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  1. Article ; Online: The immunobiology of humanized Anti-IL6 receptor antibody: From basic research to breakthrough medicine.

    Ohsugi, Yoshiyuki

    Journal of translational autoimmunity

    2019  Volume 3, Page(s) 100030

    Abstract: The clinical use of monoclonal antibodies is well established in human medicine and has been amongst the most important contributions of basic science to clinical disease. One such antibody, the humanized anti-human IL-6 receptor antibody, is used to ... ...

    Abstract The clinical use of monoclonal antibodies is well established in human medicine and has been amongst the most important contributions of basic science to clinical disease. One such antibody, the humanized anti-human IL-6 receptor antibody, is used to treat a variety of autoimmune diseases, particularly rheumatoid arthritis. It is extremely difficult and a laborious process to go from a concept at the research bench, to government approval. Such approval implies not only efficacy but, more importantly, an appropriate safety profile. In this review, the history of anti-human IL-6 receptor antibody is discussed in depth beginning with the author's experience during a sabbatical visit at the University of California at Davis in 1978. At that time, it was discovered that B cell activation was at least one critical factor in the development of autoimmunity. Approximately six years later, the cDNA encoding for IL-6 was cloned as BSF-2 (B cell stimulatory factor 2) to differentiate B cells to produce antibody. Soon after, it was suggested that this cytokine plays an important role in the development of autoimmune diseases. Based on this evidence, the journey began to search for an IL-6 inhibitor. Although there were numerous obstacles in finding lead compounds, ultimately, basic science developed the methodology for high throughput readouts that would inhibit the biologic function of IL-6. It was finally concluded that a mouse monoclonal antibody against IL-6 receptor would be optimal. In 1991, this antibody was humanized by using CDR-grafting technology in collaboration with the MRC (Medical Research Council). The drug was named tocilizumab and launched as an innovative anti-rheumatic drug in 2008 in Japan. Subsequently, the drug has been used throughout the world and has achieved enormous success in helping patients who suffer from inflammatory arthropathies. The lessons learned in the development of this antibody have application to the study of biologics and their application to other human diseases.
    Language English
    Publishing date 2019-12-23
    Publishing country Netherlands
    Document type Journal Article ; Review
    ISSN 2589-9090
    ISSN (online) 2589-9090
    DOI 10.1016/j.jtauto.2019.100030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: [Method for Measuring Noise Power Spectrum Depending on X-ray Tube Angle in Spiral Orbit of Helical CT Scan].

    Ohsugi, Yuki / Narita, Akihiro / Ohkubo, Masaki / Sakai, Kenichi / Fukaya, Takahiro / Noto, Yoshiyuki

    Nihon Hoshasen Gijutsu Gakkai zasshi

    2023  Volume 79, Issue 10, Page(s) 1144–1150

    Abstract: Purpose: The noise power spectrum (NPS) in computed tomography (CT) images potentially varies with the X-ray tube angle in a spiral orbit of the helical scan. The purpose of this study was to propose a method for measuring the NPS for each angle of the ... ...

    Abstract Purpose: The noise power spectrum (NPS) in computed tomography (CT) images potentially varies with the X-ray tube angle in a spiral orbit of the helical scan. The purpose of this study was to propose a method for measuring the NPS for each angle of the X-ray tube.
    Methods: Images of the water phantom were acquired using a helical scan. As a conventional method, we measured the two-dimensional (2D) NPS from each image and averaged them; the obtained 2D-NPS was referred to as NPS
    Results: The NPS
    Conclusion: The proposed method was demonstrated to be effective for evaluating anisotropic noise characteristics depending on the X-ray tube angle.
    Language Japanese
    Publishing date 2023-09-06
    Publishing country Japan
    Document type English Abstract ; Journal Article
    ZDB-ID 2269092-X
    ISSN 1881-4883 ; 0369-4305
    ISSN (online) 1881-4883
    ISSN 0369-4305
    DOI 10.6009/jjrt.2023-1363
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Method for measuring noise-power spectrum independent of the effect of extracting the region of interest from a noise image.

    Narita, Akihiro / Ohsugi, Yuki / Ohkubo, Masaki / Fukaya, Takahiro / Sakai, Kenichi / Noto, Yoshiyuki

    Radiological physics and technology

    2023  Volume 16, Issue 4, Page(s) 471–477

    Abstract: This study aimed to evaluate the impact of region of interest (ROI) size on noise-power spectrum (NPS) measurement in computed tomography (CT) images and to propose a novel method for measuring NPS independent of ROI size. The NPS was measured using the ... ...

    Abstract This study aimed to evaluate the impact of region of interest (ROI) size on noise-power spectrum (NPS) measurement in computed tomography (CT) images and to propose a novel method for measuring NPS independent of ROI size. The NPS was measured using the conventional method with an ROI of size P × P pixels in a uniform region in the CT image; the NPS is referred to as NPS
    MeSH term(s) Phantoms, Imaging ; Tomography, X-Ray Computed/methods ; Image Processing, Computer-Assisted/methods ; Algorithms
    Language English
    Publishing date 2023-07-29
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2433581-2
    ISSN 1865-0341 ; 1865-0333
    ISSN (online) 1865-0341
    ISSN 1865-0333
    DOI 10.1007/s12194-023-00733-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: [A Study of Longitudinal NPS Measurement in CT Images Based on the Central Cross-section Theorem].

    Narita, Akihiro / Ohkubo, Masaki / Ohsugi, Yuki / Sakai, Kenichi / Fukaya, Takahiro / Noto, Yoshiyuki

    Nihon Hoshasen Gijutsu Gakkai zasshi

    2022  Volume 78, Issue 7, Page(s) 719–725

    Abstract: Purpose: Various approaches in noise power spectrum (NPS) analysis are currently used for measuring a patient's longitudinal (z-direction) NPS from three-dimensional (3D) CT volume data. The purpose of this study was to clarify the relationship between ... ...

    Abstract Purpose: Various approaches in noise power spectrum (NPS) analysis are currently used for measuring a patient's longitudinal (z-direction) NPS from three-dimensional (3D) CT volume data. The purpose of this study was to clarify the relationship between those NPSs and 3D-NPS based on the central slice theorem.
    Methods: We defined the 3D-NPS(f
    Results: In each relationship (1)-(3), the f
    Conclusion: Based on the central slice theorem, we clarified the relationships between f
    MeSH term(s) Fourier Analysis ; Humans ; Phantoms, Imaging ; Tomography, X-Ray Computed/methods ; Water
    Chemical Substances Water (059QF0KO0R)
    Language Japanese
    Publishing date 2022-06-03
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2269092-X
    ISSN 1881-4883 ; 0369-4305
    ISSN (online) 1881-4883
    ISSN 0369-4305
    DOI 10.6009/jjrt.2022-1267
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: IL-6 as a target in inflammation.

    Hashizume, Misato / Ohsugi, Yoshiyuki

    Endocrine, metabolic & immune disorders drug targets

    2015  

    Abstract: Interleukin-6 (IL-6) has a unique feature of its own signaling pathway. IL-6 can act on various types of cells because there are abundant amounts of soluble IL-6 receptor in peripheral blood and can mediate signaling into cells. IL-6 participates in a ... ...

    Abstract Interleukin-6 (IL-6) has a unique feature of its own signaling pathway. IL-6 can act on various types of cells because there are abundant amounts of soluble IL-6 receptor in peripheral blood and can mediate signaling into cells. IL-6 participates in a broad spectrum of biological events, such as immune responses, hematopoiesis, and acute-phase reactions. In contrast, overproduction of IL-6 has been implicated in the pathogenesis of a variety of diseases, including several chronic inflammatory diseases. Future studies to clarify the molecular mechanisms of IL-6 functions as well as studies in which inhibitors of IL-6 signaling are used should provide information critical to a better understanding of the molecular mechanisms of diseases and the development of new therapeutic methods.
    Language English
    Publishing date 2015-03-16
    Publishing country United Arab Emirates
    Document type Journal Article
    ZDB-ID 2228325-0
    ISSN 2212-3873 ; 1871-5303
    ISSN (online) 2212-3873
    ISSN 1871-5303
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Er:YAG laser-assisted comprehensive periodontal pocket therapy for residual periodontal pocket treatment: A randomized controlled clinical trial.

    Aoki, Akira / Mizutani, Koji / Mikami, Risako / Ohsugi, Yujin / Kobayashi, Hiroaki / Akizuki, Tatsuya / Taniguchi, Yoichi / Takeuchi, Yasuo / Katagiri, Sayaka / Sasaki, Yoshiyuki / Komaki, Motohiro / Meinzer, Walter / Izumi, Yuichi / Iwata, Takanori

    Journal of periodontology

    2023  Volume 94, Issue 10, Page(s) 1187–1199

    Abstract: Background: This study evaluated the effectiveness of a novel pocket therapy (Er:YAG laser-assisted comprehensive periodontal pocket therapy [Er-LCPT]) for residual pocket treatment, compared with conventional mechanical treatment alone, in a randomized ...

    Abstract Background: This study evaluated the effectiveness of a novel pocket therapy (Er:YAG laser-assisted comprehensive periodontal pocket therapy [Er-LCPT]) for residual pocket treatment, compared with conventional mechanical treatment alone, in a randomized controlled clinical trial.
    Methods: Two sites in 18 patients having residual periodontal pockets of ≥5 mm depth, extant following initial active therapy, or during supportive therapy, were randomized into two groups in a split mouth design: the control group received scaling and root planing (SRP) by curette, and the test group received Er-LCPT using curette and laser. With Er-LCPT, after root debridement, inflamed connective tissue on the inner gingival surface and on the bone surface/within extant bone defects was thoroughly debrided. Furthermore, removal of proximate oral epithelium and coagulation of the blood clot in the pocket entrance were performed with laser. Clinical parameters were evaluated, before and after treatment, through 12 months.
    Results: Both groups showed significant improvements in clinical parameters. With Er-LCPT, pocket debridement was thoroughly and safely performed, without any adverse side effects and complications, and favorable healing was observed in most of the cases. At 12 months, Er-LCPT demonstrated significantly higher probing pocket depth reduction (2.78 mm vs. 1.89 mm on average; p = 0.012, Wilcoxon signed-rank test), clinical attachment gain (1.67 mm vs. 1.06 mm; p = 0.004) as primary outcomes, and reduced BOP value (0.89 vs. 0.56; p = 0.031), compared with SRP alone.
    Conclusion: The results of this study indicate that Er-LCPT is more effective for residual pocket treatment, compared with SRP alone.
    MeSH term(s) Humans ; Periodontal Pocket/surgery ; Lasers, Solid-State/therapeutic use ; Follow-Up Studies ; Root Planing/methods ; Dental Scaling/methods ; Treatment Outcome ; Periodontal Attachment Loss/surgery
    Language English
    Publishing date 2023-05-14
    Publishing country United States
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 390921-9
    ISSN 1943-3670 ; 0022-3492 ; 1049-8885 ; 0095-960X
    ISSN (online) 1943-3670
    ISSN 0022-3492 ; 1049-8885 ; 0095-960X
    DOI 10.1002/JPER.22-0552
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: IL-6 as a target in autoimmune disease and inflammation.

    Hashizume, Misato / Ohsugi, Yoshiyuki

    Nihon yakurigaku zasshi. Folia pharmacologica Japonica

    2014  Volume 144, Issue 4, Page(s) 172–177

    MeSH term(s) Autoimmune Diseases/drug therapy ; Autoimmune Diseases/immunology ; Humans ; Inflammation/drug therapy ; Inflammation/immunology ; Interleukin-6/antagonists & inhibitors ; Interleukin-6/immunology ; Neovascularization, Pathologic ; Receptors, Interleukin-6/immunology ; Signal Transduction/drug effects
    Chemical Substances Interleukin-6 ; Receptors, Interleukin-6
    Language Japanese
    Publishing date 2014
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1097532-9
    ISSN 1347-8397 ; 0015-5691
    ISSN (online) 1347-8397
    ISSN 0015-5691
    DOI 10.1254/fpj.144.172
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Recent advances in immunopathophysiology of interleukin-6: an innovative therapeutic drug, tocilizumab (recombinant humanized anti-human interleukin-6 receptor antibody), unveils the mysterious etiology of immune-mediated inflammatory diseases.

    Ohsugi, Yoshiyuki

    Biological & pharmaceutical bulletin

    2007  Volume 30, Issue 11, Page(s) 2001–2006

    Abstract: Interleukin (IL)-6 cDNA was originally cloned as a terminal B cell differentiation factor into antibody-producing plasma cells. This revealed that it is a multifunctional cytokine that acts on a variety of cells. From the clinical viewpoint, it is ... ...

    Abstract Interleukin (IL)-6 cDNA was originally cloned as a terminal B cell differentiation factor into antibody-producing plasma cells. This revealed that it is a multifunctional cytokine that acts on a variety of cells. From the clinical viewpoint, it is especially important that IL-6 acts on hepatocytes to induce acute-phase reactants, including C-reactive protein, serum amyloid A protein, and fibrinogen, and to decrease serum albumin levels. Very recently, this cytokine has been found to enhance the synthesis of a peptide called hepcidin in the liver which regulates iron recycling, resulting in anemia due to hypofferemia. It has also been shown that IL-6 is responsible for various clinical symptoms, including the appearance of autoantibodies, fatigue, anemia, anorexia, fever, and increases in the erythrocyte sedimentation rate, all of which develop in patients with various chronic autoimmune inflammatory diseases. In practice, blocking the IL-6 signaling pathway with a recombinant humanized anti-IL-6 receptor antibody, tocilizumab (TCZ), has dramatically improved all the signs and symptoms of these patients. A study in mice demonstrated that IL-6 promotes the development of a new type of T-helper cells called Th17 cells that impact the pathogenesis of autoimmune diseases. This suggests that TCZ is not only an antiinflammatory agent but also might affect basic autoimmunity. In this review, recent advances in the immunobiology of interleukin-6 related to immune-mediated diseases are discussed.
    MeSH term(s) Animals ; Antibodies, Monoclonal/genetics ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/etiology ; Autoimmune Diseases/etiology ; Humans ; Interleukin-6/immunology ; Interleukin-6/physiology ; Mice ; Receptors, Interleukin-6/immunology ; Receptors, Interleukin-6/metabolism ; Recombinant Proteins/immunology ; Recombinant Proteins/therapeutic use ; Signal Transduction ; T-Lymphocytes, Helper-Inducer/classification ; T-Lymphocytes, Helper-Inducer/immunology
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antirheumatic Agents ; Interleukin-6 ; Receptors, Interleukin-6 ; Recombinant Proteins ; tocilizumab (I031V2H011)
    Language English
    Publishing date 2007-08-29
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 1150271-x
    ISSN 1347-5215 ; 0918-6158
    ISSN (online) 1347-5215
    ISSN 0918-6158
    DOI 10.1248/bpb.30.2001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The recombinant humanized anti-IL-6 receptor antibody tocilizumab, an innovative drug for the treatment of rheumatoid arthritis.

    Ohsugi, Yoshiyuki / Kishimoto, Tadamitsu

    Expert opinion on biological therapy

    2008  Volume 8, Issue 5, Page(s) 669–681

    Abstract: Background: IL-6 is a pro-inflammatory cytokine with multiple roles in the pathogenesis of rheumatoid arthritis (RA). Targeting IL-6 with the humanized anti IL-6 receptor antibody tocilizumab was effective in several placebo-controlled clinical studies ... ...

    Abstract Background: IL-6 is a pro-inflammatory cytokine with multiple roles in the pathogenesis of rheumatoid arthritis (RA). Targeting IL-6 with the humanized anti IL-6 receptor antibody tocilizumab was effective in several placebo-controlled clinical studies in RA.
    Objectives: To address how clinically efficacious blockade of IL-6 signalling with inteleukin-6 receptor antibody is in RA patients and what the potential mode of action explaining tocilizumab activity in RA treatment could be.
    Results/conclusion: IL-6 induces autoantibody-producing plasma cells and effector T cells and is implicated in the development of clinical signs and symptoms, including increased synthesis of acute phase reactants, fatigue, anaemia and anorexia. Its effects also included significant improvements in American College of Rheumatology (ACR)20, ACR50 and ACR70 values, as well as in health-related quality of life measures, compared with controls. Tocilizumab also prevents radiographic progression of joint damage. Tocilizumab is generally well tolerated and efficacious in patients refractive to conventional DMARD therapies.
    MeSH term(s) Adult ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/pharmacokinetics ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Arthritis, Rheumatoid/drug therapy ; Clinical Trials as Topic ; Drug Approval/legislation & jurisprudence ; Female ; Humans ; Japan ; Male ; Middle Aged ; Recombinant Proteins/adverse effects ; Recombinant Proteins/pharmacokinetics ; Recombinant Proteins/pharmacology ; Recombinant Proteins/therapeutic use ; United States ; United States Food and Drug Administration
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Recombinant Proteins ; tocilizumab (I031V2H011)
    Language English
    Publishing date 2008-01-31
    Publishing country England
    Document type Journal Article
    ZDB-ID 2052501-1
    ISSN 1744-7682 ; 1471-2598
    ISSN (online) 1744-7682
    ISSN 1471-2598
    DOI 10.1517/14712598.8.5.669
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis.

    Mihara, Masahiko / Ohsugi, Yoshiyuki / Kishimoto, Tadamitsu

    Open access rheumatology : research and reviews

    2011  Volume 3, Page(s) 19–29

    Abstract: Interleukin (IL)-6 has a variety of biological functions. For example, it stimulates the production of acute-phase reactants (C-reactive protein and serum amyloid A) and hepcidin which interferes with iron recycling and absorption, causing iron-deficient ...

    Abstract Interleukin (IL)-6 has a variety of biological functions. For example, it stimulates the production of acute-phase reactants (C-reactive protein and serum amyloid A) and hepcidin which interferes with iron recycling and absorption, causing iron-deficient anemia, and augments expression of vascular endothelial growth factor and receptor activator of nuclear factor-κB ligand in synovial cells, leading to neovascularization and osteoclast formation. IL-6 also acts on lymphocytes, not only on B cells to stimulate autoantibody production, but also on naïve T helper cells to promote T
    Language English
    Publishing date 2011-02-25
    Publishing country New Zealand
    Document type Review ; Journal Article
    ZDB-ID 2508169-X
    ISSN 1179-156X
    ISSN 1179-156X
    DOI 10.2147/OARRR.S17118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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