Purine Metabolism in Man - IV: Part B: Biochemical, Immunological, and Cancer Research

These two volumes, entitled "Purine Metabolism in Man IV" con­ tain the papers presented at the Fourth International Symposium on Human Purine and Pyrimidine Metabolism", held in Maastricht (The Netherlands), June 1982. The proceedings of the three previous meet­ ings in Tel Aviv (Israel, 1973), Baden (Austria, 1976) and Madrid (Spain, 1979) were also published by Plenum Press. In the past few years interest in purine and pyrimidine metabo­ lism under normal and pathological conditions has been growing rapid­ ly. Apart from the more or less classical topics such as hyperuricae­ mia, clinical gout and urolithiasis, an increasing number of papers relating to other fields have been presented at successive meetings. Knowledge derived from the study of purine metabolism in relation to lymphocyte function, for instance, has opened up new possibilities for immunomodulation and leukaemia chemotherapy, with eventual conse­ quences for other types of cancer. At previous meetings there have been pointers implicating purine metabolism in relation to normal cardiac and skeletal muscle function. During the present meeting mych new data on both issues have been re­ ported which indicate clear differences in the pathways of ATP metabo­ lism. The widening of the field of interest is also illustrated by the recent work on infectious disease: exploitation of the differences in purine metabolic pathways in certain parasites compared with those in human cells has resulted in new rationales for therapy being devel­ oped. Front Matter....Pages i-xvi Evidence of a New Type Of Phosphoribosylpyrophosphate Synthetase With Abnormal Kinetic Properties in Hyperuricemias....Pages 1-4 Radioimmunoassay Studies of Human Phosphoribosylpyrophosphate Synthetase....Pages 5-10 Synthesis of ( 14 C)-Ribose-5-Phosphate and ( 14 C)-Phosphoribosyl-Pyrophosphate and Their use in New Enzyme Assays....Pages 11-13 Purine Synthesis During Amino Acid Starvation of Lymphoblasts With HPRT Deficiency or PP-Ribose-P Synthetase Overactivity Decreases Less Than in Normal Cells....Pages 15-19 Purine Synthesis and Salvage in Brain and Liver....Pages 21-26 Kinetic Studies of Hypoxanthine-Guanine Phosphoribosyltransferase in Intact Cells....Pages 27-31 Hypoxanthine-Guanine Phosphoribosyltransferase in Human Lymphoblastoid Cells: Confirmation of Four Structural Variants and Demonstration of a New Variant (HPRT Ann Arbor )....Pages 33-38 The Primary Structure and Posttranslational Modification of Human Hypoxanthine-Guanine Phosphoribosyltransferase....Pages 39-44 Studies of the Catalytically-Active Form of Hypoxanthine-Guanine Phosphoribosyltransferase from Yeast....Pages 45-50 Human Lymphocytic Ecto-5′-NT: Its Determination and Partial Characterization....Pages 51-54 Distribution of Ecto-5′-Nucleotidase in Plasmamembrane Subfractions of Human Lymphoblastoid Cells....Pages 55-58 AMP Deaminase Isozymes in Human Blood Cells....Pages 59-62 Immunohistochemical Localization of Adenosine Deaminase in Rat and Calf Tissues....Pages 63-66 Characterization of Adenosine Deaminating Activity in Normal and Adenosine Deaminase Deficient Human Tissue....Pages 67-70 S-Adenosylhomocysteine Hydrolase Activity in Defects of Enzymes of Purine Metabolism and Inhibition by Various Purine Compounds....Pages 71-74 Deoxyguanosine Kinase from Human Placenta....Pages 75-78 Phosphorylation of Deoxyguanosine in Rat Liver Mitochondria....Pages 79-82 5′-Methylthioadenosine is the Major Source of Adenine in Human Cells....Pages 83-88 Determination of a Histidine Residue at the Yeast Orotate Phosphoribosyltransferase Active-Site....Pages 89-92 Changes in Purine Salvage Pathway Enzyme Activities During Human Lymphocyte Differentiation Induced by Thymosin Fraction 5....Pages 93-98 Purine Metabolism in Human Thymocyte Subsets: Relevance for Lymphocytic Differentiation....Pages 99-106 Purine Metabolism in Splenocytes and Thymocytes of Various Mammalian Species....Pages 107-110 Purine Interconversion Pathways in T, B, Tγ and T-Tγ Cells from Human Peripheral Blood....Pages 111-118 Metabolism of Guanosine and Deoxyguanosine in Mammalian Lymphocytes and their Influence on Mitogenic Stimulation....Pages 119-124 Concentration of Nucleotides in Peripheral Blood Lymphocytes of Various Mammalian Species....Pages 125-128 Plasma Membrane 5′-Nucleotidase and other Purine Enzymes in Murine Lymphocytes....Pages 129-132 Biochemical Basis for Lymphocyte Dysfunction in Adenosine Deaminase and Purine Nucleoside Phosphorylase Deficiencies....Pages 133-139 Absence of Lymphocyte Ecto-5′-Nucleotidase in Infants with Reticuloendotheliosis and Immunodeficiency....Pages 141-146 Regulation of Human Lymphoblast Ecto-5′-Nucleotidase by Zinc....Pages 147-152 Decreased T Cell Ecto-5′-Nucleotidase Activity in Agammaglobulinemia Patients is Not Due to Altered Proportions of Helper and Suppressor T Cells as Defined by the Monoclonal Antibodies Okt4 and Okt8....Pages 153-158 Metabolic Findings in a Patient with Adenosine Deaminase Deficiency and Severe Combined Immunodeficiency....Pages 159-162 Purine Metabolism in Intact Cells from a Purine Nucleoside Phosphorylase Deficient Child....Pages 163-166 Inosine Formation from Hypoxanthine by Intact Erythrocytes and Fibroblasts of an Immunodeficient Child with Purine Nucleoside Phosphorylase Deficiency....Pages 167-170 Mononuclear Cells in S-Phase in a Patient with Purine Nucleoside Phosphorylase Deficiency....Pages 171-174 Involvement of Dietary Nucleotides in T Lymphocyte Function....Pages 175-178 Nucleotide Levels in Peripheral Blood Mononuclear Cells of Immunodeficient Children: Problems of Measurement....Pages 179-182 Inhibition of Murine Suppressor T Cell Development by 2′-Deoxyguanosine in Vivo ....Pages 183-188 Biochemical and Immunological Evaluation of Long Term Coformycin Administration in the Mouse....Pages 189-192 Increased Incidence of Homogeneous Immunoglobulins in Irradiated, Reconstituted Mice After Prolonged Treatment with 2′-Deoxyguanosine....Pages 193-197 S-Adenosylhomocysteine Hydrolase as a Pharmacological Target for the Inhibition of Transmethylation....Pages 199-203 Selective Inhibition of Various Mitogen Responses in Human Lymphocytes....Pages 205-210 Sensitivity of Human T and B Lymphoblasts to Immunoregulatory Drugs....Pages 211-214 Inhibition of in Vitro Lymphocyte Proliferation and B Cell Differentiation by Deoxyguanosine: Evidence for Separate Mechanisms....Pages 215-220 Effect of Purine Nucleosides on Rat Macrophage Function....Pages 221-226 Purine Metabolism in Rat Macrophages....Pages 227-232 Purine Metabolizing Enzyme Activities in Lymphoblastic Leukemia....Pages 233-240 Purine and Pyrimidine Enzyme Markers in Human Lymphoid Malignancies....Pages 241-247 Ecto-5′-Nucleotidase as a Leukemia Marker....Pages 249-253 Immunohistochemical Localization of Adenosine Deaminase in Human Lymphoid Tissues and Lymphomas....Pages 255-259 5′Nucleotidase and Adenosine Deaminase Activities in Human Lymphocytes and Lymphoblastoid Cell Lines....Pages 261-266 Properties and Activities of Phosphoribomutase in Human Leukemic Cells....Pages 267-272 Uptake of AMP into K 562 and HL-60 Leukemic Cell Lines....Pages 273-278 5′-Methylthioadenosine Phosphorylase Deficiency in Malignant Cells: Recessive Expression of the Defective Phenotype in Intra-Species (Mouse X Mouse) Hybrids....Pages 279-283 The Activity of Adenosine Desaminase in Serum and Leukocytes of Leukemic Patients....Pages 285-288 Uptake of Thymidine by Plasma Membrane Vesicles of L5178Y Murine Leukemic Cells....Pages 289-292 Adenosine Deaminase Isozymes in Transformed Cells....Pages 293-298 Adenosine Deaminase (ADA; E.C. no. 3.5.4.4.) in Colorectal Adenocarcinoma in Man....Pages 299-303 Biochemical Basis for the Differential Effects of Deoxycoformycin on Human Leukemias....Pages 305-308 Sensitivity of T-Leukemic Cells to Deoxyguanosine and Arabinosyl Guanine....Pages 309-314 Exploiting Biochemical Differences in Leukemia....Pages 315-320 Effects of 3-Deazaguanosine and 3-Deazaguanine on the Growth and Maturation of the Human Promyelocytic Leukemia Cell Line, HL-60....Pages 321-325 Intralymphocytic Adenosine Deaminase (ADA) and Purine Nucleoside Phosphorylase (PNPase) Activity in Chronic Lymphocytic Leukemia (CLL) : Effect of Thymostimulin....Pages 327-332 Deoxyadenosine Induced G 1 Phase Arrest in Leukemic T Cells....Pages 333-338 Poly(A) + RNA as a Possible Target for Deoxyadenosine Induced G 1 /G 0 Lymphotoxicity....Pages 339-344 Modulation of Arabinosyladenine Metabolism by 2′-Deoxycoformycin in the Therapy of Human Acute Leukemia....Pages 345-350 Cell Cycle Independent Lymphocytotoxicity of 2-Chlorodeoxyadenosine....Pages 351-356 Ecto-Adenosine Triphosphatase: An Enzyme Correlating with Resistance to Deoxynucleoside Growth Inhibition....Pages 357-362 Purine Deoxyribonucleoside Induced Hepatotoxicity in the Mouse....Pages 363-366 6-Mercaptopurine: Pharmacokinetics in Animals and Preliminary Results in Children....Pages 367-370 Enzyme Inhibition by Phosphonate Analogues of dTTP....Pages 371-374 Inhibition of Thymidylate Synthetase by the New Quinazoline Antifolate, CB 3717; Enzyme Purification and Kinetics....Pages 375-378 Plasma Nucleoside and Base Levels Following Treatment with the New Thymidylate Synthetase Inhibitor CB 3717....Pages 379-382 Influence of Cytostatics on ATP-Levels of Leukemic Cells....Pages 383-388 Thymidine Sensitivity and Deoxynucleotide Pools of Human Lymphoid and Melanoma Cells in Vitro....Pages 389-393 High Uridine Catabolic Activity in Cultured Human Melanoma Cells....Pages 395-399 Synergism Between Purines and Thymidine (TDR) in Reversal of Methotrexate (MTX) Toxicity in Mice Using Continuous Infusions....Pages 401-405 Cell-Cycle Dependent Variation in the Levels of Deoxyribonucleoside Triphosphate in Mouse T-Lymphoma Cells....Pages 407-410 Tumor Specific Conversion of a Pyrimidine Antimetabolite....Pages 411-414 Isotachophoretic Analysis of Some Compounds Involved in Energy Metabolism in Normal and Pathological Human Muscle Extracts....Pages 415-418 Adenine Metabolism in Rat Skeletal Muscle....Pages 419-424 Purine Nucleotide Metabolism in Primary Rat Skeletal Muscle Cultures....Pages 425-429 Metabolism of AMP in Muscle Extracts from Patients with Deficient Activity of Myoadenylate Deaminase....Pages 431-436 Effect of Hypoxia and Exercise on Nucleotide Metabolism in Man....Pages 437-442 Malignant Hyperthermia: Adenine Incorporation and Adenine Metabolism in Human Platelets, Influenced by Halothane....Pages 443-446 Enzymes of Purine Metabolism in Muscle Specimens from Patients with Duchenne-Type Muscular Dystrophy....Pages 447-450 X-Linked Recessive (Duchenne) Muscular Dystrophy (DMD) and Purine Metabolism: Effects of Oral Allopurinol and Adenylate....Pages 451-456 Non-Specific Adenylate Deaminase from Snail Foot Muscle....Pages 457-464 Potential Role of Non-Specific Snail Muscle Adenylate Deaminase in Operating of NADH-Dependent Dehydrogenases....Pages 465-468 Adenine Nucleotide Biosynthesis in Cardiac Muscle: Regulation and Intervention....Pages 469-475 Ribose Prevents the Propranolol-Induced Reduction of Myocardial Adenine Nucleotide Biosynthesis....Pages 477-481 Balance of Purine Nucleotides and Catabolites in the Isolated Ischemic Rat Heart....Pages 483-486 Inosine Incorporation into Adenine- and Guanine Nucleotides in the Isolated Perfused Rat Heart is Stimulated After Ischemia....Pages 487-490 The Ca-Antagonist Nifedipine Reduces Purine Nucleoside and Oxypurine Release from Ischemic Heart....Pages 491-496 Combined Use of Radioenzymatic Assay and High Pressure Liquid Chromatography for the Detection of Myocardial Xanthine Oxidase/Dehydrogenase....Pages 497-500 Purification and Characterization of Pig Heart AMP-Deaminase....Pages 501-504 AMP Deaminase from Necrotic Rat Heart....Pages 505-507 Back Matter....Pages 509-520 These two volumes, entitled "Purine Metabolism in Man IV" con℗Ư tain the paper presented at the "IV. International Symposium on Human Purine and Pyrimidine Metabolism," held in Maastricht (The Netherlands), June 1982. The proceedings of the three previous meet℗Ư ings in Tel Aviv (Israel, 1973), Baden (Austria, 1976) and Madrid (Spain, 1979) were also published by Plenum Press. In the past few years interest in purine and pyrimidine metabo℗Ư lism under normal and pathological conditions has been growing rapid℗Ư ly. Apart from the more or less classical topics such as hyperuricae℗Ư mia, clinical gout and urolithiasis, an increasing number of papers relating to other fields have been presented at successive meetings. Knowledge derived from the study of purine metabolism in relation to lymphocyte function, for instance, has opened up new possibilities for immunomodulation and leukaemia chemotherapy, with eventual conse℗Ư quences for other types of cancer. At previous meetings there have been pointers implicating purine metabolism in relation to normal cardiac and skeletal muscle function. During the present meeting much new data on both issues have been re℗Ư ported which indicate clear differences in the pathways of ATP metabo℗Ư lism. The widening of the field of interest is also illustrated by the recent work on infectious disease: exploitation of the differences in purine metabolic pathways in certain parasites compared with those in human cells has resulted in new rationales for therapy being devel℗Ư oped