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A Mixture of Glycosylated proBNP and BNP-32 Is a Suitable Calibrator for BNP Immunoassays

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Open Journal of Clinical Diagnostics 2019年第2期9卷 51-63页

作者： Keiichi Masuta Kenzo Funatsuki Youko inoue Izuru Masuda Toshio Nishikimi Yasuaki Nakagawa Kazukiyo Horii Hiroshi Nishi Masayo Igarashi norio Ota Biomarker R & D Department Shionogi & Co. Ltd. Toyonaka Japan Takeda Hospital Medical Examination Center Kyoto Japan Department of Cardiovascular Medicine Kyoto University Graduate School of Medicine Kyoto Japan Department of Medicine Wakakusa-Tatsuma Rehabilitation Hospital Daito Japan Horii Planning Yokohama Japan

Aim: Measurement of B-type natriuretic peptide (BNP) is widely used as a diagnostic and risk assessment tool for cardiovascular disease. Recent studies have demonstrated that BNP-32 and its precursor proBNP circulate in the blood stream, and that most commercial BNP immunoassays measure both forms. However, recombinant or synthetic BNP-32 is used as the standard for those BNP immunoassays. This gap between clinical samples and the standard might be a potential source of variation in BNP measurements among assays. The purpose of this study is to validate a more suitable calibrator for BNP immunoassays. Methods: External BNP calibrators containing both BNP-32 and glycosylated proBNP were prepared at two concentration levels. Target BNP concentrations of the low and high levels were 40 and 160 pg/mL, respectively. And to reflect clinical samples, the molar ratios of BNP-32 to glycosylated proBNP in these concentration levels were adjusted to 50:50 and 25:75, respectively. BNP concentrations of plasma samples along with the external BNP calibrators were measured at two commercial labs and using an automated analyzer MI02 Shionogi®BNP (MI02). These samples and the calibrators were also measured using an immunoradiometric assay (IRMA) as a standard assay procedure. Concentrations of the plasma samples measured at the labs or using the MI02 were adjusted according to a comparison of the measured concentrations of the external BNP calibrators with the IRMA. Results: After measured concentrations of the plasma samples were adjusted using the external BNP calibrators, the correlation between each measurement and the IRMA was improved. The range of the slopes according to Passing-Bablok regression analysis narrowed from 0.628 - 0.955 to 0.911 - 1.005. Conclusions: Our data suggests that a mixture of BNP-32 and glycosylated proBNP at different ratios by concentration level is suitable for calibration to minimize variations in BNP measurements among immunoassays.

关键词： B-Type Natriuretic Peptide (BNP) proBNP Calibrator

Extended therapy duration for therapy-refractory hepatitis C patients with genotype 2

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World Journal of Gastroenterology 2013年第34期19卷 5754-5758页

作者： Ken Sato Masatoshi Yanagisawa Hiroaki Hashizume Yuichi Yamazaki norio Horiguchi Satoru Kakizaki Masatomo Mori Department of Medicine and Molecular Science Gunma University Graduate School of Medicine

We devised an extended 72-wk peginterferon--2a/ribavirin therapy regimen for the retreatment of highly intractable cases,i.e.,48-wk peginterferon--2b/ribavirin therapy-intractable *** 2 cases achieved a rapid virological response to 72-wk peginterferon--2a/ribavirin therapy,1 case failed to achieve a sustained virological *** the reason for this difference in the effectiveness of 72-wk peginterferon--2a/ribavirin therapy between the cases was unclear,the rebound phenomenon of serum transaminase after48-wk peginterferon--2b/ribavirin therapy and the resultant lower viral load compared to that before 48-wk peginterferon--2b/ribavirin therapy might have influenced the treatment ***,it may be beneficial to consider the rebound phenomenon of serum transaminase and the changes in viral load resulting from previous interferon-based therapy and then cau-tiously determine the indication and the timing of the administration of 72-wk peginterferon--2a/ribavirin in highly intractable *** studies should be performed to confirm this strategy.

关键词： Hepatitis C Genotype 2 and high viral loads Interferon-based therapy Highly intractable case Extended therapy duration

Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer

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World Journal of Gastroenterology 2006年第5期12卷 691-696页

作者： Pei-Hong Jiang Yoshiharu Motoo Stéphane Garcia Juan Lucio Iovanna Marie-Josèphe Pébusque norio Sawabu Department of Internal Medicine and Medical Oncology Cancer Research InstituteKanazawa University Kanazawa Japan Department of Medical Oncology Kanazawa Medical University Ishikawa Japan INSERM U624 Marseille France

AIM： Overexpression of tumor protein p53-induced nudear protein 1 （TP53INP1） induces G1 cell cycle arrest and increases p53-mediated apoptosis. To clarify the clinical importance of TP53INP1, we analyzed TP53INP1 and p53 expression in gastric cancer, METHODS： TP53INP1 and p53 expression were examined using immunohistochemistry in 142 cases of gastric cancer. The apoptosis of gastric cancer cells was analyzed using the TUNEL method. The relationship between the expression of TP53INP1 and clinicopathological factors was statistically analyzed. RESULTS： TP53INP1 was expressed in 98% （139/142 cases） of non-cancerous gastric tissues and was downexpressed in 64% （91/142 cases） of gastric cancer lesions from the same patients. TP53INP1 expression was significantly decreased （43.9%） in poorly differentiated adenocarcinoma compared with well or moderately differentiated adenocarcinoma （81.6%）. Cancers invading the submucosa or deeper showed lower positively （59.1%） compared with mucosal cancers （85.2%）. Decrease or loss of TP53INP1 expression was significantly correlated with lymphatic invasion （54.3% vs 82.0% without lymphatic invasion） and node-positive patients （31.3% vs 68.3% in node-negative patients）. P53 was expressed in 68 （47.9%） patients of gastric cancer, whereas it was absent in normal gastric tissues. A significant association was also observed between TP53INP1 status and the level of apoptosis in tumor cells： the apoptotic index in TP53INP1-positive tissues was significantly higher than that in TP53INP41-negative portions. Finally, when survival data were analyzed, loss of TP53INP1 expression had a significant effect in predicting a poor prognosis （P= 0.0006）.CONCLUSION： TPS3INP1-positive rate decreases with the progression of gastric cancer. TPS3INP1 protein negativity is significantly associated with aggressive pathological phenotypes of gastric cancer. TPS3INP1 is related to the apoptosis of gastric cancer cells. The decreased expression of the TPS3INP

关键词： Tumor protein 53-induced nuclear protein 1 p53 Gastric cancer

Glycogen synthase kinase 3b biology in bone and soft tissue sarcomas

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Journal of Cancer Metastasis and Treatment 2020年第1期6卷 660-674页

作者： Kensaku Abe Shingo Shimozaki Takahiro Domoto norio Yamamoto Hiroyuki Tsuchiya Toshinari Minamoto Department of Orthopaedic Surgery Graduate School of Medical SciencesKanazawa UniversityKanazawa 920-8641Japan Division of Translational and Clinical Oncology Cancer Research InstituteKanazawa UniversityKanazawa 920-0934Japan Shimozaki Orthopaedic Hospital HakusanIshikawa 924-0802Japan

Bone and soft tissue sarcomas are malignant neoplasms probably originating from musculoskeletal and mesenchymal progenitor *** than 80 different histopathological subtypes are encountered in *** standard of care for sarcoma patients involves a multidisciplinary combination of surgery,anthracycline-based multiagent chemotherapy and ***,these are associated with adverse events and occasionally disappointing *** genomic-,biologically-,and immunologically-based therapies are still under evaluation in early-phase clinical ***,there are strong barriers to the development and clinical translation of new therapeutic *** is due to the rarity of these diseases,the broad spectrum of tumor subtypes with genetic and biological heterogeneity,and the wide variability in clinical manifestation,response to treatment and prognosis.A potential approach toward overcoming this barrier is to identify therapeutic targets that cover multiple sarcoma *** synthase kinase 3b(GSK3b)has emerged as a common therapeutic target in more than 25 different cancer *** we review the evidence for tumor-promoting roles of GSK3b in the major types of bone and soft tissue sarcomas including osteosarcoma,rhabdomyosarcoma,synovial sarcoma,and *** this review,we describe the therapeutic effects of inhibiting GSK3b in these sarcoma types,while also protecting healthy cells and tissues from detrimental effects associated with conventional therapies,such as doxorubicin-induced ***,we highlight GSK3b as a potential therapeutic target spanning multiple sarcoma types.

关键词： Osteosarcoma rhabdomyosarcoma synovial sarcoma fibrosarcoma glycogen synthase kinase 3b

Prediction of lymph node metastasis and sentinel node navigation surgery for patients with early-stage gastric cancer

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World Journal of Gastroenterology 2016年第33期22卷 7431-7439页

作者： Atsuo Shida norio Mitsumori Hiroshi Nimura Yuta Takano Taizou Iwasaki Muneharu Fujisaki Naoto Takahashi Katsuhiko Yanaga Department of Surgery Jikei University School of Medicine

Accurate prediction of lymph node(LN) status is crucially important for appropriate treatment planning in patients with early gastric cancer(EGC). However,consensus on patient and tumor characteristics associated with LN metastasis are yet to be reached. Through systematic search,we identified several independent variables associated with LN metastasis in EGC,which should be included in future research to assess which of these variables remain as significant predictors of LN metastasis. On the other hand,even if we use these promising parameters,we should realize the limitation and the difficulty of predicting LN metastasis accurately. The sentinel LN(SLN) is defined as first possible site to receive cancer cells along the route of lymphatic drainage from the primary tumor. The absence of metastasis in SLN is believed to correlate with the absence of metastasis in downstream LNs. In this review,we have attempted to focus on several independent parameters which have close relationship between tumor and LN metastasis in EGC. In addition,we evaluated the history of sentinel node navigation surgery and the usefulness for EGC.

关键词： Early-stage gastric cancer Sentinel node navigation surgery Prediction of lymph node metastasis

An Open Environment for Cooperative Equational Solving

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Wuhan University Journal of Natural Sciences 2001年第Z1期6卷 169-174页

作者： Tetsuo Ida, Mircea Marin, norio Kobayashi Institute of Information Sciences and Electronics, University of Tsukuba, Tsukuba 305 8573, Japan Institute of Information Sciences and Electronics University of Tsukuba Tsukuba Japan

We describe a system called CFLP which aims at the integration of the best features of functional logic programming (FLP), cooperative constraint solving (CCS), and distributed computing. FLP provides support for defining one's own abstractions over a constraint domain in an easy and comfortable way, whereas CCS is employed to solve systems of mixed constraints by iterating specialized constraint solving methods in accordance with a well defined strategy. The system is a distributed implementation of a cooperative constraint functional logic programming scheme that combines higher order lazy narrowing with cooperative constraint solving. The model takes advantage of the existence of several constraint solving resources located in a distributed environment (e.g., a network of computers), which communicate asynchronously via message passing. To increase the openness of the system, we are redesigning CFLP based on CORBA. We discuss some design and implementation issues of the system.

关键词： functional logic programing cooperative contraint solving distributed computing

Proposal of a Model of a Three-Dimensional Spherical Universe

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Journal of Modern Physics 2022年第9期13卷 1253-1266页

作者： Hitoshi Shibata norio Ogata Taiko Pharmaceutical Company Limited Osaka Japan R & D Department Taiko Pharmaceutical Company Limited Kyoto Japan

Despite the existence of several exact solutions to the general theory of relativity, it is still difficult to explain the entire structure of the universe. In this paper, we propose a novel three-dimensional spherical (S3) universe model. According to this model, the universe had a powerful gravity source at its origin, and a part of the gravitational source formed a bubble of spacetime in which the universe was born. The universe expanded explosively immediately after the Big Bang. The energy obtained from the gravity source at the birth of the universe is constant, that is, it remains constant from the birth of the universe to the end. The expansion and contraction of the universe is determined by the passage of coordinate time. The S3 universe observed from outside can be considered to be a two-dimensional spherical surface by projecting it onto a three-dimensional space. On the other hand, the visible universe viewed from inside is observed as a three-dimensional sphere with an arbitrary observation point. The origin of the S3 universe can be seen to be evenly spread in the outer shell of the visible universe. We define visible longitude as the difference between an observation point and its farthest light source. At an initial phase of the expansion of the universe, few stars can be seen, because the visible longitude is small. However, when the expansion of the universe progresses, the number of visible stars also increases, since visible longitude increases. In our S3 universe model, the redshifts observed and reported so far in literature appear to indicate that the expansion of the universe is accelerating. Our S3 universe model can thus lead to a novel exact solution to general relativity.

关键词： Redshift S3 Universe Expansion General Relativity Big Bang

Sentinel lymph node navigation surgery for early stage gastric cancer

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World Journal of Gastroenterology 2014年第19期20卷 5685-5693页

作者： norio Mitsumori Hiroshi Nimura Naoto Takahashi Masahiko Kawamura Hiroaki Aoki Atsuo Shida Nobuo Omura Katsuhiko Yanaga Department of surgery the Jikei University School of MedicineNisi-shinbashiMinato-kuTokyo 105-8461Japan

We attempted to evaluate the history of sentinel node navigation surgery (SNNS), technical aspects, tracers, and clinical applications of SNNS using Infrared Ray Electronic Endoscopes (IREE) combined with Indocyanine Green (ICG). The sentinel lymph node (SLN) is defined as a first lymph node (LN) which receives cancer cells from a primary tumor. Reports on clinical application of SNNS for gastric cancers started to appear since early 2000s. Two prospective multicenter trials of SNNS for gastric cancer have also been accomplished in Japan. Kitagawa et al reported that the endoscopic dual (dye and radioisotope) tracer method for SN biopsy was confirmed acceptable and effective when applied to the early-stage gastric cancer (EGC). We have previously reported the usefulness of SNNS in gastrointestinal cancer using ICG as a tracer, combined with IREE (Olympus Optical, Tokyo, Japan) to detect SLN. LN metastasis rate of EGC is low. Hence, clinical application of SNNS for EGC might lead us to avoid unnecessary LN dissection, which could preserve the patient’s quality of life after operation. The most ideal method of SNNS should allow secure and accurate detection of SLN, and real time observation of lymphatic flow during operation.

关键词： Gastric cancer Sentinel node navigation surgery Infrared Ray Electronic Endoscopes Indocyanine Green

Apparent Accelerated Expansion of the Three-Dimensional Spherical Universe Observed during Its Contraction Phase

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Journal of Modern Physics 2023年第S1期14卷 1693-1702页

作者： Hitoshi Shibata norio Ogata Taiko Pharmaceutical Company Limited Osaka Japan R & D Department Taiko Pharmaceutical Company Limited Seikacho Japan

In recent years, it has been thought that the expansion of the universe has begun to accelerate. However, there are other views against this. Here we propose a new theory based on the three-dimensional spherical (S3) universe wherein the same observations as the present universe can also be found by the accelerated contraction of the universe. According to our theory, the expansion velocity of the S3 universe slowed down after the Big Bang, and all the kinetic energy was converted into potential energy to reach the great sphere. After that, accelerated contraction begins, and the universe finally converges to an original single point. In the S3 universe, the passage of time (referred to as “proper time”) changes depending on its expansion velocity. The frequency of light emitted from celestial bodies is determined by their proper time on emission, and when the light is observed by observers having different proper time, a redshift or blueshift is observed. Observers in the expansion phase observe redshifts, because the proper time of the observer progresses faster than that of emitted light, but observers in the contraction phase observe an accelerated delay of the proper time, so the progress of the proper time is reversed based upon its order from nearby celestial bodies, a blueshift is observed, and its range of observable distance increases. The results of this early contraction phase are consistent with the observations of the current universe. In conclusion, the S3 universe may be able to explain the geometrical structure of the current universe.

关键词： Three-Dimensional Universe Spherical Universe Redshift Big Bang