SUMMARY REPORTS OF EXCHANGE SCIENTISTS
(1) Shigeo Ohno
Yokohanra City University School of Medicine
SPONSOR AND HOST INSTITUTION:
Host: Dr. Richard M, Niles, Marshall University School of Medicine
Date of Visits: January 16 - February 1, 1993
SUMMARY OF ACTIVITIES:
The major purpose of the research was to stay several days in Dr. Niles's laboratory and discuss many aspects of the collaboration as well as other areas of biology. I also presented lectures to basic scientists and to graduate students. These objectives were accomplished quite successfully and collaboration will result in identifying the biochemical role of the respective PKC members in differentiation of B6 melanoma cells and F9 embryonic carcinoma cells. The results of the first collaborative study on the involvement of PKC!
!!in B6 melanoma differentiation has been recently published in JBC. The strategy involves the overexpression of the specific PKC isoform in these cell lines and monitor cell consequence from a view point of gene expression and differentiation. The collaboration is continuing to the next step of research focusing on identification of the PKC action in B6 cells. Another line of experiments using F9 cell system are based on similar strategy as used for B6 cells. There was much success for both of these lines of collaborations. Furthermore we have also started another line of experiments on the role of a new PKC member in differentiation of embryonal carcinoma cells.
The other purpose of this program involves visiting several laboratories including Dr. Weinstein's to discuss the progress on the analysis of the involvement of PKC system in human tumors. I presented a lecture and discussed on many aspects of the current investigations ongoing in both laboratories.
In addition to the above mentioned purpose, this researcher also attended the Joint Symposium of the Keystone Symposia, "Transcription: Factors, Regulation and differentiation" and "Phosphorylation/Dephosphorylation in Signal Transduction" which was held from January 15 to 21, 1993. The applicant presented a poster under the title of "Dominant negative mutations of PKC " and had many discussion with many people who are interested in signal transduction and gene transcription.
(2) Masayuki Miyasaka
Tokyo Metropolitan Institute of Medical Science
SPONSOR AND HOST INSTITUTION:
Host: Dr. Steven D. Rosen, University of California San Francisco
Harvard University
Date of Visit February 28 - March 14, 1993
SUMMARY OF ACTIVITIES:
The major objective of my trip to the USA was to meet with US scientists actively working in the filed of lymphocyte recirculation, particularly on molecular mechanisms of lymphocyte homing and to discuss subjects of mutual interest. I visited nine institutions in six different cities and met with over 30 scientists individually. Following is my itinerary.
| Feb. 28 |
Laft Tokyo |
| Mar. 01 |
Seminar and discussion at Boehringer Ingelheim |
| Mar. 02 |
Seminar and discussion at Endogen (Boston) |
| Mar. 03 |
Visited Prof. N.L. Tilney, Head of Surgical Research Laboratory. Gave seminar and discussed with scientists of his group. |
| Mar.04 |
Seminar and discussion at Dana-Farber Cancer Institute |
| Mar.05 |
Seminar and discussion at Veterans Administration Medical Center, San Francisco |
| Mar.08 |
Visited Prof. Steven D. Rosen at University of California, San Francisco. Gave seminar and discussed with scientists of his group |
| Mar.09 |
Seminar and Discussion at Becton Dickinson, Inc. |
| Mar. 11 |
Seminar and discussion at the Michigan University Medical School |
| Mar. 12 |
Visited Upjohn Company at Kalamazoo, Michigan and discussed with various scientists. |
| Mar. 14 |
Returned to Japan |
During this trip I gave altogether eight lectures on our recent work on rat LECAM-1 (L-selectin) molecule. Other than universities and their associated institutions, I also visited private companies involved in the development of pharmaceutical agents that can modulate functions of adhesion molecules, and discussed with them possible application of " anti-adhesion therapy " in inflammatory diseases and malignant cancers. This was a very interesting experience to me and I was surprised to see that the extent of their enthusiasm in attempting to devise clinical application of "anti-adhesion therapy" in various types of inflammations as well as in the prevention of tumor metastasis is much greater than I anticipated. And indeed, they are making a rapid progress in developing various types of clinical intervention experimentally in these disease conditions.
Concerning signal transduction mechanism via adhesion molecules, particularly via LECAM molecules, which has hitherto been little studied because of unavailability of appropriate experimental systems, I have discussed with a few scientists during this trip, and obtained useful ideas in devising strategies to study this problem in detail.
Collectively, this trip allowed me to meet with various US scientists and provided me with good opportunities to discuss with them in detail various problems in adhesion molecules, particularly those involved in lymphocyte homing, which will be undoubtedly beneficial for our future work in this area.
(3) Nobuo Sakaguchi
Faculty of Medicine, Tottori University
SPONSOR AND HOST INSTITUTION:
Host: Dr. Paul W. Kincade, Oklahoma Medical Research Foundation
Date of Visits: October 19 - October 26, 1992
SUMMARY OF ACTIVITIES:
The purpose of my visit in the institutions in U.S.A. is to communicate and exchange the opinions on the current progress regarding to the immunoglobulin receptor (IgR)-associated molecules that are expressed on the surface of B lymphocytes. We have found a B cell specific gene named mb-1 that encodes a 34-kDa protein associated with the IgM receptor on the surface of B cells. In the later studies by many laboratories, the lgM receptor associated molecules are composed of two distinct polypeptides as lg-!
!!(34-kDa) and lg-!
!!(39-kDa). It is shown that the lg-!
!!is the mb-1 gene product and the lg-!
!!is encoded by another B cell specific gene named B29. Recently, we demonstrated the evidence of the signal transduction through MB-1 protein. I wished to inform widely about our recent progress in the activation of B cells at various stages of B cell development. During my visit in three most advanced laboratories for the B cell differentiation, I felt confident that our publications are already widely understood and became the basic evidences for their research projects in the activation of B cells. Especially, in the laboratories of Dr. Max D. Cooper in the University of Alabama (Birmingham), almost half of the scientific staff (about thirty-five members) are now engaging in the similar projects of the human B cell antigen receptor associated molecules and the B cell development. I could communicate and exchange the opinions with most of the scientists, which would be most useful for our future progress in our projects. I also talked about our current knowledge on the novel phosphoprotein molecule associated with the MB-1. In the discussions with Dr. William E. Paul, I could create a new opinion on the regulation of the lgR-mediated signal transduction by the action of protein kinase C pathway.
I was well treated in the four institutions in the U.S.A. during my visit. Dr. Max Cooper provided me the opportunity to discuss with almost all of the senior scientists and present a seminar of our results. Dr. William E. Paul suggested me many opinions to the results which I explained to him. Dr. Steve Bauer explained me his recent results on the expression of oncogene mRNA in various lymphoid malignant cells. I spent a most useful time with Dr. Paul W. Kincade on the current trends in the differentiation of early B lymphoid cells. We exchanged opinions and materials for the collaborative work in several kinds of systems and subjects. A manuscript appeared as a publication in The Journal of Immunology (Ishihara et al., March 15, 1993) from one of the projects.
I also could gather much useful information in science. Dr. W.E. Paul explained to me the new results of the activation of B cells with IL-4 and the recent progress on the cloning of the Xid genes done by Cohen and Paul. Drs. M.D. Cooper and H. Kubagawa told me the new evidence on the human early B cell differentiation, especially with the expression of the surrogate complex as µ,!
!!5 and VpreB proteins at the late stage of pre-B cells. Dr. P.W. Kincade explained me the approach for the analysis of CD44 isomer protein in the activation and differentiation of B cells. Dr. C. Webb showed me evidence of the active regulatory mechanism of immunoglobulin gene expression by the stimulation of antigen and/or IL-5. They found a sequence motif involved in the immunoglobulin gene expression, a part of which is regulated by the matrix binding protein. Using this information, I could publish a satisfactory review paper on the "Immunoglobulin Receptor Associated Molecules" written by Sakaguchi et al., Advances in Immunology (in press).
I also discussed their own projects and gave several suggestions or advises. One is concerning to the establishment of the hybridomas producing anti-human MB-1 monoclonal antibody. Second advise is concerning to a cDNA cloning using subtractive hybridization method.
With all these scientists, I discussed on the opportunity to send a postdoctoral fellow who wish to study in the U.S.A. for 2 to 3 years. I consider that the visit in the institutions would certainly support our scientific activities in future.
References
1) Ishihara,K., Wood,W.J., Wall, R., Sakaguchi, N., Michnoff,C., Tucker,P.W. and Kincade,P.W. (1993). Multiple B29 containing complexes on murine B lymphocytes. Common and stage restricted lg-associated polypeptide chains.
J. Immunol.(in press).
2) Sakaguchi,N., Matsuo,T., Nomura,J., Kuwahara,K., Igarashi,H. and Inui S. (1993). Immunoglobulin receptor-associated molecules. Advances in Immunology, 54, 337-392