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Measurement of AGEs and its inhibition by natural products

Maillard reaction, glycation, AGEs, lifestyle-related diseases, dietary supplements, diabetic complications, atherosclerosis

With ageing, the accumulation of Advanced glycation end-products (AGEs) increases, and the pathogenesis of age-related disorders such as lifestyle-related diseases also increases. However, measuring AGE levels in physiological samples is difficult, and there are many cases where it is impossible to evaluate levels precisely. Using specific monoclonal antibodies specific for AGEs, and using a high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS), our system is able to measure AGE levels and develop inhibitor for AGEs formation.

Researcher(s)
RYOJI NAGAI (Department of Bioscience, School of Agriculture)

Human monoclonal antibody against CD4 - A potential biologic for HIV/AIDS and immunological disorders

human antibodies, HIV, CD4, oligoclonal method

Through a cell immortalization method using Epstein-Barr virus, we have collected a number of human monoclonal antibodies from healthy volunteers. This method is excellent at recovering scarce antibodies. Recently it has been discovered that CD4 reactive antibodies derived from healthy subject IgM inhibit HIV-1 growth. The Fab clone(HO538-213) has a Kd of 6.5×10-8M in regards to CD4, and from a therapeutic development standpoint, it is expected that HO538-213 will become a seed for medicine treating the communicable disease HIV-1.

Researcher(s)
Masataka Takekoshi (Department of Molecular Life Science, Division of Basic Molecular Science and Molecular Medicine, School of Medicine)

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Development of human monoclonal antibodies possessing anti-protozoan activities

Antibody therapy, protozoan infection, toxoplasmosis, falciparum malaria

There are no practical vaccines available for preventing protozoan infections, and the side effects of antiprotozoal drugs can be strong. Our research aims to develop an antibody drug that can be particularly useful in treating and preventing the more serious symptoms of protozoan infections. We have constructed an immunoglobulin gene library derived from the peripheral lymphocytes of infected patients, and screened for antibodies that recognize protozoan surface antigens. To date, our research has found human monoclonal antibodies with antiprotozoal activities against Toxoplasma gongii and other protozoa.

Researcher(s)
Hiroshi Tachibana (Department of Infectious Diseases, School of Medicine)

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A novel strategy for sepsis in the elderly using Interferon 15

aging, septicemia, immunity

Sepsis is a serious body-wide infection, and particularly among the elderly, the mortality rate is extremely high at 30%-50%. Sepsis reportedly causes immune suppression through apoptosis in immune response cells, but the detailed immune functions among the elderly are as yet unclear. The goal of our research is to: 1) analyze immune function models of aging and septsis and advanced age mice; and 2) investigate potential treatment medicines for elderly sepsis. In this research we focus our attention on growth factor IL-15 in CD8-positive T cells and NK cells.

Researcher(s)
Shigeaki Inoue (Institute of Innovative Science and Technology)

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Pronuclear injection-based mouse targeted transgenesis by site-specific recombination

transgenic mice, site-specific induction, knockdown mice, gene expression derivation

Transgenic (Tg) mouse technology has widely been recognized as a useful tool for analysis of in vivo gene function and generation of mouse models for human disease. They are basically generated by pronuclear injection (PI) of a transgene, but have some drawbacks such as the inability to control the integration site and copy number of the transgene, which often leads to variable and unstable transgene expression. To solve these problems, we established a PI-based targeted transgenesis (PITT) system, in which a single copy of gene of interest (GOI) is inserted into the predefined locus through Cre-loxP site-specific recombination. The PITT method allows the generation of Tg mice with reliable and reproducible GOI expression via direct modification of the zygotic genome.

Researcher(s)
Masato Ohtsuka (Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, School of Medicine)

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ticc_tokai@tsc.u-tokai.ac.jp

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ticc_tokai@tsc.u-tokai.ac.jp

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