Department of Medical Technology

Pathophysiology

Name Title E-Mail address Research Area
Yujiro Arao, PhD Professor yujiarao(a)md.okayama-u.ac.jp Virus and host interaction
Yasuharu Sato, MD. Professor satou-y(a)okayama-u.ac.jp Histopathology, Cytopathology and Molecular Pathology
横田憲治
Tetsuya Ishikawa, PhD. Associate Professor t-ishika(a)okayama-u.ac.jp Cell biology, especially cancer metabolism

Biophysiology

Name Title E-Mail address Research Area
Satoshi Hirohata M.D. Ph.D. Professor hirohas(a)cc.okayama-u.ac.jp Cardiology, Cancer biology, arthritis, metalloproteinase, angiogenesis
Nobuaki Miyahara, MD, PhD. Professor miyahara(a)okayama-u.ac.jp translational science and clinical research in respiratory medicine, especially bronchial asthma, COPD, and interstitial pneumonia
Misako Shibakura, PhD. Associate Professor m_shiba(a)md.okayama-u.ac.jp Clinical Hematology, Complementary Alternative Medicine
Shinichi Usui, PhD. Associate Professor usuis(a)okayama-u.ac.jp clinical chemistry, especially lipids and lipoproteins associated with cardiovascular disease, diabetes, and metabolic syndrome
Shogo Watanabe, Ph.D senior assistant professor watanabe1224(a)okayama-u.ac.jp Cardiovascular science in metabolic syndrome
Ryoko Shinohata, PhD. Assistant Professor sinohata(a)md.okayama-u.ac.jp clinical chemistry, especially lipids and lipoproteins associated with cardiovascular disease, diabetes, and metabolic syndrome
Tomoe Ueno-Iio,PhD Assistant Professor niioto(a)cc.okayama-u.ac.jp Complemantary and alternative medicine, Aromatherapy, Exhaled breath condensate

Pathophysiology

Yujiro Arao, PhD

Research Projects
Factors enhancing virus replication and gene expression from viral promoter
We studied the effects of saccharides on transgene expression in mammalian cells by a reporter gene assay using mammalian cells and a viral promoter-controlled EGFP gene. Treatment of the mammalian cells with each of several saccharides at a relatively high concentration increased the number of fluorescent cells in fluorescence microscopic observation and significantly intensified fluorescence in the fluorometric assay (Fig. 1). Furthermore, EGFP itself and mRNA became more abundant in Western blot and RT-PCR analyses of the saccharide-treated cells, respectively. These results indicate that the elevated saccharide can activate the viral promoter-controlled transgene expression via transcriptional stimulation, at least in part. We also studied effects of un-infectious virus particles on cellular functions that might affect virus replication or disease development. Many viral diseases have been studied through detection of virion, viral antigens, and viral DNAs or RNAs on the basis of the idea that viral diseases are caused by viral replication, viral gene products, or immune responses to viral products. The causative agents of several diseases such as chronic fatigue syndrome and histiocytic necrotizing lymphadenitis have not been identified, although viruses are suspected to be the causes. To address this problem, we need to identify the effects of viruses on host cells that occur independent of virus replication. When mammalian cells encounter stress factors, cellular responses are initiated. These stress responses use energy, resulting in glucose uptake by host cells. Monitoring glucose uptake, therefore, may provide insights into whether a factor induces stress in cells. It is possible that a virus stimulates host cells to take up glucose prior to replication of the virus because viral replication requires a significant amount of energy. Thus, assessing glucose uptake may be a good way to examine early interactions between virus and host cells. We used a microplate assay with 2-NBDG (fluorescent D-glucose derivative) to assess glucose uptake by virus-infected cells, resulting in that un-infectious virus particles increase glucose uptake by host cells independent of virus replication (Fig. 2).
List of 5 publications in the field of expertise
  1. Chikasue K, Kimura M, Ikeda K, Ohnishi T, Kawanishi S, Iio T, Kataoka M, Arao Y. Detection of Torque teno virus DNA in exhaled breath by polymerase chain reaction. Acta Med Okayama. 2012;66:387-97. URL https://www.ncbi.nlm.nih.gov/pubmed/23093057
  2. Kimura M, Namba H, Okubo M, Ezumi M, Susumu N, Yamada M, Arao Y. Enhancive effects of D-glucose and its analogs on expression of d-glucose-unrelated transgenes in mammalian cells. J Biosci Bioeng. 2011;112:194-201. URL https://www.ncbi.nlm.nih.gov/pubmed/21596618
  3. Narita M, Ando Y, Soushi S, Kurata T, Arao Y. The BglII-N fragment of herpes simplex virus type 2 contains a region responsible for resistance to antiviral effects of interferon. J Gen Virol. 1998;79:565-72. URL https://www.ncbi.nlm.nih.gov/pubmed/9519835
  4. Arao Y, Soushi S, Sato Y, Moriishi E, Ando Y, Yamada M, Padilla J, Uno F, Nii S, Kurata T. Infection of a human retinal pigment epithelial cell line with human herpesvirus 6 variant A. J Med Virol. 1997;53:105-10. URL https://www.ncbi.nlm.nih.gov/pubmed/933492
  5. Arao Y, Ando Y, Narita M, Kurata T. Unexpected correlation in the sensitivity of 19 herpes simplex virus strains to types I and II interferons. J Interferon Cytokine Res. 1997;17:537-41. URL https://www.ncbi.nlm.nih.gov/pubmed/9335431

Yasuharu Sato, MD.

Research Projects
  • Approach to the pathogenesis and carcinogenesis of IgG4-related disease
  • Clinicopathologic analysis of TAFRO syndrome and Castleman disease
  • Approach to the pathogenesis of MTX-associated lymphoproliferative disorders
  • Clinicopathologic analysis of lymphomas
  • Clinicopathologic and molecular analysis of Head and Neck tumors
List of 5 publications in the field of expertise
  1. Gion Y, Iwaki N, Takata K, Takeuchi M, Nishida K, Orita Y, Tachibana T, Yoshino T, Sato Y. Clinicopathological analysis of methotrexate-associated lymphoproliferative disorders: comparison of diffuse large B-cell lymphoma and classical Hodgkin lymphoma types. Cancer Science 2017 Jun 108(6): 1271-1280. doi: 10.1111/cas.13249. https://www.ncbi.nlm.nih.gov/pubmed/28380678
  2. Miki K, Orita Y, Gion Y, Takao S, Ohno K, Takeuchi M, Ito T, Hanakawa H, Tachibana T, Marunaka H, Makino T, Minoura A, Matsukawa A, Nishizaki K, Yoshino T, Sato Y. Regulatory T cells function at the early stage of tumor progression in a mouse model of tongue squamous cell carcinoma. Cancer Immunol Immunother 2016; 65 (11); 1401-1410. DOI 10.1007/s00262-016-1902-x https://www.ncbi.nlm.nih.gov/pubmed/27614428
  3. Iwaki N, Fajgenbaum DC, Nabel CS, Gion Y, Kondo E, Kawano M, Masunari T, Yoshida I, Moro H, Nikkuni K, Takai K, Matsue K, Kurosawa M, Hagihara M, Saito A, Okamoto M, Yokota K, Hiraiwa S, Nakamura N, Nakao S, Yoshino T, Sato Y. Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease. Am J Hematol. 2016; 91 (2): 220-226. https://www.ncbi.nlm.nih.gov/pubmed/26805758
  4. Sato Y, Takeuchi M, Takata K, Ohno K, Iwaki N, Orita Y, Goto N, Hida A, Iwamoto T, Asano N, Ito T, Hanakawa H, Yanai H, Yoshino T. Clinicopathologic analysis of IgG4-related skin disease. Mod Pathol. 2013; 26(4): 523-532. https://www.ncbi.nlm.nih.gov/pubmed/23174935
  5. Sato Y, Inoue D, Asano N, Takata K, Asaoku H, Maeda Y, Morito T, Okumura H, Ishizawa S, Matsui S, Miyazono T, Takeuchi T, Kuroda N, Orita Y, Takagawa K, Kojima M, Yoshino T. Association between IgG4-related disease and progressively transformed germinal centers of lymph node. Mod Pathol. 2012; 25(7): 956-967. https://www.ncbi.nlm.nih.gov/pubmed/22481280

Tetsuya Ishikawa, PhD.

Research Projects
Identification of a biomarker of tumors in exhaled breath of mice
Malignant tumors are the number one cancer-related cause of death in Japan. Early detection of malignant tumors would reduce the number of fatalities and, therefore, is a key issue for medical science. Early detection requires appropriate testing but, currently, no screening tests exist for malignant tumors. Easy-to-perform testing would allow an increased number of persons to be screened, resulting in increased cancer detection. One such candidate test is exhaled breath testing, although a serious hurdle remains, because exhaled breath biochemical compounds that are unique to malignant tumors have not yet been identified. Previous research indicates that volatile organic compounds (VOCs) are likely involved, and multiple types have been reported. However, none of these compounds can be used in breath tests for malignant tumors. I identified a biochemical compound from exhaled breath as a potential biomarker of tumors using mice. manuscript in preparation
List of 5 publications in the field of expertise
  1. Suemitsu S, Watanabe M, Yokobayashi E, Usui S, Ishikawa T, Matsumoto Y, Yamada N, Okamoto M, Kuroda S. Fcgamma receptors contribute to pyramidal cell death in the mouse hippocampus following local kainic acid injection. Neuroscience. 2010 Mar 31;166(3):819-31. (https://www.ncbi.nlm.nih.gov/pubmed/20074624)
  2. Ishikawa T, Kawai C, Sano M, Minatogawa Y Peroxisomes exist in growth cones and move anterogradely and retrogradely in neurites of PC12D cells. Exp Cell Res. 2001 Jun 1;266(2):260-269 (https://www.ncbi.nlm.nih.gov/pubmed/11399054)
  3. Kawakami Y, Ishikawa T, Shimabara M, Tanda N, Enomoto-Iwamoto M, Iwamoto M, Kuwana T, Ueki A, Noji S, Nohno T. BMP signaling during bone pattern determination in the developing limb. Development. 1996 Nov;122(11):3557-3566. (https://www.ncbi.nlm.nih.gov/pubmed/8951071)
  4. Nohno T, Ishikawa T, Saito T, Hosokawa K, Noji S, Wolsing DH, Rosenbaum JS. Identification of a human type II receptor for bone morphogenetic protein-4 that forms differential heteromeric complexes with bone morphogenetic protein type I receptors. J Biol Chem. 1995 Sep 22;270(38):22522-22526. (https://www.ncbi.nlm.nih.gov/pubmed/7673243)

Biophysiology

Satoshi Hirohata M.D. Ph.D.

Research Projects
Research Interests and current activities
1.Virtual image-guided intervention system
Dr. Hirohata has moved to the Dept. of Health Science as s full professor in 2014 and his group has started virtual image-oriented intervention project in 2015. Using a thinner new sensor, his group has successfully merged catheter tip positional information with 3D-CT coronary image.
2.Protective effects on cardiomyocytes by eosinophilic cationic protein
3.Ventricular remodeling after myocardial infarction
4.Biological function of new metalloproteinase family, ADAMTS
5.Anti-angiogenic property of extracellular matrix (ECM)-derived molecule
Dr. Hirohata and his colleague have found that host-derived ECM play riles for tumor angiogenesis. In this research, it was made clear that versican is excreted by the surrounding cells of the cancer tissue that enter into the cancer tissue. It was also made clear that the distribution of cleavages was changed (repositioned). This result was published in the electronic version of the British science magazine "Scientific Reports" on December 8, 2017. This research result shows the importance of a "cancer microenvironment" that contains non-cancerous cells. In other words, the result shows that not only cancer tissue, but also host-derived cells are contributing to promoting tumor growth. We can easily say that this gives us new research problems in cancer treatment. This research result also shows the importance of having a new treatment strategy, such as an immunity checkpoint inhibitor, rather than a treatment that works directly on cancer cells.
  1. Asano K, Nelson CM, Nandadasa S, Aramaki-Hattori N, Lindner DJ, Alban T, Inagaki J, Ohtsuki T, Oohashi T, Apte SS, Hirohata S. Stromal Versican Regulates Tumor Growth by Promoting Angiogenesis. Sci Rep. 2017 Dec 8; 7(1): 17225. doi: 10.1038/s41598-017-17613-6. (URL: https://www.nature.com/articles/s41598-017-17613-6)
  2. Nosaka K, Miyoshi T, Iwamoto M, Kajiya M, Okawa K, Tsukuda S, Yokohama F, Sogo M, Nishibe T, Matsuo N, Hirohata S, Ito H, Doi M. Early initiation of eicosapentaenoic acid and statin treatment is associated with better clinical outcomes than statin alone in patients with acute coronary syndromes: 1-year outcomes of a randomized controlled study. Int J Cardiol. 2017 Feb 1; 228: 173-179. doi:10.1016/j.ijcard.2016.11.105. (URL: https://www.ncbi.nlm.nih.gov/pubmed/27865182)
  3. Hirohata A, Yamamoto K, Miyoshi T, Hatanaka K, Hirohata S, Yamawaki H, Komatsubara I, Murakami M, Hirose E, Sato S, Ohkawa K, Ishizawa M, Yamaji H, Kawamura H, Kusachi S, Murakami T, Hina K, Ohe T. Impact of olmesartan on progression of coronary atherosclerosis a serial volumetric intravascular ultrasound analysis from the OLIVUS (impact of OLmesarten on progression of coronary atherosclerosis: evaluation by intravascular ultrasound) trial. J Am Coll Cardiol. 2010; 55(10): 976-82 (URL: https://www.ncbi.nlm.nih.gov/pubmed/20202514)
  4. Miyoshi T, Hirohata S, Ogawa H, Doi M, Obika M, Yonezawa T, Sado Y, Kusachi S, Kyo S, Kondo S, Shiratori Y, Hudson BG, Ninomiya Y. Tumor-specific expression of the RGD-alpha3(IV)NC1 domain suppresses endothelial tube formation and tumor growth in mice. FASEB J. 2006 Sep; 20(11): 1904-1906 (URL: http://www.fasebj.org/doi/abs/10.1096/fj.05-5565fje)
  5. Hirohata S, Wang LW, Miyagi M, Yan L, Seldin MF, Keene DR, Crabb JW, Apte SS. Punctin, a novel ADAMTS-like molecule (ADAMTSL-1) in extracellular matrix. J Biol Chem. 2002; 277(14): 12182-9. (URL: http://www.jbc.org/content/277/14/12182)

Nobuaki Miyahara, MD, PhD.

Research Projects
・The role of receptor for advanced glycation end-products (RAGE) in allergen-induced airway inflammation and COPD:
RAGE is a multi-ligand receptor which belongs to the immunoglobulin superfamily, and reported to be involved in various inflammatory disorders. We identified the importance of RAGE expressed on lung structural cells in the development of allergic airway inflammation, Th2 cell activation, and group 2 innate lymphoid cell (ILC2) accumulation in the airways. Thus, manipulating RAGE represents a novel therapeutic target in controlling allergic airway responses (Am J Physiol Lung Cell Mol Physiol 309:L789-800, 2015). We also found the importance of RAGE expressed on lung structural cells in the development of elastase-induced pulmonary inflammation and emphysema (Am J Respir Cell Mol Biol 52:482-91, 2015). RAGE might be a novel therapeutic target for preventing pulmonary emphysema (Fig. 1).
・The role of leukotriene B4 (LTB4) and LTB4 receptor-1 (BLT1) in asthma:
LTB4 is a lipid mediator with potent chemoattractant properties, and rapidly generated from activated innate immune cells. Ligation of BLT1 by LTB4 is important for the activation and recruitment of inflammatory cells including neutrophils, eosinophils, monocytes, macrophages, mast cells, dendritic cells, and more recently, effector T cells to inflamed tissues in various inflammatory diseases. We have shown that the LTB4-BLT1 pathway may be important in effector T cell, and especially effector CD8 T cell movement to sites of acute inflammation to the development of airway hyperresponsivenes and inflammation (Nature Med. 10:865-9, 2004, J Allergy Clin Immunol. 121:864-71, 2008, Am J Respir Cell Mol Biol. 40:672-82, 2009). We have also shown the importance of LTB4 in accumulation of neutrophils and eosinophils in the airways during the late asthmatic responses (Am J Respir Cell Mol Biol. 45:851-7, 2011). Manipulating the LTB4-BLT1 pathway may be beneficial in the treatment of established asthma (Fig. 2).
・IL-23-Th17 axis in chronic obstructive pulmonary disease (COPD).
IL-17 is produced by a subset of CD4+ lymphocytes known as T-helper (Th) 17 cells, and contributes to the development of autoimmune disease. We identified that IL-17A plays a critical role in the development of elastase-induced emphysema (Respir Res. 14:5, 2013). The proliferation of Th17 cells is induced by IL-23, therefore, we then assessed the role of IL-23 for emphysema, and found the important contributions of IL-23 to the development of pulmonary inflammation and emphysema, mediated through an IL-23-IL-17 pathway (Fig. 3: Am J Respir Cell Mol Biol 2016;55:697-707). Targeting IL-23 in emphysema is a potential therapeutic strategy for delaying disease progression.
List of 5 publications in the field of expertise
  1. Miyahara N, et al. Effector CD8+ T cells mediate inflammation and airway hyper-responsiveness. Nature Med. 10:865-9, 2004. (https://www.nature.com/articles/nm1081)
  2. Waseda K, Miyahara N, et al. Blocking the leukotriene B4 receptor 1 inhibits late ase airway responses in established disease. Am J Respir Cell Mol Biol. 45:851-7, 2011 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208610/)
  3. Taniguchi A, Miyahara N, et al. Contrasting Roles for the Receptor for Advanced Glycation End-Products on Structural Cells in Allergic Airway Inflammation versus Airway Hyperresponsiveness. Am J Physiol Lung Cell Mol Physiol 309:L789-800, 2015 (http://www.physiology.org/doi/pdf/10.1152/ajplung.00087.2015)
  4. Fujii U, Miyahara N, et al. IL-23 is essential for the development of elastase-induced pulmonary inflammation and emphysema. Am J Respir Cell Mol Biol 2016;55:697-707 (https://www.ncbi.nlm.nih.gov/pubmed/?term=Am+J+Respir+Cell+Mol+Biol+2016%3B55%3A697-707)
  5. Oda N, Miyahara N, et al. Long-term effects of beta-blocker use on lung function in Japanese patients with chronic obstructive pulmonary disease. Int J COPD. 2017;12:1119-1124 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391992/)

Misako Shibakura, PhD.

Research Projects
Research projects: Study in anti-inflammatory effects of essential oil using murine COPD model and monocyte cell lines:
We are studying the anti-inflammatory action of the essential oil used in aromatherapy using murine model of chronic obstructive pulmonary (COPD) disease. We found that some essential oils have the anti-inflammatory effect, such as suppressing alveolar destruction and the infiltration of inflammatory cells into the alveoli. Further studies are necessary, but in the future it may be possible to use essential oils to prevent respiratory inflammation.
List of 5 publications in the field of expertise
  1. Aoe M, Ueno-Iio T, Shibakura M, Shinohata R, Usui S, Arao Y, Ikeda S, Miyahara N, Tanimoto M, Kataoka M. Lavender Essential Oil and Its Main Constituents Inhibit the Expression of TNF-α-induced Cell Adhesion Molecules in Endothelial Cells. Acta Med Okayama. 2017;71:493-503. (URL : http://doi.org/10.18926/AMO/55586)
  2. Ueno-Iio T, Shibakura M, Kataoka M. The effects of essential oils on disorders of the mind and body caused by weather conditions. Japan Journal of Aromatherapy. (in Japanese) 2015;15: 96-103.
  3. Ueno-Iio T, Shibakura M, Yokota K, Aoe M, Hyoda T, Shinohata R, Kanehiro A,Tanimoto M, Kataoka M. Lavender essential oil inhalation suppresses allergic airway inflammation and mucous cell hyperplasia in a murine model of asthma. Life Sci. 2014;108:109-115. (URL : https://doi.org/10.1016/j.lfs.2014.05.018)
  4. Aoe M, Shimada A, Muraoka M, Washio K, Nakamura Y, Takahashi T, Imada M, Watanabe T, Okada K, Nishiuchi R, Miyamura T, Chayama K, Shibakura M, Oda M, Morishima T. ABL kinase mutation and relapse in 4 pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia cases. Int J Hematol. 2014;99:609-615. (URL : https://link.springer.com/article/10.1007%2Fs12185-014-1565-3)

Shinichi Usui, PhD.

Research Projects
It has been well known that blood cholesterol is one of the major risk factors for cardiovascular disease. Cholesterol is carried on lipoproteins (VLDL, LDL, and HDL) that circulate in blood. Detailed analysis of lipoprotein subfractions will contribute to understanding of lipoprotein metabolisms in clinical and basic researches. The following research projects are our interest and in progress in our laboratory.
1) Development of new techniques for lipoprotein analysis
We are investigating new analytical methods for lipoproteins of sera from humans and animals and supernatants of cell culture media using high-performance liquid chromatography, electrophoresis, and an enzyme-linked immunosorbent assay.
2) Clinical significance of serum lipoprotein measurement
It is well known that decreased levels of HDL-cholesterol represent an independent risk factor for coronary artery disease. However, HDLs are a highly heterogeneous group and differ in lipid, protein composition, size, hydrated density, and electrophoretic mobility. Individual HDL subpopulations might play specific roles in the multiple anti-atherogenic activities associated with HDL overall. We study on clinical significance of HDLs and other lipoprotein subfractions analysis in patients with cardiovascular disease and metabolic syndrome.
3) Novel functions of HDL subfractions
HDL has been recently proposed to possess multiple biological functions including anti-inflammatory, anti-oxidative, and vasodilatory activities as well as its traditional role in reverse cholesterol transport. We study a role of apoE-rich HDL subfraction in hepatocytes and adipocytes, focusing on fatty liver, diabetes, and obesity.
List of 5 publications in the field of expertise
  1. Ikeda T, Shinohata R, Murakami M, Hina K, Kamikawa S, Hirohata S, Kusachi S, Tamura A, Usui S. A rapid and precise method for measuring plasma apoE-rich HDL using polyethylene glycol and cation-exchange chromatography: a pilot study on the clinical significance of apoE-rich HDL measurements. Clin Chim Acta. 2017;465:112-118. (URL:https://www.ncbi.nlm.nih.gov/pubmed/27993510)
  2. Miyoshi T, Doi M, Usui S, Iwamoto M, Kajiya M, Takeda K, Nosaka K, Nakayama R, Okawa K, Takagi W, Nakamura K, Hirohata S, Ito H. Low serum level of secreted frizzled-related protein 5, an anti-inflammatory adipokine, is associated with coronary artery disease. Atherosclerosis. 2014;233(2):454-9. (URL:https://www.ncbi.nlm.nih.gov/pubmed/24530778)
  3. Usui S, Ichimura M, Ikeda S, Okamoto M. Association between serum retinol-binding protein 4 and small dense low-density lipoprotein cholesterol levels in young adult women. Clin Chim Acta. 2009;399(1-2):45-8. (URL:https://www.ncbi.nlm.nih.gov/pubmed/18782570)
  4. Usui S, Kakuuchi H, Okamoto M, Mizukami Y, Okazaki M. Differential reactivity of two homogeneous LDL-cholesterol methods with LDL and VLDL subfractions, as demonstrated by ultracentrifugation and HPLC. Clin Chem. 2002;48(11):1946-54. (URL:https://www.ncbi.nlm.nih.gov/pubmed/12406980)
  5. Usui S, Hara Y, Hosaki S, Okazaki M. A new on-line dual enzymatic method for simultaneous quantification of cholesterol and triglycerides in lipoproteins by HPLC. J Lipid Res 2002;43:805-14. (URL:https://www.ncbi.nlm.nih.gov/pubmed/11971952)

Ryoko Shinohata, PhD.

Research Projects
It has been well known that blood cholesterol is one of the major risk factors for cardiovascular disease. Cholesterol is carried on lipoproteins (VLDL, LDL, and HDL) that circulate in blood. Detailed analysis of lipoprotein subfractions will contribute to understanding lipoprotein metabolisms in clinical and basic researches. The following research projects are in progress in our laboratory.
1) Development of new techniques for lipoprotein analysis
We are investigating new analytical methods for lipoproteins of sera from humans and animals and supernatants of cell culture media using high-performance liquid chromatography, electrophoresis, and an enzyme-linked immunosorbent assay.
2) Clinical significance of serum lipoprotein measurement
It is well known that decreased levels of HDL-cholesterol represent an independent risk factor for coronary artery disease. However, HDLs are a highly heterogeneous group and differ in lipid, protein composition, size, hydrated density, and electrophoretic mobility. Individual HDL subpopulations might play specific roles in the multiple anti-atherogenic activities associated with HDL overall. We study on clinical significance of HDLs and other lipoprotein subfractions analysis in patients with cardiovascular disease and metabolic syndrome.
3) Novel functions of HDL subfractions
HDL has been recently proposed to possess multiple biological functions including anti-inflammatory, anti-oxidative, and vasodilatory activities as well as its traditional role in reverse cholesterol transport. We study on a role of apoE-rich HDL subfraction in hepatocytes and adipocytes, focusing on fatty liver, diabetes, and obesity.
List of 5 publications in the field of expertise
  1. Ikeda T, Shinohata R, Murakami M, Hina K, Kamikawa S, Hirohata S, Kusachi S, Tamura A, Usui S. A rapid and precise method for measuring plasma apoE-rich HDL using polyethylene glycol and cation-exchange chromatography: a pilot study on the clinical significance of apoE-rich HDL measurements. Clin Chim Acta. 2017;465:112-118.
  2. Watanabe S, Kumazaki S, Kusunoki K, Inoue T, Maeda Y, Usui S, Shinohata R, Ohtsuki T, Hirohata S, Kusachi S, Kitamori K, Mori M, Yamori Y, Oka H. A High-Fat and High-Cholesterol Diet Induces Cardiac Fibrosis, Vascular Endothelial, and Left Ventricular Diastolic Dysfunction in SHRSP5/Dmcr Rats. J Atheroscler Thromb. 2017.

Tomoe Ueno-Iio,PhD

Research Projects
The number of patients (children and adults) with bronchial asthma in Japan is increasing and is currently estimated to be more than 8 million people. Studies have revealed that allergic airway inflammation is involved in the pathogenesis of asthma. Current treatments include inhaled steroids to reduce inflammation. However, since the etiology and pathogenesis of asthma are yet to be completely elucidated, the methods of prevention and main treatments are yet to be established. Thus, to reduce the symptoms and decrease the progression of asthma, we have focused on aromatherapy, which is easy to implement in daily life and which is classified as a complementary and alternative medicine. We also conducted research using essential oils extracted from plants. We have elucidated the anti-allergy effects of essential oils on airway hyper-responsiveness, mucus production, and eosinophil infiltration in a murine asthma model. In this study, we elucidated the anti-allergy effect of lavender essential oil in a murine model of asthma. We have also confirmed that the effects and functions differ depending on the type of essential oil, for example, in the aggravation of airway resistance due to one type of oil. An essential oil contains between 10 and 1000 organic compounds, and each of the approximately 300 different kinds of essential oils differs in its composition. Using human bronchial epithelial cells and human dermal fibroblasts, we proceed the project, is identified the essential oils that contain compounds with anti-inflammatory effects. Through elucidating the mechanism of essential oils, we aim to promote aromatherapy as a potential alternative medicine for allergic diseases.
List of 5 publications in the field of expertise
  1. Aoe M, Ueno-Iio T, Shibakura M, Shinohata R, Usui S, Arao Y, Ikeda S, Miyahara N, Tanimoto M, Kataoka M. Lavender Essential Oil and Its Main Constituents Inhibit the Expression of TNF-α-induced Cell Adhesion Molecules in Endothelial Cells. Acta Med. Okayama 2017;71(6):493-503
  2. Ueno-Iio T, Shibakura M, Yokota K, Aoe M, Hyoda T, Shinohata R, Kanehiro A, Tanimoto M, Kataoka M. Lavender essential oil inhalation suppresses allergic airway inflammation and mucous cell hyperplasia in a murine model of asthma. Life Sciences 2014;108 (2):109-115
  3. Ueno-Iio T, Shibakura M, Iio K, Tanimoto Y, Kanehiro A, Tanimoto M, Kataoka M. Effect of fudosteine, a cysteine derivative, on airway hyperresponsiveness, inflammation, and remodeling in a murine model of asthma. Life Sciences 2013;92:1015-1023
  4. Iio K, Ueno Iio T, Okui Y, Ichikawa H, Tanimoto Y, Miyahara N, Kanehiro A, Tanimoto M, Nakata Y, Kataoka M. Experimental pulmonary granuloma mimicking sarcoidosis induced by Propionibacterium acnes in mice. Acta Med Okayama 2010;64(2):75-83
  5. Ueno T, Kataoka M, Hirano A, Iio K, Tanimoto Y, Kanehiro A, Okada C, Soda R, Takahashi K, Tanimoto M. Inflammatory markers in exhaled breath condensates from patients with asthma. Respirology 2008;13(5):654-663