bowel lesions were multifocal and were evenly distributed in the small bowel. No patients failed to pass the capsule.
This is the first CE report that has studied the characteristics of small bowel injury in chronic LDA users. CE is useful to diagnose small bowel enteropathy associated with LDA.

DOI： 10.1007/s00535-009-0040-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: Coffee is one of the most popular beverages worldwide, however, few studies have examined the effects of coffee on the gastrointestinal system. The aim of this study was to determine whether there was a correlation between coffee intake and gastric emptying using a novel non-invasive technique for measuring gastric emptying with a continuous real time C-13 breath test (BreathID system: Oridion, Israel).
Methodology: Six healthy male volunteers participated in this randomized, two-way crossover study. The subjects were randomly assigned to receive a test meal (200kcal per 200mL) plus postprandial 190mL black coffee or the test meal alone after fasting overnight. A C-13-acetic acid breath test was continuously performed using the BreathID system, which monitors gastric emptying, for 4 hours after the administration of the test meal. Using Oridion Research Software (13 version), the time for emptying of 50% of the labeled meals (T 1/2) and the analog to the scintigraphy lag time for 10% emptying of the labeled meal (T lag) were calculated. The parameters between two occasions were compared using the Wilcoxon signed-rank test.
Results: After coffee intake the T 1/2 and T lag constant were significantly decreased.
Conclusions: The decrease in the T 1/2 and T lag suggests the acceleration of gastric emptying. This study showed that postprandial coffee intake enhances gastric emptying, suggesting the potential use of coffee in clinical settings for patients with functional gastrointestinal disorders.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: We aimed to estimate whether the macroscopic extent of gastric mucosal atrophy is associated with a risk for esophageal squamous cell carcinoma using a case-control study in Japanese subjects, a population known to have a high prevalence of CagA-positive H. pylori infection.
Methods: Two hundred and fifty-three patients who were diagnosed as having esophageal squamous cell carcinoma, and 253 sex-and age-matched controls were enrolled in the present study. The macroscopic extent of gastric mucosal atrophy was evaluated based on the Kimura and Takemoto Classification. A conditional logistic regression model with adjustment for potential confounding factors was used to assess the associations.
Results: Body gastritis, defined endoscopically, was independently associated with an increased risk for esophageal squamous cell carcinoma.
Conclusion: Our findings suggest that macroscopic body gastritis may be a risk factor for esophageal squamous cell carcinoma in Japan. Further studies are needed to confirm these findings.

DOI： 10.1186/1471-230X-9-34

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

The aim of the study was to evaluate bowel dysmotility in patients with a history of abdominal surgery by measuring both gastric transit time and small bowel transit time during capsule endoscopy and assessing the completeness of the examination. The study included 26 patients who had undergone abdominal surgery (postoperative group) and 52 patients who had not (control group). The capsule reached the cecum in 50.0% of the postoperative group and 80.8% of the control group (P = 0.005). While there was no significant difference in gastric transit time between the two groups (P = 0.882), small bowel transit time was significantly longer in the postoperative group (338.3 +/- A 119.2 min) than in the control group (266.4 +/- A 110.8 min, P = 0.010). This is the first study to report that the small bowel transit time during capsule endoscopy is prolonged in patients who had a history of abdominal surgery, resulting in a lower frequency of complete examination.

DOI： 10.1007/s10620-008-0467-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: The aim of this study was to evaluate the risk factors of perforation during endoscopic submucosal dissection (ESD).
Methodology: ESD was performed using a Flex knife in 64 patients with a total of 67 gastric tumors. Perforation occurred at the sites of a total of 4 lesions (5.9% [4/67]) for which conservative treatment had been effective. We evaluated several possible risk factors for perforation following ESD, such as tumor size, the location of the lesion, the operation time, and other clinical factors.
Results: All the perforations occurred in the posterior wall of the gastric upper or middle body. In an analysis adjusted for age and sex, the tumor size (odds ratio (OR), 1.017; 95% confidence interval (CI), 1.004-1.030), the location of the lesion in an upper region (OR, 10.64; 95%CI, 1.160-10.00) and the operation time (OR, 1.017; 95%CI, 1.013-1.295) were significantly associated with the incidence of perforation. All perforations were transient, resolving within 7 days, and did not require surgical treatment.
Conclusions: A large tumor size, the location of the lesion in an upper region, and a long operation time are risk factors for perforation following ESD.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Spontaneous rupture is rare complication of hepatocellular carcinoma (HCC) with high mortality rate in cirrhotic cases. The aim of this study was to determine the factors influencing prognosis in cases of spontaneously ruptured HCC and to investigate the outcomes of the treatments employed, especially transcatheter arterial embolization (TAE).
Methods: A retrospective multicenter study was conducted in 48 cirrhotic patients with spontaneous rupture of HCC. Conservative treatment was employed in 32 patients (ConT group) and TAE was performed in 16 patients (TAE group).
Results: The median survival time (MST) in the ConT group was only 13.1 days and the survival rate was extremely poor: 59.4% at 7 days, 37.5% at 14 days, and 6.3% at 30 days. On the other hand, the MST in the TAE group was 244.8 days and the survival rate was 87.5% at 1 month, 56.3% at 3 months, 23.4% at 12 months, and 15.6% at 24 months. According to the results of univariate analyses, factors associated with poor hepatic function and poor suitability for TAE was important determinants of short-term death (less than 3 weeks) among the patients (p &lt; 0.05). On the other hand, among the patients in whom initial TAE was successfully performed (n = 15), a multivariate analysis showed that a maximum tumor size not exceeding 7 cm was the only independent factor determining long-term survival (p = 0.0130).
Conclusion: Despite the inherent limitations of this retrospective study, TAE appears to be a useful treatment strategy for cirrhotic patients with spontaneous HCC rupture, as it yielded a longer survival period compared with conservative treatment in patients with ruptured HCC. Among the patients with ruptured HCC in whom initial TAE was successfully performed, the maximum tumor size was an important factor influencing survival.

DOI： 10.1186/1471-230X-9-29

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: The ideal medication for treatment of acid related diseases should have a rapid onset of action to promote hemostasis. The aim of our study was to investigate the inhibitory effects on gastric acid secretion after single intravenous administrations of lansoprazole 30 mg and famotidine 20 mg.
Methodology: Twelve Helicobacter pylori-negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 4 hours after single intravenous administration of lansoprazole 30 mg or famotidine 20 mg.
Results: The average pH during the 4-hour period after administration of famotidine was higher than after lansoprazole (median: 5.15 versus 3.55, respectively; p = 0.0376). During the 4-hour study period, famotidine 20 mg provided a longer duration of pH &gt; 3, 3.5, 4, 5, 6 and 7, compared to lansoprazole 30 mg (median: 73.6% versus 57.0%; p = 0.0414, 66.8% versus 47.8%; p = 0.0281, 60.8% versus 38.8%; p = 0.0150, 55.7% versus 29.7%; p = 0.0281, 45.0% versus 23.1%; p = 0.0414 and 23.9% versus 3.65%; p = 0.0076).
Conclusions: In Helicobacter pylori-negative healthy male subjects, an intravenous dose of famotidine 20 mg more rapidly increases intragastric pH than lansoprazole 30 mg.

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

DOI： 10.1111/j.1440-1746.2008.05765.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: In contrast to Western countries where erosive esophagitis (EE) is more prevalent in males, there is a high incidence of EE in elderly females in Japan. We aimed to examine the gender differences in the age-stratified prevalence of EE and Barrett&apos;s epithelium.
Methodology: The study population comprised 869 cases (463 men and 406 women) who had undergone an upper endoscopy at the Gastroenterology Division of Yokohama City University Hospital between August 2005 and July 2006. EE was graded according to the Los Angeles Classification. Barrett&apos;s epithelium was diagnosed based on the Prague C & M Criteria.
Results: In contrast to the decrease of the proportion of EE with aging in males, that in females remained constant. The results suggest that the suppressive effect of the increased gastric mucosal atrophy associated with aging was wiped out by the age-related effect of the increased incidence of hiatal hernia. The proportions of Barrett&apos;s epithelium in both males and females increased with aging.
Conclusions: In Japan, the prevalence of elderly females complicated with hiatal hernia, which was partly due to osteoporosis and kyphosis, may affect the proportion of EE and probably Barrett&apos;s epithelium.

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記述言語：英語   出版者・発行元：KARGER  

DOI： 10.1159/000227044

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background and Aims: Small intestinal toxicity of low-dose aspirin remains unclear. The purpose of this capsule endoscopy study was to assess the incidence of small bowel injury in healthy volunteers treated with short-term low-dose aspirin. Methods: Healthy subjects were randomly assigned to receive low-dose aspirin for 14 days (Aspirin group) or no drugs for 14 days (Control group). The two treatment occasions were separated by a washout period of at least 4 weeks. All subjects underwent capsule endoscopy at the end of each treatment period. Results: After 2 weeks of treatment, the percentages of subjects with small bowel pathology were 80% in the Aspirin group compared with 20% in the Control group (p = 0.023). The incidence of small bowel mucosal breaks in the Aspirin group was higher than that in the Control group, although the difference was not significant (30 vs. 0%; p = 0.210). Conclusions: This is the first pilot study using capsule endoscopy to report on the relation between small bowel injury and low-dose aspirin. Among the healthy subjects, the short-term administration of low-dose aspirin was associated with a mild mucosal inflammation of the small bowel. Copyright (c) 2009 S. Karger AG, Basel

DOI： 10.1159/000204465

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In human subjects, aberrant crypt foci (ACF) can be classified as dysplastic or non-dysplastic using magnifying colonoscopy. Dysplastic ACF are thought to be a biomarker for the risk of colorectal cancer (CRC). Hyperinsulinemia and insulin-like growth factor-1 (IGF-1) have also been reported to be associated with an increased risk of CRC. To clarify this association, we investigated the relationship between diabetes risk, IGF-1 and the number of dysplastic ACF. Assessment of the number of dysplastic ACF in the entire colorectum is technically difficult, and we imaged the lower rectum only. Blood collections were taken in the morning on the day of colonoscopy. A total of 512 ACF were counted in 84 male participants, and a correlation was demonstrated to exist between age, body mass index (BMI), fasting blood sugar (FBS), insulin, homeostasis model assessment-insulin resistance (HOMA-IR), plasma leptin levels, plasma IGF-1 levels and the number of dysplastic ACF. A significant association between plasma IGF-1 levels and the number of dysplastic ACF was still demonstrable after adjustment for age, BMI, FBS, insulin, HOMA-IR and plasma leptin levels. Our findings suggest that increased plasma leptin and IGF-1 levels, hyperinsulinemia and insulin resistance may promote the growth of dysplastic ACF. The results of multiple regression analysis revealed that increased plasma IGF-1 levels are associated with the number of dysplastic ACF present, and may be an independent risk factor for CRC. In conclusion, elevated plasma IGF-1 may promote the growth of dysplastic ACF and play a key role in colon carcinogenesis in male individuals.

DOI： 10.3892/mmr-00000105

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記述言語：英語   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.48.2229

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記述言語：英語  

DOI： 10.1159/000209218

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Aims: Hepatic mitochondrial beta-oxidation is considered to play a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH). The aim of this study was to determine whether there were differences between patients with NASH and healthy controls in a breath test with 13C-octanoate, a medium-chain fatty acid. Methodology: The subjects were 8 patients (5 men, 3 women, median age 46.5 years) with histologically proven NASH and 6 healthy controls (5 men, 1 women, and median age 27.8 years). The 13C breath test was performed for 4 hours using the BreathID system with a 100mL of water containing 100mg 13C-octanoate. Results: There were no significant differences between NASH patients and controls about all breath test parameters. Conclusions: NASH-mediated changes in breath test parameters after ingestion of 13C-octanoate were not observed in our study. The present study findings suggest the possible preservation of 13C-octanoate metabolism (mitochondrial beta-oxidation) in patients with NASH. © H.G.E. Update Medical Publishing S.A.

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記述言語：英語   出版者・発行元：KARGER  

DOI： 10.1159/000235922

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記述言語：英語   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.48.2823

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記述言語：英語   出版者・発行元：GEORG THIEME VERLAG KG  

DOI： 10.1055/s-2008-1077418

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記述言語：英語   出版者・発行元：SPRINGER  

DOI： 10.1007/s10620-008-0273-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Aim: Non-alcoholic steatohepatitis (NASH) is a subset of non-alcoholic fatty liver disease (NAFLD) and sometimes progresses to cirrhosis and liver failure. In this study we analyzed the expression profile of genes and biological pathways involved in NASH in comparison with non-NASH by gene set enrichment analysis (GSEA) employing a DNA microarray technique.
Methods: mRNA from liver biopsy specimens was collected from a group of NASH patients and a group of non-NASH patients. We analyzed the relative abundance of mRNA using high-density oligonucleotide microarrays containing probes for 54 675 known genes, and investigated the pathogenetic mechanisms of NASH by means of a powerful technique for analyzing molecular profiling data, GSEA.
Results: The results showed that the level of expression of 27 gene sets was significantly higher and the level of expression of 25 gene sets was significantly lower in the NASH samples than in the non-NASH samples. Based on these results we created an online, publicly available, searchable database containing the data for the gene expression profiles of the NASH patients (http://www2.genome.rcast.u-tokyo.ac.jp/__/NASH/NASH_GSEA2/).
Conclusion: Our data revealed differences in expression of many gene sets that are involved in the pathogenesis of NASH.

DOI： 10.1111/j.1872-034X.2008.00399.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：B M J PUBLISHING GROUP  

Objective: No effective drugs have been developed to date to prevent or treat non-alcoholic fatty liver disease ( NAFLD), although diet modification and exercise to improve obesity have been attempted. Therefore, development of a novel drug/strategy to treat NAFLD is urgently needed. In the present study, a novel concept is proposed for the treatment of NAFLD.
Methods: Fisher 344 male rats were given a choline-deficient, L-amino acid-defined ( CDAA) diet or a high-fat high-calorie ( HF/HC) diet with or without the antiplatelet agents, aspirin, ticlopidine or cilostazol for 16 weeks. Liver steatosis, inflammation and fibrosis, and the possible mechanisms involved were investigated.
Results: All three antiplatelet drugs, namely aspirin, ticlopidine and cilostazol, significantly attenuated liver steatosis, inflammation and fibrosis in the CDAA diet group. Of the three agents, cilostazol was the most effective, and the drug also suppressed HF/HC diet-induced liver steatosis. Cilostazol appeared to exert its beneficial effect against NAFLD by suppressing mitogen-activated protein kinase activation induced by oxidative stress and platelet-derived growth factor via intercepting signal transduction from Akt to c-Raf.
Conclusion: Antiplatelet agents, especially cilostazol, offer the promise of becoming key agents for the treatment of NAFLD.

DOI： 10.1136/gut.2007.144550

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

DOI： 10.1111/j.1440-1746.2008.05662.x

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記述言語：英語   出版者・発行元：MOSBY-ELSEVIER  

DOI： 10.1016/j.gie.2008.04.023

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

DOI： 10.1111/j.1440-1746.2008.05662.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: The changes in the liver in nonalcoholic fatty liver disease (NAFLD) range over a wide spectrum, extending from steatosis to steatohepatitis (NASH). However it has remained difficult to differentiate between NASH and non-progressive NAFLD on the basis of the clinical findings alone.
Aims: In this study we investigated the clinical usefulness of plasma Pentraxin3 (PTX3) levels to predict NASH. Plasma PTX3 was measured in 70 patients with histologically verified NAFLD (28 with non-NASH and 42 with NASH) and 10 healthy control subjects.
Results: The plasma PTX3 level was significantly higher in the NASH cases than in the non-NASH cases (p = 0.0021) and control subjects (p = 0.045). And the plasma PTX3 level was significantly higher in the stages 3-4 NAFLD cases than in the stages 0-2 NAFLD cases (p&lt;0.0001). The PTX3 values were closely correlated with the stages of liver fibrosis (p&lt;0.0001, Kruskal-Wallis test). To detect NASH compared with non-NASH, the area under the curve for plasma PTX3 were 0.755, and to detect stages 3-4 NAFLD compared with stages 0-2 NAFLD, the area under the curve for plasma PTX3 were 0.850.
Conclusion: This is the first study to demonstrate consistent and profound elevation of plasma PTX3 levels in NASH in comparison with non-NASH. The results suggest that plasma PTX3 levels may not only be laboratory values that differentiate NASH from non-NASH, but marker of the severity of hepatic fibrosis in NASH.

DOI： 10.1186/1471-230X-8-53

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

DOI： 10.1111/j.1440-1746.2008.05630.x

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記述言語：英語   出版者・発行元：SPRINGER  

DOI： 10.1007/s10620-008-0219-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Hepatocellular carcinoma with portal venous invasion has a poor prognosis. We report a case treated successfully by intra-arterial 5-fluorouracil with systemic peglated-interferon-alpha-2b instead of conventional interferon-alpha.
A 66-year-old mail was admitted to our hospital, and diagnosed with hepatocellular carcinoma with portal venous invasion. Following informed consent,, he was treated with eight week cycles of combination chemotherapy using intra-arterial 5-fluorouracil (500mg/body/day i.a., days 1-5, 8-12 continuously) and pepylated-interferon-alpha-2b (100 mu g body s.c., days 1, 8). No significant side effects were observed during his therapy. After 4 cycles, computed tomography scan revealed a partial response of tumor reduction. This is the first report of advanced hepatocellular carcinoma effectively treated using subcutaneous pegylated-interferon-alpha-2b with intra-arterial 5-fluorouracil. While the conventional therapy of interferon-alpha with 5-fluorouracil has significant side effects, no significant side effects were observed in Our case. The use of subcutaneous pegylated-interferon-alpha-2b combined with intra-arterial 5-fluorouracil, may improve patients quality of life.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: The aim of this study was to determine whether there was a correlation between body positions and gastric emptying, using a novel non-invasive technique for measuring gastric emptying with a continuous real time (13)C breath test (BreathID system).
Methodology: Ten healthy male volunteers participated in this randomized, two-way crossover study. On both occasions. the (13)C breath test was performed for 4 hours using the BreathID system with a liquid meal (200kcal per 200mL) containing 100mg (13)C-acetic acid. Subjects were randomly assigned to sit comfortable (the sitting position) or to lie supine (the lying position).
Results: In the lying position, T 1/2 and T lag were significantly delayed. The gastric emptying coefficient was also decreased in lying position.
Conclusions: This study showed that gastric emptying following a liquid meal was significantly delayed in the lying position compared to the sitting position, suggesting the potential use of these findings in the clinical setting for patients receiving enteral nutrition via the stomach.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: Barrett&apos;s epithelium is currently believed to be related to acid gastroesophageal reflux. The aim was to determine the role of pancreatic-biliary reflux in the genesis of Barrett&apos;s epithelium.
Methodology: The study population comprised 1055 cases (606 men and 449 women; median age, 67years) who had undergone an upper endoscopy at 67 the Gastroenterology Division of Yokohama City University Hospital between August 2005 and July 2006. The study population was composed of 869 cases with intact stomachs and 186 cases with distal-gastrectomies. The presence and the progression of Barrett&apos;s epithelium were diagnosed based on the Prague C & M Criteria. The correlations of clinical factors, including distal-gastrectomy, with the presence and the progression of Barrett&apos;s epithelium were examined.
Results: The study demonstrated that 42.2% of the total population was diagnosed to have Barrett&apos;s epithelium and, in 12.6% of the cases with Barrett&apos;s epithelium, the progression of Barrett&apos;s epithelium was observed during the median 72 month follow-up. A distal gastrectomy was not significantly correlated with either the incidence or progression of Barrett&apos;s epithelium.
Conclusions: This lack of association between gastric surgery and Barrett&apos;s epithelium suggests that pancreatic-biliary reflux with limited acid is not sufficient for the genesis of Barrett&apos;s epithelium.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

We report a rare case of adenosquamous carcinoma of the pancreas associated with humoral hypercalcemia of malignancy (HHM) in which parathyroid hormone-related protein (PTH-rP) was identified as the causative factor of hypercalcemia. A 72-year-old Japanese man was admitted to our institution complaining of fever and abdominal pain. Abdominal computed tomography demonstrated a large tumor in the body of the pancreas, with multiple liver metastases. Both serum calcium and PTH-rP levels were elevated. No accumulation was observed on bone scan with technetium-99. The patient died of pneumonia 3 months after admission. Autopsy demonstrated that the neoplasm in the pancreas showed an abrupt histological transition from adenocarcinoma to squamous cell carcinoma. PTH-rP was identified in the primary pancreatic tumor cells by immunohistochemical examination and a reverse-transcription polymerase chain reaction (RTPCR) method. We concluded that PTH-rP was the causative factor of the HHM, based on the laboratory data, immunohistochemical examination, and messenger RNA (mRNA) expression. This is a very rare report of adenosquamous cell carcinoma of the pancreas associated with HHM.

DOI： 10.1007/s00534-007-1258-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: There have been few reports of primary carcinoma of the cystic duct (CCD) included in advanced cases. The aim of this study was to elucidate the clinical features of resected CCD.
Methodology: Six cases of CCD were diagnosed in which the main carcinomatous component arose from the cystic bile duct, even if these carcinomas were accompanied by invasion beyond the cystic duct. Histopathologic findings (i.e., H.E. staining and cell proliferating potency assessed by ki-67 staining) were compared between the main lesion and invasive lesion of the CCD.
Results: Abdominal ultrasonography revealed swelling of the gallbladder in 3 of the 6 patients, but not in the remaining 3, who were later diagnosed as having adenomyomatosis of the gallbladder, dyst-electasis due to the carcinomatous infiltration, and atrophic gallbladder, respectively. On computed tomography, 4 of the 6 cases with nodular-type lesions fulfilling Farrar's criteria, the tumors showed contrast enhancement. Direct cholangiography demonstrated unilateral obstruction of the common bile duct in 4 out of the 6 cases. Intraductal ultrasonography revealed CCD in only I of the 6 cases. Advanced CCD shows 2 patterns of invasion; the hepatic hilum pattern and the confluence invasive pattern. The hepatic hilum pattern of invasion tends to be associated with a poorer prognosis. Histopathological study revealed papillary and/or well differentiated adenocarcinoma in the cases where the lesion predominantly involved the cystic duct, whereas those lesions which extended beyond the cystic duct were composed of moderate and/or poorly differentiated tubular adenocarcinoma. The latter was associated with a high cellular proliferative activity as assessed by immunocytochemical examination for ki-67. Invasion of the perineural space was often observed in the cases with advanced CCD.
Conclusions: CCD showed the hepatic hilum and/or confluence pattern of invasion when the tumor extended beyond the cystic duct. CCD extending beyond the cystic duct was associated with more aggressive characteristics of the tumors, with perineural infiltration and histopathologic features resembling those of pancreatic cancer. It is concluded that CCDs extending beyond the cystic duct are more aggressive and associated with a poorer prognosis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Genetic factors as well as environmental factors are important in the development of NAFLD and in this study we investigated associations between polymorphisms of peroxisome proliferators-activated receptor gamma coactivator 1 alpha polymorphism (PPARGC1A) and NAFLD.
Aims: We recruited 115 patients with biopsy-proven NAFLD, 65 with NASH and 50 with simple steatosis, and 441 healthy control subjects and investigated 15 SNPs of PPARGC1A.
Results: SNP rs2290602 had the lowest p value in the dominant mode (p = 0.00095), and the odds ratio for NAFLD (95% CI) was 2.73 (1.48-5.06). rs2290602 was significantly associated with NAFLD even when the most conservative Bonferroni&apos;s correction was applied (p = 0.0143). The frequency of the T allele of rs2290602 was significantly higher in the NASH patients than in the control subjects (p = 0.00093, allele frequency mode), and its frequency in the NASH patients tended to be higher than in the simple steatosis patients (p = 0.09). The results of the real-time RT-PCR study showed that intrahepatic mRNA expression of PPARGC1A was lower in the TT group than in the GG or GT group at SNP rs2290602 (p = 0.0454).
Conclusion: This is the first study to demonstrate a significant association between genetic variations in PPARGC1A and NAFLD. This finding suggested that PPARGC1A polymorphism and lower expression of PPARGC1A mRNA in the liver are an important genetic contribution to etiology of NAFLD.

DOI： 10.1186/1471-230X-8-27

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background. Liver fibrosis is the main predictor of the progression of nonalcoholic fatty liver disease. Transient elastography (FibroScan), which measures liver stiffness, is a novel, noninvasive method to assess liver fibrosis.
Aim. We investigated the usefulness of liver stiffness measurement in the evaluation of liver fibrosis in nonalcoholic fatty liver disease patients.
Study population. A total of 97 nonalcoholic fatty liver disease patients.
Methods. Transient elastography was performed for liver stiffness measurement in 97 nonalcoholic fatty liver disease patients. And the relationship between histological parameters and liver stiffness measurement was studied by multivariate analysis. Moreover, we investigated the relationship between liver stiffness measurement and the serum levels of hyaluronic acid and type IV collagen 7s domain.
Results. The liver stiffness was well correlated with the stage of liver fibrosis (Kruskal-Wallis test p&lt;0.0001). The areas under the receiver-operating characteristic curves were 0.927 for &gt;= F1, 0.865 for &gt;= F2, 0.904 for &gt;= F3, 0.991 for &gt;= F4. Only fibrosis stage was correlated significantly with liver stiffness measurement by multiple regression analysis. Liver stiffness was also strongly correlated with the serum levels of type IV collagen 7s domain (r = 0.525, p &lt; 0.0001) and hyaluronic acid (r = 0.457, p &lt; 0.0001).
Conclusions. Our results show a significant correlation between liver stiffness measurement and fibrosis stage in nonalcoholic fatty liver disease patients, as confirmed by the results of liver biopsy, which remains the gold standard for evaluation of the severity of liver fibrosis in patients with nonalcoholic steatohepatitis. (C) 2007 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.

DOI： 10.1016/j.dld.2007.10.019

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Background/Purpose. Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas have a favorable prognosis. However, invasive ductal carcinomas of the pancreas show a rapid progression. The aim of this study was to investigate gene mutations in pure pancreatic juice from IPMN patients and to define these genetic mutations in relation to the histopathological and clinical features of IPMNs.
Methods. Twenty-two patients with IPMN, 21 patients with ductal carcinoma, and 20 patients with normal pancreas or chronic pancreatitis were recruited for this study. We measured the main pancreatic duct's largest diameter and the maximum size of a dilated branch was assessed by ultrasonography or endoscopic ultrasonography. Pure pancreatic juice was collected and was investigated for K-ras, p16, and p53 mutations.
Results. Mutant K-ras gene was detected in 13 of the 22 patients (59.1%) with IPMNs. Different kinds of mutations were detected in the same patient in 4 cases. In the 13 patients with mutant K-ras gene, the diameter of the most dilated part of the main pancreatic duct was 2-8 mm ( average, 4.5 mm) and in 7 patients with wild-type K-ras gene, the diameter was 2 5 mm ( average, 2.7 mm). There was a significant difference in the diameter of the main pancreatic duct between patients with and without the mutant K-ras gene ( P = 0.0323).
Conclusions. The incidence of K-ras mutation may be associated with the hypersecretion of mucin.

DOI： 10.1007/s00534-007-1223-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W J G PRESS  

The differential diagnosis between intracystic hemorrhage and cystadenocarcinoma of the liver is often difficult even with the use of various imaging modalities. A 73-year-old woman was admitted to our hospital with the complaint of right upper quadrant pain. Ultrasonography (US) demonstrated a heterogeneous echogenic cyst measuring 11 cm x 8 cm in size in S2 of the liver, indicated intracystic hemorrhage of simple liver cyst or cystadenocarcinoma, but the differential diagnosis was considerably difficult. Levovist (Schering, Berlin, Germany) US revealed no enhancement of the intracystic structures, suggesting a clot in the case of intracystic hemorrhage. An operation was performed and the resected lesion showed a solitary benign liver cyst, measuring 5.5 cm x 4.7 cm x 8.5 cm containing a large blood clot. The patient had an uneventful recovery after the surgery. Levovist US may play an important role in discrimination between intracystic hemorrhage of simple hepatic cysts and cystadenocarcinoma of the liver. (C) 2008 WJG. All rights reserved.

DOI： 10.3748/wjg.14.805

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The objective of this study was to clarify the clinical features of long-time survivors with unresectable pancreatic cancer treated by gemcitabine(GEM)alone and to predict survival time by carbohydrate antigen(CA)19-9, enhanced computed tomography(CT), and 18F-fluoro-2-deoxy-D-glucose positron emission tomography(FDG-PET) in monitoring the response to chemotherapy. Twenty-one patients with unresectable pancreatic cancer were enrolled in this study. All patients were evaluated by serum CA19-9 level, tumor size of CT, maximum standardized uptake value (SUVmax)with FDG-PET and other factors before chemotherapy(GEM alone at a dose of 1,000 mg/m(2) weekly x 3 followed by 1 week of rest), and they received chemotherapy until obviously progressive disease. Serum CA19-9, tumor size of CT and SUVmax with PET were measured after three courses of chemotherapy in ten patients. We compared these three modalities in terms of two points: Which is the best modality to predict survival time ? Which is the best monitoring modality to evaluate the efficacy of chemotherapy on unresectable pancreatic cancer ? A significant difference in survival time was not found between high level group and low level group of serum CA19-9 level and SUVmax with FDG-PET and also longest length of tumor by enhanced CT. In ten patients we evaluated the response rate of each parameter CA19-9(IU/mL), CT(longest length of tumor), and SUVmax with FDG-PET. We defined the response rate(pretreatment level of CA19-9 or longest length of tumor or SUVmax-after 3 courses chemotherapy level of CA19-9 or longest length of tumor or SUVmax/pretreatment level of CA19-9 or longest length of tumor or SUVmax). Response rate of CA19-9 was significantly correlated with survival time(r=0.633, p=0.0481). However, the response rate of SUVmax with FDG-PET had no significant correlation with survival time(r=0.019, p=0.9630). In the present study, the response rate of CA19-9 is the best monitoring modality to evaluate the efficacy of chemotherapy.

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記述言語：英語  

DOI： 10.1159/000151298

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

The term nonalcoholic steatohepatitis (NASH) has recently been proposed to identify a fatty liver disease accompanied by diffuse fatty infiltration and inflammation. However, no drug therapy has been established for NASH as yet. In the present study, we demonstrate the effect of the angiotensin II type 1 receptor antagonist telmisartan on the development of NASH in a rat model. Telmisartan, but not the angiotensin receptor antagonist valsartan, markedly attenuated hepatic steatosis, inflammation, and fibrosis in these rats. The quantitative parameters of steatosis, inflammation, and fibrosis were also ameliorated by treatment with telmisartan. Compared with telmisartan, the peroxisome proliferator-activated receptor-gamma agonist pioglitazone attenuated hepatic steatosis and fibrosis of the liver to a similar degree. However, telmisartan, but not pioglitazone, dramatically decreased both subcutaneous and visceral fat. In conclusion, these results indicated that telmisartan should be the drug of first choice for the treatment of patients with NASH.

DOI： 10.1007/s10620-007-9741-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOSBY-ELSEVIER  

Background: The rates of spontaneous remission and relapse of autoimmune pancreatitis (AIP) are not known.
Objective: To study the clinicopathologic factors predictive of remission and relapse in cases of AIP.
Design: Retrospective study.
Patients: Of the 20 patients with AIP, complete response to steroid therapy was recognized in 12 patients, and the remaining 8 patients improved without steroid therapy. Seven patients experienced a relapse.
Results: Patients who were seronegative for immunoglobulin (Ig) G4, had no obstructive jaundice, no diabetes mellitus, no swelling of the duodenal papilla, negative staining of the duodenal papilla for IgG4, and focal pancreatic swelling showed a greater tendency toward spontaneous remission (P &lt;.05). The results of multivariate analysis revealed that negative staining of the duodenal papilla for IgG4 was the only independent predictor of spontaneous remission of AIP (odds ratio [OR] 1.395, P =.0304). Seropositivity for IgG4, diffuse swelling of the pancreas, and the presence of stricture in the lower part of the bile duct were significantly associated with a relapse of AIP (P &lt;.05) according to the results of univariate analysis, whereas the results of multivariate analysis revealed only diffuse pancreatic swelling as an independent predictor of a relapse of AIP (OR 26.197, P =.0331).
Conclusions: Endoscopic findings are of useful prognostic value, because patients with AIP and with negative staining of the duodenal papilla for IgG4 appeared to have a higher frequency of remission without steroid therapy. Patients with AIP and with diffuse pancreatic swelling were found to be at an increased risk of relapse after the initial steroid administration.

DOI： 10.1016/j.gie.2007.06.059

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

Insulin resistance (IR) is known to be associated with the visceral adipose tissue area. Elucidation of the relationship between hepatitis C virus (HCV) and IR is of great clinical relevance, because IR promotes liver fibrosis. In this study, we tested the hypothesis that HCV infection by itself may promote IR. We prospectively evaluated 47 patients with chronic HCV infection who underwent liver biopsy. Patients with obesity, type 2 diabetes mellitus (DM), or a history of alcohol consumption were excluded. IR was estimated by calculation of the modified homeostasis model of insulin resistance (HOMA-IR) index. Abdominal fat distribution was determined by computed tomography. Fasting blood glucose levels were within normal range in all the patients. The results of univariate analysis revealed a significant correlation between the quantity of HCV-RNA and the HOMA-IR (r = 0.368, P = 0.0291). While a significant correlation between the visceral adipose tissue area and the HOMA-IR was also observed in the 97 control, nondiabetic, non-HCV-infected patients (r = 0.398, P &lt; 0.0001), no such significant correlation between the visceral adipose tissue area and the HOMA-IR (r = 0.124, P = 0.496) was observed in the patients with HCV infection. Multiple regression analysis with adjustment for age, gender and visceral adipose tissue area revealed a significant correlation between the HCV-RNA and the HOMA-IR (P = 0.0446). HCV is directly associated with IR in a dose-dependent manner, independent of the visceral adipose tissue area. This is the first report to demonstrate the direct involvement of HCV and IR in patients with chronic HCV infection.

DOI： 10.1111/j.1365-2893.2006.00836.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Background. The changes in nonalcoholic fatty liver disease (NAFLD) range over a wide spectrum, extending from steatosis to steatohepatitis (NASH). However, it has remained difficult to differentiate between NASH and nonprogressive NAFLD by clinical examination. We investigated the interrelationships between serum high-sensitivity C-reactive protein (hs-CRP) and the pathogenesis and progression of NASH. Methods. Hs-CRP was measured in 100 patients with histologically verified NAFLD (29 with steatosis and 71 with NASH), and a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed to measure the intrahepatic mRNA expressions of CRP and interleukin (IL)-6. Results. The results of a multiple regression analysis revealed that in comparison with cases of steatosis, hs-CRP was significantly elevated (P = 0.0048) in cases of NASH. Furthermore, among patients with NASH, hs-CRP was significantly elevated in those with advanced fibrosis compared with that in those with mild fibrosis (P = 0.0384), even after adjustment for age, sex, presence of diabetes, body mass index, visceral fat area, subcutaneous fat area, homeostasis model assessment for insulin resistance, high-density lipoprotein cholesterol, triglyceride, and low-density lipoprotein cholesterol. The results of the RT-PCR analysis showed that intrahepatic mRNA expression of CRP, but not IL-6, was increased in patients with NASH compared with those with steatosis (P = 0.0228). Conclusions. This is the first report to demonstrate consistent and profound elevation of hs-CRP in cases of NASH compared with in cases of simple nonprogressive steatosis. Our results suggest that hs-CRP may be a clinical feature that not only distinguishes NASH from simple nonprogressive steatosis but also indicates the severity of hepatic fibrosis in cases of NASH.

DOI： 10.1007/s00535-007-2060-x

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記述言語：英語   出版者・発行元：SPRINGER TOKYO  

DOI： 10.1007/s00535-007-2024-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Background. The changes in nonalcoholic fatty liver disease range over a wide spectrum, extending, from simple steatosis to nonalcoholic steatohepatitis (NASH). We investigated the clinical usefulness of the type IV collagen 7s domain and hyaluronic acid for predicting the severity of fibrosis before progression to the cirrhotic stage in NASH patients. Methods. The type IV collagen 7s domain and hyaluronic acid were measured in 72 patients with histologically verified NASH. Results. In a univariate analysis, marked elevation of hyaluronic acid and the type IV collagen 7s domain was observed in the NASH patients with advanced fibrosis compared with those with mild fibrosis (P = 0.0028, P = 0.0006, respectively). For detection of NASH with advanced fibrosis, the area under the receiver-operating characteristic curves for type IV collagen 7s domain and hyaluronic acid were 0.767 and 0.754, respectively. However, multiple regression analysis revealed that the type IV collagen 7s domain, but not hyaluronic acid, was significantly elevated in patients with advanced fibrosis even after adjustment for age, sex, platelet count, prothrombin time, aspartate aminotransferase/alanine aminotransferase ratio, body mass index, and presence of underlying type 2 diabetes mellitus, all of which have previously been reported as useful predictors of advanced fibrosis in patients with NASH (P = 0.0127, P = 0.2804, respectively). Conclusions. This is the first report to demonstrate a consistent and profound elevation of the type IV collagen 7s domain in NASH patients with advanced fibrosis (before progression to the stage of cirrhosis) compared with those with mild fibrosis.

DOI： 10.1007/s00535-007-2014-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Background There have been few reports of separate orifices (SPO) for the bile and pancreatic ducts. The aim of this study was to elucidate the clinical significance of SPO. Methods Clinical data of patients with SPO (n = 21) were compared with those of 324 patients without SPO. The duodenal papillae in the patients with SPO were classified endoscopically into three types. Furthermore, we compared three subgroups (n = 221) among 345 patients (group A, 10 patients with bile duct stones with SPO; group B, 66 patients with bile duct stones without SPO; and group C, 145 patients without bile duct dysfunction) to evaluate the bile stasis of SPO. Various factors were retrospectively analyzed to identify any relationship in patients with SPO. Results Univariate analysis revealed that the diameter of the common bile duct, cholangiographic angulation, and the presence of common bile duct stones (CBDS) were significantly associated with the presence of SPO. Multivariate analysis of the different risk factors for SPO in all patients revealed that the presence of CBDS (relative risk, 3.000; 95% confidence interval, 1.083-8.313; P = 0.0346) and cholangiographic angulation (relative risk, 1.041; 95% confidence interval, 1.010-1.072; P = 0.0085) were independent risk factors. Moreover, univariate analysis among the three subgroups revealed that age, the presence of periampullary diverticula, the diameter of the common bile duct, and the length of the short narrow distal segment were significantly associated with the presence of SPO. Conclusions CBDS and cholangiographic angulation are independent risk factors for SPO. This result suggests that SPO may be associated with an elevated risk of CBDS owing to bile stasis.

DOI： 10.1007/s00535-006-1973-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. The spectrum of NAFLD is broad, extending from simple steatosis through nonalcoholic steatohepatitis (NASH). Insulin resistance has been found to increase the risk of NASH, and obesity, and decreased levels of adiponectin are important factors in determining the severity of insulin resistance. Recent evidence has indicated that hypoadiponectinemia is involved in hepatic steatosis and NASH.
Methods: To investigate whether hypoadiponectinemia causes hepatic steatosis in type 2 diabetes mellitus (DM) patients independently of visceral adipose tissue, we measured the plasma adiponectin concentration, hepatic fat content based on the liver-to-spleen ratio (L/S ratio) according to computed tomography (CT) attenuation values, and the amount of visceral adipose tissue and subcutaneous adipose tissue by CT in 248 type 2 DM patients. We also investigated the relationship between the serum level of adiponectin and hepatic fibrosis.
Results: Significant correlations were observed between the L/S ratios and aspartate aminotransferase, alanine aminotransferase, visceral adipose tissue, subcutaneous adipose tissue, and serum adiponectin values (r=0.300, p=0.0007), and there was a highly significant inverse correlation between the visceral adipose tissue values and the serum adiponectin levels (r=-0.327, p &lt; 0.0002). The subcutaneous adipose tissue values, however, were not correlated with the serum adiponectin levels. Multiple regression analysis was used to quantify the impact of measured variables on the L/S ratio. After adjustment for age, gender, and visceral adipose tissue, the serum adiponectin levels were still significantly correlated with the L/S ratios (p=0.0064). And there was a stepwise decrease in the serum adiponectin in parallel to the severity of hepatic fibrosis.
Conclusions: Hypoadiponectinemia is concluded to be involved in the etiology of hepatic steatosis independently of visceral adipose tissue content, and is considered to be an important factor in the progression of fibrosis; further studies will be necessary to elucidate the exact physiological role of adiponectin and its contribution to the progression of NASH.

DOI： 10.1111/j.1530-0277.2006.00281.x

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記述言語：英語   出版者・発行元：KARGER  

DOI： 10.1159/000106753

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記述言語：英語   出版者・発行元：KARGER  

DOI： 10.1159/000104729

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER INST ULTRASOUND MEDICINE  

Objectives. To select an appropriate treatment regimen, it is essential to accurately characterize the nature of a thrombus. This study prospectively assessed the ability of contrast-enhanced sonography to differentiate between benign and malignant portal vein thrombosis in a population of high-risk patients. Methods. Fifty-five patients (43 men and 12 women, mean age, 66 years,- range, 55-83 years) with thrombi of the portal venous system were examined by power Doppler sonography and contrast-enhanced sonography with the intravenous contrast agent SH U 508A (Levovist; Schering AG, Berlin, Germany). Of the thrombi, 40 were characterized as malignant and 15 as benign. Pulsatile flow in the thrombus on power Doppler sonography and positive enhancement of the thrombus on contrast-enhanced sonography were judged as indications of a malignant thrombus. The sensitivity and specificity of both methods in differentiating the nature of the thrombus were evaluated. Results. The detection of pulsatile flow in a portal vein thrombus as the criterion for diagnosing malignant portal vein thrombus yielded overall sensitivity of 82.5% and specificity of 100%, whereas positive enhancement of the portal vein thrombus itself as a criterion for diagnosing malignancy yielded overall sensitivity and specificity of 100% for each. Conclusions. Contrast-enhanced sonography can be helpful in discriminating between benign and malignant portal vein thrombi.

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記述言語：英語   出版者・発行元：SPRINGER TOKYO  

DOI： 10.1007/s00535-006-1817-y

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記述言語：英語   出版者・発行元：KARGER  

DOI： 10.1159/000100968

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

A case of undifferentiated spindle-cell carcinoma of the gallbladder is described. A 72-year-old man presented with right hypochondralgia and fever. Imaging studies revealed a well-demarcated solid tumor (with a necrotic center) in the gallbladder that invaded the liver and transverse colon. On gross examination of the surgical specimen, the cut surface of the polypoid tumor showed nodular invasive growth. Microscopically, the tumor was composed of atypical spindle-shaped tumor cells that proliferated in a whirling or interlacing pattern. The tumor also showed foci with a malignant epithelial component that simulated a carcinosarcoma. Immunohistochemically, the biphasic differentiation of the tumor was highlighted by the different immunoreactivity to antibodies against cytokeratins, epithelial membrane antigen (EMA), and vimentin shown by the malignant epithelial components and the spindle-cell components. However the latter showed faint positivity for cytokeratin antibody. These results suggested that the spindle-cell carcinoma of the gallbladder originated from cholecystic mucosa and showed sarcomatous reaction or dedifferentiation, as indicated by the presence of vimentin-positive cells. The proliferation index, as detected by ki-67, in the spindle-cell component was higher than that in the epithelial component, which may account for the more aggressive biological behavior of the spindle-cell component.

DOI： 10.1007/s00534-006-1100-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Background Medication for the relief of heartburn should have the rapid onset of action required for on-demand use. We studied the inhibition of gastric acid secretion by lafutidine and rabeprazole, given in single doses to fasting and postprandial subjects. Methods. A total of 22 healthy male, Helicobacter pylori-negative volunteers participated in this randomized, two-way crossover study. They were randomly assigned to receive a single oral dose of 10mg lafutidine or 20mg rabeprazole after fasting overnight (12 subjects, fasting study) or after eating a test meal (noodles, 364kcal; protein, 10.1g; fat, 16g; carbohydrates, 44.9g; NaCl, 1.1g; 10 subjects, postprandial study). Intragastric pH was monitored continuously for 6h after treatment. The other drug was given after a washout period of at least 7 days, and intragastric pH was similarly monitored. Results. In the fasting study, lafutidine sustained pH at &gt; 3 and &gt; 4 during the second, third, fourth, fifth, and sixth hours of the study for significantly longer than rabeprazole. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. In the postprandial study, lafutidine sustained pH &gt; 3 and &gt; 4 for longer periods than rabeprazole during the third, fourth, fifth, and sixth hours of the study. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. Conclusions. Lafutidine 10mg produces a prompter rise in intragastric pH than rabeprazole 20mg in fasting and postprandial Helicobacter pylori-negative male subjects.

DOI： 10.1007/s00535-005-1569-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: Triple therapy consisting of lansoprazole, amoxicillin, and clarithromycin (LAC regimen) is widely used to eradicate Helicobacter pylori in Japan. However, the need for appropriate treatment after failure of initial therapy to eradicate H. pylori has been increasing. We therefore assessed the efficacy of a combination of rabeprazole, amoxicillin, and faropenem for second-line eradication therapy.
Methodology: The subjects were 116 patients positive for H. pylori infection. Patients initially received lansoprazole 60mg/day, amoxicillin 1500mg/day and clarithromycin 400mg/day in two divided doses for 7 days. Patients in whom eradication treatment failed were given rabeprazole 20mg/day and amoxicillin 1500mg/day in two divided doses, and faropenem 600mg/day in three divided doses (RAF regimen) for 7 consecutive days. H. pylori status was assessed by the C-13-urea breath test combined with rapid urease test or H. pylori culture method 8 weeks after completion of therapy. Susceptibility to clarithromycin was determined by the agar dilution method, and genetic polymorphism of CYP2C19 was analyzed by polymerase chain reaction-restriction fragment length polymorphism.
Results: The initial H. pylori eradication rate with the LAC regimen was 76.4% (84/110). Assessment of the CYP2C19 genotypes of the patients in whom eradication therapy failed revealed that homozygous,extensive metabolizers accounted for 70.0%. (16/23) and heterozygous extensive metabolizers, for 30.0% (7/23), with no poor metabolizers. The acquired resistance rate for clarithromycin was 52.0% (12/23), The success rate of re-eradication with the RAF regimen was 91.3% (21/23) with no serious adverse effects.
Conclusions: Triple therapy comprising rabeprazole, amoxicillin, and faropenem is effective for second-line eradication treatment of H. pylori infection, regardless of the genetic polymorphism of CYP2C19 or the presence of resistance to clarithromycin.

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記述言語：英語   出版者・発行元：SPRINGER TOKYO  

DOI： 10.1007/s00535-004-1521-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Endoscopic gallbladder stenting is useful palliative therapy for acute cholecystitis in high-risk patients. Although the success rate of endoscopic gallbladder stenting is 79%-100%, an alternative method has not been reported. We succeeded in employing a method for percutaneous gallbladder stenting (PTGS) and herein describe this new method. A patient with acute acalculous cholecystitis related to ischemic atherosclerotic vascular disease, cholangitis due to Lemmel syndrome, and severe congestive heart failure underwent PTGS through the cystic duct from the gallbladder to the duodenal papilla, because an endoscopic method failed in the treatment of Lemmel syndrome. Because we were unable to place endoscopic transpapillary gallbladder drainage, percutaneous transhepatic gallbladder drainage (PTGBD) was performed and both the cholecystitis and cholangitis ceased. PTGS was performed as an alternative to endoscopic gallbladder stenting. Access to the cystic duct and gallbladder was obtained by the PTGBD route, using a guidewire (0.035-inch diameter) and seeking catheter (6.5 Fr) under fluoroscopic control. A 7-Fr 12-cm double-pigtail biliary polyethylene stent was placed. The patient remained asymptomatic for 3 months after the PTGS until he died, of an acute recurrent myocardial infarction. This new PTGS placement is an alternative treatment for symptomatic gallbladder disease in patients with increased operative risk when the endoscopic method is unsuccessful.

DOI： 10.1007/s00534-005-0989-9

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER-VERLAG TOKYO  

Background The ideal medication for the treatment of acid-related diseases, for example, hemorrhagic ulcers and stress-related gastric bleeding, should have a rapid onset of action to promote hemostasis and alleviate symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion after single intravenous administrations of omeprazole 20 mg and famotidine 20 mg. Methods. Ten healthy Helicobacter pylori-negative male subjects participated in this randomized, double-masked, two-way crossover study. Intragastric pH was monitored continuously for 4 h after a single intravenous administration of omeprazole 20 mg and after a single intravenous administration of famotidine 20 mg. The administration of the two agents was separated by a 7-day washout period. Results. In all ten subjects, the length of time that intragastric pH remained over 3, during the 0- to 3- and 0- to 4-h study periods, was greater after famotidine treatment than after treatment with omeprazole, and famotidine increased the average pH during the 0 to 3- and 0 to 4-h study periods significantly more than omeprazole did. During the 4-h study period, famotidine provided a longer duration of pH of more than 2, 3, 3.5, 4, 5, 6, and 7, compared to omeprazole. Conclusions. In Helicobacter pylori-negative healthy male subjects, an intravenous dose of 20 mg famotidine increased intragastric pH more rapidly than intravenous omeprazole 20 mg.

DOI： 10.1007/s00535-003-1240-6

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 52-year old man was admitted to the hospital because of epigastralgia after heavy drinking. Computer tomography (CT) revealed segmental pancreas swelling suggestive of pancreas head carcinoma. We evaluated this pancreas head mass by 18F-fluorodexyglucose positron emission tomography (FDG-PET) using the standardized uptake value (SUV). Accumulation of FDG in this mass was very high and the SUV was 6. 61. We could not completely role out a malignant lesion but treated the case as acute pancreatitis because of the clinical symptoms. We followed this mass for 6 months by CT and FDG-PET. The pancreas head mass gradually diminished in size and finally vanished from the CT findings. FDG-PET accumulation also decreased with the recovery from acute pancreatitis. FDG-PET is a useful and sensitive means for evaluating pancreas carcinoma. But FDG accumulation also occurs in acute, chronic, tumor-forming, and autoimmune-related case of pancreatitis. So it is important to follow up a pancreas mass when observed by FDG-PET.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING ASIA  

Background and Aims: An ideal medication for heartburn should have the rapid onset of action needed for on-demand treatment. However, assessment of the onset of action of proton pump inhibitors has been largely subjective. We compared the inhibitory effect on gastric acid secretion of a single oral dose of omeprazole with that of rabeprazole.
Methods: Fourteen Helicobacter pylori -negative men participated in this randomized, double-masked, two-way cross-over study. Intragastric pH was monitored continuously for 6 h after a single, randomly assigned 20 mg oral dose of either omeprazole or rabeprazole. After a 7-day washout period, the other drug was administered. Each patient's S-mephenytoin 4'-hydroxylase (CYP2C19 ) genotype was determined by polymerase chain reaction-restriction fragment length polymorphism.
Results: Intragastric pH and pH holding time did not differ between treatments when the data were analyzed for the whole group without stratifying for CYP2C19 status. In CYP2C19 homozygous and heterozygous extensive metabolizers (10 subjects), rabeprazole maintained the intragastric at pH &gt; 3 and&gt; 4 for longer than omeprazole during both the 5 and 6 h study periods, and the average pH during the 6 h study period was higher with rabeprazole than with omeprazole. In these extensive metabolizers, rabeprazole maintained the pH &gt; 2,&gt; 3,&gt; 3.5 and&gt; 4 for longer during the 6 h study period than did omeprazole.
Conclusions: In H. pylori -negative men who are CYP2C19 homozygous or heterozygous extensive metabolizers, the intragastric pH after a single dose of 20 mg rabeprazole is higher during first 5-6 h than that after a single dose of 20 mg omeprazole. (C) 2003 Blackwell Publishing Asia Pty Ltd.

DOI： 10.1046/j.1440-1746.2003.03126.x

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

WNT signaling molecules, playing key roles in embryogenesis and carcinogenesis, are potent targets for regenerative medicine and clinical oncology. We have previously cloned and characterized the human orthologue of mouse proto-oncogene Wnt-10b using bioinformatics and cDNA-PCR. Human WNT10B is moderately expressed in MKN45 and MKN74 cells derived from human gastric cancer, and is up-regulated by tumor necrosis factor a (TNFalpha) in MKN45 cells. Here, expression and regulation of WNT10B in human cancer other than gastric cancer were investigated using cDNA-PCR. WNT10B mRNA was expressed in the majority of squamous cell carcinoma cell lines derived from esophageal cancer and cervical cancer. WNT10B mRNA was relatively highly expressed in TE3, TE6, TE10, TE11 (esophageal cancer), Hs700T (pancreatic cancer), SKG-IIIa, HeLa S3 (cervical cancer), and T-47D (breast cancer). Expression of WNT10B mRNA was up-regulated by B-estradiol in MCF-7 cells expressing estrogen receptors. Expression of WNT10B mRNA was down-regulated by all-trans retinoic acid in NT2 cells with the potential of self renewal and neuronal differentiation. WNT10B might be implicated in self renewal of stem cells as well as in carcinogenesis through activation of the WNT - beta-catenin pathway.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

WNT signals are transduced through seven-transmembranc-type WNT receptors encoded by Frizzled (FZD) genes to the beta-catenin - TCF pathway, the JNK pathway or the Ca2+-releasing pathway. WNT signaling molecules are potent targets for diagnosis of cancer (susceptibility, metastasis, and prognosis), for prevention and treatment of cancer, and for regenerative medicine or tissue engineering. We have so far cloned and characterized human WNT signaling, molecules WNT2B/WNTI3, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT10A, WNT10B, WNT11, WNT14, WNT14B/WNT15, FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD10, FRAT1, FRAT2, NKD1, NKD2, VANGL1/STB2, ARHU/WRCH1, ARHV/WRCH2, GIPC2, G1PC3, betaTRCP2/FBXW1B, SOX17, and TCF-3 using bioinformatics, cDNA-library screening, and cDNA-PCR. Here, expression of WNT7A in human normal tissues and cancer, and regulation of WNT7A and WNT7B in human cancer were investigated. WNT7A was highly expressed in fetal lung, adult testis, lymph node, and peripheral blood leukocytes, WNT7A was relatively highly expressed in temporal lobe, occipital lobe, parietal lobe, paracentral gyrus of cerebral cortex, caudate nucleus, hippocampus, medulla oblongata and putamen within adult brain. WNT7A was highly expressed in SW480 (colorectal cancer), BxPC-3 and Hs766T (pancreatic cancer), and was also expressed in MKN7 and MKN45 (gastric cancer), WNT7B rather than WNT7A was expressed in MCF-7 (breast cancer) and NT2 (embryonal tumor). beta-estradiol did not affect expression levels of WNT7A and WNT7B in MCF-7 cells. WNT7B, but not WNT7A, was slightly up-regulated by all-trans retinoic acid in NT2 cells.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

Expression of some members of the trefoil factor (TFF) and the WNT gene families is regulated together by estrogen., We have cloned and characterized human WNT signaling molecules using bioinformatics, cDNA-library screening and cDNA-PCR to investigate expression profile of WNT signaling molecules in human gastric cancer. Here, we investigated expression profile of TFF1/pS2, TFF2/SP and TFF3/ITF in human gastric cancer. Among 7 gastric cancer cell lines, TFF1 was expressed in OKAJIMA, TMK1, MKN45, and KATO-III, TFF2 in KATO-III, and TFF3 in MKN45 and KATO-III. TFFs were preferentially expressed in diffuse-type gastric cancer cell lines. Expression of TFFs in primary gastric cancer was next investigated. TFF1 was down-regulated in 7 cases out of 12 cases (58.3%) of primary gastric cancer. TFF2 was down-regulated in 10 out of 12 cases (83.3%) of primary gastric cancer. TFF3 was down-regulated in 2 out of 12 cases (16.7%) of primary gastric cancer, and was up-regulated in 5 out of 12 cases (41.7%). TFF1 and TFF2 were frequently down-regulated in primary gastric cancer, while TFF3 was up-regulated in some cases of primary gastric cancer. This is the first report on comprehensive expression analyses on TFFs in gastric cancer.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

We have recently cloned and characterized ST7R (ST7-like, ST7L), WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT10A, WNT10B, WNT11, WNT14, WNT14B/WNT15, NKD1, NKD2, ARHU/WRCH1, ARHV/ WRCH2, and VANGLI/ STB2 using bioinformatics, cDNA-PCR and RACE. ST7R is a paralog of tumor suppressor gene ST7 in the human genome. ST7R gene is clustered with WNT2B gene in human chromo-some 1p13 region, while ST7 gene is clustered with WNT2 gene in human chromosome 7q31 region. Multiple ST7R mRNAs (ST7R1-ST7R4) are transcribed due to alternative splicing. ST7R4 is divergent from ST7R1-ST7R3 in the C-terminal region. Here, we investigated expression of ST7R mRNAs in normal human tissues and human cancer. Northern blot analysis with S7S1 probe corresponding to ST7R], ST7R2 and ST7R3 isoforms detected 4.2 kb ST7R mRNA in various normal tissues, and also large amounts of 2.2-2.4 kb ST7R mRNAs in testis. Northern blot analysis with S7S4 probe corresponding to ST7R4 isoform detected 2.0 kb ST7R mRNA in testis. Expression of ST7R mRNAs in human cancer was next investigated using cDNA-PCR. Although ST7R mRNAs were almost ubiquitously expressed in 7 gastric cancer cell lines, expression levels of ST7R mRNAs were relatively lower in TMK1 cells, ST7R mRNAs were expressed in most cases of primary gastric cancer, and were up-regulated in 2 out of 10 cases of primary gastric cancer. This is the first report on expression analyses on ST7R.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

GIPC1/GIPC, GIPC2, and GIPC3 are a family of central PDZ-domain proteins. GIPC1/GIPC interacts with TGFbeta type III receptor, receptor tyrosine kinase TrkA, integrin alpha6A subunit, and GTPase-activating protein RGS-GAIP, while Xenopus homologue of human GIPCs interacts with Frizzled-3 (FZD3) class of WNT receptor. Here, we investigated expression of GIPC2 mRNA in human gastric, pancreatic, and breast cancer cell lines. GIPC2 mRNA was relatively highly expressed in OKAJIMA, TMK1, MKN45, and KATO-III cells derived from diffuse type of gastric cancer, but was almost undetectable in MKN7, MKN28, and MKN74 cells derived from intestinal type of gastric cancer as well as in other cell lines derived from pancreatic and breast cancer. Tumor necrosis factor alpha and interferon gamma, which are elevated in gastric mucosa with Helicobacter pylori infection, did not affect the expression level of GIPC2 mRNA in MKN45 cells. Up-regulation of GIPC2 mRNA was detected in 7 out of 10 cases of primary gastric cancer by using cDNA-PCR, and in 4 out of another 8 cases of primary gastric cancer by using expression array filter hybridization. GIPC2 might play important roles in human gastric cancer through modulation of growth factor signaling or cell adhesion.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

GIPC1/RGS19IP1/GIPC, GIPC2, and GIPC3 are a family of central PDZ-domain proteins with GH1 and GH2 domains. GIPC1 interacts with GTPase-activating protein RGS19/RGS-GAIP, TGFbeta type III receptor, receptor tyrosine kinase TrkA, and integrin alpha6A subunit. Xenopus homologue of human GIPCs interacts with Frizzled-3 class of WNT receptor. We investigated expression of human GIPC1 mRNA in normal tissues, cancer cell lines, and primary tumors. GIP1A probe (nucleotide position 1075-1483 of GIPC1 cDNA) hybridized to GIPC1 mRNA of 1.8 kb in size. GIPC1 mRNA was almost ubiquitously expressed in various normal tissues. Expression level of GIPC1 mRNA was relatively lower in bone marrow and peripheral blood leukocytes. GIPC1 mRNA was relatively highly expressed in gastric cancer cell lines OKAJIMA, TMK1, MKN28, MKN45, MKN74, KATO-III, pancreatic cancer cell line AsPC-1, colorectal cancer cell line SW480, and lung cancer cell line A549. On the other hand, GIPC1 mRNA was almost undetectable in leukemia/lymphoma cell lines HL-60, Raji, and Daudi. Expression of GIPC1 mRNA was down-regulated in 12 out of 14 cases of primary kidney tumors, 10 out of 18 cases of primary colorectal tumors, 3 out of 8 cases of primary gastric cancer, 3 out of 3 cases of primary prostate cancer. Because GIPC1 induces increased expression of TGFbeta type III receptor at the cell surface and enhanced responsiveness to TGFbeta, down-regulation of GIPC1 mRNA in tumors might promote cellular proliferation through interference of TGFbeta signaling.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

Secreted-type glycoprotein WNTs bind to seven-transmembrane-type WNT receptors encoded by Frizzled genes (FZD1-FZD10) to transduce signals to the beta-catenin TCF pathway, the JNK pathway, or the Ca2+-releasing pathway. Wrch1 gene is a down-stream target gene of Wnt1 in C57MG cells, and encodes a Cdc42-related GTPase with the potential to activate the JNK pathway. Here, we isolated human WRCH1 cDNAs (accession no. AB074878) from gastric cancer cell lines OKAJIMA, MKN7, MKN28, MKN45, MKN74, and KATO-III. all of which showed a nucleotide substitution (343 C--&gt;T) without amino-acid substitution compared with WRCH1 cDNA isolated by another group. WRCH1 gene, consisting of at least 3 exons. was mapped to human chromosome 1q42.11-q42.3 by using bioinformatics. WRCH1 mRNA was more highly expressed in corpus callosum, hippocampus, cerebral cortex, and also in several parts within adult brain than in other normal tissues including stomach, pancreas, and placenta. Amounts of WRCH1 mRNA in 40 human cancer cell lines were lower than that in normal stomach, pancreas, or placenta. WRCH1 mRNA was significantly up-regulated in 4 cases of primary kidney tumors, 1 case each of primary colon, gastric, breast, ovarian, and uterus cancer. On the other hand, WRCH1 mRNA was significantly down-regulated in 6 cases of colon tumors. 2 cases of primary kidney cancer and breast cancer. Expression of WRCH1 mRNA was down-regulated by beta-estradiol in MCF-7 cells. This is the first report on comprehensive expression analyses on WRCH1 mRNA.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

PDZ-domain protein GIPC1/GIPC interacts with GTPase-activating protein RGS-GAIP, TGFbeta type III receptor, and integrin alpha6A subunit. Kermit, a Xenopus orthologue of human GIPC1, interacts with some class of WNT receptor. In this study, we identified a novel GIPC1-related gene in human genome by using bioinformatics, and isolated GIPC2 cDNAs by using cDNA-PCR. GIPC2 encoded a 315-amino-acid protein with a central PDZ domain, which showed 62.0% total-amino-acid identity with GIPC1. Both GIPC2 gene on human chromosome 1 and GIPC1 gene on human chromosome 19p13.1 were found to consist of 6 exons. Exon-intron structures of GIPC2 gene and GIPC` gene were well conserved. GIPC2 mRNA was relatively highly expressed in ascending colon, followed by kidney and pancreas. Among 3.7-, 2.6-, and 1.7-kb GIPC2 mRNAs generated due to alternative polyadenylation, 2.6-kb GIPC2 mRNA was the major GIPC2 transcript in adult kidney. Expression of GIPC2 mRNA was significantly down-regulated in 6 out of 14 cases of primary kidney tumors, in 5 out of 11 cases of primary colon tumors, and in 1 out of 7 cases of primary rectal tumors. Because GIPC2 might bind to TGFbeta type III receptor or some class of WNT receptor, just like GEPC1 or Kermit, down-regulation of GIPC2 mRNA in human primary tumors might lead to interference of TGFbeta signaling or some class of WNT signaling. This is the first report on molecular cloning of GIPC2, the second member of the GIPC gene family, which is down-regulated in human primary kidney and colorectal tumors.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

WNTs are a family of secreted-type glycoproteins implicated in embryogenesis and carcinogenesis. We have previously cloned and characterized human WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT10A, WNT10B, WNT11, WNT14, and WNT14B/WNT15. WNT14B gene is clustered with WNT3 gene in human chromosome 17q21, and mRNA expression of WNT14B is significantly up-regulated by retinoic acid during the early phase of neuronal differentiation in human NT2 cells. Here, we identified mouse Wnt14b gene fragments in mouse genome draft sequence AL596108.5 by using bioinformatics, and isolated mouse Wnt14b cDNAs by using cDNA-PCR. Mouse I,Wnt14b was found to encode a 359-amino-acid WNT family protein with the N-terminal signal peptide, an N-linked glycosylation site, and 24 conserved cysteine residues. Mouse Wnt14b showed 92.5% total-amino-acid identity with human WNT14B, and 64.2% total-amino-acid identity with human WNT14. Mouse Wnt14b gene, consisting of 4 exons, was clustered with mouse Wnt3 gene in mouse chromosome 11. Mouse Wnt14b mRNA was relatively highly expressed in 17-day embryo, and also expressed in adult brain, kidney, liver, 7-day embryo, and 11-day embryo. This is the first report on molecular cloning and characterization of mouse Wnt14b.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

WNT signaling pathway is implicated in carcinogenesis. Here, we cloned and characterized human WNT11, which showed three amino-acid substitutions (Ala121Thr, Gly156Arg, and Ser271Trp) compared with human WNT11 cDNA previously isolated by another group. WNT11 encoded a 354 amino-acid polypeptide with five N-glycosylation sites. Gly156 of human WNT11 was conserved in other members of the human WNT family, such as WNT2B1, WNT2B2, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT10A, and WNT14. The Ala121-Glyl156-Ser271 WNT11 allele isolated in this study was also identified in human genome draft sequence AC069055. Expression profile of WNT11 was next investigated. The 4.3-kb WNT11 mRNA was expressed in fetal lung, kidney, adult heart, liver, skeletal muscle, and pancreas. WNT11 mRNA was significantly up-regulated in a,gastric cancer cell line MKN45 and a cervical cancer cell line SKG-IIIa. Among various types of human primary tumors, WNT11 mRNA was up-regulated in four cases of colorectal adenocarcinoma, and a case of renal cell carcinoma. Up-regulation of WNT11 mRNA might play an important role in human carcinogenesis through activation of the WNT signaling pathway.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Genetic alterations of WNT signaling molecules lead to carcinogenesis through activation of the beta-catenin-TCF signaling pathway. We have previously cloned and characterized WNT2B/WNT13 gene on human chromosome 1p13, which is homologous to protooncogene WNT2 on human chromosome 7q31. WNT2B1 and WNT2B2 mRNAs, generated from the WNT2B gene due to alternative splicing of the alternative promoter type, encode almost identical polypeptides with divergence in the N-terminal region. WNT2B2 mRNA rather than WNT2B1 mRNA is preferentially expressed in NT2 cells with the potential of neuronal differentiation. Here, we describe our investigations of expression of WNT2B mRNAs in various types of human primary cancer. Matched tumor/normal expression array analysis revealed that WNT2B mRNAs were significantly up-regulated in 2 of 8 cases of primary gastric cancer. WNT2B2 mRNA rather than WNT2B1 mRNA was found to be preferentially up-regulated in a case of primary gastric cancer (signet ring cell carcinoma). Function of WNT2B1 mRNA and that of WNT2B2 mRNA were investigated by using Xenopus axis duplication assay. Injection of synthetic WNT2B1 mRNA into the ventral marginal zone of fertilized Xenopus eggs at the 4-cell stage did not induce axis duplication. In contrast, ventral injection of synthetic WNT2B2 mRNA induced axis duplication in 90% of embryos (complete axis duplication, 24%). These results strongly suggest that WNT2B2 up-regulation in some cases of gastric cancer might lead to carcinogenesis through activation of the beta-catenin-TCF signaling pathway. (C) 2001 Elsevier Science.

DOI： 10.1006/bbrc.2001.6076

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

WNT proteins play key roles in carcinogenesis. We have previously cloned and characterized WNT14 and WNT14B/WNT15. WNT14 and WNT3A genes are clustered on human chromosome 1q42, while WNT14B and WNT3 genes are clustered on human chromosome 17q21. Here, we investigated expression of WNT14 and WNT14B mRNAs in human cancer. WNT14 was significantly up-regulated in 1 out of 9 cases of primary breast cancer. WNT14B was not expressed in primary breast, gastric and colorectal cancers. Among 3 human breast cancer cell lines, WNT14 mRNA was expressed in T-47D cells, and weakly expressed in MCF-7 cells. WNT14 mRNA was also detected in 7 out of 7 pancreatic cancer cell lines, 12 out of 12 esophageal cancer cell lines, 4 out of 4 cervical cancer cell lines, and 5 out of 7 brain tumor cell lines by using cDNA-PCR. These results indicate that WNT14 rather than WNT14B is preferentially expressed in various types of human cancer, such as breast cancer, gastric cancer, and pancreatic cancer. WNT14 mRNA was up-regulated by inferferon gamma (IFN gamma), but not by tumor necrosis factor alpha (TNF alpha), in MKN45 cells derived from gastric cancer, while expression of WNT14B mRNA was not affected by IFN gamma and TNF alpha in MKN45 cells. Although expression of WNT14 mRNA was not affected by beta -estradiol in MCF-7 cells, WNT14B mRNA was transiently up-regulated by beta -estradiol in MCF-7 cells. These results indicate that WNT14 is a target gene of IFN gamma in MKN45 cells, and that WNT14B is a target gene of estrogen in MCF-7 cells.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

WNT10A and WNT10B genes are human orthologues of mouse proto-oncogene Wnt-10b. We have previously cloned and characterized WNT10A, and demonstrated upregulation of WNT10A by tumor necrosis factor a (TNF alpha) in gastric cancer. Here, we cloned and characterized human WNT10B, which showed Gly60Asp amino-acid substitution compared with human WNT10B previously reported by another group. Gly60 WNT10B allele was identified in 2 human genome draft sequences and 7 human ESTs, while Asp60 WNT10B allele was not identified in any human genome draft sequences or ESTs. The Gly60-type WNT10B cDNA isolated in this study might be derived from more common WNT10B allele. WNT10B was most homologous to WNT10A (64.5% total amino-acid identity) among human WNTs. Variable region in the WNT core domain of WNT10B and WNT10A were longer than that of other WNTs, such as WNT2B1 I, WNT2B2, WNT3, WNT3A, WNT5B, WNT7B, WNT8A, WNT 11, WNT 14, and WNT 14B/WNT 15. We next investigated expression of WNT10B in human gastric cancer. WNT10B was moderately expressed in MKN45 and MKN74 cells, and weakly expressed in OKAJIMA, TMK1, MKN7, MKN28, and KATO-III cells. Because interferon gamma (IFN gamma) and TNF alpha were frequently elevated in gastric mucosa with Helicobacter pylori infection, effects of IFN gamma and TN-Fa on WNT10B expression in MKN45 cells were investigated. TNFa induced transient up-regulation of WNT10B mRNA in MKN45 cells. Up-regulation of WNT10B in human gastric mucosa might lead to gastric carcinogenesis through activation of the beta -catenin - TCF signaling pathway, just like up-regulation of Wnt-10b in mouse mammary gland leads to mammary carcinogenesis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

WNT14B was cloned and characterized in this study. WNT14B encoded 357-amino acid WNT family protein with the signal peptide and an N-linked glycosylation C, site. WNT14B was most homologous to WNT14 (61.4% total amino acid identity). WNT15 cDNA fragment previously isolated by another group corresponds to a part of ORF of the WNT14B cDNA (codon 216-335). Exon-intron boundaries were conserved between WNT14B and WNT14 genes. WNT14B and WNT3 genes were clustered in the human chromosome 17q21 region in head to head manner. Intergenic region between WNT14B and WNT3 genes was about 33 kb in size. The 6.6-kb WNT14B mRNA was moderately expressed in fetal kidney and adult kidney. Although WNT14B mRNA was not detected in fetal brain and adult brain by Northern blot analyses, WNT14B mRNA was detected in brain, especially in occipital lobe, by RNA dot blot analysis. Among 48 human cancer cell lines derived from various tissues, WNT14B was expressed in a teratocarcinoma cell line NT2 with the potential to differentiate into neuronal cells. WNT14B mRNA was significantly up-regulated by all-trans retinoic acid in NT2 cells. These results strongly suggest that WNT14B might be implicated in the early process of neuronal differentiation of NT2 cells induced by retinoic acid.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

WNT signaling, pathway is implicated in carcinogenesis and embryogenesis. We have previously cloned and characterized WNT10A, and demonstrated up-regulation of WNT10A in gastric cancer. Here, we investigated expression of WNT10A mRNA in various types of human cancer. WNT10A mRNA was detected in 10 out of 12 esophageal cancer cell lines by cDNA-PCR, and was significantly up-regulated in esophageal cancer cell lines TE2, TE3, TE4, and a brain tumor cell line A-172. WNT10A mRNA was not up-regulated by retinoic acid in a teratocarcinorna cell line NT2. TFF1/pS2 mRNA, but not WNT10A mRNA, was up-regulated by beta -estradiol in a breast cancer cell line MCF-7. Expression of WNT10A mRNA in various types of primary cancers was next investigated by using Matched tumor/normal expression array fitter. WNT10A mRNA was significantly up-regulated in 2 out of 8 cases of primary gastric cancer, and in 1 out of 7 cases of primary rectal cancer. Expression of WNT10A mRNA in esophageal cancer was not investigated, because. such samples were not blotted on the expression array filter. Up-regulation of WNT10A mRNA might play key roles in some cases of esophageal, gastric, and colorectal cancer.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ROENTGEN RAY SOC  

OBJECTIVE. The purpose of our study was to evaluate the usefulness of percutaneous ethanol installation using CO2-enhanced sonography for patients with nonresectable, hepatocellular carcinoma (HCC).
SUBJECTS AND METHODS. Forty-six patients with 65 HCC lesions were examined with contrast-enhanced sonography with direct injection of CO2 into the proper hepatic artery during arteriography. We performed percutaneous ethanol injection guided by CO2-enhanced sonography for the treatment of hypervascular HCC lesions that could not be treated with conventional percutaneous ethanol injection or with transcatheter arterial embolization.
RESULTS. CO2-enhanced sonography detected five additional small HCC lesions before treatment (p &lt; 0.05) and 14 new lesions during follow-up (p &lt; 0.01), than conventional sonography detected. CO2-enhanced sonography showed positive enhancement of residual lesions after initial treatment (n = 3) and incomplete local treatment (n = 5) that were not detected on conventional sonography. These 27 lesions were successfully treated with percutaneous ethanol injection using a mixture of iodized oil and ethanol and guided by CO2-enhanced sonography.
CONCLUSION. CO2-enhanced sonography is a sensitive method for detecting residual viable lesions and small new HCC lesions that cannot be detected with conventional sonography. Percutaneous ethanol injection guided by CO2-enhanced sonography can treat hypervascular HCC lesions that cannot be treated with conventional percutaneous ethanol injection or transcatheter arterial embolization.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

Frizzled (FZD) genes encode seven-transmembrane type WNT receptors, which are implicated in carcinogenesis and embryogenesis. We have previously cloned and characterized FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, and FZD10. Here, we investigated expression profiles of all members of the FZD gene family in human gastric cancer. FZD mRNAs were detected by onestep cDNA-PCR. Specificity of cDNA-PCR was confirmed by nucleotide sequence analyses of cDNA-PCR products. Among seven gastric cancer cell lines, FZD7 was up-regulated in MKN7, which was consistent with a previous report. FZD5 was up-regulated in MKN45. FZD9 and FZD10 were up-regulated together in TMK1 and MKN74. FZD2 was upregulated in TMK1, MKN7, MKN28, MKN45, MKN74 and KATO-III. Among 10 cases of primary gastric cancer, FZD9 was up-regulated in 2 cases, FZD2 and FZD8 were upregulated in 4 cases. Effects of Helicobacter pylori (H. pylori) on expression of FZDs were further investigated, and it was revealed that FZDs were not up-regulated by H. pylori in MKN45 cells. These results indicate that FZD2, FZD8, and FZD9 might play key roles in human gastric cancer.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

WNT signaling molecules are implicated in carcinogenesis and embryogenesis. Only partial coding sequence of human WNT7B is reported so far, and human genome draft sequence corresponding to the WNT7B gene in human chromosome 22q13 region is not available at present. Here, we have cloned human WNT7B cDNAs, spanning the complete coding sequence, by using rapid amplification of cDNA ends (RACE) and cDNA-PCR. WNT7B encoded a 349-amino-acid polypeptide with three N-linked glycosylation sites and consensus amino-acid residues conserved among members of the WNT family. WNT7B showed 77.1% total-amino-acid identity with WNT7A. The 4.0-kb WNT7B was moderately expressed in fetal brain, weakly expressed in fetal lung and kidney, and faintly expressed in adult brain, lung and prostate. Expression levels of WNT7B mRNA in a lung cancer cell line A549, esophageal cancer cell lines TE2, TE3, TE4, TE5, TE6, TE7, TE10, TE12, a gastric cancer cell line TMK1, and pancreatic cancer cell lines BxPC-3, AsPC-1 and Hs766T were significantly higher than that in fetal kidney. In addition, WNT7B was up-regulated in 5 out of 10 cases of primary gastric cancer. These results strongly suggest that WNT7B might play important roles in various types of human cancer.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

WNT signaling pathway is implicated in carcinogenesis and embryo genesis. We have previously cloned and characterized WNT10A and WNT6, which are clustered in human chromosome 2q35 region. In this study, we investigated expression of WNT10A and WNT6 in gastric cancer. The 3.0- and 2.4-kb WNT10A mRNAs were expressed in gastric cancer cell lines MKN7, MKN45 and MKN74. The 2.0-kb WNT6 mRNA was expressed in gastric cancer cell lines MKN28 and MKN74. WNT10A was up-regulated in 3 out of 6 cases of primary gastric cancer, while WNT6 was not up-regulated in primary gastric cancer. Effects of inflammatory cytokines and Helicobacter pylori (H. pylori) on expression of WNT10A and WNT6 were next investigated. Interferon gamma (IFN gamma) failed to induce up-regulation of WNT10A and WNT6. Tumor necrosis factor alpha (TNF alpha) induced upregulation of WNT10A in MKN45 cells. Up-regulation of WNT10A reached maximum at 6 h after TNF alpha treatment. H. pylori also induced up-regulation of WNT10A in MKN45 cells. These results strongly suggest that up-regulation of WNT10A induced by TNF alpha and H. pylori might play key roles in human gastric cancer through activation of WNT beta -catenin - TCF signaling pathway.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBL LTD.  

A 66-year-old woman complained of supraclavicular lymph node swelling during her initial visit to an outpatient clinic. Computed tomography revealed a hypervascular tumor in the uncus of the pancreas (2.0x2.0cm), therefore a needle biopsy of the pancreas was performed. A poorly differentiated adenocarcinoma was identified. Transcatheter arterial embolization using adriamycin and gelatin sheet was performed. To alleviate her symptoms (movement disorder of neck, etc.), initial chemotherapy; FP (5-fluorouracil and cisplatin intravenously) was continued for 6 cycles with her consent, and subsequently MY (methotrexate and 5-fluorouracil intravenously) for 14 cycles. This patient survived with transcatheter arterial embolization, FP and MF combination chemotherapies for 24 months after presenting with the symptoms. To our knowledge, this is the longest surviving case of pancreatic poorly differentiated adenocarcinoma (Stage IV). In conclusion, this present case suggests that transcatheter arterial embolization, FP and MIT combination therapy may have an effect at prolonging survival in poorly differentiated pancreatic adenocarcinoma.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

Human Frizzled-7 (FZD7) and human FzE3, showing 98.8% nucleotide identity, encode almost identical WNT receptors with nine amino-acid substitutions. FzE3 is claimed to be expressed specifically in esophageal cancer. We determined the structure of the FZD7 gene and the FZD7 cDNA expressed in esophageal cancer. The FZD7 gene without intron and the FZD7 cDNAs isolated from esophageal cancer cell lines TE4 and TE5 were found to encode WNT receptor identical to FZD7, but not to FzE3. Nucleotide sequence of FzE3 was not identified on the human genome draft sequence. Thus, we could not obtain any data suggesting the existence of FzE3. Expression profile of FZD7 was also investigated. FZD7 was expressed throughout normal gastrointestinal tract, from esophagus to rectum. Among human esophageal and gastric cancer cell lines, expression level of FZD7 was relatively lower in esophageal cancer cell lines, and was highest in the gastric cancer cell line MKN7. FZD7 was up-regulated in one out of six cases of human primary gastric cancer. As over-expression of Frizzled-7 leads to activation of the WNT-beta -catenin-TCF pathway, up-regulation of FZD7 in human gastric cancer might play key roles in carcinogenesis through activation of the WNT-beta -catenin-TCF pathway.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC  

Human WNT10A and WNT6 were cloned and characterized. WNT10A encoded a 417-amino-acid polypeptide with WNT core domain, and WNT6 encoded a 365-amino-acid polypeptide with N-terminal signal peptide, WNT core domain, and RGD motif. WNT10A and WNT6 genes were clustered in the head-to-tail manner with an interval less than 7.0 kb in human chromosome 2q35 region. Among human WNT family, WNT10A was most homologous to WNT10B (59.2% amino-acid identity), and WNT6 was most homologous to WNT1 (47.4% amino-acid identity). WNT10B and WNT1 genes were also clustered in human chromosome 12q13 region. Two WNT gene clusters in human chromosome 2q35 and 12q13 regions might be generated due to duplication of ancestral gene cluster. The 3.0- and 2.4-kb WNT10A mRNAs were expressed in fetal kidney, placenta, adult spleen and kidney. The 2.0-kb WNT6 mRNA was coexpressed with WNT10A in placenta and adult spleen. WNT10A and WNT6 were strongly coexpressed in SW480 (colorectal cancer). In addition to SW480, WNT10A was strongly expressed in HL-60 (promyelocytic leukemia) and Raji (Burkitt's lymphoma), and WNT6 in HeLa S3 (cervical cancer). Overexpression WNT10A and WNT6 might play key roles in human carcinogenesis through activation of WNT-beta -catenin-TCF signaling pathway, just like Wnt10b and Wnt1. (C) 2001 Academic Press.

DOI： 10.1006/bbrc.2001.4855

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC  

Frizzled-1 (FZD1)-FZD10 are seven-transmembrane-type WNT receptors, and SFRP1-SFRPS are soluble-type WNT antagonists. These molecules are encoded by mutually distinct genes. We have previously isolated and characterized the 7.7-kb FZD4 mRNA, encoding a seven-transmembrane receptor with the extracellular cysteine-rich domain (CRD), Here, we have cloned and characterized FZD4S, a splicing variant of the FZD4 gene. FZD4S, corresponding to the 10.0-kb FZD4 mRNA, consisted of exon 1, intron 1, and exon 2 of the FZD4 gene. FZD4S encoded a soluble-type polypeptide with the N-terminal part of CRD, and was expressed in human fetal kidney. Injection of synthetic FZD4S mRNA into the ventral marginal zone of Xenopus embryos at the 4-cell stage did not induce axis duplication by itself, but augmented the axis duplication potential of coinjected Xwnt-8 mRNA These results indicate that the FZD1 gene gives rise to soluble-type FZD4S as well as seven-transmembrane-type FZD4 due to alternative splicing, and strongly suggest that FZD4S plays a role as a positive regulator of the WNT signaling pathway. (C) 2001 Academic Press.

DOI： 10.1006/bbrc.2001.4634

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC  

Frizzled genes, encoding WNT receptors, play key roles in cell fate determination. Here, we isolated two Xenopus frizzled genes (Xfz10A and Xfz10B), probably reflecting pseudotetraploidy in Xenopus. Xfz10A (586 amino acids) and Xfz10B (580 amino acids) both encoded by a single exon, consisted of the N-terminal cysteine-rich domain, seven transmembrane domains, and the C-terminal Ser/Thr-X-Val motif. Xfz10A and Xfz10B were 97.0% identical at the amino acid level, and Xfz10B was 100% identical to previously reported Xfz9, yet Xfz10A was 85.3% and 62.4% identical to FZD10 and FZD9, respectively. Xfz10 mRNA appeared as 3.4 kb in adult tissues and embryos. RT-PCR analyses revealed the expression of more Xfz10A mRNA in stomach, kidney, eye, skeletal muscle, and skin, and more Xfz10B mRNA in heart and ovary, but in embryos, two mRNAs were equally expressed from the blastula stage with their peak expression at the late gastrula stage. The main site of Xfz10 mRNA expression was neural fold at the neurula stage and the dorsal region of midbrain, hindbrain, and spinal cord at the tadpole stage. These results suggest that XflzlO has important roles in neural tissue formation. (C) 2000 Academic Press.

DOI： 10.1006/bbrc.2000.3808

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC  

Secreted glycoprotein WNTs play important roles in carcinogenesis and development, We have previously reported molecular cloning of WNT-2B/WNT-13. Here, we have isolated a novel WNT-2B isoform (WNT-2B2), in addition to the original WNT-2B isoform (WNT-2B1). WNT-2B1 and WNT-2B2 are completely different in the 5'-UTR and in the N-terminal part of the coding region. The N-terminal hydrophobic domain is contained in WNT-2B1, but not in WNT-2B2. WNT-2B1 and WNT-2B2 share the WNT-core domain, and show 87.0% amino-acid identity. We have determined the structure of the WNT-2B gene. The WNT-2B1 mRNA consists of exons 1, 2, and 4-7, while the WNT-2B2 mRNA consists of exons 3-7, WNT-2B2 was expressed in fetal brain, fetal lung, fetal kidney, caudate nucleus, testis, glioblastoma cell lines A172, SW1783, gastric cancer cell lines MHN28, MKN74, and cervical cancer cell line HeLa S3. WNT-2B1 expression level was relatively higher in fetal brain and fetal lung than in other tissues or cell lines expressing WNT-2B2. These results indicate that the WNT-2B1 and WNT-2B2 mRNAs are transcribed due to alternative splicing with distinct expression profile. This is the first report on the WNT isoforms derived from the same gene due to alternative splicing. (C) 2000 Academic Press.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC  

The fibroblast growth factors (FGFs) play important roles in morphogenesis, angiogenesis, tissue remodeling, and carcinogenesis, Human FGF-SO has been cloned and characterized in this study. FGF-SO encodes a 211-amino-acid polypeptide with the FGF-core domain. A strong hydrophobic region was found in the FGF-core domain of FGF-20; however, no typical N-terminal signal sequence was found in FGF-20, just as in FGF-9 and FGF-16. Total amino acid identities are as follows: FGF-20 vs FGF-9, 71.6%; FGF-20 vs FGF-16, 66.2%; FGF-9 vs FGF-16, 72.4%. Phylogenic analysis indicated that FGF-20, FGF-9, and FGF-16 constitute a subfamily among the FGF family, FGF-20 mRNA of 2.4 kb in size was detected in colon cancer cell line SW480 by Northern blot analysis. Lower levels of FGF-SO mRNA were detected in human fetal tissues and primary cancers by cDNA-PCR. The nucleotide sequence of FGF-20 cDNA is split into three parts in the human genome sequence of the chromosome 8p21.3-p22 region (Accession No. AB020858). These results indicate that the FGF-20 gene, located on human chromosome 8p21.3-p22, consists of three exons, Compared with the nucleotide sequence of FGF-20 cDNA determined in this study, one nucleotide deletion and one nucleotide substitution in the putative coding region mere identified in human genome sequence AB020858. (C) 2000 Academic Press.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC  

WNT receptors encoded by the Frizzled genes are implicated in carcinogenesis as well as in embryonic development. Human Frizzled-3 (FZD3) gene, encoding seven-transmembrane receptor with the N-terminal cysteine-rich domain, has been cloned and characterized. Expression of the FZD3 mRNAs was investigated by using three FZD3 specific probes: HF3S1, corresponding 60 the 5'-UTR and a part of the coding region; HF3S2, corresponding to a part of the coding region; HF3S3, corresponding to the 3'-UTR. HF3S1 and HF3S2 hybridized to the 14.0-, 9.0-, 4.0- and 1.8-kb FZD3 mRNA, while HF3S3 hybridized to the 14.0-, 9.0-, and 4.0-kb FZD3 mRNA. The 14.0-kb FZD3 mRNA was the major transcript in fetal brain and adult cerebellum, while the 1.8-kb FZD3 mRNA was the major transcript in adult pancreas, and many cancer cell lines examined. The 1.8-kb FZD3 mRNA, alternatively polyadenylated by the internal AATAAA signal in the coding region, is predicted to encode the truncated FZD3 protein lacking the region through the second extracellular loop to the C-terminal tail, and might function as the transmembrane-type antagonist for WNTs. The FZD3 gene consists of 8 exons, and has been mapped to human chromosome 8p21. (C) 2000 Academic Press.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC  

The WNT receptors, encoded by the Frizzled genes, are implicated in a variety of cellular processes such as cell fate determination, cell polarity control, and malignant transformation. Human Frizzled-4 (FZD4) cDNAs have been cloned and characterized. FZD4 spans a total of 7392 nucleotides and encodes a 537-amino-acid protein with the N-terminal cysteine-rich domain, seven transmembrane domains, and the C-terminal S/T-X-V motif, The FZD4 mRNA of 7.7 kb in size were detected almost ubiquitously in normal human tissues and larger amounts in fetal kidney, adult heart, skeletal muscle, and ovary. Among cancer cell lines, the FZD4 mRNA level was higher in HeLa S3. The FZD4 gene has been mapped to human chromosome 11q14-q21. FZD4 is homologous to FZD9 and FZD10, and overall amino acid identity is as follows: FZD4 vs FZD9, 51.6%; FZD4 vs FZD10, 51.2%; FZD9 vs FZD10, 65.7%. FZD4 consists of two exons, while FZD9 and FZD10 consist of a single exon, FZD4 might belong to rather the independent FZD subfamily than the FZD9-FZD10 subfamily. (C) 1999 Academic Press.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL SCIENCE INC  

We assessed a possible correlation between the hepatic tumor index (as the ratio of the tumoral peak systolic velocity to the peak systolic velocity of the right or left hepatic artery) and grade of tumor vessel in large hepatocellular carcinomas (HCCs). Color Doppler sonographic findings were evaluated and compared with selective hepatic arteriographic findings in 78 patients with 93 hepatocellular carcinomas larger than 2.0 cm in diameter. Pulsatile color flow images were obtained in 78 of 93 lesions. The hepatic tumor index was equal to or greater than 1.0 in 57 of 78 lesions. These lesions were revealed arteriographically to have distinct tumor vessels and/or arteriovenous shunting. When this index was 1.0 or greater, we calculated 90% accuracy in distinguishing HCCs with distinct tumor Vessels from those without distinct tumor vessels. The hepatic tumor index correlated with the grade of tumor vessels and the presence of arteriovenous shunting.

DOI： 10.1046/j.1525-1500.1999.99057.x

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE BV  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：神奈川県医師会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

74歳女。原発性胆汁性肝硬変のため外来通院中であった。黒色便と吐血のため救急搬送され、食道静脈瘤破裂の診断で内視鏡的静脈瘤結紮術を施行した。入院翌日に赤血球濃厚液(RCC)を輸血し、明らかな副作用は認めなかったが、輸血後8日に溶血性貧血を認め、精査の結果、間接Coombs試験陽性、不規則抗体陽性が判明した。1ヵ月後に食道静脈瘤破裂のため再入院となり、再びRCCの輸血を開始したところ、開始直後から発熱と呼吸困難が出現した。輸血の副作用の精査で血清ハプトグロビン(Hp)が検出限界以下、抗Hp抗体が陽性を示し、核酸増幅検査では通常認められる476bpのバンドが本例にはなく、Hpdel遺伝子特異的な増幅断片を示す315bpに濃厚なバンドを認めた。Hp遺伝子欠失アリルが検出され、先天性Hp欠損症の診断に至った。

DOI： 10.2169/naika.102.2980

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

Web of Science

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

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記述言語：日本語   出版者・発行元：診断と治療社  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2012373136

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE BV  

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

30歳女性。スプーン誤飲を主訴に著者らの施設へ受診となった。腹部単純X線では胃内にスプーンの陰影が認められたが、縦隔気腫や遊離ガスはみられなかった。更に緊急上部消化管内視鏡を施行するも、胃内残渣多量でスプーンを発見することは困難であった。しかし翌日、上部消化管内視鏡にて十二指腸下行脚のスプーンが確認され、スネアを用いて摘出した。尚、スプーン(全長11cm、幅2.5cm)抜去後に粘膜損傷や出血、縦隔・皮下気腫、気胸などの合併症は認められなかった。

DOI： 10.11641/pde.79.2_52

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(公社)日本生化学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

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記述言語：日本語   出版者・発行元：胃病態機能研究会  

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記述言語：日本語   出版者・発行元：胃病態機能研究会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(株)響文社  

2002年〜2007年に肝生検を施行した非アルコール性脂肪性肝疾患(NAFLD)患者のうち、病理組織学的に単純性脂肪肝(SFL)診断された22例(男性5例、女性17例、平均44.2歳)と線維化ステージ1または2の軽度線維化非アルコール性脂肪性肝炎(NASH)と診断された62例(男性35例、女性27例、平均49.3歳)を対象に、軽度線維化NASHとSFLの脾サイズを比較し、両者の鑑別における脾サイズの有用性について検討した。また、両者のspleen-body index(SBI)を比較検討した。軽度線維化NASHで有意に高値であったものは皮下脂肪、AST、フェリチン、CRPであった。またSBIについてはSFL群におけるSBI平均値は15.83、軽度線維化NASH群におけるSBI平均値は18.69で有意に軽度線維化NASH群においてSBIが高かった。ROC曲線の曲線下面積は0.661でoptimal cut off値16.25、感度66.1%、特異度68.2%、陽性的中率85.4%、陰性的中率41.7%であった。軽度線維化NASHを規定する因子として単変量解析で有意差を認めた項目を用い、ロジスティック回帰分析を行ったところ、性別およびSBIが独立してNASH軽度線維化を規定する因子として認められた。

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記述言語：日本語   出版者・発行元：(株)響文社  

1年以内に肝生検を施行した非アルコール性脂肪性肝疾患(NAFLD)患者54人および年齢、性別をマッチさせ、メタボリックシンドロームや肝疾患(ウイルス性肝炎、脂肪肝、アルコール飲酒)のない正常対照群10例を対象に、NAFLD患者に局所の硬さの定量を可能にしたAcoustic Radiation Force Impulse imaging(ARFI)を用い、肝線維化を評価した。ステージ0〜2の間ではせん断弾性波の違いは軽度で、その原因として肝臓の脂肪沈着が考えられたため、正常対照群と線維化のない単純性脂肪肝群でARFI elastographyでのせん断弾性波の測定を比較したところ、有意に単純性脂肪肝群の方が、せん断弾性波が低値であった。ROCカーブを用いステージ3以上の診断有用性を検討したところ、せん断弾性波のカットオフ値1.77m/s、ROC下の面積は0.973で、感度100%、特異度90.9%であった。ARFI elastographyのせん断弾性波とFibroscanの肝弾性度との相関を調べるために同一症例で検討を行ったところ、極めて有意な相関を認めた。

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記述言語：日本語   出版者・発行元：(株)響文社  

1995年1月〜2009年7月に診断または初回治療を施行した肝細胞癌(HCC)372例(男性258例、女性114例)を対象に、非B非C型HCC(HBs抗原陰性・HCV抗体陰性)62例、B型、C型HCC310例に分け、その臨床的特徴と治療成績について検討した。非B型非C型HCCのうちアルコール摂取量男性50g以上・女性30g以上をアルコール性群(AL群)26例、それ以外を非B型非C型群(NBNC群)36例とした。B型、C型HCC症例(BC群)は310例(HBV40例・HCV266例・HBV+HCV4例)であった。自己免疫性肝炎、原発性胆汁性肝硬変症例は除外した。B型、C型HCC症例と比較して、非B型非C型HCCの非アルコール性において高齢、進行HCC、糖尿病合併が有意に多く、アルコール性において有意に若年症例が多く、肝機能不良症例が多い傾向が認められた。内科的予後はB型、C型HCC症例と比較し、非B型非C型HCCの非アルコール性、アルコール性共に統計学的有意差を認めなかった。非アルコール性症例の早期発見、アルコール性症例の肝保護を重視すれば、今後更に予後が改善する可能性が考えられた。今回の検討から、高齢の糖尿病患者にはHCC危険群としての認識において、定期的な画像検査や腫瘍マーカー測定などの経過観察が必要で、アルコール性肝障害患者には禁酒の徹底などの肝保護が重要と思われた。

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会