Report on the Visit Program of Prominent Foreign Researcher

Itinerary of Stay

Date

Names and Details of Places of Visit (Research Discussion, Lectures, Visits, etc.)

Monday, February 17, 2003

3:50 pm: Arrival at Kansai International Airport; transfer to Shin-Osaka Station by taxi; travel by Shinkansen (Nozomi 28, 19:53 ~ 22:10) to Shin-Yokohama. During this train journey, briefing was given on the outline of the research progress on the joint research topic, "Investigation of cell function regulation through the nitration and denitration of proteins" and discussions were conducted thereon. Then, with the direction and instruction received, the Osaka University, Division of Pathogenesis and Control of Oral Diseases (Department of Pharmacology) was contacted and preliminary research was started in order to make research findings more concrete. Overnight stay at the Yokohama Grand Intercontinental Hotel.

Tuesday, February 18, 2003

Morning: Visit to the Yokohama City University School of Medicine; with the participation of Associate Professor Atsushi Nakajima of the Yokohama City University School of Medicine Department of Internal Medicine III, which is engaged in joint research with the Osaka University Division of Pathogenesis and Control of Oral Diseases (Department of Pharmacology), discussions were conducted on the research topic, "Functional change due to the nitration of PPARγ." The possibility that nitration is not simply a functional disorder was pointed out. 16:00 ~ : A special lecture was held at the Yokohama City University School of Medicine; in front of an audience of 300, a lecture was given on the course of research undertaken by Dr. Murad up to the award of the Nobel Prize; the audience was told of the difficulty in conceiving a new research theme and the importance of continuing with the research; overnight stay at the hotel as above.

Wednesday, February 19, 2003

Transfer to Shin-Yokohama Station by taxi; travel by Shinkansen (Nozomi 7, 9:09 ~ 11:10) to Kyoto; visit to the Kyoto University Graduate School of Pharmaceutical Sciences; an informal research discussion was held with young researchers including postgraduate students; travel by Shinkansen (Nozomi 79, 18:38 ~ 18:53) to Shin-Osaka; transfer to hotel by taxi; overnight stay at the Osaka Rihga Royal Hotel.

Thursday, February 20, 2003

Morning: Transfer by taxi to the Osaka University Graduate School of Dentistry; at the Osaka University Ityo-Hall Minerva and the Osaka University Graduate School of Dentistry, former Japanese researchers who had worked in the Murad Lab were invited (Toshihiro Dohi, Professor of Biomedical Sciences, Hiroshima University Graduate School; Takayoshi Kuno, Professor of Pharmacology, Kobe University School of Medicine; Kunio Ishii, Professor of Pharmacy, Kitasato University; Shuichi Saeki, Professor of Health Services Center, Ehime University) to join in the discussions; members of the Osaka University Graduate School of Dentistry, Integrated Oral Sciences and Stomatology; Division of Pathogenesis and Control of Oral Diseases (Department of Pharmacology) gave a presentation on the research and findings of the joint research already being conducted on the "Investigation of cell function regulation through the nitration and denitration of proteins;" Dr. Ferid Murad gave a presentation on research being conducted at The University of Texas, Houston Medical School, Department of Integrative Biology, Pharmacology and Physiology; comments and ideas were exchanged and under Dr. Muradfs guidance, research was carried out; overnight stay at the hotel as above.

Friday, February 21, 2003

Participation in the 22nd Conference of Japanese Society of Oral Therapeutics and Pharmacology to give a special lecture (11:00 ~ 12:00) on medicinal therapy in the oral cavity field. Afternoon: transfer by taxi to the Osaka University Graduate School of Dentistry to give special research instruction; then return to the said conference to take part in the discussion session with members of the society attending the conference; overnight stay at the hotel as above.

Saturday, February 22, 2003

Participation in the above-mentioned conference; overnight stay at the hotel as above.

Sunday, February 23, 2003

Morning: Rest at the hotel. Afternoon: Transfer by taxi from hotel to Kansai International Airport; departure at 15:45.

Guest Researcher Visits and Their Achievements

This is the third and the final year of this grant program, and therefore, in addition to the unidirectional lectures such as special lectures given by Dr. Murad, we introduced research and informal discussions as instruments to attaining greater success. The format was that of Japanese researchers giving a presentation on the diverse research projects they are currently engaged in and of their receiving the Nobel laureate Dr. Murad's valuable comments.

What in effect took place was the gathering of virtually all of the Japanese researchers who had studied in Dr. Murad's laboratory (namely, Toshihiro Dohi, Biomedical Sciences, Hiroshima University Graduate School; Takayoshi Kuno, Professor of Pharmacology, Kobe University School of Medicine; Kunio Ishii, Professor of Pharmacy, Kitasato University; Shuichi Saeki, Professor of Health Services Center, Ehime University; Miyuki Kuno, Associate Professor of Physiology, Osaka City University Medical School; Koichiro Wada, Lecturer, Osaka University Graduate School of Dentistry; Yasuo Irie, Research Assistant, Osaka University Graduate School of Medicine; Makio Saeki, Research Assistant, Osaka University Graduate School of Dentistry). A research discussion session took place. Although these researchers had all received research training from Dr. Murad, it can undoubtedly be surmised that giving a briefing on ongoing research and receiving Dr. Murad's comments were extremely useful in carrying on future research in Japan.

In addition, similar research presentation sessions took place with young researchers, chiefly some PhD candidates, in the Osaka University Graduate School of Dentistry and the Kyoto University Graduate School of Pharmaceutical Sciences, involving research discussions with Dr. Murad. More than fifty participants took part in total. Because preliminary research data were discussed with lecturers and graduate students studying for master's degrees, the sessions gave participants great stimuli and motivation, far beyond one-way lectures given by the prominent guest researcher hitherto.

Though this visit was amidst the Iraq crisis and in the wake of the Space Shuttle disaster, the program was executed as planned. This is a manifestation of the strong commitment of Dr. Murad towards the joint research project with our host department. This is all the more notable because of Dr. Muradfs last visit to Japan, which took place soon after the events of September 11.

Here, we wish to comment mainly on the results of this recent guest visit and also include observations on the achievement of the joint research project as a whole over the past three years.

The status and achievements of the host institution, the Osaka University Graduate School of Dentistry, Division of Pathogenesis and Control of Oral Diseases (Department of Pharmacology)

As in other years, briefings and presentations were given by both sides regarding the research topic, "Investigation of cell function regulation through the nitration and denitration of proteins." Both the Osaka University and Dr. Murad, presented research findings so far and an exchange of views was held. We were able to achieve valuable results that would have been impossible to obtain through remote discussions via e-mail. This system of regular research findings exchange by the two laboratories working on the same theme has enabled both parties to adjust the course of research and was therefore very useful. The results obtained from this joint research are huge, as can be readily surmised from the list of papers published, which is given below.

Furthermore, Dr.Makio Saeki, who is a research assistant at the host laboratory, was able to stay and conduct research as a Ministry of Education-sponsored young overseas research fellow from April to October 2001 at The University of Texas, Houston Medical School, Department of Integrative Biology, Pharmacology and Physiology, which is where Dr. Murad is based. Our grant program is responsible not only for this opportunity becoming available but also for a good deal of results being achieved despite the short time available for research, with research commencing immediately after Dr. Saeki's arrival in Houston. The host institution is already playing a full international role; however, in view of such a specific example as mentioned above, there is no doubt that this international role has been enhanced further.

Additionally, although not mentioned in this report, it goes without saying that thanks to suggestions given by our lab, Dr. Murad's research has been promoted, resulting in better research achievements being made.

Meanwhile, under the direction of Dr. Murad, our lab members were instructed in conducting research on "Communication via NO, a gas molecule, Between micro-organisms in the process of life formation." However, since such research was carried out only at the time of Dr. Murad's visit to Japan, satisfactory results were not obtained. As it is inconceivable that Dr. Murad, the Nobel prize-winner, will have direct personal involvement in the research, the research budget allocated for each of the visits is not adequate to produce a fully satisfactory result by means of this joint research.

Given below is a list of publications that resulted from this joint research project, describing research relating to nitric oxide and the nitration of proteins. Besides these, there are currently several other research papers in the pipeline for publication.

  1. Saeki, M., Kamisaki, Y., Maeda, S.: Potentiation of carbachol-induced Ca2+ release by peroxynitrite in human neuroblastoma SH-SY5Y cells. Neurochem Res, 25: 909-914, 2000.
  2. Saeki, M., Kamisaki, Y., Maeda, S.: Involvement of mitogen-activated protein kinase in peroxynitrite-induced cell death of human neuroblastoma SH-SY5Y cells. Neurosci Res, 238: 213-216, 2000.
  3. Fujimori, Y., Maeda, S., Saeki, M., Kamisaki, Y.: Inhibition by nifedipine of adherence- and activated macrophage-induced death of human gingival fobroblasts. Eur J Pharmacol, 415(1): 95-103, 2001.
  4. Saeki, M., Maeda, S., Wada, K., Kamisaki, Y.: Insulin-like growth factor-1 protects peroxynitrite-induced cell death by preventing cytochrome c-induced caspase-3 activation. J Cell Biochem, 84: 708-716, 2002.
  5. Saeki, M., Maeda, S., Kamisaki, Y.: Vanadate protects human neuroblastoma SH-SY5Y cells against peroxynitrite-induced cell death. J Cell Biochem, 85: 721-727, 2002.
  6. Shiojiri, T., Wada, K., Nakajima, A., Katayama, K., Shibuya, A., Kudo, C., Kadowaki, T., Mayumi, T., Yura, Y., and Kamisaki, Y.: PPARE ligands inhibit nitorotyrosine formation and inflammatory mediator expressions in adjuvant-induced rheumatoid arthritis mice. Eur J Pharmacol, 448: 231-138, 2002.
  7. Shibuya, A., Wada, K., Nakajima, A., Saeki, M., Katayama, K., Mayumi, T., Kadowaki, T., Niwa, H., and Kamisaki, Y.: Nitration of PPARE inhibits ligand-dependent translocation into the nucleus in a macrophage-like cell line, RAW 264. FEBS Lett, 525(1-3): 43-47, 2002.
  8. Yonehara, N. Amano, K., Kamisaki, Y.: Involvement of the NMDA-nitric oxide pathway in the development of hypersensitivity to tactile stimulation in dental injured rats. Jpn J Pharmacol, 90: 145-155, 2002.
  9. Yonehara, N., Kudo, C., and Kamisaki, Y.: Involvement of NMDA-nitric oxide pathways in the development of tactile hypersensitivity evoked by the loose-ligation of inferior alveolar nerves in rats. Brain Res, 963: 232-243, 2003.
  10. Katayama, K., Wada, K., Nakajima, A., Mizuguchi, H., Hayakawa, T., Nakagawa, S., Kadowaki, T., Nagai, R., Kamisaki, Y., Blumberg, R.S., and Mayumi, T.: A novel PPARE-gene therapy to control inflammation associated with inflammatory bowel disease in a murine model. Gastroenterol., in press, 2003.
  11. Kudo, C., Kori, M., Matsuzaki, K., Yamai, K., Nakajima, A., Shibuya, A., Kamisaki, Y., Wada, K.: Diclofenac inhibits proliferation and differentiation of neural stem cells. Biochem. Pharamcol. in press, 2003.

Hosting by Osaka University as a Whole and Achievements:

In this year's program, lectures and research discussion sessions were conducted in universities visited for the first time, namely the Yokohama City University and Kyoto University. This meant that Dr. Murad's stay in Osaka became shorter and thus contribution to Osaka University as a whole was little. However, the research discussion was held as an open session and not limited to the host lab. Consequently, within the Graduate School of Dentistry, Dr. Ichiro Nakagawa, Lecturer in the Division of Oral Infections and Diseases Control, made a presentation for Dr. Murad, discussing the role of nitric oxide in oral cavity infection. Comments were received from Dr. Murad and discussions proceeded.

In addition, discussions had already been carried out on research details with the Graduate School of Medicine, Department of Pharmacology (Miki Lab), Institute for Protein Research (Hatanaka Lab, Aimoto Lab), and the Graduate School of Pharmaceutical Sciences (Kita Lab, Mayumi Lab), including the possibility of engaging in joint research. Therefore, both direct and indirect benefits are thought to be considerable.

In these and other ways, there is no end to listing the benefits and achievements, both tangible and intangible, of receiving Dr. Murad in Japan.

Special Lectures and Their Achievements

As already pointed out, the emphasis this year was on discussion-style exchanges, and therefore, no special lecture was given at Osaka University.

Still, for new places and for students and researchers in new areas, special lectures were offered as before. Namely, these were the lecture given at the Yokohama City University School of Medicine and the special lecture delivered at the 22nd Conference of Japanese Society of Oral Therapeutics and Pharmacology. These were targeted at those working in faculties of medicine and in dental care. Participants totaled 300 and 500 respectively. In particular, at the Yokohama City University School of Medicine, the lecture was so popular that the large lecture theater with a maximum audience seating of 300 exceeded capacity for the first time since it was built and some students stood to listen to the lecture. The title of the lecture was "The Role of Nitric Oxide and Cyclic GMP in Cell Regulation." In addition to the academic content suggested from this title, the lecture included an explanation of how the Nobel Prize-winning research was conceived and embarked upon. For researchers in the field, we believe the lecture was useful in terms of identifying research themes and continuing with research.

When Dr. Murad first came to Japan in October 2001, he gave a special lecture at the Osaka University Faculty of Dentistry, entitled "Signal Transmission and Nitric Oxide." In September 2002 in Kyoto, he gave a lecture for Neuro 2001 and engaged in conference discussions with members of the Japanese Neurochemical Society and Neuroscience Society. Thanks to these activities, it is believed that Dr. Muradfs ideas on research have become well known among Japanese researchers in different fields. Above all, for participating students, they came into close contact with a world-renowned researcher, and for researchers, they were able to understand how ideas were formed that led to the award of the Nobel Prize and how research topics were found and how the research progressed and developed. These must have assisted them in reconfirming the importance of attitudes and ideas in future research.

Contribution of Guest Researcher towards Host Institution

(E.g. stimulus to young researchers, internationalization of host organization as a whole)

This year, a new format of research discussion session was adopted. Researchers were invited not only from the Osaka University Graduate School of Dentistry but also from Osaka University at large and from outside the university as well to conduct exchanges including young researchers. This was an unprecedented format in which, rather than receiving one-way lectures from Dr. Murad, researchers made presentations of their own work to receive comments from Dr. Murad. This was an attempt whereby Japanese researchers would add his or her own ideas onto ideas gleaned from the previous year's lecture, develop them and demonstrate them. The results of these efforts would be deliberated together with Dr. Murad. This format was thought to be in perfect accord with the purpose of this grant program, giving even more lucid embodiment to Dr. Muradfs concepts relating to research. This format was taken not only at the host institution concerned but also at the Kyoto University Graduate School of Pharmaceutical Sciences, where a similar energetic research discussion session took place with young researchers. The results of these discussions, we hope, would be published from different labs throughout Japan and not be confined to the Osaka University Graduate School of Dentistry, Division of Pathogenesis and Control of Oral Diseases (Department of Pharmacology).

In first-time areas and audiences, the conventional lecture format was adopted whereby Dr. Murad's ideas were communicated to the relevant researchers. In other words, at the Yokohama City University School of Medicine and at the 22nd Conference of Japanese Society of Oral Therapeutics and Pharmacology, lectures were given under the title "The Role of Nitric Oxide and Cyclic GMP in Cell Regulation." Participants numbered 300 and 500 in the respective venues. The lectures were tailored to the target audience, medical faculty members and those involved in dental care. In particular, as the content of the lectures was the regulatory mechanism of nitric oxide, whose application in clinical practice is raising expectations, it was thought that they were useful to clinicians and medical researchers as well. The previous reports have already stated that highly satisfactory results have been obtained through face-to-face discussions in friendly meetings and lectures at Neuro 2001 in Kyoto as well as in the Osaka University Graduate School of Dentistry and Faculty of Dentistry.

We wish to add that during this grant period, Dr.Makio Saeki, research assistant in the host department (Osaka University Graduate School of Dentistry, Division of Pathogenesis and Control of Oral Diseases [Department of Pharmacology]) and Dr.Yasuo Irie, research assistant in the Osaka University Graduate School of Medicine, Department of Pharmacology were able to study at The University of Texas, Houston Medical School, Department of Integrative Biology, Pharmacology and Physiology where Dr. Murad belongs. It is clear that this grant program led to the study opportunity becoming available. Furthermore, postgraduate students who completed studies at the Osaka University Graduate School of Medicine have been dispatched to Dr. Murad's laboratory as post-doctoral fellows and research is currently being pursued energetically. In this way, there is no doubt that the visits by Dr. Murad under this grant program have been instrumental in the overseas study of young researchers at Osaka University.