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Fatal liver failure caused by reactivation of lamivudine-resistant hepatitis B virus:A case report

World Journal of Gastroenterology 2007年第6期13卷 964-969页

作者： Yuka Suzuki Hiroshi Yotsuyanagi Chiaki Okuse Yoshihiko Nagase hideaki takahashi Kyoji Moriya Michihiro Suzuki Kazuhiko Koike Shiro Iino Fumio Itoh Division of Gastroenterology and Hepatology Department of Internal Medicine St. Marianna University School of Medicine 2-16-1 Sugao Miyamae-ku Kawasaki 216-8511 Japan Division of Infectious Diseases Department of Internal Medicine University of Tokyo 7-3-1 Hongo Bunkyo-ku Tokyo 113-0033 Japan Center for Liver Diseases Seizankai Kiyokawa Hospital 2-31-12 Asagayaminami Suginami Tokyo 166-0004 Japan

We present a case of fetal liver failure caused by the activation of larnivudine-resistant hepatitis B virus （HBV） nine months after lamivudine treatment. A 57-year old man visited our hospital for the treatment of decornpensated chronic hepatitis B. Lamivudine was started in December 2001. Subsequently, serum HBV was negative for HBV DNA with seroconversion from HBeAg to anti-HBe and improvement of liver function. However, HBV DNA and HBeAg were again detected in September 2002. He was complicated by breakthrough hepatitis and admitted to our hospital in November for severely impaired liver function. Vidarabine treatment was started and serum HBV DNA and alanine aminotransferase （ALT） decreased transiently. However, after the start of m-interferon treatment, HBV DNA level increased and liver function deteriorated. He died 1 mo after admission. An analysis of amino acid sequences in the polymerase region revealed that rtM204I/V with rtLSOI/V occurred at the time of viral breakthrough. After the start of antiviral treatment, rtL180M was detected in addition to rtM204I/V and rtLSOI/V, and became predominant in the terminal stage of the disease. HBV clone with a high replication capacity may be produced by antiviral treatment leading to the worsening of liver function. Antiviral therapy for patients with breakthrough hepatitis in advanced liver disease should be carefully performed.

关键词： Hepatitis B virus Lamivudine Polymerase Interferon Tyrosine-methionine-aspartate-aspartate

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Correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis

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World Journal of Gastroenterology 2014年第45期20卷 17065-17074页

作者： hideaki takahashi Ryuta Shigefuku Yoshihito Yoshida Hiroki Ikeda Kotaro Matsunaga Nobuyuki Matsumoto Chiaki Okuse Shigeru Sase Fumio Itoh Michihiro Suzuki Division of Gastroenterology and Hepatology Department of Internal Medicine St.Marianna University School of Medicine Division of Gastroenterology Department of Internal Medicine Sapporo Shirakabadai Hospital Department of Molecular Biology Sapporo Medical University School of Medicine Anzai Medical Co. Ltd.

AIM: To elucidate the correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis (AL-LC).

关键词： Alcoholic liver cirrhosis Hepatic tissue blood flow Liver function Indocyanine green Xenon computed tomography

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Myofiber Permeability and Force Production of Rat Muscles Following Eccentric Contractions: The Repeated Bout Effect Depends on the Interval

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Journal of Biomedical Science and Engineering 2020年第12期13卷 275-289页

作者： Keishi Hayao Hiroyuki Tamaki Keigo Tamakoshi hideaki takahashi hideaki Onishi Institute for Human Movement and Medical Sciences Niigata University of Health and Welfare Niigata Japan Southern Tohoku General Hospital Fukushima Japan National Institute of Fitness and Sports in Kanoya Kagoshima Japan

Past eccentric contraction (ECC)-induced muscle injury reduces the severity of symptoms of subsequent muscle injury;this phenomenon is known as a repeated bout effect (RBE). It has been reported that increases in the duration of the interval between the first and second bouts are linked to weakening of the RBE. However, the histology following the attenuation of the RBE remains unclear. We examined the sustained effects of the second bout with regard to myofiber permeability and muscle force. Sixty-four male rats were randomly assigned to eight groups that varied in the number of exercise sessions and the duration of the interval between the first and second bouts: the non-ECC (Control);the single-injury (Post 1st bout);groups that were allowed to recover for 1, 2, and 4 weeks after a single injury (Pre 2nd bout_1w, Pre 2nd bout_2w, and Pre 2nd bout_4w);and groups that were subjected to second injuries 1, 2, and 4 weeks after the first (Post 2nd bout_1w, Post 2nd bout_2w, and Post 2nd bout_4w). The tibialis anterior was electrically stimulated in each ECC group. Twenty-four hours before muscle sampling, Evans blue dye (EBD) (a marker of myofiber damage) was administered. The maximal isometric contraction tension was measured immediately before sampling. The number of EBD-positive (+) fibers was determined via histological analysis. An RBE was revealed by functional examination at the 1- and 2-week and histological examination at the 1-, 2-, and 4-week time points (P < 0.05). In terms of myofiber permeability, prolongation of the interval before the second bout weakened this effect (P < 0.05). Experiments with 1-, 2-, and 4-week intervals indicated that prolongation of the interval before the second bout weakened the RBE with regard to myofiber permeability.

关键词： Eccentric Contraction Muscle Injury Repeated Bout Effect Myofiber Membrane Permeability Maximal Isometric Contraction Tension

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Efficacy of MK615 for the treatment of patients with liver disorders

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World Journal of Gastroenterology 2012年第31期18卷 4118-4126页

作者： Atsushi Hokari Tomohisa Ishikawa Hisao Tajiri Takahide Matsuda Osamu Ishii Nobuyuki Matsumoto Chiaki Okuse hideaki takahashi Takeshi Kurihara Ko-ichi Kawahara Ikuro Maruyama Mikio Zeniya Department of Internal Medicine Division of General Internal MedicineSt.Marianna University School of MedicineKawasaki 2168511Japan Department of Internal Medicine Division of Gastroenterology and HepatologySt.Marianna University School of MedicineKawasaki 2168511Japan Keio University Graduate School of Media and GovernanceFujisawa 2520882Japan Department of Biomedical Engineering Osaka Institute of TechnologyOsaka 5358585Japan Department of Systems Biology in Thromboregulation Kagoshima University Graduate School of Medical and Dental SciencesKagoshima 8908580Japan Department of Internal Medicine Division of Gastroenterology and HepatologyThe Jikei University School of MedicineTokyo 1058471Japan

AIM： To investigate the hepatoprotective effect of MK615, a Japanese apricot extract, in an animal model, and its clinical therapeutic effect. METHODS： Wistar rats were administered physiologi- cal saline （4 mL/kg） or MK615 solution （4 mL/kg） for 7 d. On the sixth d, acute hepatic injury was induced by administering a single intraperitoneal injection （ip） of D-galactosamine hydrochloride （D-GaIN）（600 mg/kg）. Plasma levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined, and liver tissues were used for histopathological analy- sis. Fifty-eight patients with liver disorders [hepatitis C （n = 40）, non-alcoholic fatty liver disease （n = 15）, and autoimmune liver disease （n = 3）] were orally admin- istered commercially available Misatol ME-containing MK615 （13 g/d） daily for 12 wk. Blood and urine were sampled immediately before and 6 wk, 12 wk, and 16 wk after the start of intake to measure various bio- chemical parameters. The percentage change in ALT and AST levels after 12 wk from the pre-intake baseline served as a primary endpoint. RESULTS： D-GaIN effectively induced acute hepatic injury in the rats. At 48 h after the ip injection of D-GaIN, the plasma levels of ALT （475.6 ：t： 191.5 IU/L vs 225.3 ＋ 194.2 IU/L, P 〈 0.05） and AST （1253.9：1：223.4 IU/L vs 621.9 ＋ 478.2 IU/L, P 〈 0.05） in the MK615 group were significantly lower than the control group. Scattered single cell necrosis, loss of hepatocytes, and extensive inflammatory cell infiltration were observed in hepatic tissue samples collected from the control group. However, these findings were less pronounced in the group receiving MK615. At the end of the clinical study, serum ALT and AST levels were significantly de- creased compared with pre-intake baseline levels from 103.5 ：l： 58.8 IU/L to 71.8 ＋ 39.3 IU/L （P 〈 0.05） and from 93.5 ：E 55.6 IU/L to 65.5 ＋ 34.8 IU/L （P 〈 0.05）, respectively. A reduction of 〉~ 30% from the pre-study baseline ALT level was observed in 26 （45

关键词： Prunus mume MK615 Liver damage Hep-atitis C Non-alcoholic fatty liver disease

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Acute hepatitis B of genotype H resulting in persistent infection

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World Journal of Gastroenterology 2014年第11期20卷 3044-3049页

作者： Norie Yamada Ryuta Shigefuku Ryuichi Sugiyama Minoru Kobayashi Hiroki Ikeda hideaki takahashi Chiaki Okuse Michihiro Suzuki Fumio Itoh Hiroshi Yotsuyanagi Kiyomi Yasuda Kyoji Moriya Kazuhiko Koike Takaji Wakita Takanobu Kato Department of Virology Ⅱ National Institute of Infectious DiseasesShinjyuku-KuTokyo 162-8640Japan Department of Internal Medicine Center for Liver DiseasesKiyokawa HospitalSuginamiTokyo 166-0004Japan Division of Gastroenterology and Hepatology Department of Internal MedicineSt. Marianna University School of MedicineKanagawa 216-8511Japan Department of Infectious Diseases Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Infection Control and Prevention Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Gastroenterology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan

A 47-year-old man presented with general fatigue and dark *** laboratory data showed increased levels of hepatic *** patient was positive for hepatitis B virus(HBV)markers and negative for antihuman immunodeficiency *** HBV-DNA titer was set to 7.7 log copies/*** patient was diagnosed with acute hepatitis *** HBV infection route was *** serum levels of hepatic transaminases decreased to normal ranges without any treatment,but the HBVDNA status was maintained for at least 26 mo,indicating the presence of persistent *** isolated HBV from the acute-phase serum and determined the genome sequence.A phylogenetic analysis revealed that the isolated HBV was genotype *** this patient,the elevated peak level of HBV-DNA and the risk alleles at human genome single nucleotide polymorphisms s3077and rs9277535 in the human leukocyte antigen-DP locus were considered to be risk factors for chronic *** case suggests that there is a risk of persistent infection by HBV genotype H following acute hepatitis;further cases of HBV genotype H infection must be identified and ***,the complete determination of the HBV genotype may be essential during routine clinical care of acute hepatitis B outpatients.

关键词： Acute hepatitis Chronic hepatitis Genotyping Hepatitis B virus Single nucleotide polymorphisms

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Clinical experience of hyperthermia for deep-seated malignant glioma

Clinical experience of hyperthermia for deep-seated malignan...

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中国医师协会神经外科医师分会首届全国代表大会

作者： hideaki takahashi Ryuichi Tanaka Takeo Uzuka Igor Grinev Department of Neurosurgery Brain Research Institute Niigata University 1-757 Asahimachi-dori951-8585NiigataJAPAN Department of Neurosurgery Brain Research Institute Niigata University 1-757 Asahimachi-dori951-8585NiigataJAPAN Department of Neurosurgery Brain Research Institute Niigata University 1-757 Asahimachi-dori951-8585NiigataJAPAN Department of Neurosurgery Brain Research Institute Niigata University 1-757 Asahimachi-dori951-8585NiigataJAPAN

＜正＞Purpose We introduce our clinical experience with radio frequency （RF） interstitial hyperthermia for malignant glioma. From the preliminary experimental study to the prospect of the near future, we will dicuss. Material We retrospectively reviewed 76 patients. Fortythree primary malignant gliomas and 33 recurrent malignant gliomas were treated with thermoradiotherapy （60 Gy, conventionally fractionated external beam radiation）. These patients received no reductive surgery. Electrodes （RF antennas） were set into the tumor and thermistor catheter was placed through the tumor center with stereotactic procedure under local anesthesia. Hyperthermia was given by RF interstitial hyperthermia of 13. 56 MHz, and the tumor was heated by measuring the temperature at the tumor margin （Tt: temperature of target point）. Tumor response was evaluated according by follow - up CT scan. TTPs and survivals were estimated by Kaplan - Meier method. Result Tumor responses of primary malignant gliomas were CR in 10 cases and PR in 17 cases. The response rate （CR + PR / all） amounted to 62. 8%. These of recurrent cases were CR in 3 cases and PR 12 cases. The response rate amounted to 45. 5 % . In primary malignant gliomas, median survival was 18months. In comparison with control group （ n = 35）, it was 10 months longer. According to achieved temperature at the target point, these patients were divided in two groups. The first group was adequate heating group achieved Tt of 42 ℃at least and the second was inadequate heating group Tt of less than 42 ℃. The response rate of adequate heating group was 68% Comparing gliomas heated to a Tt ＞ 42 ℃and those heated to a Tt ＜ 42℃, Kaplan- Meier survival and TTP curves displayed improvement in adequate heating group. In adequate heating group, median TTP was 4months longer and median survival was 11 months longer than those of inadequate group. Conclusion RF interstitial hyperthermia resulted in a higher response rate for primary malignant gliomas.

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Association of Bovine Fatty Acid Desaturase 2 Gene Single-Nucleotide Polymorphisms with Intramuscular Fatty Acid Composition in Japanese Black Steers

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Open Journal of Animal Sciences 2016年第2期6卷 105-115页

作者： hideaki takahashi Masayuki Hayashi Koichi Ushizawa Kagetomo Nishino Yasutoshi Haga Takao Saito Yuki Fujimori Nagako Iwama Hisato Takeda Masanori Komatsu Aduli E. O. Malau-Aduli Institute of Livestock and Grassland Science NARO Tsukuba Japan Wako Safety Center RIKEN Wako Japan Beef Cattle Institute Ibaraki Prefectural Livestock Research Center Hitachi-Ohmiya Japan Ibaraki Agricultural Academy Ibaraki Japan Ibaraki Prefectural Ken-Nan Livestock Hygiene Service Center Tsuchiura Japan Nagano Animal Industry Experiment Station Siojiri Japan Ibaraki Prefectural en-Nan Office of Agriculture and Forestry Tsuchiura Japan University of Tasmania Hobart Australia

Beef from Japanese Black cattle (JBK), is popular in Japan and valued for its highly marbled fat content. In JBK, genes affecting oleic acid content in meat have been studied mainly to lower the fat melting point and improve tenderness;however, there has been no direct correlation demonstrated between beef taste and oleic acid. To investigate genes affecting other fatty acids other than oleic acid, polymorphisms of the fatty acid desaturase 2 (FADS2) gene were genotyped and associations with fatty acid profile in JBK beef were investigated. Amplifications of 5’-flanking regions, 12 exons, and 3’-untranslated regions of the FADS2 gene in three Japanese and five Western cattle breeds via PCR, were amplified, sequenced and SNPs were identified using specific TaqMan genotyping assay. Fatty acid composition of intramuscular adipose tissue of the Trapezius muscle was analyzed in JBK steers. Six of the 15 identified SNPs are novel and have never been registered in any public bovine SNP database. A non-synonymous SNP (rs211580559;C > T;294 Ala > Val) in exon 7 was examined in order to evaluate its association with fatty acid profiles. The data showed that highly significant association existed between rs211580559 and C18:2 (n-6) composition, and accounted for 22.3% of the variation. There were no significant relationships between rs2115-80559 and the other fatty acids. It was concluded that rs211580559 of the FADS2 gene may be a useful selection marker for reducing unfavorable volatiles generated from linoleic acid in JBK beef during the cooking process.

关键词： Japanese Black Cattle Beef Fatty Acid Desaturase 2 Single-Nucleotide Polymorphism Fatty Acid Composition

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Familial pancreatic cancer: Concept, management and issues

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World Journal of Gastroenterology 2017年第6期23卷 935-948页

作者： Hiroyuki Matsubayashi Kyoichi Takaori Chigusa Morizane Hiroyuki Maguchi Masamichi Mizuma hideaki takahashi Keita Wada Hiroko Hosoi Shinichi Yachida Masami Suzuki Risa Usui Toru Furukawa Junji Furuse Takamitsu Sato Makoto Ueno Yoshimi Kiyozumi Susumu Hijioka Nobumasa Mizuno Takeshi Terashima Masaki Mizumoto Yuzo Kodama Masako Torishima Takahisa Kawaguchi Reiko Ashida Masayuki Kitano Keiji Hanada Masayuki Furukawa Ken Kawabe Yoshiyuki Majima Toru Shimosegawa Division of Endoscopy Shizuoka Cancer Center Clinic of Genetic Medicine Shizuoka Cancer Center Department of Surgery Kyoto University Graduate School of Medicine Division of Hepatobiliary and Pancreatic Oncology National Cancer Center Hospital Center for Gastroenterology Teine-Keijinkai Hospital Department of Surgery Tohoku University Graduate School of Medicine Department of Hepatobiliary and Pancreatic Oncology National Cancer Center Hospital East Department of Surgery Teikyo University School of Medicine Division of Cancer Genomics National Cancer Center Research Institute Institute for Integrated Medical Sciences Tokyo Women’s Medical University Department of Internal Medicine Kyorin University School of Medicine Division of Gastroenterology Yokohama City University Graduate School of Medicine Division of Hepatobiliary and Pancreatic Medical Oncology Kanagawa Cancer Center Department of Gastroenterology Aichi Cancer Center Hospital Department of Gastroenterology Kanazawa University Graduate School of Medicine Department of Surgery Japan Bapist Hospital Department of Gastroenterology and Hepatology Kyoto University Graduate School of Medicine Clinical Genetics Unit Kyoto University Graduate School of Medicine Center for Genomic Medicine Kyoto University Graduate School of Medicine Osaka Medical Center for Cancer and Cardiovascular Diseases Second Department of Internal Medicine Wakayama Medical University Department of Gastroenterology Onomichi General Hospital Department of Gastroenterology NationalKyushu Cancer Center Department of Medicine and Bioregulatory Sciences Kyushu University Graduate School of Medical Science Pancreatic Cancer Action Network Department of Gastroenterology Tohoku University Graduate School of Medicine

Familial pancreatic cancer (FPC) is broadly defined as two first-degree-relatives with pancreatic cancer (PC) and accounts for 4%-10% of PC. Several genetic syndromes, including Peutz-Jeghers syndrome, hereditary pancreatitis, hereditary breast-ovarian cancer syndrome(HBOC), Lynch syndrome, and familial adenomatous polyposis (FAP), also have increased risks of PC, but the narrowest definition of FPC excludes these known syndromes. When compared with other familial tumors, proven genetic alterations are limited to a small proportion (Caucasian) and a younger onset are common also in FPC. In European countries, "anticipation" is reported in FPC families, as with other hereditary syndromes; a trend toward younger age and worse prognosis is recognized in the late years. The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia (Pan IN) foci, with various K-ras mutations, similar to colorectal polyposis seen in the FAP patients. As with HBOC patients, a patient who is a BRCA mutation carrier with unresectable pancreatic cancer (accounting for 0%-19% of FPC patients) demonstrated better outcome following platinum and Poly (ADP-ribose) polymerase inhibitor treatment. Western countries have established FPC registries since the 1990 s and several surveillance projects for highrisk individuals are now ongoing to detect early PCs. Improvement in lifestyle habits, including non-smoking, is recommended for individuals at risk. In Japan, the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society.

关键词： familial pancreatic cancer registry high risk genetic surveillance

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Does Helicobacter pylori eradication therapy for peptic ulcer prevent gastric cancer?

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World Journal of Gastroenterology 2009年第34期15卷 4290-4297页

作者： Katsuhiro Mabe Mikako takahashi Haruhumi Oizumi hideaki Tsukuma Akiko Shibata Kazutoshi Fukase Toru Matsuda Hiroaki Takeda Sumio Kawata Division of Gastroenterology KKR Sapporo Medical Center Internal Medicine Tsuruoka Kyoritsu Hospital Internal Medicine Oizumi Medical Clinic Department of Cancer Control and Statistics Osaka Medical Center for Cancer and Cardiovascular Diseases Yamagata Prefectural Medical Center for Cancer and Lifestyle-Related Disease Internal Medicine Yamagata Prefectural Central Hospital Yamagata Prefectural Shonai Public Health Center Department of Gastroenterology Faculty of MedicineYamagata University

AIM:To investigate the effects of Helicobacter pylori (H pylori)eradication therapy for treatment of peptic ulcer on the incidence of gastric cancer. METHODS:A multicenter prospective cohort study was conducted between November 2000 and December 2007 in Yamagata Prefecture,*** study included patients with H pylori-positive peptic ulcer who decided themselves whether to receive H pylori eradication(eradication group)or conventional antacid therapy(non-eradication group).Incidence of gastric cancer in the two groups was determined based on the results of annual endoscopy and questionnaire surveys,as well as Yamagata Prefectural Cancer Registry data,and was compared between the two groups and by results of H pylori ***:A total of 4133 patients aged between 13 and 91 years(mean 52.9 years)were registered,and 56 cases of gastric cancer were identified over a mean follow-up of 5.6 *** sex-and age-adjusted incidence ratio of gastric cancer in the eradication group, as compared with the non-eradication group,was 0.58 (95%CI:0.28-1.19)and ratios by follow-up period(3 years)were 1.16(0.27-5.00),0.50 (0.17-1.49),and 0.34(0.09-1.28),*** follow-up tended to be associated with better prevention of gastric cancer,although not to a significant *** significant difference in incidence of gastric cancer was observed between patients with successful eradication therapy(32/2451 patients,1.31%)and those with treatment failure(11/639 patients,1.72%).Among patients with duodenal ulcer,which is known to be more prevalent in younger individuals,the incidence of gastric cancer was significantly less in those with successful eradication therapy(2/845 patients,0.24%)than in those with treatment failure(3/216 patients,1.39%). CONCLUSION:H pylori eradication therapy for peptic ulcer patients with a mean age of 52.9 years at registration did not significantly decrease the incidence of gastric cancer.

关键词： Helicobacter pylori Peptic ulcer Gastric cancer Eradication therapy Cancer prevention

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Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma

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World Journal of Gastroenterology 2007年第3期13卷 414-420页

作者： Kiminori Uka Hiroshi Aikata Shintaro Takaki Hiroo Shirakawa Soo Cheol Jeong Keitaro Yamashina Akira Hiramatsu hideaki Kodama Shoichi takahashi Kazuaki Chayama Department of Medicine and Molecular Science Division of Frontier Medical Science Programs for Biomedical Research Graduate School of Biomedical Sciences Hiroshima University Hiroshima Japan

AIM: To assess the clinical features and prognosis of 151 patients with extrahepatic metastases from primary hepatocellular carcinoma (HCC), and describe the treatment strategy for such patients. METHODS: After the diagnosis of HCC, all 995 consecutive HCC patients were followed up at regular intervals and 151 (15.2%) patients were found to have extrahepatic metastases at the initial diagnosis of primary HCC or developed such tumors during the follow-up period. We assessed their clinical features, prognosis, and treatment strategies. RESULTS: The most frequent site of extrahepatic metastases was the lungs (47%), followed by lymph nodes (45%), bones (37%), and adrenal glands (12%). The cumulative survival rates after the initial diagnosis of extrahepatic metastases at 6, 12, 24, and 36 mo were 44.1%, 21.7%, 14.2%, 7.1%, respectively. The median survival time was 4.9 mo (range, 0-37 mo). Fourteen patients (11%) died of extrahepatic HCC, others died of primary HCC or liver failure. CONCLUSION: The prognosis of HCC patients with extrahepatic metastases is poor. With regard to the cause of death, many patients would die of intrahepatic HCC and few of extrahepatic metastases. Although most of HCC patients with extrahepatic metastases should undergo treatment for the primary HCC mainly, treatment of extrahepatic metastases in selected HCC patients who have good hepatic reserve, intrahepatictumor stage (T0-T2), and are free of portal venous invasion may improve survival.

关键词： Hepatocellular carcinoma Extrahepatic metastases Prognosis Causes of death

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