125 results on '"Takanori, Kitamura"'
Search Results
2. Jeffrey W. Pollard: a tribute
- Author
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Takanori Kitamura
- Subjects
Medicine ,Pathology ,RB1-214 - Published
- 2023
- Full Text
- View/download PDF
3. A fluorogenic probe for granzyme B enables in-biopsy evaluation and screening of response to anticancer immunotherapies
- Author
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Jamie I. Scott, Lorena Mendive-Tapia, Doireann Gordon, Nicole D. Barth, Emily J. Thompson, Zhiming Cheng, David Taggart, Takanori Kitamura, Alberto Bravo-Blas, Edward W. Roberts, Jordi Juarez-Jimenez, Julien Michel, Berber Piet, I. Jolanda de Vries, Martijn Verdoes, John Dawson, Neil O. Carragher, Richard A. O’ Connor, Ahsan R. Akram, Margaret Frame, Alan Serrels, and Marc Vendrell
- Subjects
Science - Abstract
Granzyme B is found in activated T cells and can be used as a marker of T cell activation. Here, the authors generate a fluorescent probe that can detect Granzyme B levels in tumours, and has the potential to be used as a biomarker of response to immunotherapy.
- Published
- 2022
- Full Text
- View/download PDF
4. Use of multi-color flow cytometry for canine immune cell characterization in cancer.
- Author
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Maciej Parys, Spela Bavcar, Richard J Mellanby, David Argyle, and Takanori Kitamura
- Subjects
Medicine ,Science - Abstract
Although immunotherapy is becoming a standard approach of human cancer treatment, only a small but critical fraction of patients responds to the therapy. It is therefore required to determine the sub-populations of patients who will respond to immunotherapies along with developing novel strategies to improve efficacy of anti-tumor immune reactions. Current development of novel immunotherapies relies heavily on mouse models of cancer. These models are important for better understanding of mechanisms behind tumor immune escape and investigation of novel strategies to overcome it. Nevertheless, the murine models do not necessarily represent the complexity of spontaneously occurring cancers in humans. Dogs spontaneously develop a wide range of cancer types with an intact immune system under similar environment and exposure to humans, which can serve as translational models in cancer immunotherapy research. To date though, there is still a relatively limited amount of information regarding immune cell profiles in canine cancers. One possible reason could be that there are hardly any established methods to isolate and simultaneously detect a range of immune cell types in neoplastic tissues. To date only a single manuscript describes characterization of immune cells in canine tumour tissues, concentrating solely on T-cells. Here we describe a protocol for multi-color flow cytometry to distinguish immune cell types in blood, lymph nodes, and neoplastic tissues from dogs with cancer. Our results demonstrate that a 9-color flow cytometry panel enables characterization of different cell subpopulations including myeloid cells. We also show that the panel allows detection of minor/aberrant subsets within a mixed population of cells in various neoplastic samples including blood, lymph node and solid tumors. To our knowledge, this is the first simultaneous immune cell detection panel applicable for solid tumors in dogs. This multi-color flow cytometry panel has the potential to inform future basic research focusing on immune cell functions in translational canine cancer models.
- Published
- 2023
- Full Text
- View/download PDF
5. Metastasis-associated macrophages constrain antitumor capability of natural killer cells in the metastatic site at least partially by membrane bound transforming growth factor β
- Author
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Demi Brownlie, Dahlia Doughty-Shenton, Daniel YH Soong, Colin Nixon, Neil O Carragher, Leo M Carlin, and Takanori Kitamura
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Metastatic breast cancer is a leading cause of cancer-related death in women worldwide. Infusion of natural killer (NK) cells is an emerging immunotherapy for such malignant tumors, although elimination of the immunosuppressive tumor environment is required to improve its efficacy. The effects of this “metastatic” tumor environment on NK cells, however, remain largely unknown. Previous studies, including our own, have demonstrated that metastasis-associated macrophages (MAMs) are one of the most abundant immune cell types in the metastatic tumor niche in mouse models of metastatic breast cancer. We thus investigated the effects of MAMs on antitumor functions of NK cells in the metastatic tumor microenvironment.Methods MAMs were isolated from the tumor-bearing lung of C57BL/6 mice intravenously injected with E0771-LG mouse mammary tumor cells. The effects of MAMs on NK cell cytotoxicity towards E0771-LG cells were evaluated in vitro by real-time fluorescence microscopy. The effects of MAM depletion on NK cell activation, maturation, and accumulation in the metastatic lung were evaluated by flow cytometry (CD69, CD11b, CD27) and in situ hybridization (Ncr1) using colony-stimulating factor 1 (CSF-1) receptor conditional knockout (Csf1r-cKO) mice. Finally, metastatic tumor loads in the chest region of mice were determined by bioluminescence imaging in order to evaluate the effect of MAM depletion on therapeutic efficacy of endogenous and adoptively transferred NK cells in suppressing metastatic tumor growth.Results MAMs isolated from the metastatic lung suppressed NK cell-induced tumor cell apoptosis in vitro via membrane-bound transforming growth factor β (TGF-β) dependent mechanisms. In the tumor-challenged mice, depletion of MAMs increased the percentage of activated (CD69+) and mature (CD11b+CD27–) NK cells and the number of Ncr1+ NK cells as well as NK cell-mediated tumor rejection in the metastatic site. Moreover, MAM depletion or TGF-β receptor antagonist treatment significantly enhanced the therapeutic efficacy of NK cell infusion in suppressing early metastatic tumor outgrowth.Conclusion This study demonstrates that MAMs are a main negative regulator of NK cell function within the metastatic tumor niche, and MAM targeting is an attractive strategy to improve NK cell-based immunotherapy for metastatic breast cancer.
- Published
- 2021
- Full Text
- View/download PDF
6. Does Everyday Conversation Contribute to Cognitive Functioning? A Comparison of Brain Activity During Task-Oriented and Life-Worldly Communication Using Near-Infrared Spectroscopy
- Author
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Yasuko Fukaya PhD, RN, Minato Kawaguchi PhD, and Takanori Kitamura
- Subjects
Geriatrics ,RC952-954.6 - Abstract
This study aimed to explore differences in frontal lobe brain activity associated with two types of communication: task-oriented and life-worldly , the latter of which largely overlaps with everyday conversation. Using near-infrared spectroscopy, we explored differences by comparing oxygenated hemoglobin concentrations associated with periods of rest and conversation in two experimental groups comprising older and younger adults. Artifacts were removed from the signals using discrete wavelet transforms. Paired t -tests were used to compare the resulting data for the two types. The results showed that oxygenated hemoglobin levels during life-worldly communication were significantly higher than at baseline or during task-oriented communication, particularly for the older adult group. In addition, during life-worldly communication, relatively high levels of brain activity were found in the upper part of the Broca area and in the premotor cortex. These results, which suggest that life-worldly communication generates more activity in the frontal lobe, could potentially contribute to improving how caregivers communicate with older patients/residents in hospitals and nursing homes.
- Published
- 2020
- Full Text
- View/download PDF
7. Effect of Arm Length on Tensile Strength of Resistance Spot Welded L-type Joints
- Author
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Takanori KITAMURA, Tetsuya AKIYAMA, Hibiki HIRAYAMA, Shintaro HAMASAKI, Ken CHIKANO, and Daisuke KAWANO
- Subjects
Mechanics of Materials ,Mechanical Engineering ,Metals and Alloys ,Surfaces, Coatings and Films - Published
- 2023
8. Effect of Plate Deformation Around the Nugget during Tensile Test on Tensile Shear Strength of Resistance Spot Welded Lap Joints
- Author
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Takanori KITAMURA, Tetsuya AKIYAMA, Mitsuhiro IMAMURA, Tomoya KAWABATA, Atsuro UEMURA, Chinatsu MIHARA, and Koki IWATANI
- Subjects
Mechanics of Materials ,Mechanical Engineering ,Metals and Alloys ,Surfaces, Coatings and Films - Published
- 2023
9. Targeting Macrophage-Recruiting Chemokines as a Novel Therapeutic Strategy to Prevent the Progression of Solid Tumors
- Author
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David Argyle and Takanori Kitamura
- Subjects
cancer ,metastasis ,tumor-associated macrophage ,chemokine ,antagonist ,immunotherapy ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Solid tumors are initiated by genetic mutations in non-hematopoietic cells and progress into invasive malignant tumors. This tumor progression often culminates in metastatic disease that is largely refractory to current therapeutic modalities and thus dramatically reduces survival of tumor patients. As solid tumors account for more than 80% of cancer-related deaths, it is necessary to develop novel therapeutic strategies to treat the diseases. An attractive strategy is to target macrophages in both primary tumors [known as tumor-associated macrophages (TAMs)] and metastatic tumors [called metastasis-associated macrophages (MAMs)]. TAMs and MAMs are abundant in most solid tumors and can promote tumor metastasis. Several studies in various models of solid tumors suggest that the accumulation of TAMs, MAMs, and their progenitor cells is regulated by chemokine ligands released by tumor and stromal cells. Consequently, these macrophage-recruiting chemokines could be potential therapeutic targets to prevent malignant tumor development through disruption of the accumulation of pro-metastatic macrophages. This review will discuss the role of chemokine ligands and their receptors in TAM and MAM accumulation in primary and secondary tumor sites, and finally discuss the therapeutic potential of inhibitors against these macrophage-recruiting chemokines.
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- 2018
- Full Text
- View/download PDF
10. Figure S6 from Mammary Tumor Cells with High Metastatic Potential Are Hypersensitive to Macrophage-Derived HGF
- Author
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Jeffrey W. Pollard, Neil Carragher, Dahlia Doughty-Shenton, Jiufeng Li, Nicolle Kippen, Gaël Sugano, Daniel Y.H. Soong, Demi Brownlie, Yu Kato, and Takanori Kitamura
- Abstract
Detection and depletion of NK cells in mice with metastatic tumors.
- Published
- 2023
11. Data from Mammary Tumor Cells with High Metastatic Potential Are Hypersensitive to Macrophage-Derived HGF
- Author
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Jeffrey W. Pollard, Neil Carragher, Dahlia Doughty-Shenton, Jiufeng Li, Nicolle Kippen, Gaël Sugano, Daniel Y.H. Soong, Demi Brownlie, Yu Kato, and Takanori Kitamura
- Abstract
Metastasis-associated macrophages (MAM) promote persistent growth of breast cancer cells at the metastatic site and are, thus, an attractive therapeutic target to treat breast cancer metastasis, a leading cause of cancer-related death in women. However, the precise mechanisms behind MAM-mediated metastatic tumor outgrowth have not been fully elucidated. Using mouse models of metastatic breast cancer, we showed that MAMs uniquely expressed hepatocyte growth factor (HGF) in metastatic tumors. We also demonstrated that a selected population of cancer cells with high metastatic potential (cancer cells that can establish metastatic tumors in mice with higher number and incidence than parental cells) had higher expression of HGF receptor, MNNG HOS transforming gene (MET), and were more responsive to HGF released from macrophages compared with the parental cells. Blockade of MET signaling in cancer cells suppressed metastatic tumor expansion, in part, through activation of natural killer cells. Results from this study suggest an approach to prevent life-threatening metastatic tumor formation using blockade of MAM-induced MET signal activation in metastatic cancer cells.
- Published
- 2023
12. Effect of Combined Use of Brazing or Soldering around the Nugget on Tensile Shear Strength of Resistance Spot Welded Lap Joint.
- Author
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Takanori Kitamura, Tetsuya Akiyama, Atsuro Uemura, and Chinatsu Mihara
- Subjects
SPOT welding ,BRAZING ,SHEAR strength ,SOLDER & soldering ,BRAZING alloys ,TENSILE strength ,ADHESIVE joints ,LAP joints - Abstract
Resistance spot welding is used in the assembly of automobile bodies. The use of high tensile strength steel plates in automobile bodies is expanding, and there is a need to develop a welding process that improves the joint strength per resistance spot weld point. To improve the joint strength per resistance spot weld, resistance spot welding can be combined with other joining methods, such as the WeldBond method. As an additional joining method around the nugget, other than using adhesives as in the WeldBond method, brazing can be used to obtain a strong joint without melting the base metal. In this paper, it was proposed that the joint strength can be enhanced by using resistance spot welding and brazing or soldering based on the rule of mixture. And, based on this concept, effect of additional joint around a nugget, such as brazing or soldering, on rotational deformation of joint part and tensile shear strength of resistance spot welded lap joint was examined. First, three types of lap joint specimens that were using only resistance spot welding, using only brazing and using both joining methods (called WeldBraze) were prepared. A high-strength steel sheet HT590 with a thickness of 1.0mm was used. For the brazing filler metal, lead-free solder (composition: Sn--0.3Ag--0.7Cu) was used. Next, tensile shear tests were conducted using all the test specimens. In general, rotational deformation of the joint occurs due to the offset of the load axis for the tensile shear test of the lap joint. It is necessary to investigate the effect of the rotational deformation on joint strength. Therefore, a tensile shear test was performed using a test specimen in which the welded joint part was sandwiched between two steel blocks to suppress rotational deformation. As a result, it was confirmed that the new joining method using both brazing and resistance spot welding increased the joint strength and the amount of displacement up to fracture as compared with the case of brazing or resistance spot welding only. So, it was clarified that the factor of the strengthening of the joint was the rule of mixture, and the increase of displacement up to the fracture was affected by the suppression of rotational deformation. In conclusion, it was found that the joining method using both brazing and resistance spot welding was effective in improving the joint strength. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
13. Tumour-associated macrophages as a potential target to improve natural killer cell-based immunotherapies.
- Author
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Takanori Kitamura
- Published
- 2023
- Full Text
- View/download PDF
14. Targeting Tumor-Associated Macrophages as a Potential Strategy to Enhance the Response to Immune Checkpoint Inhibitors
- Author
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Luca Cassetta and Takanori Kitamura
- Subjects
tumor microenvironment ,immunotherapy ,checkpoint inhibitor ,CD8+ T cell ,macrophage ,TAM ,Biology (General) ,QH301-705.5 - Abstract
Inhibition of immune checkpoint pathways in CD8+ T cell is a promising therapeutic strategy for the treatment of solid tumors that has shown significant anti-tumor effects and is now approved by the FDA to treat patients with melanoma and lung cancer. However the response to this therapy is limited to a certain fraction of patients and tumor types, for reasons still unknown. To ensure success of this treatment, CD8+ T cells, the main target of the checkpoint inhibitors, should exert full cytotoxicity against tumor cells. However recent studies show that tumor-associated macrophages (TAM) can impede this process by different mechanisms. In this mini-review we will summarize recent studies showing the effect of TAM targeting on immune checkpoint inhibitors efficacy. We will also discuss on the limitations of the current strategies as well on the future scientific challenges for the progress of the tumor immunology field.
- Published
- 2018
- Full Text
- View/download PDF
15. Monocytes Differentiate to Immune Suppressive Precursors of Metastasis-Associated Macrophages in Mouse Models of Metastatic Breast Cancer
- Author
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Takanori Kitamura, Dahlia Doughty-Shenton, Luca Cassetta, Stamatina Fragkogianni, Demi Brownlie, Yu Kato, Neil Carragher, and Jeffrey W. Pollard
- Subjects
breast cancer ,metastasis ,macrophage ,myeloid-derived suppressor cell ,immune suppression ,CD8+ T cell ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Metastasis-associated macrophages (MAMs) play pivotal roles in breast cancer metastasis by promoting extravasation and survival of metastasizing cancer cells. In a metastatic breast cancer mouse model, we previously reported that circulating classical monocytes (C-MOs) preferentially migrated into the tumor-challenged lung where they differentiated into MAMs. However, the fate and characteristics of C-MOs in the metastatic site has not been defined. In this study, we identified that adoptively transferred C-MOs (F4/80lowCD11b+Ly6C+) differentiated into a distinct myeloid cell population that is characterized as F4/80highCD11bhighLy6Chigh and gives rise to MAMs (F4/80lowCD11bhighLy6Clow) within 18 h after migration into the metastatic lung. In mouse models of breast cancer, the CD11bhighLy6Chigh MAM precursor cells (MAMPCs) were commonly found in the metastatic lung, and their accumulation was increased during metastatic tumor growth. The morphology and gene expression profile of MAMPCs were distinct from C-MOs and had greater similarity to MAMs. For example MAMPCs expressed mature macrophage markers such as CD14, CD36, CD64, and CD206 at comparable levels with MAMs, suggesting that MAMPCs have committed to a macrophage lineage in the tumor microenvironment. MAMPCs also expressed higher levels of Arg1, Hmox1, and Stab1 than C-MOs to a comparable level to MAMs. Expression of these MAM-associated genes in MAMPCs was reduced by genetic deletion of colony-stimulating factor 1 receptor (CSF1R). On the other hand, transient CSF1R blockade did not reduce the number of MAMPCs in the metastatic site, suggesting that CSF1 signaling is active in MAMPCs but is not required for their accumulation. Functionally MAMPCs suppressed the cytotoxicity of activated CD8+ T cells in vitro in part through superoxide production. Overall, our results indicate that immediately following migration into the metastatic tumors C-MOs differentiate into immunosuppressive cells that have characteristics of monocytic myeloid-derived suppressor cell phenotype and might be targeted to enhance efficacy of immunotherapy for metastatic breast cancer.
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- 2018
- Full Text
- View/download PDF
16. Effect of Combined Use of Brazing or Soldering around the Nugget on Tensile Shear Strength of Resistance Spot Welded Lap Joint
- Author
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Tetsuya Akiyama, Atsuro Uemura, Takanori Kitamura, and Chinatsu Mihara
- Subjects
Materials science ,Combined use ,Metals and Alloys ,Welding ,Condensed Matter Physics ,Tensile shear ,law.invention ,Lap joint ,Mechanics of Materials ,law ,Soldering ,Materials Chemistry ,Brazing ,Composite material - Published
- 2021
17. Effect of Heating Order on Interference between Deformations by Curved Line Heating in Laser Forming
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Tetsuya Akiyama, Yuta Maeda, Ryosuke Izutsu, and Takanori Kitamura
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Materials science ,business.industry ,Metals and Alloys ,Line heating ,Condensed Matter Physics ,Laser ,law.invention ,Optics ,Interference (communication) ,Mechanics of Materials ,law ,Order (business) ,Materials Chemistry ,business - Published
- 2021
18. Enzyme-Activatable Chemokine Conjugates for In Vivo Targeting of Tumor-Associated Macrophages
- Author
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Nicole D. Barth, Floris J. Van Dalen, Utsa Karmakar, Marco Bertolini, Lorena Mendive‐Tapia, Takanori Kitamura, Martijn Verdoes, and Marc Vendrell
- Subjects
General Medicine ,General Chemistry ,Cathepsins ,Catalysis ,prodrugs ,Tumor-Associated Macrophages ,Tumor Microenvironment ,cancer ,Receptors, Chemokine ,Cysteine ,Chemokines ,cathepsins ,probes ,Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] ,CCL2 - Abstract
Contains fulltext : 287053.pdf (Publisher’s version ) (Open Access) Increased levels of tumor-associated macrophages (TAMs) are indicators of poor prognosis in most cancers. Although antibodies and small molecules blocking the recruitment of macrophages to tumors are under evaluation as anticancer therapies, these strategies are not specific for macrophage subpopulations. Herein we report the first enzyme-activatable chemokine conjugates for effective targeting of defined macrophage subsets in live tumors. Our constructs exploit the high expression of chemokine receptors (e.g., CCR2) and the activity of cysteine cathepsins in TAMs to target these cells selectively over other macrophages and immune cells (e.g., neutrophils, T cells, B cells). Furthermore, we demonstrate that cathepsin-activatable chemokines are compatible with both fluorescent and therapeutic cargos, opening new avenues in the design of targeted theranostic probes for immune cells in the tumor microenvironment.
- Published
- 2022
19. Mammary Tumor Cells with High Metastatic Potential Are Hypersensitive to Macrophage-Derived HGF
- Author
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Jeffrey W. Pollard, Yu Kato, Gaël Sugano, Dahlia Doughty-Shenton, Demi Brownlie, Takanori Kitamura, Neil O. Carragher, Jiufeng Li, Daniel Y.H. Soong, and Nicolle Kippen
- Subjects
0301 basic medicine ,Cancer Research ,Lung Neoplasms ,Immunology ,Population ,Mice, Transgenic ,Mice, SCID ,Article ,03 medical and health sciences ,0302 clinical medicine ,Mice, Inbred NOD ,Cell Line, Tumor ,Animals ,Humans ,Macrophage ,Medicine ,education ,Lung ,Mammary tumor ,education.field_of_study ,Hepatocyte Growth Factor ,business.industry ,Macrophages ,Mammary Neoplasms, Experimental ,Proto-Oncogene Proteins c-met ,medicine.disease ,Metastatic breast cancer ,3. Good health ,Killer Cells, Natural ,Mice, Inbred C57BL ,030104 developmental biology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Experimental pathology ,Female ,Hepatocyte growth factor ,business ,medicine.drug - Abstract
Metastasis-associated macrophages (MAM) promote persistent growth of breast cancer cells at the metastatic site and are, thus, an attractive therapeutic target to treat breast cancer metastasis, a leading cause of cancer-related death in women. However, the precise mechanisms behind MAM-mediated metastatic tumor outgrowth have not been fully elucidated. Using mouse models of metastatic breast cancer, we showed that MAMs uniquely expressed hepatocyte growth factor (HGF) in metastatic tumors. We also demonstrated that a selected population of cancer cells with high metastatic potential (cancer cells that can establish metastatic tumors in mice with higher number and incidence than parental cells) had higher expression of HGF receptor, MNNG HOS transforming gene (MET), and were more responsive to HGF released from macrophages compared with the parental cells. Blockade of MET signaling in cancer cells suppressed metastatic tumor expansion, in part, through activation of natural killer cells. Results from this study suggest an approach to prevent life-threatening metastatic tumor formation using blockade of MAM-induced MET signal activation in metastatic cancer cells.
- Published
- 2019
20. A Fluorescent Activatable AND‐Gate Chemokine CCL2 Enables In Vivo Detection of Metastasis‐Associated Macrophages
- Author
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Emily J. Thompson, Antonio Fernandez, Jeffrey W. Pollard, Takanori Kitamura, and Marc Vendrell
- Subjects
Chemokine ,Lung Neoplasms ,Receptors, CCR2 ,Apoptosis ,Breast Neoplasms ,CCL2 ,010402 general chemistry ,01 natural sciences ,Catalysis ,Metastasis ,immunology ,Mice ,Immune system ,In vivo ,fluorophores ,Tumor Cells, Cultured ,medicine ,molecular logic ,Animals ,Humans ,Cell Proliferation ,Fluorescent Dyes ,Mice, Knockout ,biology ,Tumour Imaging ,Chemistry ,010405 organic chemistry ,Communication ,Macrophages ,imaging ,General Chemistry ,General Medicine ,medicine.disease ,Xenograft Model Antitumor Assays ,Fluorescence ,Communications ,Molecular Imaging ,Cell biology ,0104 chemical sciences ,3. Good health ,Mice, Inbred C57BL ,Spectrometry, Fluorescence ,biology.protein ,Female ,tumour microenvironment ,Chemical design ,Intracellular - Abstract
We report the novel chemical design of fluorescent activatable chemokines as highly specific functional probes for imaging subpopulations of immune cells in live tumours. Activatable chemokines behave as AND‐gates since they emit only after receptor binding and intracellular activation, showing enhanced selectivity over existing agents. We have applied this strategy to produce mCCL2‐MAF as the first probe for in vivo detection of metastasis‐associated macrophages in a preclinical model of lung metastasis. This strategy will accelerate the preparation of new chemokine‐based probes for imaging immune cell function in tumours., Live show: Fluorescent activatable chemokines have been designed as the first chemical probes for in vivo detection of tumour‐associated macrophages in lung metastasis. Activatable chemokines behave as AND gates since they emit only after receptor binding and intracellular activation, thereby showing enhanced selectivity over existing agents.
- Published
- 2019
21. Multicolour flow cytometry protocol for dogs v1
- Author
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Takanori Kitamura
- Abstract
Although immunotherapy is becoming a standard approach of human cancer treatment, only a minor fraction of patients responds to the therapy. It is therefore required to determine the sub-populations of patients who will respond to immunotherapies along with developing novel strategies to improve efficacy of anti-tumor immune reactions. Development of novel immunotherapies is currently heavily relying on mouse models of cancer. These models are important for better understanding of mechanisms behind tumor immune escape and investigation of novel strategies to overcome it. Nevertheless, the murine models do not necessarily represent the complexity of spontaneously occurring cancers in humans. Dogs spontaneously develop a wide range of cancer types with an intact immune system under similar environment and exposure to humans, which can serve as translational models in cancer immunotherapy research. To date though, there is still relatively limited amount of information regarding immune cell profiles in canine cancers. One possible reason could be the lack of established method to isolate and simultaneously detect different immune cell types in neoplastic tissues. Here we describe a protocol for multi-color flow cytometry to distinguish immune cell types in blood, lymph nodes, and neoplastic tissues from dogs with cancer. Our results demonstrate that a 9-color flow cytometry panel enables to characterize different cell subpopulations including myeloid cells. We also show that the panel allows to detect minor/aberrant subsets within a mixed population of cells in various neoplastic samples including blood, lymph node and solid tumors. To our knowledge, this is the first simultaneous immune cell detection panel applicable for solid tumors in dogs. This multi-color flow cytometry panel has the potential to inform future basic research focusing on immune cell functions in translational canine cancer models.
- Published
- 2021
22. Metastasis-associated macrophages constrain antitumor capability of natural killer cells in the metastatic site at least partially by membrane bound transforming growth factor β
- Author
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Leo M. Carlin, Dahlia Doughty-Shenton, Takanori Kitamura, Demi Brownlie, Neil O. Carragher, Colin Nixon, and Daniel Yh Soong
- Subjects
Cancer Research ,Lung Neoplasms ,medicine.medical_treatment ,Immunology ,Cell ,Breast Neoplasms ,Metastasis ,killer cells ,Gene Knockout Techniques ,Mice ,Immune system ,Transforming Growth Factor beta ,Tumor-Associated Macrophages ,medicine ,Animals ,Antigens, Ly ,tumor microenvironment ,Immunology and Allergy ,RC254-282 ,natural ,Pharmacology ,Tumor microenvironment ,Mammary tumor ,Immune Cell Therapies and Immune Cell Engineering ,Natural Cytotoxicity Triggering Receptor 1 ,Chemistry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immunotherapy ,medicine.disease ,Adoptive Transfer ,Metastatic breast cancer ,macrophages ,Killer Cells, Natural ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Oncology ,Receptors, Granulocyte-Macrophage Colony-Stimulating Factor ,Cancer research ,Molecular Medicine ,Female ,immunotherapy ,Neoplasm Transplantation ,Transforming growth factor - Abstract
BackgroundMetastatic breast cancer is a leading cause of cancer-related death in women worldwide. Infusion of natural killer (NK) cells is an emerging immunotherapy for such malignant tumors, although elimination of the immunosuppressive tumor environment is required to improve its efficacy. The effects of this “metastatic” tumor environment on NK cells, however, remain largely unknown. Previous studies, including our own, have demonstrated that metastasis-associated macrophages (MAMs) are one of the most abundant immune cell types in the metastatic tumor niche in mouse models of metastatic breast cancer. We thus investigated the effects of MAMs on antitumor functions of NK cells in the metastatic tumor microenvironment.MethodsMAMs were isolated from the tumor-bearing lung of C57BL/6 mice intravenously injected with E0771-LG mouse mammary tumor cells. The effects of MAMs on NK cell cytotoxicity towards E0771-LG cells were evaluated in vitro by real-time fluorescence microscopy. The effects of MAM depletion on NK cell activation, maturation, and accumulation in the metastatic lung were evaluated by flow cytometry (CD69, CD11b, CD27) and in situ hybridization (Ncr1) using colony-stimulating factor 1 (CSF-1) receptor conditional knockout (Csf1r-cKO) mice. Finally, metastatic tumor loads in the chest region of mice were determined by bioluminescence imaging in order to evaluate the effect of MAM depletion on therapeutic efficacy of endogenous and adoptively transferred NK cells in suppressing metastatic tumor growth.ResultsMAMs isolated from the metastatic lung suppressed NK cell-induced tumor cell apoptosis in vitro via membrane-bound transforming growth factor β (TGF-β) dependent mechanisms. In the tumor-challenged mice, depletion of MAMs increased the percentage of activated (CD69+) and mature (CD11b+CD27–) NK cells and the number of Ncr1+ NK cells as well as NK cell-mediated tumor rejection in the metastatic site. Moreover, MAM depletion or TGF-β receptor antagonist treatment significantly enhanced the therapeutic efficacy of NK cell infusion in suppressing early metastatic tumor outgrowth.ConclusionThis study demonstrates that MAMs are a main negative regulator of NK cell function within the metastatic tumor niche, and MAM targeting is an attractive strategy to improve NK cell-based immunotherapy for metastatic breast cancer.
- Published
- 2021
23. Does Everyday Conversation Contribute to Cognitive Functioning? A Comparison of Brain Activity During Task-Oriented and Life-Worldly Communication Using Near-Infrared Spectroscopy
- Author
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Minato Kawaguchi, Yasuko Fukaya, and Takanori Kitamura
- Subjects
medicine.medical_specialty ,oxygenated hemoglobin ,Brain activity and meditation ,communication ,near-infrared spectroscopy ,media_common.quotation_subject ,Audiology ,lcsh:Geriatrics ,frontal lobe ,Article ,Premotor cortex ,lcsh:RC952-954.6 ,medicine.anatomical_structure ,Older patients ,Frontal lobe ,Younger adults ,medicine ,Task oriented ,Conversation ,Cognitive skill ,Geriatrics and Gerontology ,Psychology ,older adults ,media_common - Abstract
This study aimed to explore differences in frontal lobe brain activity associated with two types of communication: task-oriented and life-worldly, the latter of which largely overlaps with everyday conversation. Using near-infrared spectroscopy, we explored differences by comparing oxygenated hemoglobin concentrations associated with periods of rest and conversation in two experimental groups comprising older and younger adults. Artifacts were removed from the signals using discrete wavelet transforms. Paired t-tests were used to compare the resulting data for the two types. The results showed that oxygenated hemoglobin levels during life-worldly communication were significantly higher than at baseline or during task-oriented communication, particularly for the older adult group. In addition, during life-worldly communication, relatively high levels of brain activity were found in the upper part of the Broca area and in the premotor cortex. These results, which suggest that life-worldly communication generates more activity in the frontal lobe, could potentially contribute to improving how caregivers communicate with older patients/residents in hospitals and nursing homes.
- Published
- 2020
24. Mouse Classical and Non-Classical Monocytes Express Comparable Levels of Chemokine Receptor CX3CR1
- Author
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van der Akker E, Luca Cassetta, Matilionyte G, Jeffrey W. Pollard, Takanori Kitamura, Kippen N, Stamatina Fragkogianni, and Heideveld E
- Subjects
0303 health sciences ,Messenger RNA ,CCR2 ,Wild type ,Biology ,Molecular biology ,03 medical and health sciences ,Chemokine receptor ,0302 clinical medicine ,medicine.anatomical_structure ,CX3CR1 ,medicine ,biology.protein ,Bone marrow ,Antibody ,Receptor ,030304 developmental biology ,030215 immunology - Abstract
Human and mouse monocytes are divided into two subpopulations, classical (C-Mo) and non-classical (NC-Mo) monocytes. CC-chemokine receptor 2 (CCR2) and CX3C-chemokine receptor 1 (CX3CR1) are common features of monocyte subsets between humans and mice, i.e., C-Mo and NC-Mo are characterized as CCR2highCX3CR1low and CCR2lowCX3CR1high. Since many studies utilize mouse models to investigate roles of monocytes in human diseases, it is important to understand the similarities and differences between human and mouse monocytic subsets. In this study, we show that the expression of Cx3cr1 mRNA and CX3CR1 cell surface protein are different between circulating monocytic subsets in human but not in mice. We analyzed monocyte subsets in the blood using wild type C57BL/6 and Cx3cr1-GFP knock-in (Cx3cr1GFP/+) reporter mice. We observed higher Cx3cr1 promoter activity indicated by GFP expression in NC-Mo compared to C-Mo. However, there were no differences between the subsets in CX3CR1 mRNA nor surface protein expression determined by anti-CX3CR1 antibody or binding of fluorophore-conjugated ligand. However in the bone marrow of Cx3cr1GFP/+ mice, CX3CR1 expression was higher in NC-Mo compared to C-Mo, suggesting that mouse NC-Mo express higher level of CX3CR1 than C-Mo in the bone but this difference disappears in the blood. In contrast, human NC-Mo differentially expressed CX3CR1 compared to C-Mo in both blood and bone marrow. Given these findings, the discrepancy between promoter activity and protein levels should be considered when the roles of CX3CR1 are investigated in mouse models of human diseases.Summary sentenceIn this study, we show that the expression of Cx3cr1 mRNA is different between circulating monocytic subsets in human but not in mice.
- Published
- 2020
- Full Text
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25. Generation of mouse bone marrow-derived macrophages using tumor coculture assays to mimic the tumor microenvironment
- Author
-
Esra, Güç, Demi, Brownlie, Carolina, Rodriguez-Tirado, Takanori, Kitamura, and Jeffrey W, Pollard
- Subjects
Mice ,Cell Line, Tumor ,Macrophages ,Neoplasms ,Tumor Microenvironment ,Animals ,Bone Marrow Cells ,Cell Differentiation ,Cell Separation ,Flow Cytometry ,Cells, Cultured ,Coculture Techniques - Abstract
Macrophages are one of the key immune cells within the tumor microenvironment that encourage the growth of tumors at the primary site as well as contributing to all parts of the metastatic cascade. Although it is possible to isolate macrophages directly from the tumor, this can be a laborious process and due to their plasticity, it is not possible to maintain their in vivo phenotype in vitro. For this reason, differentiating macrophages from bone marrow is an attractive alternative. Here we present robust methods to study in vitro derived macrophages including (i) the isolation and generation of macrophages from bone marrow, (ii) differentiation/characterization of classically activated, alternatively activated and tumor-conditioned macrophages, as well as (iii) in vitro co-culturing assays for tumor cell-macrophage interaction/transmigration.
- Published
- 2020
26. Influence of Order on Curved Surface Shape in Laser Forming with Multiple Parallel Heating
- Author
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Daisuke Kishi, Takanori Kitamura, Kengo Higashi, Hiroaki Kuramoto, and Tetsuya Akiyama
- Subjects
010302 applied physics ,Materials science ,business.industry ,Metals and Alloys ,02 engineering and technology ,Condensed Matter Physics ,Laser ,Surface shape ,01 natural sciences ,020501 mining & metallurgy ,law.invention ,Optics ,0205 materials engineering ,Mechanics of Materials ,law ,Order (business) ,0103 physical sciences ,Materials Chemistry ,business - Published
- 2018
27. Dependence of Load Angle on Static Strength of Resistance Spot Welded Lap Joint under Combined Load Test
- Author
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Tetsushi Ono, Takanori Kitamura, and Tetsuya Akiyama
- Subjects
Materials science ,Mechanical Engineering ,Static strength ,Welding ,Condensed Matter Physics ,computer.software_genre ,law.invention ,Load testing ,Lap joint ,Mechanics of Materials ,law ,General Materials Science ,Composite material ,computer ,Spot welding ,Load angle - Published
- 2018
28. Dependence of Load Angle on Static Strength of Resistance Spot Welded Lap Joint in Combined Load Test
- Author
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Tetsuya Akiyama, Takanori Kitamura, and Tetsushi Ono
- Subjects
010302 applied physics ,0205 materials engineering ,Mechanics of Materials ,0103 physical sciences ,Materials Chemistry ,Metals and Alloys ,02 engineering and technology ,Condensed Matter Physics ,01 natural sciences ,020501 mining & metallurgy - Published
- 2018
29. Guideline of Innovative Structural Design
- Author
-
Takanori Kitamura
- Subjects
Materials science ,Design evaluation ,business.industry ,Mechanical Engineering ,Metals and Alloys ,Structural engineering ,Welding ,Guideline ,Surfaces, Coatings and Films ,law.invention ,Mechanics of Materials ,law ,business ,Joint (geology) - Published
- 2018
30. Structural Evolution Induced by Interfacial Lattice Mismatch in Self-Organized YBa2Cu3O7−δ Nanocomposite Film
- Author
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Kaname Matsumoto, Satoru Yoshioka, Takanori Kitamura, Tomoya Horide, and Fumitake Kametani
- Subjects
Range (particle radiation) ,Nanocomposite ,Materials science ,Condensed matter physics ,General Engineering ,General Physics and Astronomy ,chemistry.chemical_element ,02 engineering and technology ,021001 nanoscience & nanotechnology ,01 natural sciences ,Atomic units ,Oxygen ,Crystallography ,Matrix (mathematics) ,chemistry ,Distortion ,0103 physical sciences ,General Materials Science ,Nanorod ,010306 general physics ,0210 nano-technology ,Perovskite (structure) - Abstract
Intriguing properties of self-organized nanocomposites of perovskite oxides are usually derived from the complex interface of constituent material phases. A sophisticated control of such a system is required for a broad range of energy and device applications, which demand a comprehensive understanding of the interface at the atomic scale. Here, we visualized and theoretically modeled the highly elastically strained nanorod, the interface region with misfit dislocations and heterointerface distortion, and the matrix with strain-induced oxygen vacancies in the self-organized YBa2Cu3O7−δ nanocomposite films with Ba perovskite nanorods. Large misfit strain was elastically accommodated in the nanocomposites, but since the elastic strain was mainly accommodated by the nanorods, the concentration of strain-induced oxygen vacancies was small enough for the matrix to keep high critical temperature (>85 K). The interfacial bonding distorted the atomic structure of YBa2Cu3O7−δ, but the thickness of distortion was l...
- Published
- 2017
31. Real Time Detection of In Vitro Tumor Cell Apoptosis Induced by CD8+ T Cells to Study Immune Suppressive Functions of Tumor-infiltrating Myeloid Cells
- Author
-
Takanori, Kitamura, Dahlia, Doughty-Shenton, Jeffrey W, Pollard, and Neil O, Carragher
- Subjects
Mice ,Tumor Microenvironment ,Animals ,Humans ,Apoptosis ,Myeloid Cells ,CD8-Positive T-Lymphocytes - Abstract
Potentiation of the tumor-killing ability of CD8
- Published
- 2019
32. Real Time Detection of In Vitro Tumor Cell Apoptosis Induced by CD8+ T Cells to Study Immune Suppressive Functions of Tumor-infiltrating Myeloid Cells
- Author
-
Neil O. Carragher, Jeffrey W. Pollard, Dahlia Doughty-Shenton, and Takanori Kitamura
- Subjects
General Immunology and Microbiology ,General Chemical Engineering ,General Neuroscience ,General Biochemistry, Genetics and Molecular Biology - Published
- 2019
33. Development of Life-Worldly Communication Scale for Older Persons: A Pilot Study
- Author
-
Yasuko Fukaya, Minato Kawaguchi, Takanori Kitamura, and Ritsuko Wakabayashi
- Subjects
Scale (ratio) ,Applied psychology ,Psychology ,Pilot Study, Scale Development, Life-Worldly Communication, Reliability, Validity, Home Care, Nursing Home - Abstract
Objectives: Our prior study revealed that the speech duration of older people in long-term care facilities in Japan is four minutes in one day, owing to the lack of “life-worldly communications.” This study is a pilot study for the development and validation of the Life-Worldly Communication Scale (LWCS) that can efficiently measure the life-worldly communication duration of older people. Methods: The subjects were 65 individuals, 65 years of age or older, who were chosen among people living in long-term care facilities and in home care in Japan. The items of LWCS were generated from related literature. The content validity of LWCS was examined from the content validity ratio. Construct validity of LWCS was verified by exploratory and confirmatory factor analyses. Convergent or discriminant validity was examined from the relation between LWCS and the life-worldly communication time or depression level. Reliability was examined by inspecting internal consistency and stability. Results: The LWCS proved satisfactory in the goodness-of-fit index (GFI = .92, NFI = .91, CFI = .99, RMSEA =.03) by confirmatory factor analysis. Convergent validity of LWCS was supported by a significant correlation between LWCS and the life-worldly communication time (r = .62, P
- Published
- 2019
- Full Text
- View/download PDF
34. Strengthening of cross tension strength of spot-welded lap joints by increasing the opening angle on the nugget edge
- Author
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Tetsuya Akiyama, Takanori Kitamura, and Tomohito Tateishi
- Subjects
Materials science ,Tension (physics) ,business.industry ,Mechanical Engineering ,Bent molecular geometry ,Metals and Alloys ,Bending ,Welding ,Structural engineering ,Edge (geometry) ,law.invention ,Lap joint ,Mechanics of Materials ,law ,business ,Spot welding - Abstract
This paper deals with the strengthening of spot-welded lap joints by increasing the opening angle on the nugget edge. Based on the equation proposed by past researchers to predict the strength, the factor necessary for the strengthening was extracted. And, based on this factor, the strengthening of spot-welded lap joints was examined. First of all, in order to increase the opening angle on the nugget edge, the vicinity of the nugget edge was bent with a bending machine. Next, cross tension strength (CTS) tests were conducted into the spot-welded lap joints with various opening angles on the nugget edge. Finally, the relationship between CTS and the opening angels of the nugget edge was clarified. As a result, by increasing the opening angles on the nugget edge, we found that the CTS could be improved by 20%.
- Published
- 2016
35. Application of Paper Processing on Carbon, Jute and Paper Fiber Reinforced Plastic
- Author
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Suguru Teramura, Kanta Ito, Takanori Kitamura, Zhiyuan Zhang, Mitsunori Suda, Keisuke Kitai, and Hiroyuki Hamada
- Subjects
Paperboard ,Materials science ,Scanning electron microscope ,Recycled paperboard ,Composite number ,0211 other engineering and technologies ,Izod impact strength test ,Carbo fiber ,02 engineering and technology ,Bending ,Fibre-reinforced plastic ,021001 nanoscience & nanotechnology ,Hybrid fabric ,Energy(all) ,Jute fiber ,visual_art ,021105 building & construction ,Fracture (geology) ,visual_art.visual_art_medium ,Composite material ,0210 nano-technology ,FRP ,Tensile testing - Abstract
In this study, the chopped carbon fibers and jute fibers were used to fabricate hybrid paperboard. The paper making process was used. Combined with unsaturated polyester resin, paperboard fiber reinforced plastic (FRP), carbon hybrid FRP and jute hybrid FRP were fabricated and the mechanical property included tensile test, bending test and Izod impact test were carried out to compared the mechanical property of these three kinds of materials. The drilled holes tensile test was also carried out to examine the drilled holes property. Scanning electron microscope was employed to observe the fracture characteristic on failure specimens. It was found due to the manufacture process of paperboard, the materials expressed obvious anisotropic property. The paperboard composite has an excellent static property but lower impact property compared with carbon hybrid FRP.
- Published
- 2016
- Full Text
- View/download PDF
36. Macrophage targeting: opening new possibilities for cancer immunotherapy
- Author
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Luca, Cassetta and Takanori, Kitamura
- Subjects
Killer Cells, Natural ,Lung Neoplasms ,Macrophages ,tumour immunology ,Animals ,Humans ,cancer ,immunotherapy ,Review Article ,macrophage ,CD8-Positive T-Lymphocytes ,Melanoma ,Review Articles - Abstract
Summary Tumour‐infiltrating immune cells regulate tumour development and progression either negatively or positively. For example, cytotoxic lymphocytes (CTL) such as CD8+ T and natural killer (NK) cells can recognize and eliminate cancer cells, and thereby restrict the tumour growth and metastasis, if they exert full cytotoxicity. In contrast, tumour‐infiltrating myeloid cells such as tumour‐associated macrophages (TAM) promote the expansion and dissemination of cancer cells depending on their functional states. Given the tumour‐killing ability of CTL, the augmentation of CTL‐induced antitumour immune reactions has been considered as an attractive therapeutic modality for lethal solid tumours and several promising strategies have emerged, which include immune checkpoint inhibitors, cancer vaccines and adoptive CTL transfer. These immunotherapies are now tested in clinical trials and have shown significant antitumour effects in patients with lymphoma and some solid tumours such as melanoma and lung cancer. Despite these encouraging results, these therapies are not efficient in a certain fraction of patients and tumour types with tumour cell‐intrinsic mechanisms such as impaired antigen presentation and/or tumour cell‐extrinsic mechanisms including the accumulation of immunosuppressive cells. Several animal studies suggest that tumour‐infiltrating myeloid cells, especially TAM, are one of the key targets to improve the efficacy of immunotherapies as these cells can suppress the functions of CD8+ T and NK cells. In this review, we will summarize recent animal studies regarding the involvement of TAM in the immune checkpoint, cancer vaccination and adoptive CTL transfer therapies, and discuss the therapeutic potential of TAM targeting to improve the immunotherapies.
- Published
- 2018
37. Towards a Conversion of the Nursing Communication Paradigm: A View from the Analysis of Actual Nurse-Elderly Interactions
- Author
-
Yasuko Fukaya and Takanori Kitamura
- Subjects
Nursing ,General Engineering ,Task oriented ,Elderly people ,Duration (project management) ,Nursing homes ,Psychology ,Spontaneous speech - Abstract
We have conducted a series of studies on communication between nurses and elderly patients in geriatric facilities in Japan. The average speech duration per day for elderly people in nursing homes was roughly 4 minutes. The reason for such a short speech duration was that 76% of the nurses’ communication content was composed of “type I” communication (“task oriented” communication) and that “type II” communication (“life-worldly” communication) made up for only 24% of the total. We also analyzed the ways in which “type I” communication constrained spontaneous speech by the elderly whereas “type II” communication tended to promote and encourage it. This article, based on the findings obtained from our research, aims to encourage reconsideration and advancement in the research of nursing communication.
- Published
- 2018
38. Enhancement of Cross-Tension Strength of Resistance Spot-Welded Lap Joints by Laser Heating
- Author
-
Masaru Asada, Takanori Kitamura, and Tetsuya Akiyama
- Subjects
Lap joint ,Materials science ,Mechanics of Materials ,Tension (physics) ,law ,Materials Chemistry ,Metals and Alloys ,Welding ,Composite material ,Laser heating ,Condensed Matter Physics ,law.invention - Published
- 2015
39. Effect of Heat Input and Initial Curvature Radius on Deformation of Thin Plate Heated on Concave or Convex Surface by Laser Beam
- Author
-
Tetsuya Akiyama, Minoru Kido, and Takanori Kitamura
- Subjects
Materials science ,Optics ,Mechanics of Materials ,business.industry ,Materials Chemistry ,Metals and Alloys ,Regular polygon ,Geometry ,Condensed Matter Physics ,Curvature ,business ,Laser beams ,Radius of curvature (optics) - Published
- 2015
40. Effect of Heating Order on Twisted Curved Surface Forming by Orthogonal Laser Line Heating on Top and Bottom Surfaces Alternately
- Author
-
Tetsuya Akiyama, Takanori Kitamura, Hirohiko Kakiuchi, Ryohei Hada, and Akira Gotoh
- Subjects
Mechanics of Materials ,Materials Chemistry ,Metals and Alloys ,Condensed Matter Physics - Published
- 2015
41. Study of Expert Technology on Producing Paper Tubes
- Author
-
Hamada Hiroyuki, Takanori Kitamura, Kanta Ito, Zhang Zhiyuan, Suguru Teramura, Tomoko Ota, and Mitsunori Suda
- Subjects
Engineering ,Work (electrical) ,business.industry ,Mechanical engineering ,Factory (object-oriented programming) ,Production (economics) ,Work site ,business ,Motion (physics) ,Manufacturing engineering ,Task (project management) - Abstract
Paper tubes are usually produced by expert workers who are trained from experience. The manufacture technology can also be developed by this empirical rule. The so-called expert is non-expert person who is trained in the daily working and improve the technology by himself. It is a task for middle and small-sized enterprises in how to train the workers in a short time effectively. This is not only for paper tubes production, but also for a small factory on how to inherit its technology in a short time effectively. The objective of this is to analyze the motion for paper tubes fabricating by observe difference between expert and non-expert at work site as one of “Great master’s work” in middle and small-sized enterprises.
- Published
- 2017
42. Structural Evolution Induced by Interfacial Lattice Mismatch in Self-Organized YBa
- Author
-
Tomoya, Horide, Fumitake, Kametani, Satoru, Yoshioka, Takanori, Kitamura, and Kaname, Matsumoto
- Abstract
Intriguing properties of self-organized nanocomposites of perovskite oxides are usually derived from the complex interface of constituent material phases. A sophisticated control of such a system is required for a broad range of energy and device applications, which demand a comprehensive understanding of the interface at the atomic scale. Here, we visualized and theoretically modeled the highly elastically strained nanorod, the interface region with misfit dislocations and heterointerface distortion, and the matrix with strain-induced oxygen vacancies in the self-organized YBa
- Published
- 2017
43. Strengthening of spot-welded lap joints by new hardened zone
- Author
-
Takanori Kitamura, Yu Masuda, and Tetsuya Akiyama
- Subjects
Materials science ,Lap joint ,Mechanics of Materials ,law ,Mechanical Engineering ,Metals and Alloys ,Fracture (geology) ,Welding ,Edge (geometry) ,Composite material ,Spot welding ,Tensile shear ,law.invention - Abstract
This paper deals with strengthening of spot-welded lap joints by a new hardened zone. Based on the equation to predict the strength proposed by past researchers, the factors necessary for strengthening were extracted. And, based on these factors, the strengthening of spot-welded lap joints was examined. First of all, in order to increase the hardened zone, the vicinity of the nugget edge was heated with a laser. Next, tensile shear tests were conducted by using spot-welded lap joints, which were heated by laser at various distances from the nugget. Finally, the relationship between tensile shear strength and the distance from the nugget centre to the crack was clarified. As a result, by increasing the hardened zone, we found that the fracture position was far away from the nugget edge. And, we found that the tensile shear strength could be improved by 15%.
- Published
- 2014
44. Strengthening of Cross Tension Strength of Spot Welded Lap Joints by Increasing the Opening Angle on the Nugget Edge
- Author
-
Takanori KITAMURA, Tetsuya AKIYAMA, and Tomohito TATEISHI
- Subjects
Mechanics of Materials ,Mechanical Engineering ,Metals and Alloys ,Surfaces, Coatings and Films - Published
- 2014
45. Analysis of Fracture Mechanism on Paper Tubes and Relationship Between Paperboard Property and Property of Paper Tubes
- Author
-
Mitsunori Suda, Takanori Kitamura, Zhiyuan Zhang, and Hiroyuki Hamada
- Subjects
Paperboard ,Mechanism (engineering) ,Materials science ,Property (philosophy) ,Tension (physics) ,visual_art ,visual_art.visual_art_medium ,Fracture (geology) ,Fracture process ,Adhesive ,Composite material - Abstract
According to the report in May, 2015 by Japan Paper Recycling Promotion Center, quantity of paper and paperboard product in Japan decreases is about 18% from 2007 to 2014. Japanese quantity of waste paper in 2014 is 21750000ton, the rate of collected waste paper is 80.8%. Nevertheless Japanese consumption of waste paper is 17190000ton, the rate of utilizing waste paper is 63.9%. It means that quantity of collected waste paper become bigger than quantity of utilizing waste paper, a lot of waste-paper is exported to East Asia (especially China). Balance of waste paper demand and supply in Japan has already broken. It could be expected that waste paper will be collected more and more, but it is difficult to solve the problem that all domestic collected waste paper is used, in order to increasing phenomenon of helpful to recycle, energy saving, environmental protection movement. It is considered that the usage of paper tube need to be expanded which is produced by waste paper. Paper tube has been widely applied in many areas, such as packaging industry, film rolls, adhesive-tape industry, furniture decoration, temporary structures in building and so on. For example churches could be made from paper. The mechanical property of paper tube need to be investigated to get wide application. At current study, the mechanical property of 8 kinds of paperboards for paper tubes fabrication were investigated included tension, compression and peeling properties combining with anisotropic property. These kinds of paperboards have different mechanical properties but same dimension. By this method, the effects of different properties including tension, compression and peeling on mechanical property of paper tubes could be evaluated. A series of paper tubes with different layers was fabricated and the lateral compression test was carried out and evaluated. The fracture form of paper tubes and fracture position on paper tubes were discussed together with paperboards properties. The cause of delamination behavior of laminated paper was analysis based on the detailed observation and finite element analysis. From fracture process, it was found that the main fracture of paper tube is delamination during lateral compression action which was considered peeling action has a big influence. According to this phenomenon, acoustic emission (AE) and observation of peeling paperboard were conducted.
- Published
- 2016
46. Abstract 2808: Investigating the role of macrophage-mediated suppression in the efficacy of NK cell immunotherapy for metastatic outgrowth of breast cancer cells
- Author
-
Demi Brownlie, Dahlia Doughty-Shenton, Jeffrey W. Pollard, and Takanori Kitamura
- Subjects
Cancer Research ,Oncology - Abstract
Breast cancer is the leading cause of cancer-related death in females worldwide. Although 5-year survival of breast cancer patients in early stages is 89-100%, that of patients with metastatic tumours is reduced to just 21%, suggesting the requirement of more effective therapies for metastatic breast cancer (MBC). As MBC is refractory to current therapies, NK cell infusion has been suggested as an alternative therapy. However, its efficacy is modest in MBC possibly due to the suppressive nature of the tumour microenvironment, especially through the tumour-associated macrophages (TAMs) within it. Here we investigated the effects of TAMs in metastatic tumours on NK cell cytotoxicity, as well as the mechanism behind TAM-mediated NK cell suppression. To evaluate NK cell cytotoxicity, we established a method whereby mouse breast cancer cells were cultured with splenic NK cells, and the resultant tumour cell apoptosis was determined by quantitative fluorescence microscopy. To investigate the effects of TAMs on this NK cytotoxicity, we purified them from lungs with metastatic tumours and added them to this co-culture. We also investigated the suppressive effects of bone marrow-derived macrophages cultured with M-CSF (M-BMMs). To further investigate the mechanism, we depleted TAMs in mice with metastatic tumours and detected inhibitory receptor expression on NK cells as well as NK cell inhibitory ligands on TAMs in the metastatic lung and on M-BMMs by flow cytometry. TAMs from metastatic tumours significantly reduced NK cell cytotoxicity toward tumour cells. M-BMMs (resembling TAMs) also reduced NK cell cytotoxicity. We also found that TAMs and M-BMMs expressed high levels of NK cell inhibitory ligands. There was no difference in the expression of inhibitory receptors on NK cells between tumour bearing lungs with or without TAMs. To conclude, we have shown that TAMs in metastatic tumours, as well as their mimetic M-BMMs, can suppress NK cell cytotoxicity towards breast cancer cells in vitro. Our data suggest that TAMs express higher levels of inhibitory ligands and thereby transmit suppressive signals possibly through direct contact with NK cells. Further investigation of mechanisms behind TAM-mediated NK suppression might lead to the improvement of NK cell-based immunotherapy for MBC. Citation Format: Demi Brownlie, Dahlia Doughty-Shenton, Jeffrey W. Pollard, Takanori Kitamura. Investigating the role of macrophage-mediated suppression in the efficacy of NK cell immunotherapy for metastatic outgrowth of breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2808.
- Published
- 2019
47. Long-term High-Resolution Intravital Microscopy in the Lung with a Vacuum Stabilized Imaging Window
- Author
-
Takanori Kitamura, John S. Condeelis, Yu Kato, Carolina Rodriguez-Tirado, Jeffery W. Pollard, and David Entenberg
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Materials science ,Intravital Microscopy ,Vacuum ,General Chemical Engineering ,Image processing ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,medicine ,Lung ,General Immunology and Microbiology ,medicine.diagnostic_test ,General Neuroscience ,Resolution (electron density) ,Magnetic resonance imaging ,030104 developmental biology ,medicine.anatomical_structure ,Positron emission tomography ,Microvessels ,Perfusion ,Intravital microscopy ,Ex vivo ,Biomedical engineering - Abstract
Metastasis to secondary sites such as the lung, liver and bone is a traumatic event with a mortality rate of approximately 90% 1. Of these sites, the lung is the most difficult to assess using intravital optical imaging due to its enclosed position within the body, delicate nature and vital role in sustaining proper physiology. While clinical modalities (positron emission tomography (PET), magnetic resonance imaging (MRI) and computed tomography (CT)) are capable of providing noninvasive images of this tissue, they lack the resolution necessary to visualize the earliest seeding events, with a single pixel consisting of nearly a thousand cells. Current models of metastatic lung seeding postulate that events just after a tumor cell's arrival are deterministic for survival and subsequent growth. This means that real-time intravital imaging tools with single cell resolution 2 are required in order to define the phenotypes of the seeding cells and test these models. While high resolution optical imaging of the lung has been performed using various ex vivo preparations, these experiments are typically single time-point assays and are susceptible to artifacts and possible erroneous conclusions due to the dramatically altered environment (temperature, profusion, cytokines, etc.) resulting from removal from the chest cavity and circulatory system 3. Recent work has shown that time-lapse intravital optical imaging of the intact lung is possible using a vacuum stabilized imaging window 2,4,5 however, typical imaging times have been limited to approximately 6 hr. Here we describe a protocol for performing long-term intravital time-lapse imaging of the lung utilizing such a window over a period of 12 hr. The time-lapse image sequences obtained using this method enable visualization and quantitation of cell-cell interactions, membrane dynamics and vascular perfusion in the lung. We further describe an image processing technique that gives an unprecedentedly clear view of the lung microvasculature.
- Published
- 2016
48. Mechanical Property and Function of Bamboo Charcoal Paperboard
- Author
-
Suguru Teramura, Kanta Ito, Takanori Kitamura, Noriaki Kuwahara, Hamada Hiroyuki, Hiroki Nishimura, and Zhang Zhiyuan
- Subjects
Paperboard ,Mechanical property ,Materials science ,visual_art ,Bamboo charcoal ,Corrugated fiberboard ,visual_art.visual_art_medium ,Brain waves ,Composite material - Abstract
In this research, the bamboo charcoal paperboards (BCPs) were manufactured by paper making method. The paperboards constitute of many layers and each layer could be produced by different fibers materials. Bamboo charcoal was used and combined with recycled paper such as magazine, newspaper and corrugated paper box and so on. The mechanical properties included tension, compression, and pealing were tested to evaluate its potential applications. The scanning electron microscope observation was also conducted on the bamboo charcoal particle. At the same time, the benefit of bamboo charcoal paperboards on promoting attention for study was also evaluated. For attention effects on study, questionnaire survey was conducted from student to evaluate the effects of BCPs environment on studying. The brain wave data could be obtained during this process and investigated. The results indicated bamboo charcoal walls have good effect on concentrate attention to study.
- Published
- 2016
49. Analysis of Utterances by Older Persons in 'Life-Worldly' Communication with Caregivers in Japan
- Author
-
Yasuko Fukaya, Takanori Kitamura, Kanako Yamakuma, Sachiyo Koyama, and Shinobu Sato
- Subjects
Gerontology ,Average duration ,Wheelchair ,Elderly persons ,Duration (music) ,Geriatric care ,Psychology ,Utterance - Abstract
Objective: The purpose of this study is to grasp the actual conditions of utterances by elderly persons in geriatric care facilities in Japan. Specifically, the study considers utterance frequency, duration, and structure according to the two types of communication: Type I (Task-oriented) and Type II (Life-worldly). Method: Study subjects were comprised of 37 residents in three long-term care facilities in Japan. The study surveyed the personal attributes of each elderly person, and the type and duration of utterances they made within 1 day. Type I and II communication characteristics were both quantitatively and qualitatively investigated. Results: The duration of utterances from older residents was very short, at about 4 min. The average duration of utterances by elderly persons who are bedridden was 115.54 s (SD=131.55), which was significantly lower (p
- Published
- 2016
50. Effect of Paper Property on Mechanical Property of Paper Tube
- Author
-
Mitsunori Suda, Takanori Kitamura, Zhiyuan Zhang, and Ratchaneekorn Wongpajan
- Subjects
Paperboard ,Paper recycling ,Fracture toughness ,Materials science ,Tension (physics) ,visual_art ,Delamination ,visual_art.visual_art_medium ,Fracture (geology) ,Tube (container) ,Composite material ,Compression (physics) - Abstract
Paper recycling is an effective way in reducing deforestation and energy consumption. Therefore recycling paper and paper products has been widely applied in many areas, such as packaging industry, film rolls, adhesive-tape industry, furniture decoration and temporary structures in building. They can be produced into various structure according to different requirement, such as paper tube, corrugated paperboard and normal paperboard. Paper-tubes gain more and more applications as a traditional structure due to their excellent mechanical property and environmentally friendly property. In order to meet various needs of paper-tube and produce high performance paper-tubes, designing for paper-tubes fabrication is needed. It is necessary to research the lateral compression strength of paper tube because various paper-tubes are used as packages, cores, poles and structure materials. To establish a relation of mechanical property between paperboards and paper-tubes is an important aspect. The current study is to investigate this relation. Paperboards are built from cellulose fibers jointed by hydrogen bonds and some additional elements like talc. The fibers are distributed randomly on the paperboards. However due to the tension action during fabrication process, more fibers are distributed in machine rolling direction which is defined as machine direction (MD, TD for transverse direction). The material expresses obvious anisotropic property. On the other hand, due to the laminated structure of paper materials, it is possible to generate interlaminar fracture in the usage process, especially in the construction made of paper such as paper tubes. The mechanical property of three kinds of paperboards used for paper-tubes fabrication was investigated included tension, compression and peeling combining with anisotropic property. These three kinds of paperboards have different mechanical properties but same dimension for paper-tubes fabrications. By this method, the effects of different properties including tension, compression and peeling on mechanical property of paper-tube could be evaluated. A series of paper-tubes with different layers was fabricated and the lateral compression test was carried out and evaluated. The fracture form of paper-tubes and fracture position on paper-tube were discussed together with paperboards. The cause of delamination behavior of laminated paper was analysis based on the detailed observation. The optical observation were employed to evaluate the fracture properties of paper-tubes after lateral compression test. It was found that the initial fracture of paper-tubes occurred inside the paperboards rather than between layers and the peeling property of paperboard has a signification effects on lateral compression property of paper-tubes.
- Published
- 2015
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