Publications by authors named "Mizuo H"

A man in his 60s with hyperamylasemia underwent contrast-enhanced computed tomography, which revealed masses in his pelvic cavity on the right side and in the left axilla. Hence, a detailed examination was performed. Upon performing Sonazoid (perfluorobutane) contrast-enhanced ultrasound, it was discovered that the right-sided pelvic cavity mass exhibited centripetal contrast-enhancement right from the early stage.

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Lenvatinib (Lenvima) is a tyrosine kinase inhibitor on the market and has been used for the treatment of various types of cancer. It is important to understand differences in pharmacokinetics (PK) between nonclinical animals and humans, and thus, we evaluated PK of lenvatinib in mice, rats, dogs, and monkeys. A simple assay for lenvatinib was developed by high performance liquid chromatography with ultraviolet detection and validated in accordance with the bioanalytical guidelines.

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Sleeve gastrectomy was covered by Japan's national health insurance as bariatric surgery for morbid obesity in 2014. There are a few cases of gastric bypass surgery, which is a different procedure. Given that the current incidence of gastric cancer in Japan is higher than that in the EU and US, the difficulty that gastric bypass surgery presents in examining the bypassed stomach necessitates a cautious approach to the indication of gastric bypass surgery in Japan.

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Article Synopsis
  • A preliminary analysis of the virome in wild sika deer in Japan discovered a new parvovirus closely related to existing strains but only 44.7-60.7% genetically similar.
  • The virus was found in 15% of the 206 sika deer sampled across 7 prefectures, with prevalence rates varying significantly by region, ranging from 0% to 66.7%.
  • The higher rates of the virus in southern Japan may be linked to factors like deer population density and the presence of ticks, which could facilitate virus transmission.
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Hepatitis E virus (HEV) is a zoonotic agent mainly transmitted through the consumption of uncooked or undercooked meat products derived from infected animals. In Japan, domestic pigs and wild boars are the major animal reservoirs, and whether or not deer are an HEV reservoir remains controversial. We analyzed 395 serum and 199 liver samples from 405 sika deer (Cervus nippon) caught in the wild between 1997 and 2020 in 11 prefectures of Japan for markers of HEV infection.

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To further investigate the prevalence of hepatitis E virus (HEV) infection and characterize HEV genomes among Japanese wild boars (Sus scrofa leucomystax), 1880 boars captured in 17 prefectures in Japan from 2013 to 2019 were studied. Overall, anti-HEV IgG was detected in 8.9 % and HEV RNA was detected in 3.

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To reveal putative bioactivation pathways of diclofenac, human liver materials such as microsomal fractions and hepatocytes were used to confirm metabolic activation of diclofenac by S-cysteine trapping assay and covalent binding assay. Candidate human liver proteins possibly targeted by C-diclofenac via bioactivation were investigated using two-dimensional gel electrophoresis followed by detection of remaining radioactivity on the modified proteins with bio-imaging analyzer.In the S-cysteine trapping assay, three and two adducts with S-cysteine were observed in NADPH-fortified and UDPGA-fortified human liver microsomes, respectively.

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Plasma protein binding (PPB) can be different depending on the status of hepatic or renal functions. In this study, the PPB of lenvatinib was determined using equilibrium dialysis in plasma from healthy volunteers and from subjects with mild, moderate, or severe hepatic impairment or renal impairment. Plasma from these subjects, fortified with lenvatinib at four concentrations (20, 200, 500, or 1200 ng/ml), was dialysed against phosphate buffered saline (PBS), and then determinations of the total concentrations of lenvatinib in plasma and unbound concentrations in PBS were made.

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Hepatitis E virus subtype 3f (HEV-3f) strains are usually isolated in Europe and Thailand. Recently, HEV-3f strains were detected from six acute hepatitis E patients in Japan, none of whom had a history of travel to endemic areas. We inferred the origin and transmission route of the six HEV-3f strains.

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Lenvatinib is a multikinase inhibitor that targets vascular endothelial growth factor (VEGF) receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor-alpha, and RET and KIT proto-oncogenes. Lenvatinib is approved for the treatment of radioiodine-refractory differentiated thyroid cancer in the United States (US), European Union (EU), Canada, Japan, and Switzerland. It is also approved in combination with everolimus for the treatment of advanced renal cell carcinoma following ≥1 VEGF-targeted treatment in the US and EU.

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Lenvatinib is an oral, multiple receptor tyrosine kinase inhibitor. Preclinical drug metabolism studies showed unique metabolic pathways for lenvatinib in monkeys and rats. A human mass balance study demonstrated that lenvatinib related material is mainly excreted via feces with a small fraction as unchanged parent drug, but little is reported about its metabolic fate.

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Lenvatinib is a multityrosine kinase inhibitor that inhibits vascular endothelial growth factor receptors, and is being developed as an anticancer drug. P450s are involved in one of the elimination pathways of lenvatinib, and mono-oxidized metabolites, such as N-oxide (M3) and desmethylated metabolite (M2), form in rats, dogs, monkeys, and humans. Meanwhile, two other oxidative metabolites are produced only in monkey and human liver S9 fractions, and their structures have been identified using high-resolution mass spectrometry as a quinolinone form of lenvatinib (M3') and a quinolinone form of desmethylated lenvatinib (M2').

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We report a case of a 68-year-old woman with chronic hepatitis C who presented with a small hepatocellular carcinoma in segment 8 (S8) of liver and a portal hepatic tumor. Transhepatic arterial infusion therapy was performed, followed by partial hepatic resection of S8 and excision of the portal hepatic tumor with lymph node metastasis. Histologically, the lymph nodes showed marked infiltration of large histiocytes with clear cytoplasm and emperipolesis in the specimen stained with hematoxylin-eosin.

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Lenvatinib, a potent inhibitor of multiple tyrosine kinases, including vascular endothelial growth factor receptors 2 and 3, generated unique metabolites after oral administration of [(14)C]lenvatinib (30 mg/kg) to a male cynomolgus monkey. Lenvatinib was found to be transformed to a GSH conjugate, through displacement of an O-aryl moiety, at the quinoline part of the molecule in the liver and kidneys. The GSH conjugate underwent further hydrolysis by γ-glutamyltranspeptidase and dipeptidases, followed by intramolecular rearrangement, to form N-cysteinyl quinoline derivatives, which were dimerized to form disulfide dimers and also formed an N,S-cysteinyl diquinoline derivative.

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Recent evidence has indicated the cross-species transmission of hepatitis E virus (HEV) from pigs and wild boars to humans, causing zoonosis, mostly via consumption of uncooked or undercooked animal meat/viscera. However, no efficient cell culture system for swine and boar HEV strains has been established. We inoculated A549 cells with 12 swine and boar HEV strains of liver, feces, or serum origin at an HEV load of ≥2.

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The patient was a 61-year-old female with alcoholic liver cirrhosis, who was admitted to our hospital due to elevation of AFP.During the evaluation, both abdominal ultrasound and enhanced abdominal CT revealed a hepatocellular carcinoma measuring 4 cm in the S6-7 region, complicated with an arteriovenous shunt.Additionally, the lung CT examination showed 20 isolated bilateral lung tumors, all of which were less than 1.

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We recently developed a cell culture system for hepatitis E virus (HEV) in PLC/PRF/5 and A549 cells, using fecal specimens from HEV-infected patients. Since transfusion-associated hepatitis E has been reported, we examined PLC/PRF/5 and A549 cells for the ability to support replication of HEV in various serum samples obtained from 23 patients with genotype 1, 3, or 4 HEV. HEV progenies emerged in culture media of PLC/PRF/5 cells, regardless of the coexistence of HEV antibodies in serum but dependent on the load of HEV inoculated (31% at 2.

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To investigate nationwide the prevalence of hepatitis E virus (HEV) infection in the general population of Japan, serum samples were collected from 22,027 individuals (9,686 males and 12,341 females; age, mean +/- standard deviation: 56.8 +/- 16.7 years; range: 20-108 years) who lived in 30 prefectures located in Hokkaido, mainland Honshu, Shikoku, and Kyushu of Japan and underwent health check-ups during 2002-2007, and were tested for the presence of IgG, IgM, and IgA classes of antibodies to HEV (anti-HEV) by in-house ELISA and HEV RNA by nested RT-PCR.

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Hepatitis E virus (HEV) is one of the causative agents of acute or fulminant hepatitis. Viral factors may play a role in the pathogenesis of fulminant hepatitis E. We aimed to investigate the nucleotide substitutions of the HEV genome affecting the severity of hepatitis E.

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We developed an efficient cell culture system for genotype 4 hepatitis E virus using the HE-JF5/15F strain recovered from a fulminant hepatitis patient. The sixth-passage virus in the culture supernatant reached 1.5 x 10(8) copies/ml at 10 days postinoculation and possessed 10 nucleotide mutations with four amino acid changes.

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To investigate the duration of fecal shedding and changing loads of hepatitis E virus (HEV) in feces and serum from patients with acute HEV infection, HEV RNA was quantitated in periodic serum and fecal specimens obtained from 11 patients with sporadic acute hepatitis E. All 11 patients had detectable HEV RNA in serum at admission, with the highest viral load being 1.9 x 10(3) to 1.

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We report a case of hemostatic treatment by transcatheter arterial embolization (TAE) of the left gastric artery and a branch of the left bronchial artery for oozing hemorrhage in the lower esophagus, because of incomplete endoscopic hemostasis. A 52-year-old woman with systemic lupus erythematosus was previously admitted three times to our hospital for endoscopic treatment of hemorrhage in the lower esophageal lesions. The procedure of TAE for esophageal hemorrhage seems to be a useful treatment for cases of incomplete endoscopic hemostasis.

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It was suggested that hepatitis E virus (HEV) genotype 4 is associated more closely with the severity of hepatitis E than genotype 3, although the virological basis remains unknown. The aim of this study was to examine whether genomic differences among genotype 4 HEVs are responsible for the development of fulminant hepatitis. Full-length sequences of genotype 4 HEVs from three patients with fulminant hepatitis and six patients with acute self-limited hepatitis were determined.

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We report a patient with Graves' disease in whom thyroid function was changed from initial hyperthyroidism to transient hypothyroidism and back to hyperthyroidism during interferon (IFN) therapy. A 43-year-old man was admitted to our hospital to receive IFN treatment for chronic active hepatitis (type C) in June 1998. His thyroid function was normal and testing for thyroid gland antibodies (TSH binding inhibitor immunoglobulins; TBII, anti-thyroglobulin antibodies; TgAb and anti-thyroid peroxidase antibodies; TPOAb) was negative before IFN therapy.

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