The introduction of insulin therapy for the management of diabetes mellitus is arguably the greatest milestone in the history of modern medicine. beta-cell replacement therapy is the only treatment that reestablishes and maintains long-term physiological normoglycemia. Until recently, successful clinical outcomes of pancreas transplantation for patients with long-standing diabetes were much superior to that of islet transplantation. Significant advances in islet isolation and purification technology, the development of more specific and less diabetogenic immunosuppressants and the prophylactic administration of antiviral agents have rekindled a worldwide interest in islet transplantation. This chapter will review the rationale of islet transplantation and the development of islet isolation and purification. The challenges facing clinical islet transplantation in the twenty-first century will also be introduced.
The introduction of insulin therapy for the management of diabetes mellitus is arguably the greatest milestone in the history of modern medicine. P-cell replacement therapy is the only treatment that reestablishes and maintains longterm physiological normoglycemia. Until recently, successful clinical outcomes of pancreas transplantation for patients with long-standing diabetes were much superior to that of islet transplantation. Significant advances in islet isolation and purification technology, the development of more specific and less diabetogenic immunosuppressants and the prophylactic administration of antiviral agents have rekindled a worldwide interest in islet transplantation. This chapter will review the rationale of islet transplantation and the development of islet isolation and purification. The challenges facing clinical islet transplantation in the twenty-first century will also be introduced.
The synthesis, interconversion, and catabolism of purine bases, ribonucleosides, and ribonucleotides in wild-type Saccharomyces cerevisiae were studied by measuring the conversion of radioactive adenine, hypoxanthine, guanine, and glycine into acid-soluble purine bases, ribonucleosides, and ribonucleotides, and into nucleic acid adenine and guanine. The pathway(s) by which adenine is converted to inosinate is (are) uncertain. Guanine is extensively deaminated to xanthine. In addition, some guanine is converted to inosinate and adenine nucleotides. Inosinate formed either from hypoxanthine or de novo is readily converted to adenine and guanine nucleotides.
Three preparations of radioactive yeast nucleic acids were fed to mice. One was labeled predominantly in the guanine moiety, one was labeled predominantly in the adenine moiety, and in one adenine and guanine were labeled equally. Most of the nucleic acid purines produced by digestion were excreted in the urine. However, a small amount was utilized for nucleotide and nucleic acid synthesis in the mouse tissues. Small intestine, liver and skeletal muscle contained most of the purines that were retained in the tissues. Dietary nucleic acid adenine appeared to be utilized somewhat more efficiently than was dietary nucleic acid guanine.
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