'sohhaku OHYAMA' memorial

Institute of Natural Health Science

Oriental Medicine Research Center
Central Research Laboratories

　Dr. Hiroyuki Ohyama, Ph.D.　selfportrait in 1999 (April).

General Manager
Dr. HIROYUKI　OHYAMA (Ph.D)
岡山大学医学博士（分子細胞医学神経情報学）
徳島大学薬学修士（生物薬品化学）

　　　　　　　　　　　　' Model of DNA in combined wire and space filling forms.'

1)

Age-related difference in synaptosomal membrane fluidity

Hiroyuki Ohyama, Midori Hiramatsu, Norio Ogawa, Akitane Mori

Biochemistry and Molecular Biology International 37,133-140,1995

Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical

School, 2-5-1 Shikatacho, Okayama 700, Japan and *Division of Medical Science, Institute for Life

Support Technology, Yamagata Technopolis Foundation, Yamagata 683 Kurumanomae, Numagi, Yamagata 990, Japan


2)

Effect of Japanese herbal medicine(TJ-960) on neuronal membrane fluidity of mice

Hiroyuki Ohyama, Midori Hiramatsu, Rei Edamatsu, Akitane Mori

Magnetic Resonance in Medicine 6, 279-281, 1995


3)

Effect of Japanese herbal medicine(TJ-960), on aging

Midori Hiramatsu, Rei Edamatsu, Hiroyuki Ohyama, Akitane Mori

Lipid-Soluble Antioxidants:Biochemistry and Clinical Applications.

pp.535-552,Birkhauser Verlag,Basel,1992


4)

Combined treatment of Japanese herbal medicine(TJ-960)with low dose of dipropylacetate increased the latent time for

pentylenetetrazol induced convulsion and decreased brain lipid peroxidation in mice.

Hiramatsu,M., Liu J, Edamatsu,R., Kadowaki,D., Hamada,H., Ohyama,H., Watanabe,S., Mori,A.

Neuroscience 18, 71-76,1992


5)
Estimation of nitric oxide and nitric oxide synthase activity in SAMP8 mouse brain

Habu,H., Yokoi,I., Kabuto,H., Ohyama,H., Mori,A., Teraoka,H., Komaru,N.

in: The SAM Model of Senescence (T.Takeda, ed.) pp.343-346,Elsevier Science B.V., Amsterdam, 1994


6)

Age-related changes in nitric oxide content and nitric oxide synthase activity

in senescence-accelerated mouse (SAM P8) brain

Yokoi,I., Inada,K., Habu,H., Kabuto,H., Mori,A., Ohyama,H., Iwaya,K., Koyama,S., Nishijima,Y., Nishijima,K.

in: Oxidative Stress and Aging (R.G.Cutler, L.Packer, J.Bertram, A.Mori, eds.)

pp387-391, Birkhauser Verlag, Basel, 1995


7)

UNESCO / Costam Workshop on Lipid-soluble Antioxidants in Biochemistry of Nutrition and Environmental Health

1991.9.21 (Malaysia)

Effect of Japanese herbal medicine(TJ-960), on aging

Midori Hiramatsu, Rei Edamatsu, Hiroyuki Ohyama, Akitane Mori


8)

Society for Free Radical Research 1991.9027 (Paris)

Japanese herbal medicine(TJ-960) affected free radicals, SOD activity,

lipid peroxidation and neurotransmitter in aged rat brain

Midori Hiramatsu, Rei Edamatsu, Hiroyuki Ohyama, Akitane Mori


9)

5th International Congress on Oxygen Radicals 1991.11.18 (Kyoto)

Decreased membrane fluidity in rat synaptosomes induced by active oxygen species,

guanidino compounds and convulsants

Midori Hiramatsu, Rei Edamatsu, Hajime Hamada, Hiroyuki Ohyama, Akitane Mori


10)

5th International Congress on Oxygen Radicals 1991.11.20 (Kyoto)

Antioxidant effects of the extracts of gastrodia fleta bl. and uncaria rhynchophylla (MJQ) jacks

Jiankang Liu, Hajime Hamada, Hiroyuki Ohyama, Akitane Mori.


11)

The First International Conference on Senescence: The SAM Model 1994.3.17 (Kyoto)

Estimation of nitric oxide and nitric oxide synthase activity in SAMP8 mouse brain

Habu,H., Yokoi,I., Kabuto,H., Ohyama,H., Mori,A., Teraoka,H., Komaru,N.


12)

The First International Conference on Oxidative Stress and Aging 1994.3.25 (Hawaii)

Age-associated changes in nitric oxide (NO) content and nitric oxide synthase (NOS) activity

in senescence accelerated mouse (SAM P8) brain

Yokoi,I., Inada,K., Habu,H., Kabuto,H., Mori,A., Ohyama,H., Iwaya,K., Koyama,S., Nishijima,Y., Nishijima,K.


13)

International Conference on Bioradicals Detected by ESR Spectroscopy 1994.6.13 (Yamagata)

Effect of Japanese herbal medicine(TJ-960) on neuronal membrane fluidity of mice

Hiroyuki Ohyama, Midori Hiramatsu, Rei Edamatsu, Akitane Mori


14)

International Symposium on Natural Antioxidants: Molecular Mechanisms and Health Effects (ISNA) 1995.6.21 (Beijin)

Antioxidant defenses of Japanese herbal medicine(TJ-960) , against free radical induced neural cell damages

Akitane Mori, Hajime Hamada, Hiroyuki Ohyama, Midori Hiramatsu, Seiichi Shinohara


Reference

1)

Mixed Japanese Herbs and Age-Related Neuronal Functions

Midori Hiramatsu and Makiko Komatsu

Antioxidant Food Supplements in Human Health,edited by Lester Packer,

Midori Hiramatsu,Toshikazu Yoshikawa,pp.412-428,1999

2)

Effects of Japanese herbal medicine(TJ-960), on neuronal membrane fluidity of mice

Hiroyuki Ohyama,Midori Hiramatsu,Rei Edamatsu,Akitane Mori.

Magnetic Resonance in Medicine 6,279-281,1995

3)

Antioxidant effect of TJ-960, a Japanese herbal medicine, against free radical-induced neuronal cell damage

Akitane Mori, Hajime Hamada, Hiroyuki Ohyama, Midori Hiramatsu, Seiichi Shinohara

International Symposium on Natural Antioxidants: Molecular Mechanisms and Health Effects(ISNA),pp.45-53.1996

4)

Effect of TJ-960 on generalized seizure in amygdaloid kindled cats

Susumu Iizuka, Atsushi Ishige, Kyoji Sekiguchi, Akira Sugimoto, Kouichi Itoh, Masaki Aburada, Eikichi Hosoya, Eiichi Sugaya

Recent Advances in the Pharmacology of Kampo Medicines pp.62-68,1988

5)

Normalizing effect of SK commercial formula on cytochalasin-B distorted neurites using primary cultured neurons of rat cerebeal cortex

Aiko Sugaya, Mitsutoshi Yuzurihara, Tadashi Tsuda, Eiichi Sugaya

J. Ethnopharmacol., 21: 193-199,1987.

6)

Effect of Kampo Medicine Preparations Using the Pathological Model of Dementia

Michihiro Fujiwara

Brain Research Conference for Japanese Kampo Medicine pp.67-81,1990

7)

Estimation of nitric oxide and nitric oxide synthase activity in SAMP8 mouse brain

Habu,H.,Yokoi,I.,Kabuto,H.,Ohyama,H.,Mori,A.,Teraoka,H.,Komaru,N.

The SAM Model of Senescence(T.Takeda,ed.) pp.343-346,

Elsevier Science  B.V.,Amsterdam,1994

8)

Mixed Natural Antioxidants

Hiramatsu,M.

Food and Free Radicals,edited by Hiramatsu et al.

Plenum Press,New York,pp.113-117,1997


References Vo.1

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(2) Price D.L., Whitehouse P.J. and Struble R.G. Alzheimer's diseases. Ann. Rev. Med. 36, 349-356, 1985.

(3) Appleyard M.E., Smith A.D., Wilcock G.K and Esiri M.M. Decreased CSF acetylcholinesterase activity in Alzheimer's disease. Lancet 20, 452, 1983

(4) Lovell M.A., Ehmann W.D., Butler S.M. and Markesbery W.R. Elevated thiobarbituric acid reactive substances and antioxident enzyme activity in the brain in Alzheimer's disease. Neurology 45, 1594-1601, 1995.

(5)Mutisya E.M., Bowling A.B. and Beal M.F. Cortical cytochrome oxidase activity is reduced in Alzheimer's disease. J. Neurochem. 63, 2179-2184, 1994.

(6) Hensley K., Carney J.M., Mattson M.P., Aksenova M., Harris M., Wu J.F. and Floud R.A. A model for α-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: Relevance to Alzheimer disease. Proc. Natl. Acad. Sci. USA 91, 3270-3274, 1994.

(7) Kasai H. and Nishimura S. Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents. Nucleic Acids Res. 12, 2137-2145, 1984.

(8) Shibutani S., Takeshita M. and Grollman A.P. Insertion of specific nases during DNA synthesis past the oxidation damage base 8-oxodG. Nature 349, 431-434, 1991.

(9) Cheng K.C., Cahill D.S., Kasai H., Nishimura S. and Loeb L.A. 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G→T and A→C substitutions. J. Biol. Chem. 267, 166-172, 1992.

(10) Prasad G.S., Lovell M.A. and Markesbery W.R. Increased nuclear DNA oxidation in the brain in Alzheimer's diseases. J. Neurochem. 71, 2034-2040, 1998.

(11) Sohal R.S., Agarwal S. and Sohal B.H. Oxidative stress and aging in the Mongolian gerbil (Meriones unquiculatus). Mech. Ageing and Dev. 81, 15-25, 1995.

(12) Asuncion J.G., Millan A., Pla R., Bruseghini L, Esteras A., Pallardo F.V., Sastre J. and Vina J. Mitochondrial glutathione oxidation correlates with age-associated oxidative damage to mitochondrial DNA. FASEB J. 10, 333-338, 1996.

(13) Sastre J., Millan A., Asuncion J.G., Pla R., Juan G., Pallardo F., O'Conner E., Martin J.A., Droy-Refaix M.T. and Vina J. A Ginkgo biloba extract (EGb 761) prevents mitochondrial aging by protecting against oxidative stress. Free Rad. Biol. Med. 24, 298-304, 1998.

(14) Mecocci P., Fano G., Fulle S., MacGarvey U., Shinobu L., Polidori M.C., Cherubini A., Vecchiet J., Senin U. and Beal M.F. Age-dependent increases in oxidative damage to DNA, lipids, and proteins in human skeletal muscle. Free Rad. Biol. Med. 26, 303-308, 1999.

(15) Ciani E., Groneng L., Voltattorni M., et al. Inhibition of free radical production or free radical scavenging protects from the excitotoxic cell death mediated by glutamate in cultures of cerebellar granule neurons., Brain Res. 728, 1-6, 1996.

(16) Dawson V.L. and Dawson T.M. Free radicals and neuronal cell death. Cell Death and Differentiation 3, 71-78, 1996.

(17) Pillot T., Drouet B., Queille S., Labeur C., Vandekerckhove J., Rosseneu M., Pincon-Raymond M. and Chambaz J. The nonfibrillar amyloid _-peptide induces apoptotic neuronal cell death: Involvement of its c-terminal fusogenic domain. J. Neurochem. 73, 1626-1634, 1999.

(18) Herbison A.E., Augood S.J. and Slmonian S.X. Regulation of GABA transport activity and mRNA expression by estrogen in rat preoptic ares. J. Neurosci. 15, 8302-8309, 1995.

References Vol.2

1. Chartier-Harlin,M.C. et al. Early-onset Alzheimer's disease caused bymutations at codon precursor protein gene. Nature 353, 844-846 (1991).

2. Sherrington,R.et al. Cloning of a gene bearing missense mutations inearly-onset familial Alzheimer's disease. Nature 375, 754-760 (1995).

3. Rogaev,E.I. et al. Familial Alzheimer's disease in kindreds withmissense mutations in a gene on chromosome 1 related to the Alzheimer'sdisease type 3 gene. Nature 376, 775-778 (1995).

4. Borchelt,D.R. et al. Familial Alzheimer's disease-linked presenilin 1variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron 17,1005-1013 (1996).

5. Duff,K. et al. Increased amyloid beta42 (43) in brains of miceexpressing mutant presenilin 1. Nature 383, 710-713 (1996).

6. Nakano,Y.et al. Accumulation of murine amyloid beta42 with a gene-dosagedependent manner in PS1 'knock-in' mice. Eur.J.Neurosci. 11, 2577-2581(1999).

7. Iwatsubo,T. et al. Visualization of A?42 (43) and A?40 in senileplaques with end-specific A?monoclonals: evidence that an initiallydeposited species is A?42 (43). Neuron 13, 45-53 (1994).

8. Scheuner,D. et al. Secreted amyloid beta-protein similar to that in thesenile plaques of Alzheimer's disease is increased in vivo by thepresenilin a and 2 and APP mutations linked to familial Alzheimer'sdisease. Nature Med. 2, 864-870 (1996).

9. Wong,P.C. et al. Presenilin 1 is required for Notch and Dll1 expressionin the paraxial mesoderm. Nature 387, 288-292 (1997).

10. Davis,J.A. et al. An Alzheimer's disease-linked PS1 variant rescues thedevelopmental abnormalities of PS1-deficient embryos. Neuron 20, 603-609(1998).

11. De Strooper,B. et al. Deficiency of presenilin-1 inhibits the normalcleavage of amyloid precursor protein. Nature 391, 387-390 (1998).

12. Wolfe,M.S. et al. Two transmembrane aspartates in presenilin-1required for presenilin endoproteolysis and gamma-secretase activity.Nature 398, 513-517 (1999).

13. Guo,Q.et al. Alzheimer's presenilin mutation sensitizes neural cells toapoptosis induced by trophic factor withdrawal and amyloid?-peptide:involvement of calcium and oxyradicals. J.Neurosci. 17, 4212-4222 (1997).

14. Guo,Q.et al. Increased vulnerability of hippocampal neurons toexcitotoxic necrosis in presenilin-1 mutant knock-in mice. Nature Med. 5,101-106 (1999).

15. Sidrauski,C.et al. The unfolded protein response: an intracellularsignalling pathway with many surprising features. Trends in Cell Biol. 8,245-249 (1998).

16. Tirasophon,W. et al. A stress response pathway from the endoplasmicreticulum to the nucleus requires a novel bifunctional proteinkinase/endoribonuclease (Ire1p) in mammalian cells. Genes Dev. 12,1812-1824(1998).

17. Wang,X-Z.et al. Cloning of mammalian Ire1 reveals diversity in the ERstress responses. EMBO J. 17, 5708-5717 (1998).

18. Katayama, T. et al. Presenilin-1 mutations downregulate the signalling pathway of unfolded protein response. Nature Cell Biol. in press (1999).

19. Iwatsubo, T. et al. Purification and characterization of Lewy bodiesfrom the brains of patients with diffuse Lewy body disease. Am.J.Pathol.148, 1517-1529 (1996).

20. DiFiglia,M. et al. Aggregation of huntingtin in neuronal intranuclearinclusions and dystrophic neurites in brain. 　Science 277, 1990-1993(1997).

References Vol.3

1) Raff, M. C., Barres, B. A., Burne, J. F., Coles, H. S., Ishizaki, Y., and Jacobson, M. D. (1993) Programmed cell death and the control of cell survival: lessons from the nervous system. Science, 262:695-700.

2) Purves, D.(1988) "Body and Brain" Harverd University Press.

3) Levi-Montalcini, R. And Angeletti, P. (1968) Nerve growth factor, Pysiol. Rev., 48:534-569.

4) Cohen, S. And Levi-Montalcini, R. (1956) A nerve growth-stimulating factor isolated from snake venom. Proc. Natl. Acad Sci. USA, 42:571-574.

5) Johnson, E. M., Gorin, P. D., Brandeis, L. D. And Pearson, J. (1980) Science, 210:916-918.

6) Smeyne, R. J., Klein, R., Schnapp, A., Long, L. K., Bryant, S., Lewin, S. A. and Barbacid, M. (1994) Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF. Nature, 368:246-248.

7) Davies, A. M., Enokido, Y. and Wyatt, S.(1999) Paradigms of neurotrophic factor action in regulating neuronal survival in the developing nervous system. Taniguchi Symposium, in press.

8) Davies, A. M., Bandtlow, C., Heumann, R., Korsching, S., Rohrer, H. And Thoenen, H. (1988) Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor. Nature, 326:353-358.

9) Wyatt, S. And Davies, A. M.(1993) Regulation of expression of mRNAs encoding the nerve growth factor receptors p75 and trkA in developing sensory neurons. Development, 119:635-648.

10) Buchman, V. L., and Davies, A. M.(1993) Different neurotrophins are expressedand act in a developmental sequence to promote the survival of embryonic sensory neurons. Development, 118: 989-1001.

11) Davies, A. M. (1997) Neurotrophin switching: where does it stand? Curr. Opin. Neurobiol.,7:110-118.

12) Verdi, J. M. And Anderson, D. J. (1994) Neurotrophins regulate sequential changes in neurotrophin receptor expression by sympathetic neuroblasts.Neuron, 13:1359-1372.

13) Wang, H. And Tessier-Lavigne, M.(1999) En passant neurotrophic action of and intermediate axonal target in the developing mammalian CNS. Nature, 401;765-769.

14) Davies , A. M. and Wright, E. M. (1995) Neurotrophin autocrine loops. Curr. Biol., 5:723-726.

15) ElShamy, W. M., Fridvall, L. K. and Ernfors, P.(1998) Growth arrest failure, G1 restriction point override, and S phase death of sensory precursor cells in the absence of neurotrophin-3.Neuron, 21:1003-15

16) Enokido, Y., Wyatt, S. and Davies, A. M. (1999) Developmental changes in the response of trigeminal neurons to neurotrophins: influence of birthdate and the ganglion environment. Development, 126:4365-4373.

17) Ma, Q., Fode, C., Guillemot, F. and Anderson, D. J.(1999) NEUROGENIN1 and NEUROGENIN2 control two distinct waves of neurogenesis in developing dorsal root ganglia. Genes & Dev., 13:1717-1728.

18) Ma, Q., Chen, Z., del Barco Barrantes, I., de la Pompa, J. L. and Anderson, D. J. (1998) Neurogenin1 is essential for the determination of neuronal precursors for proximal cranial sensory ganglia. Neuron, 20:469-82

19) Fode, C., Gradwohl, G., Morin, X., Dierich, A., LeMeur, M., Goridis, C. and Guillemot, F. (1998) The bHLH protein NEUROGENIN 2 is a determination factor for epibranchial placode-derived sensory neurons. Neuron, 20:483-94

20) O'Connor, R. and Tessier-Lavigne, M.(1999) Identification of maxillary factor, a maxillary process-derived chemoattractant for developing trigeminal sensory axons. Neuron, 24:165-178.

21) Lumsden, A. G., and Davies, A. M. (1983) Earliest sinsory nerve fibers are guided to peripheral targets by attractants other than nerve growth factor. Nature,306:786-788.

22) Tessier-Lavigne, M., and Placzek, M. (1991) Target attraction: are developing axons guided by chemotropism? Trends Neurosci., 14:303-310.

23) Blasschke, A. J., Staley, K. and Chun, J.(1996) Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex. Development, 122:1165-1174.




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