Staff
Nobuyuki Hamada, Ph D
Present Address: Department of Infectious Medicine, Division of Infectious Disease, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Fukuoka, Japan
E-mail: nhamada@med.kurume-u.ac.jp
Specialty; Virology
Degrees;
Doctor of Agriculture (1981, Kyushu University)
Doctor of Medical Science (1991, Kurume University School of Medicine)
Qualifications;
First Grade Radiation Control Manager in Japan
Infection Control Doctor in Japan
Research project (it contains completed projects)
- Molecular epidemiology of rotavirus, enterovirus and influenza virus.
- Analysis of carcinogenesis by mouse mammary tumor virus
- Analysis of antibody dynamics in HSV-1 infection
- Characterization of influenza virus RNA polymerase
- Functional analysis of reticulon
- Characterization of G protein of human metapneumovirus
List of major publications
1) Honda H., Iwahashi J., Kashiwagi T., Anraku T., Ueda S.,Imamura Y., Hamada N. et al. Outbreak of human metapneumovirus infection in elderly inpatients in Japan JAGS (Journal of american geriatrics society) 54,177-180, 2006
Significance
We found outbreak of pneumoniae of aged people in a hospital. We first failed to identify the pathogens (bacteria, RSV, parainfluenza virus, enterovirus, rhinovirus, influenza virus). Finally we detected human metapneumovirus gene in eight patients out of eighteen patients. Then we confirmed the 4-fold increase of antibody in all eight patients. This is a first report concerning outbreak of human metapneumovirus infection.
2) Honda H., Imamura Y., Matsueda S., Hamada N.：Mutation analysis of Influenza viruses detected in medical stuffs within short period RINSHOTOUIRUSU 33, 347-352, 2005 (in Japanese)
Significance
In influenza outbreak, it is difficult to survey the route of infection. This report describes that precise analysis of influenza virus gene contributes to unveil a part of infection route.
3) Kashiwagi, T., Hara, K., Kohara, M., Kohara, K., Iwahashi, J., Hamada, N., Yoshino, H., Toyoda, T.: Kinetic analysis of C-terminally truncatedRNA-dependent RNA polymerase of hepatitis C virus. : BBRC 290: 1188-1194, 2002
4) Kashiwagi, T., Hara, K., Kohara, M., Iwahashi, J., Hamada, N., Honda-Yoshino, H., Toyoda, T.: Promoter/ Origin structure of the complementary strand of Hepatitis C virus genome. JBC277: 28700-28705, 2002
5) Iwahashi, J., Kawasaki, I., Kohara, Y., Gengyo-Ando, K., Mitani, S., Ohshima, Y., Hamada, N., Hara, K., Kashiwagi, T., Toyoda, T.: Caenorhabditis elegans reticulon interacts with RME-1 during embryogenesis. BBRC 293: 698-704, 2002
6) Hamada, N., Iwahashi, J., Suzuki, K., Ogi, H., Kashiwagi, T., Hara, K., Toyoda, M., Yamada, T., Toyoda, T.: Molecular cloning and characterization of the mouse reticulon 3 cDNA. Cell. Molec. Biol. 48: 163-172, 2002
Significance
During another project we discovered the new gene by chance which strongly expressed in neuron. It was recognized to be one of the RTN family proteins, and we registered in GenBank as mRTN3 (accession number: AB046114). We performed the cloning and characterization of mRTN3. During our study, one of the function of RTN4, which contributes to inhibition of neurite outgrowth, was reported and a report suggested likelihood of drug development for central nervous system reproduction. References with glucosylseramide synthase concerned with the fat raft build-up, apoptosis induction (Bcl-xL) , virus adsorption and cell function were also reported. Recently, RTN3, which is orthologue of mRTN3, inhibited b-secretase (BACE1), which produces amyloid-b for the Alzheimer onset（He, W. et al.: Reticulon family members modulate BACE1 activity and amyloid-β peptide generation. Nature Medicine Online 1 August, 2004）. In a recent review in FASEB Journal our paper was quoted as murine RTN study. After completion of this study, we also found RTNs to function in intracellular vesicular transport (5, 6). RTN was known as a useful neuroendocrine marker of lung small cell carcinoma. We thought that RTN might be related to carcinogenesis. We want to study the relationship between hepatitis C virus continuous infection and hepatocellular carcinoma.
7) Iwahashi, J., Tsuji, K., Ishibashi, T., Kajiwara, J., Imamura, Y., Mori, R., Hara, K., Kashiwagi, T., Ohtsu, Y., Hamada, N., Maeda, H., Toyoda, M., Toyoda, T.: Isolation of amatadine-resistant influenza A viruses (H3N2) from patients following administration of amantadine in Japan. J. Clin. Micro. 39: 1652-1653, 2001
8) Hara K., Kashiwagi, T., Ohtsu Y., Masunaga, K., Akasu-Tsuji Y., Tsumura N., Kato H.,Iwahashi, J., Hamada, N., Toyoda, M., Toyoda, T.: Molecular evolution of human echovirus 9 isolated from patients with aseptic meningitis in northern kyushu during the summer of 1997. Microbiol. Immunol. 45: 717-720, 2001
9) Toyoda, T., Imamura, Y., Takaku, H., Kashiwagi, T., Hara, K., Iwahashi, J., Ohtsu, Y., Tsumura, N., Kato, H. Hamada, N.: Inhibition of influenza virus replication in cultured cells by RNA-cleaving DNA enzyme. FEBS lett. 484: 113-116, 2000
10) Kashiwagi, T., Hamada, N., Iwahashi, J., Hara, K., Ueda, T., Noguchi, H., Toyoda, T.: Emergence of new influenza A virus which carry an escape mutation of the HLA-B27-restricted CTL-epitope of NP in Japan. Microbiol. Immunol. 44: 867-870, 2000
11) Hamada, N., Masunaga, K., Ohtsu, Y., Tsuji, K., Shingu, M., Toyoda, T.: Nucleotide sequence of the gene encoding the RNA polymerase and the 3’non-coding region of a bovine enterovirus Japanese isolate: Rapid synonymous substitution between European and Japanese strains. Arch. Virol. 143: 815-821, 1998
Significance
Recently, anticancer therapy by virus is reevaluated as one of carcinomatous multidisciplinary therapeutics (A trial of oncolytic virotherapy using herpes simplex virus HF10 strain. The 11th Japan Herpesvirus Infections Forum. Nishiyama, Y. (Nagoya University), Otaru, Japan, 2004/8). On the other hand, in recent reviews related to oncolytic virotharapy（J. Gen. Virol. 85: 3195 - 3203, 2004）previous report by our colleagues（Shingu, M. et al. Therapeutic effects of bovine enterovirus infection on rabbits with experimentally induced adult T cell leukaemia. J Gen Virol 72, 2031-2034, 1991）was quoted as a significant therapy. This paper described the characterization of enterovirus MZ468 strain, which was used in above paper. This study is focusing on mutation during its propagation in living cells. This paper was also quoted as an example of viral evolution rate in recent report（Smits, SL. et al.: Phylogenetic and evolutionary relationships among Torovirus field variants: Evidence for multiple intertypic recombination events. J Virol. 77: 9567-9577, 2003）.
We think that this paper may offer extremely useful information for researcher, who wants to apply enterovirus to anticancer therapy, and who studies viral evolution.
12) Komine T., Kameyama T., Terasaki S., Fujita H., and Hamada N. Recurrent behavior after primary infection with Herpes simplex virus type 1 (Report of 2 cases) J. Jpn. Stomatol. Soc.47: 392-396, 1998 (in Japanese)
Significance
During recurrent infection with HSV type I, dynamics of antibody is complex. This report describes dynamics of antibody (IgG, IgM, NT) for about one year. This datum may supply an useful information to researcher, who want to interpret the elevation of various antibody in a patient at one point.
13) Yamamoto, S., Hamada, N., Shingu, M.: Two novel genes of Herpes simplex virus type 1 involved in cell fusion. Kurume Med. J. 40: 169-175, 1996
14) Iwai, H., Day, N.K., Hamada, N., Inaba, M.M., Ikehara, S., Good, R.A.: Bone marrow transplantation therapy using resistant donors for retrovirus-induced leukaemia in mice. Clin. Exp. Immunol. 95: 135-140, 1994
Significance
The HAART therapy has been standardized recently, but exclusion of HIV is impossible even now. This report describes a bone marrow transplantation therapy against AIDS using mouse AIDS model
15) Imamura, Y., Hamada, N., Nagai, T., Shingu, M.: Detection and typing of human rotavirus in reference to repeated acute gastroenteritis in infants. Microbiol. Immunol. 38: 673-676, 1994
Significance
Stool specimens from infants who visited a clinic because of acute gastroenteritis were tested for the presence of human rotavirus. Among the samples obtained were specimens taken from seven patients who had visited the clinic at two different times. In six of these seven children, human rotavirus (HRV) was detected in only one of the specimens taken (i.e. during only one of the two visits). One patient was shown to have excreted HRV twice; in both cases the HRV was serotyped to be type 1. The present results indicate that the symptomatic reinfection of HRV was not a widely occurring phenomenon in the group of infants tested.
16) Engelman, R.W., Fukaura, Y., Hamada，N.，Good, R.A., Day, N.K.: Dietary restriction permits normal parturition and lactation but suppresses mouse mammary tumor virus proviral transcription even after mammary involution. Cancer Research 51: 5123-5128, 1991
17) Hamada, N., Engelman, R.W., Tomita, Y., Chen. R-F., Iwai, H., Good, R.A., Day, N.K.: Prolactin effects on the dietary regulation of mouse mammary tumor development. Proc. Natl. Acad. Sci. USA. 87: 6733-6737, 1990
Significance
Recently, the onset of mammary cancer increases in Japan, and the prevention is important. A mammary tumor virus of human is not known, but pathology of the mammary cancer by murine MMTV resembles it. We studied the prophylaxis using the laboratory mouse which autonomously developed breast cancer. We discovered that a dietary calorie restriction completely inhibited the mammary cancer onset. A calorie restriction of a diet causes reduction of prolactin, and it inhibits the mammary cancer onset, namely MMTV mRNA expression decreases. Furthermore, expression of MMTV mRNA was inhibited clearly by parous mouse when it limited a diet calorie, the expression increased when we removed a limit of a meal calorie for lactation. In other words a calorie restriction regulates expression of MMTV mRNA reversibly. It was also found that a calorie restriction did not influence childbirth(No.16). These studies produced the significant publication by our colleagues（Engelman RW, Day NK, Good RA.: Mammary and submandibular gland epidermal growth factor expression is reduced by calorie restriction. Cancer Res. 55:1289-1295, 1995）. This study is also quoted in the latest paper（Michels, KB., Ekbom, A.: Caloric Restriction and Incidence of Breast Cancer JAMA291:1226-1230, 2004）.
18) Chen, R-F., Good, R.A., Engelman, R.W., Hamada, N., Tanaka, A., Nonoyama, M., Day, N.K.: Suppression of mouse mammary tumor proviral DNA and protooncogene expression: Association with nutritional regulation of mammary tumor development. Proc. Natl. Acad. Sci. USA. 87: 2385-2389, 1990
19) Hamada, N., Tamada, S., Shingu, M.: A trial of molecular epidemiology using bovine enteroviruses isolated monthly from cattle. Arch. Virol. 111: 63-74, 1990
Significance
Inapparent infection holds over 90% in enterovirus infection. We usually obtain specimen only from the patient for virus isolation. Therefore, most studies on the route of infection, we usually use the limited specimen. As it were, the analysis using the limited samples might have some biased results. We used 47 cows of a certain ranch to elucidate epidemiologic status as an infection model. As a result, I clarified viral genetic diversity increased as enteroviral transmission progressed. When infection from other individuals occurred, genetic variety suddenly increased. We may eradicate poliomyelitis in future. There are some obstacles for the eradication: prevalence of inapparent infection and revertant strain of vaccine. Declaration of WHO eradication of poliomyelitis in the world is postponed every year. The result will be some contributions to eraborate the eradication strategy for polio.
20) Makadam, A.J., Arnold, C., Howlett, J., John, A., Marsden, S., Taffs, F., Reeve, P.,Hamada, N., Wareham, K., Almond, J., Cammack, N., Minor, P.D.: Reversion of the attenuated and temperature-sensitive phenotypes of the sabin type-3 strain of poliovirus in vaccinees. Virology 172: 408-414, 1989
21) Hamada，N.，Imamura, Y., Shingu, M.: Correlation between plaue size and genetic variation of type 3 poliovirus from a vaccinate. J. Medical Virol. 24: 1-9, 1988
Significance
It has been thought that the polio vaccine is almost finished product. However, vaccine-related paralysis is reported in a ratio of around 1 example by millions of people. At first we examined dynamics of a vaccine virus in healthy person to elucidate vaccine-related paralytic eruption mechanism. As a result, we found the rare virulent strain that was not a genetic recombinant strain. The researcher of British Research Institute (NBSC) investigated the virulence to a monkey. They found that the virus was virulent, and named the strain "Poliovirus type 3 NH strain". (No.20）. This report (No. 21) is also indispensable for the No.20. The No. 20 is a valuable report even now and it is quoted at least 11 times on J Virol between 2003 since 1998, also it is quoted to a standard textbook of picornavirus（Molecular Biology of Picornaviruses (a 2002 version, ASM publication) Chapter 30 p.383）.
REVIEW
Nobuyuki Hamada “Influenza Enteritis” SOUGOURINSHOU 51: 2977-2983, 2002 (in Japanese)
Significance
Most clinician thinks that influenza enteritis may exist. At the same time, they think that it is difficult to prove it. This review describes that the significance of “influenza enteritis” diagnosis and the methods to prove it.
This review also describes that influenza enteritis is often observed in influenza type B infection. Finally the mechanism of influenza enteritis by influenza virus was presumed.