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Serial changes in expression of functionally clustered genes in progression of liver fibrosis in hepatitis C patients

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World Journal of Gastroenterology 2008年第13期14卷 2010-2022页

作者： Yoshiyuki Takahara Mitsuo Takahashi Qing-Wei Zhang Hirotaka Wagatsuma Maiko Mori Akihiro Tamori susumu shiomi Shuhei Nishiguchi Exploratory & Applied Pharmaceutical Research Department Pharmaceutical Company Ajinomoto Co. Inc. 1-1 Suzuki-cho Kawasaki-ku Kawasaki 210-8681 Japan Department of Nuclear Medicine Graduate School of Medicine Osaka City University Osaka Japan Division of Hepatobiliary and Pancreatic Diseases Department of Internal Medicine Hyogo College of Medicine Nishinomiya Japan

AIM: To investigate the relationship of changes in expression of marker genes in functional categories or molecular networks comprising one functional category or multiple categories in progression of hepatic fibrosis in hepatitis C (HCV) patients. METHODS: Marker genes were initially identified using DNA microarray data from a rat liver fibrosis model. The expression level of each fibrosis associated marker gene was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) in clinical biopsy specimens from HCV-positive patients (n = 61). Analysis of changes in expression patterns and interactions of marker genes in functional categories was used to assess the biological mechanism of fibrosis. RESULTS: The profile data showed several biological changes associated with progression of hepatic fibrosis. Clustered genes in functional categories showed sequential changes in expression. Several sets of clustered genes, including those related to the extracellular matrix (ECM), inflammation, lipid metabolism, steroid metabolism, and some transcription factors important for hepatic biology showed expression changes in the immediate early phase (F1/F2) of fibrosis. Genes associated with aromatic amino acid (AA) metabolism, sulfur-containing AA metabolism and insulin/ Wnt signaling showed expression changes in the middle phase (F2/F3), and some genes related to glucose metabolism showed altered expression in the late phase of fibrosis (F3/F4). Therefore, molecular networks showing serial changes in gene expression are present in liver fibrosis progression in hepatitis C patients. CONCLUSION: Analysis of gene expression profiles from a perspective of functional categories or molecular networks provides an understanding of disease and suggests new diagnostic methods. Selected marker genes have potential utility for biological identification of advanced fibrosis.

关键词：肝纤维化丙肝标记基因基因表达新陈代谢转录因子

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Natural history of major complications in hepatitis C virus-related cirrhosis evaluated by per-rectal portal scintigraphy

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World Journal of Gastroenterology 2005年第25期11卷 3882-3886页

作者： Etsushi Kawamura Daiki Habu Takehiro Hayashi Ai Oe Jin Kotani Hirotaka Ishizu Kenji Torii Joji Kawabe Wakaba Fukushima Takashi Tanaka Shuhei Nishiguchi susumu shiomi Department of Nuclear Medicine Department of Hepatology Department of Public Health

AIM: To examine the correlation between the porto-systemic hypertension evaluated by portal shunt index (PSI) and life-threatening complications, Including hepatocellular carcinoma (HCC), liver failure (Child-Pugh stage progression),and esophagogastric varices.METHODS: Two hundred and twelve consecutive subjects with HCV-related cirrhosis (LC-C) underwent per-rectal portal scintigraphy. They were allocated into three groups aocording to their PSI: group Ⅰ, PSI≤10%; group Ⅱ, 10%＜PSI＜30%;and group Ⅲ, 30%≤PSI. Of these, selected 122 Child-Pugh stage A (Child A) subjects were included in analysis (a mean follow-up period of 5.9±5.4 years, range 6 mo-21 years).RESULTS: No significant correlation between PSI and cumulative probability of HCC Incidence was observed.Cumulative probability of Child A to B progression was tended to be higher in group Ⅲ than in group Ⅰ, and significantly higher in group Ⅲ than in group Ⅱ (62% vs 34%, 62% vs 37%; P = 0.060, ＜0.01; respectively).Cumulative probability of varices tended to be higher In group Ⅲ than in group Ⅰ (31% vs 12%, P = 0.090). On multivariate analyses, significant correlation between PSI and Child A to B progression was observed, and no significant correlation between PSI and HCC incidence or varices progression was observed.CONCLUSION: Patients with LC-C of Child A will progress to Child B rapidly after their PSI reaches 30% or higher.PSI can be used to predict occult progressive porto-systemic shunting and liver failure non-invasively. It indicates that PSI may play an important role in follow-up of the portosystemic hypertension gradient for outpatients with LC unlike hepatic venous catheterization.

关键词：并发症丙型肝炎闪烁扫描法肝硬化

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Usefulness of noninvasive transient elastography for assessment of liver fibrosis stage in chronic hepatitis C

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World Journal of Gastroenterology 2006年第48期12卷 7768-7773页

作者： Tadashi Takeda Takahiro Yasuda Yuji Nakayama Mika Nakaya Megumi Kimura Mariko Yamashita Ayumi Sawada Koji Abo Setsuko Takeda Hiroki Sakaguchi susumu shiomi Hitoshi Asai Shuichi Seki Department of Hepatology Graduate School of Medicine Osaka City University Osaka Japan Central Clinical Laboratory Osaka City University Medical School Hospital Osaka Japan Department of Nuclear Medicine Graduate School of Medicine Osaka City University Osaka Japan Hitoshi Asai Health Service Center Osaka Kyoiku University Osaka Japan

AIM:To evaluate the method of noninvasive transient elastography for assessment of histological stage of liver fibrosis in patients with chronic hepatitis C (CHC). METHODS: Two hundred and thirty-seven patients with CHC were included in this study. Liver biopsy was performed under ultrasonography on 217 of the patients, excluding twenty with clear clinical evidence of liver cirrhosis. Fifty subjects without liver disease were enrolled as a control group (stage 0). Twenty- five patients with sustained virological response (SVR) to interferon (IFN) therapy were also enrolled. These patients underwent liver biopsy before IFN therapy. Examination of liver stiffness (LS) was performed by elastography. RESULTS: Medians (50% levels) of LS were 4.1 (3.5-4.9), 6.3 (4.8-8.5), 8.8 (6.8-12.0), 14.6 (10.5-18.6), and 22.2 (15.4-28.0), respectively, in the fibrosis stages 0-4 (P < 0.001). LS was significantly correlated with four serum fibrosis markers. LS values in patients with SVR were 3.8 (3.5-5.6), 5.2 (4.4-6.8), 6.8 (6.1-7.6), and 6.1 (3.6-7.9), respectively, in the fibrosis stages 1-4. In all stages, LS for patients with SVR was significantly lower than that for patients who did not undergo IFN therapy. LS was significantly correlated with serum concentrations of hyaluronic acid, type Ⅳ collagen, type Ⅳ collagen 7S, and type Ⅲ procollagen N peptide. CONCLUSION: LS correlated well with the histologicalstage of fibrosis. Changes in liver fibrosis stage may thus be estimated noninvasively using transient elastography.

关键词：瞬时现象肝纤维化慢性丙型肝炎治疗

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Z-shaped incision without epithelial resection in pterygium surgery

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1262-1266页

作者： Satoru Kase Shinki Chin susumu Ishida Department of Ophthalmology Faculty of Medicine and Graduate School of MedicineHokkaido UniversitySapporo 060-8638Japan

AIM:To introduce a novel surgical technique using a Z-shaped incision without epithelial resection in ophthalmic pterygia.METHODS:This was a prospective study.During pterygium surgery,all proliferative tissues were separated from the cornea and conjunctiva without resection of the tissues.The unaffected conjunctiva was incised in a Z-shape.The upper(or lower)conjunctival flap was sutured to the lower(or upper)normal conjunctiva on the limbal sclera,while the proliferative tissue was sutured to the upper conjunctiva(or lower)near the fornix.RESULTS:Ten patients with pterygia were eligible for this study.Eight patients with primary pterygia and 2 with recurrent pterygia were included.The age of patients at surgery ranged from 47 to 90y(average:71.9y).Five patients each showed right and left-sided pterygia.The postoperative follow-up periods were from 8 to 78mo(average:25.0mo).The surgery was successfully conducted and wounds were favorably reconstructed in all patients.The proliferative tissues sutured to the normal conjunctiva showed palor and attenuated neovessles,and never showed re-growth after surgery.Nine patients did not show recerrence.Recerrent pterygium was noted in 1 patient,but additional treatments were not required.CONCLUSION:The procedure involves the reconstruction of pterygial tissue and normal conjunctiva using a Z-shaped incision.The scleral limbal wound can be covered with nonaffected conjunctiva without any excision of conjunctival epithelia in patients with primary or recurrent pterygia.

关键词： pterygium surgery Z-shape non-resection

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Cisplatin-induced activation of TGF-βsignaling contributes to drug resistance

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Oncology Research 2024年第1期32卷 139-150页

作者： SAYAKA IMATSUJI YUKIKO UJIE HIROYUKI ODAKE MASAYA IMOTO susumu ITOH ETSU TASHIRO Department of Biosciences and Informatics Faculty of Science and TechnologyKeio UniversityYokohama223-8522Japan Department of Neurology Juntendo University Graduate School of MedicineTokyo113-8421Japan Laboratory of Biochemistry Showa Pharmaceutical UniversityTokyo194-8543Japan

Growing evidence suggests an association between epithelial-mesenchymal transition(EMT),a hallmark of tumor malignancy,and chemoresistance to a number of anti-cancer drugs.However,the mechanism of EMT induction in the process of acquiring anti-cancer drug resistance remains unclear.To address this issue,we obtained a number of cisplatin-resistant clones from LoVo cells and found that almost all of them lost cell-cell contacts.In these clones,the epithelial marker E-cadherin was downregulated,whereas the mesenchymal marker N-cadherin was upregulated.Moreover,the expression of EMT-related transcription factors,including Slug,was elevated.On the other hand,the upregulation of other mesenchymal marker Vimentin was weak,suggesting that the mesenchymal-like phenotypic changes occurred in these cisplatin-resistant clones.These mesenchymal-like features of cisplatin-resistant clones were partially reversed to parental epithelial-like features by treatment with transforming growth factor-β(TGF-β)receptor kinase inhibitors,indicating that TGF-βsignaling is involved in cisplatin-induced the mesenchymallike phenotypic changes.Moreover,cisplatin was observed to enhance the secretion of TGF-βinto the culture media without influencing TGF-βgene transcription.These results suggest that cisplatin may induce the mesenchymal-like phenotypic changes by enhancing TGF-βsecretion,ultimately resulting in drug resistance.

关键词： Cisplatin EMT Chemo-resistance TGF-β

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Assessment of corrected time-step method for nominal ionospheric gradient calculation: A comparative analysis with spatial approaches

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Earth and Planetary Physics 2024年第4期8卷 641-649页

作者： Slamet Supriadi Prayitno Abadi susumu Saito Harry Bangkit Dwiko Unggul Prabowo Adi Purwono Ginaldi Ari Nugroho Research Center for Smart Mechatronics National Research and Innovation Agency(BRIN)BandungIndonesia Research Center for Climate and Atmosphere BRINBandungIndonesia School of Electrical Engineering Telkom UniversityKab.BandungIndonesia Electronic Navigation Research Institute National Institute of MaritimePort and Aviation TechnologyTokyoJapan Research Center for Space BRINBandungIndonesia

The effect of ionospheric delay on the ground-based augmentation system under normal conditions can be mitigated by determining the value of the nominal ionospheric gradient(σvig).The nominal ionospheric gradient is generally obtained from Continuously Operating Reference Stations data by using the spatial single-difference method(mixed-pair,station-pair,or satellite-pair)or the temporal single-difference method(time-step).The time-step method uses only a single receiver,but it still contains ionospheric temporal variations.We introduce a corrected time-step method using a fixed-ionospheric pierce point from the geostationary equatorial orbit satellite and test it through simulations based on the global ionospheric model.We also investigate the effect of satellite paths on the corrected time-step method in the region of the equator,which tends to be in a more north–south direction and to have less coverage for the east–west ionospheric gradient.This study also addresses the limitations of temporal variation correction coverage and recommends using only the correction from self-observations.All processes are developed under simulations because observational data are still difficult to obtain.Our findings demonstrate that the corrected time-step method yieldsσvig values consistent with other approaches.

关键词： ground-based augmentation system nominal ionospheric gradient time-step correction global ionospheric model

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Computationally Efficient Large-Eddy Simulation of Periodic Unsteady Flow using Harmonic Balance Method

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Journal of Thermal Science 2022年第1期31卷 62-71页

作者： YUMA Iwamoto susumu Teramoto KOJI Okamoto Department of Aeronautics and Astronautics University of TokyoTokyo 113-8656Japan Department of Advanced Energy University of TokyoTokyo 113-8656Japan

To improve the efficiency and fidelity of the numerical analysis for cascade flutter, we propose an efficient scale-resolving simulation method dedicated to time-periodic flows by incorporating the harmonic balance approach into the large-eddy simulation. This method combined convergence calculations of the steady-state problem based on the harmonic balance method for periodic components, and the nonlinear time-marching method for turbulent fluctuations. Using the proposed method, deterministic periodic components and stochastic turbulent fluctuations were calculated simultaneously, and the effect of turbulent fluctuations on deterministic periodic components was directly calculated without using turbulence models. In this paper, we explain the algorithm and feature of this simulation technique and present the results of the computation for channel flow excited in the streamwise direction as an analysis example using the proposed method. In order to validate the proposed method, an analysis of sinusoidally pulsating channel flow at the central friction-velocity Reynolds numbers Rer = 180 was conducted, confirming that the amplitude and phase of the mean velocity oscillation computed by the proposed method were in good agreement with those of the conventional LES. The present calculation achieved an order of magnitude improvement in computational efficiency compared to conventional LES.

关键词： harmonic balance LES turbulent channel flow

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Interactive Restoration of Three-Dimensional Implicit Surface with Irregular Parts

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Computer Modeling in Engineering & Sciences 2023年第9期136卷 2111-2125页

作者： Jiayu Ren Yoshihisa Fujita susumu Nakata Graduate School of Information Science and Engineering Ritsumeikan UniversityShiga525-8577Japan College of Information Science and Engineering Ritsumeikan UniversityShiga525-8577Japan

Implicit surface generation based on the interpolation of surface points is one of the well-known modeling methods in the area of computer graphics.Several methods for the implicit surface reconstruction from surface points have been proposed on the basis of radial basis functions,a weighted sum of local functions,splines,wavelets,and combinations of them.However,if the surface points contain errors or are sparsely distributed,irregular components,such as curvature-shaped redundant bulges and unexpectedly generated high-frequency components,are commonly seen.This paper presents a framework for restoring irregular components generated on and around surfaces.Users are assumed to specify local masks that cover irregular components and parameters that determine the degree of restoration.The algorithm in this paper removes the defects based on the user-specific masks and parameters.Experiments have shown that the proposed methods can effectively remove redundant protrusions and jaggy noise.

关键词： Shape modeling implicit surfaces interactive restoration

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A case of conjunctival intraepithelial neoplasia with spheroidal degeneration:a clinicopathological study

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International Journal of Ophthalmology(English edition) 2022年第8期15卷 1401-1403页

作者： Shoichiro Ota Satoru Kase Takayuki Tanaka susumu Ishida Department of Ophthalmology Faculty of Medicine and Graduate School of MedicineHokkaido UniversitySapporo 060-8638Japan

Dear Editor,I am Shoichiro Ota from Hokkaido University hospital,Japan.Conjunctival intraepithelial neoplasia(CIN)is a disease concept that includes dysplasia and carcinoma in situ.Pathologically,CIN is characterized by tumor cell proliferation located within the epithelium with preservation of the basement membrane[1].In addition to histological diagnosis,anterior segment optical coherence tomography(ASOCT)plays an important role in clinical diagnosis,showing diffuse epithelial thickening with homogeneous high-intensity reflection in case of CIN[2-3].

关键词： diagnosis degeneration neoplasia

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Performance Evaluation of Electromagnetic Shield Constructed from Open-Cell Metal Foam Based on Sphere Functions

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Computer Modeling in Engineering & Sciences 2022年第7期132卷 43-53页

作者： Yuya Hanaoka Taku Itoh Kohei Tateyama susumu Nakata Keiko Watanabe Graduate School of Industrial Technology Nihon UniversityNarashinoChiba 275-8575Japan College of Industrial Technology Nihon UniversityNarashinoChiba 275-8575Japan College of Science and Engineering Ritsumeican UniversityKusatsuShiga 525-8577Japan College of Information Science and Engineering Ritsumeican UniversityKusatsuShiga 525-8577Japan

This study evaluates the performance of a model of open-cell metal foams generated by sphere functions.To this end,an electromagnetic shield constructed from the model was inserted between two horn antennas in an electromagnetic wave propagation simulation.The foam-hole diameter in the electromagnetic shield model was varied as d=2.5 and 5.0 mm,and the frequency of the electromagnetic waves was varied from 3 to 13 GHz.In the numerical experiments of shield effectiveness,the shields with foam holes of both diameters attenuated the electromagnetic waves across the studied frequency range.The shield effectiveness was enhanced at low frequencies and in the shield with smaller hole diameter.

关键词： Electromagnetic propagation electromagnetic shielding materials metal foams numerical simulation

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