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  1. Article: A Multiple Step Active Stiffness Integration Scheme to Couple a Stochastic Cross-Bridge Model and Continuum Mechanics for Uses in Both Basic Research and Clinical Applications of Heart Simulation.

    Yoneda, Kazunori / Okada, Jun-Ichi / Watanabe, Masahiro / Sugiura, Seiryo / Hisada, Toshiaki / Washio, Takumi

    Frontiers in physiology

    2021  Volume 12, Page(s) 712816

    Abstract: In a multiscale simulation of a beating heart, the very large difference in the time scales between rapid stochastic conformational changes of contractile proteins and deterministic macroscopic outcomes, such as the ventricular pressure and volume, have ... ...

    Abstract In a multiscale simulation of a beating heart, the very large difference in the time scales between rapid stochastic conformational changes of contractile proteins and deterministic macroscopic outcomes, such as the ventricular pressure and volume, have hampered the implementation of an efficient coupling algorithm for the two scales. Furthermore, the consideration of dynamic changes of muscle stiffness caused by the cross-bridge activity of motor proteins have not been well established in continuum mechanics. To overcome these issues, we propose a multiple time step scheme called the multiple step active stiffness integration scheme (MusAsi) for the coupling of Monte Carlo (MC) multiple steps and an implicit finite element (FE) time integration step. The method focuses on the active tension stiffness matrix, where the active tension derivatives concerning the current displacements in the FE model are correctly integrated into the total stiffness matrix to avoid instability. A sensitivity analysis of the number of samples used in the MC model and the combination of time step sizes confirmed the accuracy and robustness of MusAsi, and we concluded that the combination of a 1.25 ms FE time step and 0.005 ms MC multiple steps using a few hundred motor proteins in each finite element was appropriate in the tradeoff between accuracy and computational time. Furthermore, for a biventricular FE model consisting of 45,000 tetrahedral elements, one heartbeat could be computed within 1.5 h using 320 cores of a conventional parallel computer system. These results support the practicality of MusAsi for uses in both the basic research of the relationship between molecular mechanisms and cardiac outputs, and clinical applications of perioperative prediction.
    Language English
    Publishing date 2021-08-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2021.712816
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: A thermodynamically consistent monte carlo cross-bridge model with a trapping mechanism reveals the role of stretch activation in heart pumping.

    Yoneda, Kazunori / Kanada, Ryo / Okada, Jun-Ichi / Watanabe, Masahiro / Sugiura, Seiryo / Hisada, Toshiaki / Washio, Takumi

    Frontiers in physiology

    2022  Volume 13, Page(s) 855303

    Abstract: Changes in intracellular calcium concentrations regulate heart beats. However, the decline in the left ventricular pressure during early diastole is much sharper than that of the ... ...

    Abstract Changes in intracellular calcium concentrations regulate heart beats. However, the decline in the left ventricular pressure during early diastole is much sharper than that of the Ca
    Language English
    Publishing date 2022-09-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2022.855303
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Ionic mechanisms of ST segment elevation in electrocardiogram during acute myocardial infarction.

    Okada, Jun-Ichi / Fujiu, Katsuhiko / Yoneda, Kazunori / Iwamura, Takashi / Washio, Takumi / Komuro, Issei / Hisada, Toshiaki / Sugiura, Seiryo

    The journal of physiological sciences : JPS

    2020  Volume 70, Issue 1, Page(s) 36

    Abstract: ST elevation on an electrocardiogram is a hallmark of acute transmural ischemia. However, the underlying mechanism remains unclear. We hypothesized that high ischemic sensitivities of epicardial adenosine triphosphate-sensitive potassium ( ... ...

    Abstract ST elevation on an electrocardiogram is a hallmark of acute transmural ischemia. However, the underlying mechanism remains unclear. We hypothesized that high ischemic sensitivities of epicardial adenosine triphosphate-sensitive potassium (IK
    MeSH term(s) Action Potentials ; Computer Simulation ; Electrocardiography ; Finite Element Analysis ; Heart Rate ; Humans ; KATP Channels/metabolism ; Models, Cardiovascular ; Pericardium/metabolism ; Pericardium/physiopathology ; Potassium/metabolism ; Predictive Value of Tests ; ST Elevation Myocardial Infarction/diagnosis ; ST Elevation Myocardial Infarction/metabolism ; ST Elevation Myocardial Infarction/physiopathology ; Sodium/metabolism ; Time Factors
    Chemical Substances KATP Channels ; Sodium (9NEZ333N27) ; Potassium (RWP5GA015D)
    Language English
    Publishing date 2020-07-13
    Publishing country Japan
    Document type Comparative Study ; Journal Article ; Video-Audio Media
    ZDB-ID 2234472-X
    ISSN 1880-6562 ; 1880-6546
    ISSN (online) 1880-6562
    ISSN 1880-6546
    DOI 10.1186/s12576-020-00760-3
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  4. Article ; Online: Patient-specific heart simulation can identify non-responders to cardiac resynchronization therapy.

    Isotani, Akihiro / Yoneda, Kazunori / Iwamura, Takashi / Watanabe, Masahiro / Okada, Jun-Ichi / Washio, Takumi / Sugiura, Seiryo / Hisada, Toshiaki / Ando, Kenji

    Heart and vessels

    2020  Volume 35, Issue 8, Page(s) 1135–1147

    Abstract: To identify non-responders to cardiac resynchronization therapy (CRT), various biomarkers have been proposed, but these attempts have not been successful to date. We tested the clinical applicability of computer simulation of CRT for the identification ... ...

    Abstract To identify non-responders to cardiac resynchronization therapy (CRT), various biomarkers have been proposed, but these attempts have not been successful to date. We tested the clinical applicability of computer simulation of CRT for the identification of non-responders. We used the multi-scale heart simulator "UT-Heart," which can reproduce the electrophysiology and mechanics of the heart based on a molecular model of the excitation-contraction mechanism. Patient-specific heart models were created for eight heart failure patients who were treated with CRT, based on the clinical data recorded before treatment. Using these heart models, bi-ventricular pacing simulations were performed at multiple pacing sites adopted in clinical practice. Improvement in pumping function measured by the relative change of maximum positive derivative of left ventricular pressure (%ΔdP/dt
    MeSH term(s) Aged ; Aged, 80 and over ; Cardiac Resynchronization Therapy/adverse effects ; Clinical Decision-Making ; Decision Support Techniques ; Excitation Contraction Coupling ; Female ; Heart Failure/diagnosis ; Heart Failure/physiopathology ; Heart Failure/therapy ; Humans ; Male ; Middle Aged ; Models, Cardiovascular ; Myocardial Contraction ; Patient Selection ; Patient-Specific Modeling ; Recovery of Function ; Risk Assessment ; Risk Factors ; Treatment Failure ; Ventricular Function, Left ; Ventricular Function, Right
    Language English
    Publishing date 2020-03-12
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 89678-0
    ISSN 1615-2573 ; 0910-8327 ; 0935-736X
    ISSN (online) 1615-2573
    ISSN 0910-8327 ; 0935-736X
    DOI 10.1007/s00380-020-01577-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Ventricular fiber optimization utilizing the branching structure.

    Washio, Takumi / Yoneda, Kazunori / Okada, Jun-Ichi / Kariya, Taro / Sugiura, Seiryo / Hisada, Toshiaki

    International journal for numerical methods in biomedical engineering

    2016  Volume 32, Issue 7

    Abstract: In this paper, we propose an algorithm that optimizes the ventricular fiber structure of the human heart. A number of histological studies and diffusion tensor magnetic resonance imaging analyses have revealed that the myocardial fiber forms a right- ... ...

    Abstract In this paper, we propose an algorithm that optimizes the ventricular fiber structure of the human heart. A number of histological studies and diffusion tensor magnetic resonance imaging analyses have revealed that the myocardial fiber forms a right-handed helix at the endocardium. However, the fiber formation changes its orientation as a function of transmural depth, becoming a left-handed helix at the epicardium. To determine how nature can construct such a structure, which obtains surprising pumping performance, we introduce macroscopic modeling of the branching structure of cardiac myocytes in our finite element ventricular model and utilize this in an optimization process. We put a set of multidirectional fibers around a central fiber orientation at each point of the ventricle walls and simulate heartbeats by generating contraction forces along each of these directions. We examine two optimization processes using the workloads or impulses measured in these directions to update the central fiber orientation. Both processes improve the pumping performance towards an optimal value within several tens of heartbeats, starting from an almost-flat fiber orientation. However, compared with the workload optimization, the impulse optimization produces better agreement with experimental studies on transmural changes of fiber helix angle, streamline patterns of characteristic helical structures, and temporal changes in strain. Furthermore, the impulse optimization is robust under geometrical changes of the heart and tends to homogenize various mechanical factors such as the stretch and stretch rate along the fiber orientation, the contraction force, and energy consumption. Copyright © 2015 John Wiley & Sons, Ltd.
    Language English
    Publishing date 2016-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 2540968-2
    ISSN 2040-7947 ; 2040-7939
    ISSN (online) 2040-7947
    ISSN 2040-7939
    DOI 10.1002/cnm.2753
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  6. Article: Polymorphic mutations of the Mn-SOD gene in intact human lymphocytes and oral squamous cell carcinoma cell lines.

    Kamatani, Takaaki / Yamamoto, Tetsuya / Yoneda, Kazunori / Osaki, Tokio

    Biochemistry and cell biology = Biochimie et biologie cellulaire

    2003  Volume 81, Issue 1, Page(s) 43–50

    Abstract: Mutations of the superoxide dismutase (SOD) genes are associated with neoplastic and non-neoplastic diseases. However, the existence of polymorphic mutations of manganese SOD (Mn-SOD) has not been explored in squamous cell carcinoma (SCC) cells or in ... ...

    Abstract Mutations of the superoxide dismutase (SOD) genes are associated with neoplastic and non-neoplastic diseases. However, the existence of polymorphic mutations of manganese SOD (Mn-SOD) has not been explored in squamous cell carcinoma (SCC) cells or in normal cells. In the present study, we examined mutations in the 5' flanking region of the Mn-SOD gene and Mn-SOD mRNA using 10 human oral SCC (OSC) cell lines and intact lymphocytes obtained from 10 healthy donors and one patient with OSC. The polymerase chain reaction products of DNA obtained from lymphocytes revealed insertions at many sites (-1833, -1575, -1093, -1056, -325, -318, and -310) in 10 of the 11 donors. Transitions and (or) transversions were also observed at -1638 and -216 in lymphocytes from six donors and one donor, respectively. In DNA obtained from OSC cells, insertions and transitions and (or) transversions were more frequent than those in DNA from lymphocytes. In addition, deletions at -1341 and -1288 were observed in all lines except for one line. In these mutations, the transcription factor binding sites were not involved except for the AP-2 binding site (-102) in three cell lines. In Mn-SOD mRNA, Val at -9 position was varied to Ala in lymphocytes from two donors and three OSC cell lines, respectively. In the remaining cell lines, Mn-SOD mRNA from lymphocytes and OSC cell lines revealed heterozygosity (Ala/Val) and homozygosity (Val/Nal), respectively. The Mn-SOD activities in lymphocytes were 3.8-5.8 x 10(-4) U/10(6) cells and the activities in OSC cell lines were 1.8-8.3 x 10(-4) U/10(6) cells. These Mn-SOD activities were not correlated with the mutations of DNA and mRNA. From these results, it is indicated that polymorphic mutations of Mn-SOD exist in human normal cells and that the deletions might be obtained in the course of malignant transformation of OSC although decrease in Mn-SOD activity is not involved in the transformation.
    MeSH term(s) 5' Flanking Region/genetics ; Base Sequence ; Carcinoma, Squamous Cell/enzymology ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/pathology ; DNA/chemistry ; DNA/genetics ; Genotype ; Humans ; Lymphocytes/cytology ; Lymphocytes/enzymology ; Lymphocytes/metabolism ; Molecular Sequence Data ; Mutation ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Superoxide Dismutase/genetics ; Superoxide Dismutase/metabolism ; Tumor Cells, Cultured/enzymology
    Chemical Substances DNA (9007-49-2) ; Superoxide Dismutase (EC 1.15.1.1)
    Language English
    Publishing date 2003-02
    Publishing country Canada
    Document type Journal Article
    ZDB-ID 54104-7
    ISSN 0829-8211
    ISSN 0829-8211
    DOI 10.1139/o03-020
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  7. Article: Risk Factors of Metastasis in Oral Squamous Cell Carcinomas

    Osaki, Tokio / Kimura, Tsuyoshi / Tatemoto, Yukihiro / Yamamoto, Tetsuya / Yoneda, Kazunori

    Oncology

    2000  Volume 58, Issue 2, Page(s) 137–143

    Abstract: Lymph node and distant metastasis were comparatively studied in 225 oral carcinomas, and factors predisposing toward metastasis were investigated using clinical and immunohistopathological approaches. Neither the sites of tumors nor T-stage was ... ...

    Institution Department of Oral Surgery, Kochi Medical School, Kohasu, Japan
    Abstract Lymph node and distant metastasis were comparatively studied in 225 oral carcinomas, and factors predisposing toward metastasis were investigated using clinical and immunohistopathological approaches. Neither the sites of tumors nor T-stage was correlated with either type of metastasis. Tumor cell differentiation was weakly correlated with lymph node metastasis, and stromal reaction (the degree of cell infiltration) did not differ greatly between metastasis-positive and negative tumors, although natural killer (NK) activities were correlated with lymph node metastasis. However, the mode of tumor cell invasion was closely associated with both lymphnode and distant metastases. In grade 4C and 4D tumors, distant and lymph node metastases were observed in 8 (16%) and 31 (62%) cases, respectively, while of 68 grade 1 and 2 tumors, distant metastasis was not observed in any, and lymph node metastasis occurred in only 15 (22.1%). In addition, the expression of p53 protein was correlated with lymph node metastasis; of 70 tumors without p53 protein expression, 23 (32.9%) revealed lymph node metastasis, while it occurred in 54 out of 96 tumors positive for p53 protein. However, p53 protein expression was not associated with distant metastasis, and p24 protein, a cyclin-dependent kinase inhibitor, did not show any relationship with either type of metastasis. These results indicate that lymph node metastasis is correlated with multiple factors in the host and tumor cells, but distant metastasis is only correlated with the mode of tumor cell invasion, suggesting that the former can be highly accurately predicted by invasion mode, p53 protein expression and NK activity.
    Keywords p53 and p21 proteins ; NK activity ; Oral carcinoma ; Metastasis ; Invasion mode of tumor cells
    Language English
    Publishing date 2000-02-23
    Publisher S. Karger AG
    Publishing place Basel, Switzerland
    Document type Article
    Note Laboratory/Clinical Translational Research
    ZDB-ID 250101-6
    ISSN 1423-0232 ; 0030-2414
    ISSN (online) 1423-0232
    ISSN 0030-2414
    DOI 10.1159/000012090
    Database Karger publisher's database

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  8. Article: Clinical Investigation on Pulmonary Metastasis of Head and Neck Carcinomas

    Osaki, Tokio / Yoneda, Kazunori / Yamamoto, Tetsuya / Kimura, Tsuyoshi / Matuoka, Hisakazu / Sakai, Hiroatsu / Ryoke, Kazuo

    Oncology

    2000  Volume 59, Issue 3, Page(s) 196–203

    Abstract: Objective: To establish a treatment strategy for pulmonary metastases, we clinically investigated the characteristics of distant metastases from head and neck carcinomas. Methods: In 636 head and neck carcinomas, the pathophysiology of distant metastases ...

    Institution Department of Oral Surgery, Kochi Medical School, Kochi, and Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Tottori University, Tottori, Japan
    Abstract Objective: To establish a treatment strategy for pulmonary metastases, we clinically investigated the characteristics of distant metastases from head and neck carcinomas. Methods: In 636 head and neck carcinomas, the pathophysiology of distant metastases was investigated by charts, roentgenographies, computed tomographies and scintigraphies. Results: Of the squamous cell carcinomas, oropharyngeal tumors were most highly metastatic, followed by lower gingiva, floor of the mouth, maxillary sinus, and tongue. In distant metastases, 30 (4.7%), 5 (0.8%), and 7 (1.1%) metastasized to the lungs only, lungs and other organs, and organs excluding the lungs, respectively. In pulmonary metastases, the right, left and both lungs were involved in 18, 5, and 8 patients, respectively, although details were not obtained for 4 patients. Pulmonary metastases consisted of 1, 2, and 3 or more tumors in 18, 4, and 6 patients, respectively. Diffuse cancer cell infiltration was observed in 3 patients. Of the 42 patients with distant metastases, 12 patients died of progressive pulmonary metastases, and 5 of these patients manifested only 1 pulmonary lesion throughout life. However, the metastatic pulmonary tumors were controlled surgically or conservatively in 3 patients. Conclusion: These results indicate that distant metastases from head and neck carcinomas involve the lungs most frequently and that chemoimmunotherapy and surgical removal of the metastatic tumors are recommended when indicated.
    Keywords Head and neck carcinomas ; Distant metastases ; Pulmonary metastases
    Language English
    Publishing date 2000-10-02
    Publisher S. Karger AG
    Publishing place Basel, Switzerland
    Document type Article
    Note Clinical Study
    ZDB-ID 250101-6
    ISSN 1423-0232 ; 0030-2414
    ISSN (online) 1423-0232
    ISSN 0030-2414
    DOI 10.1159/000012161
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  9. Article: Diffuse Mode of Tumor Cell Invasion and Expression of Mutant p53 Protein But Not of p21 Protein Are Correlated with Treatment Failure in Oral Carcinomas and Their Metastatic Foci

    Osaki, Tokio / Kimura, Tsuyoshi / Tatemoto, Yukihiro / Dapeng, Lu / Yoneda, Kazunori / Yamamoto, Tetsuya

    Oncology

    2000  Volume 59, Issue 1, Page(s) 36–43

    Abstract: Lack of control of metastatic foci is the most prevalent cause of death in patients with oral carcinomas, and it is important for tumor control to identify the factors that predispose patients to death. In the present study, we examined 225 patients with ...

    Institution Department of Oral Surgery, Kochi Medical School, Kochi, Japan
    Abstract Lack of control of metastatic foci is the most prevalent cause of death in patients with oral carcinomas, and it is important for tumor control to identify the factors that predispose patients to death. In the present study, we examined 225 patients with oral squamous cell carcinoma and investigated the immunohistopathological characteristics of 43 tumors that led to death, comparing them with those of the non-lethal tumors. In the 43 patients, lack of control of the primary site, lymph node and distant metastatic tumors were noted in 20, 18 and 16 patients, respectively. The mode of tumor cell invasion was closely correlated with death. The diffuse invasion modes of grades 4C and 4D were observed in 15 (34.9%) of the 43 tumors with a poor outcome and in 35 (19.2%) of the 182 controlled tumors (p < 0.02). The expression of p53 was highly correlated with death. Of the tumors with poor prognosis, p53 protein was expressed in 32 tumors (76.2%). However, p53 protein expression was observed in 52.7% of the tumors with good prognosis (p < 0.02). In contrast, the expression of p21 protein in the well-controlled tumors (30.4%) was almost equal to that of the 43 lethal tumors (26.2%). Compared with the ratios of local recurrence, metastases and their treatment failures in the p53-negative grade 1 and 2 tumors, those in the mutant p53-positive grade 3, 4C and 4D tumors were mostly high. These results indicate that measuring p53 protein expression and evaluating the mode of tumor cell invasion are important for oral carcinoma therapy because the expression of mutant p53 protein and the diffuse modes of tumor cell invasion indicate a predisposition toward a poor prognosis.
    Keywords Invasion mode, tumor cells ; Metastasis ; Oral carcinoma ; p53 protein ; p21 protein ; Prognosis ; Tumor control
    Language English
    Publishing date 2000-06-30
    Publisher S. Karger AG
    Publishing place Basel, Switzerland
    Document type Article
    Note Laboratory/Clinical Translational Research
    ZDB-ID 250101-6
    ISSN 1423-0232 ; 0030-2414
    ISSN (online) 1423-0232
    ISSN 0030-2414
    DOI 10.1159/000012135
    Database Karger publisher's database

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