Purine and Pyrimidine Metabolism in Man V: Basic science aspects

The Fifth International Symposium on Human Purine and Pyrimidine Metabolism was held in San Diego, California (U.S.A.) in July and August of 1985. Previous meetings in this series were held in Tel Aviv (Israel), Baden (Austria), Madrid (Spain) and Maastricht (The Netherlands). The proceedings of each of these meetings were published by Plenum. The next meeting will be in Japan. This Symposium differed from those that went before in that it permitted us to honor Dr. J.E. Seegmiller, Professor of Medicine at the University of California San Diego, for his many contributions to our understanding of purine metabolism in man. This publication is dedicated as a Festschrift to Jay. Dr. Richard W.E. Watts delivered the keynote address outlining in scholarly fashion the history of Dr. Seegmiller's accomplishments in research on purine metabolism and the great number of currently active scientists in this field who have worked with him. This address is published as the first contribution to Volume I. Dr. Dewitt Stetten, Jr., was scheduled to be the speaker at our banquet. Unfortunately, he could not be with us. Dr. Seegmiller has written an appreciation of Dr. Stetten and his contributions to our field, and this has been published following Dr. Watts' paper. The growth of knowledge in purine and pyrimidine metabolism continues to be exponential. The variety of subjects included in these volumes is impressive. New or previously unrecognized disorders of purine metabolism continue to be uncovered. An entire section on disorders of purine and pyrimidine metabolism other than deficiency of HPRT is led off by two papers on adenylosuccinase deficiency. Among the disorders of pyrimidine metabolism there are papers on orotic aciduria and dihydrothymine dehydrogenase deficiency. Clinical and biochemical studies of gout and urolithiasis continue to be actively pursued. At the same time the study of purine metabolism has become an integral feature of immunology. The importance of purines in clinical oncology was first demonstrated with the synthesis by George Hitchings of 6-mercaptopurine. Its continuing impact on hematology and oncology is seen throughout these volumes, particularly in the effects of inhibition of adenosine deaminase on T cells and on T cell leukemia. This publication has implications for internal medicine, pediatrics, urology, biochemistry, immunology, genetics, hematology, and oncology. Modern molecular biology and techniques involving recombinant DNA were evident in papers on HPRT and on adenosine deaminase, as well as in studies on APRT and UMP synthase. The genes for HPRT, adenosine deaminase and puine nucleoside phosphorylase have been cloned. The background for ultimate approaches to gene therapy in man was provided in papers from Dr. Seegmiller's laboratory on the insertion of HPRT cDNA into human bone marrow cells and on metabolic cooperation. Purine receptors have been discovered in the central nervous system, in lymphocytes and in a variety of other tissues. There are also adenosine receptors in Leishmania and a number of purine riboside analogs are under study as potential therapeutic agents in leishmaniasis.