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Long-term effects of lamivudine treatment in Japanese chronic hepatitis B patients

World Journal of Gastroenterology 2011年第24期17卷 2945-2952页

作者： Masayuki Murata Norihiro Furusyo Mami Unno eiichi ogawa Kazuhiro Toyoda Hiroaki Taniai Hachiro Ohnishi Jun Hayashi Department of General Internal Medicine Kyushu University Hospital Department of Environmental Medicine and Infectious Disease Faculty of Medical SciencesKyushu University

AIM： To analyze the association between the emergence of tyrosine-methionine-asparatate-asparatate （YMDD） mutants （reverse transcription; rtM204I/V） and deterioration of liver function during long-term lamivudine treatment of Japanese patients with chronic hepatitis B virus （HBV） infection. METHODS： The data of 61 consecutive Japanese pa- tients with chronic hepatitis B who underwent continu- ous lamivudine treatment for more than 24 mo and had a virological response were analyzed. Analysis of YMDD mutants was done by real-time polymerase chain reaction with LightCycler probe hybridization assay for up to 90 mo （mean, 50.8 too; range, 24-90 too）.RESULTS： A mixed mutant-type （YMDD ＋ tyrosine-iso- leucine-asparatate-asparatate： YIDD or tyrosine-valineasparatate-asparatate： YVDD） or a mutant-type （YIDD or YVDD） were found in 57.4% of 61 patients at i year, 78.7% of 61 patients at 2 years, 79.6% of 49 patients at 3 years, 70.5% of 34 patients at 4 years, 68.4% of 19 patients at 5 years, 57.1% of 14 patients at 6 years, and 33.3% of 6 patients at 7 years. Of the 61 patients, 56 （92%） had mixed mutant- or a mutant-type. Only 5 （8%） had no mutants at each observation point. Vi- rological breakthrough was found in 26 （46.4%） of 56 patients with YMDD mutants, 20 of whom had a hepa- titis flare-up： the remaining 30 （53.6%） had neither a virological breakthrough nor a flare-up. All 20 patients who developed a hepatitis flare-up had a biochemical and virological response after adefovir was added to the lamivudine treatment. CONCLUSION： Our results suggest that it is possible to continue lamivudine treatment, even after the emergence of YMDD mutants, up to the time that the patients develop a hepatitis flare-up.

关键词： Tyrosine-methionine-asparatate-asparatatemutant Hepatitis B virus Lamivudine Drug resistance

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Pre-treatment role of inosine triphosphate pyrophosphatase polymorphism for predicting anemia in Egyptian hepatitis C virus patients

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World Journal of Gastroenterology 2013年第9期19卷 1387-1395页

作者： Walaa H Ahmed Norihiro Furusyo Saad Zaky Abeer Sharaf Eldin Hany Aboalam eiichi ogawa Masayuki Murata Jun Hayashi Department of Environmental Medicine and Infectious Diseases Kyushu University Hospital Fukuoka 812-8582 Japan Department of General Internal Medicine Kyushu University Hospital Fukuoka 812-8582 Japan Department of Tropical Medicine and Gastroenterology Assiut University Hospital Assuit 71515 Egypt National Center for Treatment of Chronic Hepatitis C Ministry of Health Assiut 71329 Egypt

AIM: To investigate and clarify, for the first time, the role of inosine triphosphate pyrophosphatase (ITPA ) polymorphism in Egyptian chronic hepatitis C virus (HCV) ***:The human genomic DNA of all patients was extracted from peripheral blood cells in order to determine the single nucleotide polymorphism (SNP) of ITPA (rs1127354). SNP genotyping was performed by real time polymerase chain reaction (PCR, ABI TaqMan allelic discrimination kit) for 102 treatment-naive Egyptian patients with chronic HCV. All patients had no evidence of cardiovascular or renal diseases. They received a combination treatment of pegylated interferon α (PEG-IFNα) as a weekly subcutaneous dose plus an oral weight-adjusted dose of ribavirin (RBV). The majority received PEG-IFNα2a (70.6%) while 29.4% received PEG-IFNα2b. The planned duration of treatment was 24-48 wk according to the viral kinetics throughout the course of treatment. Pre-treatment liver biopsy was done for each patient for evaluation of fibrosis stage and liver disease activity. The basal viral load level was detected quantitatively by real time PCR while viral load throughout the treatment course was performed qualitatively by COBAS TaqMan assay. RESULTS: Ninety-three patients (91.2%) had ITPA SNP CC genotype and 9 (8.8%) had non-CC genotype (CA and AA). The percentage of hemoglobin (Hb) decline was higher for CC patients than for non-CC patients, particularly at weeks 4 and 8 (P=0.047 and 0.034, respectively). During the first 12 wk of treatment, CC patients had significantly more Hb decline > 3 g/dL than non-CC patients: 64.5% vs 22.2% at weeks 8 and 12, respectively, (P=0.024 and 0.038). Reduction of the amount of the planned RBV dose was significantly higher for CC patients than non-CC patients during the first 12 wk (18% ± 12.1% vs 8.5% ± 10.2%, P=0.021). The percentage of CC patients with RBV dose reduction was significantly greater than that of non-CC patients (77.4% vs 44.4%, P=0.044). Multivariate anal

关键词： Anemia Dose reduction Hepatitis C Inosine triphosphate Ribavirin Rs1127354

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Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B

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World Journal of Gastroenterology 2015年第7期21卷 2116-2123页

作者： Motohiro Shimizu Norihiro Furusyo Hiroaki Ikezaki eiichi ogawa Takeo Hayashi Takeshi Ihara Yuji Harada Kazuhiro Toyoda Masayuki Murata Jun Hayashi Department of General Internal Medicine Kyushu University Hospital Kyushu General Internal Medicine Center Haradoi Hospital

AIM:To investigate the predictors of proximal kidney tubular dysfunction(PKTD)induced by adefovir dipivoxil(ADV)treatment for chronic hepatitis ***:Seventy-nine patients(age at the evaluation of PKTD:56.9±10.7 years)with chronic hepatitis B undergoing long-term oral antiviral nucleos(t)ide analogue treatment were consecutively *** was defined by the presence of at least two of the following five abnormalities:phosphate diabetes,nondiabetic glucosuria,metabolic acidosis,β2-microglobulinuria,or renal *** single-nucleotide polymorphisms(SNPs)in the SLC22A6 gene encoding human organic anion transporter 1(h OAT1)and ABCC2 encoding multidrug resistance protein 2(MRP2)were analyzed using the Taq Man Allelic Discrimination Demonstration ***:Nine(30.0%)of the 30 ADV-treated patients were diagnosed with PKTD,while no patients without ADV developed PKTD(P<0.001).Three patients with ADV were diagnosed with symptomatic *** the patients who took ADV,those with PKTD were of higher age at initiation,had significantly longer treatment duration,and had a significantly lower body mass index than those without *** incidence of PKTD dramatically increased after 96 mo from the start of ADV *** contrast,the SNPs were not correlated with *** regression analysis extracted older age at initiation(OR=5.0,95%CI:1.1-23.4;P=0.040)and longer treatment duration(OR=3.2,95%CI:1.2-8.6;P=0.020)as significant factors associated with ***:Our results suggest that the tubular function of the kidney of older patients undergoing longterm ADV treatment should be carefully evaluated.

关键词： Adefovir dipivoxil Proximal kidney tubular dysfunc

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Importance of virological response in the early stage of telaprevir-based triple therapy for hepatitis C

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World Journal of Hepatology 2015年第26期7卷 2688-2695页

作者： Satoshi Hiramine Norihiro Furusyo eiichi ogawa Makoto Nakamuta Eiji Kajiwara Hideyuki Nomura Kazufumi Dohmen Kazuhiro Takahashi Takeaki Satoh Koichi Azuma Akira Kawano Toshimasa Koyanagi Kazuhiro Kotoh Shinji Shimoda Jun Hayashi Depart- ment of General Internal Medicine Kyushu University Hospital Department of Gastroenterology Kyushu Medical CenterNational Hospital Organization Department of Hepatology Steel Memorial Yahata Hospital the Center for Liver Disease Shin-Kokura Hospital Department of Internal Medicine Chihaya Hospital Department of Medicine Hamanomachi Hospital Center for Liver Disease National Hospital Organization Kokura Medical Center Department of Medicine Kyushu Central Hospital Department of Medicine Kitakyushu Municipal Medical Center Department of Medicine Fukuoka City Hospital Department of Medicine and Bioregulatory Science Graduate School of Medical Sciences Kyushu University Kyushu General Internal Medicine Center Hara- Doi Hospital

AIM: To investigate the efficacy of virological response(VR) to telaprevir(TVR)-based triple therapy in predicting treatment outcome of hepatitis ***: This prospective, multicenter study consisted of 253 Japanese patients infected with hepatitis C virus(HCV) genotype 1b. All received 12 wk of TVR in combination with 24 wk of pegylatedinterferon-α(IFN-α) and ribavirin. Serum HCV RNA was tested at weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24. VR was defined as undetectable serum HCV RNA. Sustained virological response(SVR) was VR at 24 wk after the end of treatment and was regarded as a successful ***: Of 253 patients, 207(81.8%) achieved SVR. The positive predictive value of VR for SVR was 100% at week 2, after which it gradually decreased, and was over 85% to week 12. The negative predictive value(NPV) gradually increased, reaching 100% at week 12. The upslope of the NPV showed a large increase from week 4(40.6%) to week 6(82.4%). There was a moderate concordance between the SVR and VR at week 6(kappa coefficient = 0.44), although other VRs had poor concordance to SVR. Multiple logistic regression analysis extracted VR at week 6(P < 0.0001, OR = 63.8) as an independent factor contributing to SVR. In addition, the interleukin-28 B single nucleotide polymorphism and response to previous pegylated-IFN-α and ribavirin therapy were identified as independent factors for ***: VR at week 6, but not at week 4, is an efficient predictor of both SVR and non-SVR to TVRbased triple therapy.

关键词： Chronic hepatitis C Direct-acting antiviral agent

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A Generalization of Hardy Spaces H^p by Using Atoms

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Acta Mathematica Sinica,English Series 2008年第8期24卷 1243-1268页

作者： eiichi NAKAI Department of Mathematics Osaka Kyoiku UniversityKashiwaraOsaka 582 8582Japan

Let X = （X, d,μ） The purpose of this paper is to be a space of homogeneous type in the sense of Coifman and Weiss. generalize the definition of Hardy space H^P（X） and prove that the generalized Hardy spaces have the same property as H^P（X）. Our definition includes a kind of Hardy- Orlicz spaces and a kind of Hardy spaces with variable exponent. The results are new even for the R^n case. Let （X, δ, μ） be the normalized space of （X, d, μ） in the sense of Macias and Segovia. We also study the relations of our function spaces for （X, d, μ） and （X, δ,μ）.

关键词： Hardy space Hard-Orlicz space variable exponent Campanato space space of homogeneous type

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Singular and fractional integral operators on preduals of Campanato spaces with variable growth condition

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Science China Mathematics 2017年第11期60卷 2219-2240页

作者： NAKAI eiichi Department of Mathematics Ibaraki University

We investigate the boundedness of singular and fractional integral operators on generalized Hardy spaces defined on spaces of homogeneous type, which are preduals of Campanato spaces with variable growth condition. To... 详细信息

关键词： singular integral fractional integral Hardy space Campanato space variable exponent space of homogeneous type

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Simultaneous intermetallics suppression and residual-stress relaxation of heat-resistant Nb-interlayer-inserted Ti-6Al-4V/Si_(3)N_(4)joints via one-step transient liquid phase bonding and brazing

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Journal of Materials Science & Technology 2023年第8期139卷 79-91页

作者： Fei Shen Ong Hirobumi Tobe eiichi Sato Institute of Space and Astronautical Science Japan Aerospace Exploration Agency3-1-1 YoshinodaiChuoSagamihara 252-5210Japan Department of Materials Engineering Graduate School of EngineeringThe University of Tokyo7-3-1 HongoBunkyoTokyo 113-8656Japan

This work has successfully proposed a solution to produce robust Nb-interlayer-inserted Ti-6Al-4V/Si_(3)N_(4)joints optimized for a maximum operating temperature of 873 K;transient liquid phase bonding(TLPB)of Ti-6Al-4V/Nb side was carried out with Cu and Ni fillers to suppress brittle intermetallic compounds(IMCs),whereas brazing of Nb/Si_(3)N_(4)side was performed using a highly ductile Ti-added Ag-rich filler for effective residual-stress relaxation.A sound yet simple one-step bonding process incorporating simul-taneous TLPB and brazing was achieved with a relatively short holding time of 10 min at 1213 *** of Ti-6Al-4V/Nb side with Cu and Ni foils of 2-μm-thick each as a laminated filler suppressed brittle Ti-based IMCs and developed a homogenized microstructure consisting mainly of(α+β)-Ti via isothermal ***,brazing of Nb/Si_(3)N_(4)side with 100-μm-thick SILVER-ABA filler(92.75Ag-5Cu-1Al-1.25Ti mass%)foil enhanced interfacial bonding with sufficient total Ti content and accommodated residual stress better than conventional eutectic Ag-Cu-based fillers,and it was verified by finite element analysis with consideration of materials’temperature-dependent elasto-plastic *** joints with a bonding area of 10 mm×10 mm were tested via symmetrical four-point bending from room temper-ature(RT)to 873 K fractured from Nb/Si_(3)N_(4)*** re-heating the joints from RT to 673 K,frac-ture initiation gradually shifted from Si_(3)N_(4)towards interfacial-compounds/Si_(3)N_(4)interface and bending strengths maintained∼220 MPa as weakening of SILVER-ABA filler was compensated by residual-stress relaxation in Si_(3)N_(4).When tested at 873 K,joints fractured mainly across the Ag-rich solid solution in a ductile manner and bending strength degraded by∼20%to 171 MPa as weakening of SILVER-ABA filler dominated.

关键词： Transient liquid phase bonding Brazing Ceramics Residual stress Finite element analysis

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Effect of Cavities inside Tube Banks on Acoustic Resonance

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Journal of Thermal Science 2010年第1期19卷 67-71页

作者： Hiromitsu HAMAKAWA Hidenobu MIYAGI eiichi NISHIDA Department of Mechanical Engineering Oita University700 DannoharuOita 870-1192Japan Cyuouhatsujyou Kougyou 503 Jyuuni-machiHita877-8501Japan Department of Mechanical Systems Engineering Shonan Institute of Technology1-1-25 Tujidou NisikaiganFujisawa251-8511Japan

In the present paper the attention is focused on the effect of small cavities inside in-line tube banks on acoustic resonance which occurred in the two-dimensional model of boiler. We measured the sound pressure level, the amplitude and the phase delay of acoustic pressures and the gap velocity. As a result, we found many peak frequencies of sound pressure level with different Strouhal numbers, mainly about S1=0.15, 0.26 and 0.52. The variation of SPL for S,=0.26, 0.52 components in the tube banks with cavities was the same as the result of no cavities. The existence of cavities inside in-line tube banks caused the resonance of St=0.15. And the acoustic resonance of the first mode in the transverse direction was generated if the small cavities existed inside the tube banks. This resonance was not generated from the tube banks of no cavities. The resonance onset velocity in the transverse mode was fairly slower than that of no cavities. It was easy to generate acoustic resonance when there were small cavities inside in-line tube banks.

关键词： Acoustic Resonance Flow Induced Noise In-line Tube Banks Cavity Boiler

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Orlicz-Hardy spaces and their duals

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Science China Mathematics 2014年第5期57卷 903-962页

作者： NAKAI eiichi SAWANO Yoshihiro Department of Mathematics Ibaraki UniversityMitoIbaraki 310-8512Japan Department of Mathematics and Information Sciences Tokyo Metropolitan UniversityMinami-Ohsawa 1-1Hachioji-shiTokyo 192-0397Japan

We establish the theory of Orlicz-Hardy spaces generated by a wide class of *** class will be wider than the class of all the *** particular,we consider the non-smooth atomic *** relation between Orlicz-Hardy spaces and their duals is also *** an application,duality of Hardy spaces with variable exponents is *** work is different from earlier works about Orlicz-Hardy spaces H（Rn）in that the class of admissible functions is largely *** can deal with,for example,Ф（r）≡（rp1（log（e＋1/r））q1,0〈r≤1,r^p2 （log（e＋r））q2,r〉1,with p1,p2∈（0,∞）and q1,q2∈（.∞,∞）,where we shall establish the boundedness of the Riesz transforms on H（Rn）.In particular,is neither convex nor concave when 0〈p1〈1〈p2〈∞,0〈p21〈p1〈∞or p1=p2=1 and q1,***（r）≡r（log（e＋r））q,then H（Rn）=H（logH）q（Rn）.We shall also establish the boundedness of the fractional integral operators I of order∈（0,∞）.For example,I is shown to be bounded from H（logH）1^1-α/n（Rn）to Ln/（n-α）（log L）（Rn）for 0〈α〈n.

关键词： Hardy space Orlicz space atomic decomposition Campanato space bounded mean oscillation

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Effect of DOPO-containing Flame Retardants on Poly（lactic acid）： Non-flammability, Mechanical Properties and Thermal Behaviors

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Chemical Research in Chinese Universities 2017年第1期33卷 143-149页

作者： GU Liqiang QIU Jianhui SAKAI eiichi Department of Machine Intelligence and Systems Engineering Faculty of Systems Science and Technology Akita Prefectural University Yurihonjo 015-0055 Japan

The flame retardancies of three kinds of 9,10-dihydro-9-oxa-10-phosphaphenan-threne 10-oxide（DOPO）- containing flame retardant（A1, A2, A3）/poly（lactic acid）（PLA） composites[PA-n/（Ax-y）, n= 1--12; x= l, 2, 3, denoting three kinds of flame retardants; y= 10%, 20%, 30%, 40%, denoting the mass fraction of Ax] were greatly enhanced by melt blending of flame retardant Ax with PLA, including twin-screw extrusion and injection-molding processes. With only 10%（mass fraction） of Ax added to PLA, good flame retardancy with limiting oxygen index（LOI） values of more than 33% was achieved. As the Ax mass fraction was further increased to 20%, PA-n/（Ax-20%） composites showed much better flame retardancy（LOI~〉35% and UL-94 V-0 rating）. Moreover, the thermal degradation behaviors and mechanical properties of PA-n/（Ax-y） composites were investigated via thermogravimetric analysis（TGA）, differen- tial thermal analysis（DTA）, tensile testing, notched impact-bar testing, and dynamic mechanical analysis（DMA）. TGA results show that PA-n/（Ax-y） composites have slower rate of mass loss and much higher char yield, compared to neat PLA. With the addition of Ax to PLA, the DTA and DMA results indicate slight variations in glass transition tcmpe- ratures（Tg） of PA-n/（Ax-y） composites. Based on TGA results under nonisothermal conditions, the thermal degrada- tion kinetics of PA-n/（Ax-y） composites were studied by KAssinger＇s and Ozawa＇s methods. These thermal degrada- tion dynamic analyses show lower activation energies（EK or Eo） for PA-n/（Ax-y） composites, corresponding to higher mass fractions of Ax（from 10% to 40%）. The PA-n/（Ax-y） composites with good flame retardancy and good mecha- nical properties obtained in this study could be potential candidates for fire- and heat-resistant applications in auto- motive engineering and building fields with more safety and excellent performance.

关键词： Poly(lactic acid) composite Flame retardancy Thermal degradation kinetics

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