SUMMARY REPORTS OF EXCHANGE SCIENTISTS

(1) William F. Benedict, M.D.
Childrens Hospital of Los Angeles 4650 Sunset Boulevard, Los Angeles, CA 90027

Sponsor and Host Institution:
Dr. Yoji Ikawa, M.D., Ph. D., Institute of Physical & Chemical Research, Hirosawa 2-1 Wako-Shi, Saitama 351, Japan
Dates of Visit: September 11 - October 2, 1985

Summary of Activities:
The purpose of my visit was to share our information on the retinoblastoma gene throughout Japan as well as to consider possible collaborative research. I gave numerous lectures throughout Japan which included Tsukuba, Tokyo, Mishima, Kyoto, Okayama, Kobe and Osaka. I believe the frank interchange with my Japanese colleagues was very much appreciated. Following my visit various 1 3 chromosome probes were provided throughout Japan and are now being utilized in several laboratories for various purposes. In addition, ongoing collaborative research has been set up between our laboratory and various laboratories in Japan regarding the cloning of the retinoblastoma gene. These include Dr. Ikuko Kondo in Tsukuba and Dr. Masao Sasaki in Kyoto. Several new collaborations have been set up between individuals within Japan as the result of my visit. In addition Dr. Taketoshi Sugiyama will be sending us an excellent post doctoral fellow in the Fall of this year as well as an additional post doctoral fellow at the beginning of next year to participate in our program. Therefore, I believe this exchange was extremely beneficial and I expect that it will result in a long term collaboration and scientific interchange between my laboratory and several laboratories in Japan. I am also told that it has stimulated a considerable amount of research activity among various investigators in Japan as well.



Scientist Exchange Summary Report
Full Name: Takeshi Watanabe
Home Institution: Medical Institute of Bioregulation, Kyushu University

Sponsor and Host Institution:
Dr. Pawl W. Kincade, Oklahoma Medical Research Foundation
Dates of Visit: March 18, 1986- March 30, 1986

Summary of Activities:
Long-term bone marrow culture and its application on the study of immunoglobulin gene expression. In the laboratory of Dr. Kincade, culture system of long-term bone marrow culture has been set up by Dr. P. Witte. They also succeeded to establish the stroma cell line which maintain B-lymphocyte differentiation in vitro. I learned the condition and techniques for that culture. We have discussed on the study of control mechanism of immunoglobulin gene expression using long-term bone marrow culture.
Analysis of the mechanisms involved in cell-specific and differentiation-stage specific gene expression of immunoglobulin genes and T-cell receptor genes. We have determined cis-acting DNA elements which are responsible for a cell-specific expression of Ig gene and transacting factors responsible for activation of enhancer elements. Concerning these problems, I discussed with Drs. R. Wall, K. Calame, O. Witte and J. Braun of UCLA, and Drs. M. Davis, I. Weissman of Stanford University. We reported previously the presence of repressor molecules which negatively control Ig gene expression. Dr. R. Wall also reported the similar repressor which acts on Ig gene. With Dr. Calame, we discussed on the transacting factor which meight bind to enhancer sequence.
Production of human monoclonal antibody by DNA-recombinant technology. We have established the method to produce human monoclonal antibody by using human enhancer gene and human Immunoglobulin genes. Dr. Irie of UCLA and we decided to start to produce human monoclonal antibody against melanoma by applying our method.
In summary, in the present trip, I met and discussed with many researchers in the various field. Discussion and exchange of information were very stimulatory to me and fruitful.
Signature
Date: Apr. 3, 1986



Scientist Exchange Summary Report
Full Name: Takeshi Watanabe
Home Institution: Institute for Cancer Research, Osaka University Medical School, 1-1-50 Fukushima, Fukushimaku, Osaka, Japan

Sponsor and Host Institution:
Mark I. Greene, M.D., Ph. D. Prof. and Director Department of Immunobiology, The School of Medicine University of Pennsylvania
Richard Hodes, M.D. Chief, Immunotherapy Section Immunology Branch, National Cancer Institute NIH
Dates of Visit: January 1 2, 1986- January 26, 1986

Summary of Activities:
The purpose of this visit was to exchange the recent information of the manifestation of immunological property of tumor cells and host responses against it. In the laboratory of Dr. Mark Greene, they recently cloned a new oncogene designated as neu from the rat neuroblastoma cell line. This oncogene analogous to the human erbB2 encodes a transmembrane molecule, probably representing a receptor for some yet unidentified cell growth factor. They established a monoclonal antibody to this molecule and found that blocking of this receptor-1ike molecule by this monoclonal antibody completely inhibits the growth of neuroblastoma cells both in vitro and in vivo. We have been analyzing the mechanism of host response against surface molecules of tumor cells and recently found very intriguing pathway of tumor antigen-recognition associated with the host's tumor eradication. In the laboratory of Dr. Mark Greene, I exchanged these informations of our mutual interest with particular emphasis on the molecular and cellular mechanisms of expression and recognition of surface molecule on the tumor cells. I also gave a lecture at Amphitheater of the University of Pennsylvania, entitled by "Regulation of B Cell Differentiation: Interaction of Factors and Corresponding Receptors", and made this chance to exchange recent informations of immunology and receptor biochemistry with other scientists in Philadelphia county. These include Dr. Peter Nowell for the subject of oncogene and IL-2-, IL-2 receptor-, transferrin receptor- and insulin receptor-gene expressions associated with T cell growth, and Dr. John Cebra for IgA-B cell clonal analysis in gut lymphoid organ. I also visited Wister Institute and discussed with Dr. B. Knowles about establishment of thymic epithelial cell clones and analysis of T cell education process in vitro, utilizing SV 40- T antigen gene- transgenic mice.
In the laboratory of Dr. Richard Hodes, I discussed with his group about our mutual interest of cell-cell interaction at the stage of the antigen recognition of the host, and obtained anti-LFAI monoclonal antibody-producing hybridoma and some of auto-reactive T cell clones for my future experiments. I also exchanged informations with Dr. Ronald N. Germain about the molecular biology of la-antigen and its role in antigen recognition. I obtained la-gene transfected L cells for my analyses of the mechanism of tumor-antigen recognition. I met Dr. David H. Sachs to obtain anti-idiotypic antibodies against various anti-Ia monoclonal antibodies, and Dr. Jay A. Berzofsky to obtain unique antigenic fragments of staphylococcal nuclease to initiate our collaboration studies for the analysis of genetic control of antigen recognition. Discussions with such leading scientists and gifts from them will surely facilitate my future research projects directly connected to the tumor immunology.
Finally, as an advisor of the U.S.-Japan Cooperative Cancer Research Program, I dis-cussed with Dr. Richard Hodes about our future plan of the program in the tumor immunology field. It was great opportunity for me to visit these scientists and to have a chance to exchange recent information from aspect of tumor immunology as well as for making future productive plan of the U.S.-Japan Cooperative Cancer Research Program.
Toshiyuki Hamaoka
February 25, 1 986



Scientist Exchange Summary Report
Full Name: Kazuo Todokoro
Tsukuba Life Science Center, The Institute of Physical and Chemical Research, 3-1-1, Kohyadai, Yatabecho, Tsukuba-gun, Ibaragi, 305, JAPAN

Sponcer and Host Institution:
Dr. Kenichi ARAI. DNAX Research Institute of Molecular and Cellular Biology, 901 California Avenue, Palo Alto, CA 94304
Date of Visit: March 7, 1986- March 26, 1 986

Summary of Activities:

  1. prepared polyA-mRNA from mouse erythropoietin (EPO) sensitive cells and human Burst Promoting Activity (BPA) secreting cells.
  2. prepared vector primer and linker DNAs for expression cDNA Iibrary.
  3. prepared excellent expression cDNA Iibrary for human BPA and mouse EPO receptor.
  4. Iearned efficient DNA transfection methods to mammalian cells,
  5. discussed about possibility of direct DNA cloning method of particular membrane receptor proteins by flow cytometry
  6. exchanged up-to-date research informations, ideas and technical problems on on-going projects.

Items listed above are absolutely required steps to achieve my on-going research project "growth factor (EPO and BPA) and their receptors". It was impossible to accomplish these steps without co-operation with the experts at DNAX Research Institute. The visit was very successful and I obtained very useful informations and know-hows. I do continue our collaboration on this projects. This research project and co-operation will contribute, in the long run, to clarify the mechanism of cancer development (especially, leukemia).
Besides DNAX Research Institute, I visited the Laboratory of Dr. Takaji MIYAKE at University of California at Santa Barbara. We discussed and exchanged the recent research progress on growth factors (especially on EPO and thrombopoietin) researches. It was also very fruitful visit. The collaboration will continue on the search of EPO.
April 20, 1986