Purine And Pyrimidine Metabolism In Man Vii: Part A: Chemotherapy, Atp Depletion, And Gout (advances In Experimental Medicine And Biology)

These two volumes record the scientific and clinical work presented at the VIIth International and 3rd European joint symposium on purine and pyrimidine metabolism in man held at the Bournemouth International Conference Centre, Bournemouth, UK, from 30th June to 5th July 1991. The series of international meetings at three yearly intervals have previously been held initially in 1973 in Israel, then Austria, Spain, the Netherlands, USA and Japan. The European society for the Study of Purine and Pyrimidine Metabolism in Man (ESSPPM) which has its own executive and some finance first met in Switzerland in 1987, then in Germany in 1989. The steady evolution of the science in this series of meetings is intellectually satisfying; the subsequent clinical progress is emotionally and economically reassuring. As befits the position of purines and pyrimidines at the centre of biochemistry, there has been steady scientific development into molecular genetics and now onto developmental controls and biochemical pharmacology. The complexities of the immune system are being unravelled but an understanding of the human brain largely eludes us. Laboratory based scientists now predominate over those who work as clinical specialists in vii rheumatology, immunology, oncology and paediatrics. However, there continue to be major clinical objectives since large sections are concerned with major causes of death like ATP depletion, cancer and now AIDS; the laboratory work is providing clinical solutions. Front Matter....Pages i-xxi Biochemical Approach to New Medications....Pages 1-6 Antimetabolites in Cancer Chemotherapy....Pages 7-13 2-Chlorodeoxyadenosine Chemotherapy Triggers Programmed Cell Death in Normal and Malignant Lymphocytes....Pages 15-18 ICI D1694, An Inhibitor of Thymidylate Synthase for Clinical Study....Pages 19-23 Action and Sequence Dependent Interaction of Acivicin and 6-Thioguanine in Human Derived Malignant T-All and Calla+ Cell Lines....Pages 25-28 Conversion of Acyclic Nucleoside Phosphonates to Their Diphosphate Derivatives by 5-Phosphoribosyl-1-Pyrophosphate (PRPP) Synthetase....Pages 29-32 Derivation of New Drugs for Therapy of Aids....Pages 33-40 Biochemical and Pharmacological Properties of CI-972, a Novel 9-Deazaguanine Analog Purine Nucleoside Phosphorylase (PNP) Inhibitor....Pages 41-44 Pyrrolo[3,2-D]Pyrimidines, a New Class of Purine Nucleoside Phosphorylase (PNP) Inhibitors as Potential T-Cell Selective Immunosuppressive Agents....Pages 45-48 Modulation of Metabolism and Anti-HIV-1 Activity of Purine 2′,3′-Dideoxynucleosides by IMP Dehydrogenase Inhibitors....Pages 49-53 Acadesine (AICA Riboside) Inhibits Platelet Aggregation in Human Whole Blood....Pages 55-55 Concentration and Time Dependent Growth Inhibition and Metabolism in vitro by 2’,2’-Difluoro-Deoxycytidine (Gemcitabine)....Pages 57-60 Thiopurine Methyltransferase Activity and Efficacy of Azathioprine Immunosuppression in Transplant Recipients....Pages 61-64 Increase in 2’,5’-Oligoadenylate Synthetase Caused by Deoxycoformycin in Hairy Cell Leukaemia....Pages 65-68 A Dual Anti-Tumor Effect of a Combination of Interferon-α and 5-Flurouracil or 2-Chlorodeoxyadenosine on Natural Killer (NK) Cell Mediated Cytotoxicity....Pages 69-73 The Effect of Methotrexate on the Folate Coenzyme Pools in Human Hepatoma Cells in Culture....Pages 75-78 Purine Nucleotide Biosynthesis in Leukemic Promyelocytes Treated with Retinoids....Pages 79-82 6-Mercaptopurine Metabolism in Two Leukemic Cell Lines....Pages 83-86 Synergistic Interaction of Methotrexate and 6-Mercaptopurine in Human Derived Malignant T-All and Calla + Cell Lines....Pages 87-91 6-Thioguanine Metabolism in Human Erythrocytes....Pages 93-96 Nucleotide Status in Erythrocytes of Rats Infected with Plasmodium Berghei....Pages 161-164 Hypoxanthine Depletion Induced by Xanthine Oxidase Inhibits Malaria Parasite Growth in Vitro....Pages 165-168 New Nucleoside Transport Pathways Induced in the Host Erythrocyte Membrane of Malaria and Babesia Infected Cells....Pages 169-172 The Impact of Selected Nucleosides on the Cytotoxicity of ARA-C in HL60 Cells....Pages 97-100 Effect of Chloroadenosine on Phosphoinositide Turnover in Human T Lymphoblasts Activated through the TCR/CD3 Complex....Pages 101-104 Isolated Liver Perfusion Versus Hepatic Artery Infusion with 5-Fluorouracil in a Rat Model; Effects on Thymidylate Synthase....Pages 105-108 Effect of Polyethylene Glycol-Modified Adenosine Deaminase (PEG-ADA) Therapy in Two ADA-Deficient Children: Measurement of Erythrocyte Deoxyadenosine Triphosphate as a Useful Tool....Pages 173-176 Changes of Purine Nucleotide Metabolism of Ehrlich Ascites Cells During Transition of Tumour Growth....Pages 109-112 Purine Nucleotides, Nucleosides and Nucleobases of Liver, Skeletal Muscle, Blood and Tumor Cells During the Growth of Ehrlich Ascites Tumor in Mice....Pages 113-116 Uridine Fluxes in Healthy Proliferating T-Lymphocytes, Molt-3 T-ALL Cell-Line Cells and Differentiated Molt-3 Cells....Pages 117-120 Some Aspects of Purine Nucleotide Metabolism in Human Lymphocytes: Nucleotide Content in Human Lymphoblastoid Lines Transfected with HIV-1....Pages 121-124 Metabolism and Action of 2′, 2′ -Difluorodeoxycytidine: Self-Potentiation of Cytotoxicity....Pages 125-130 Effect of Leucovorin on 5-Fluorouracil Induced Inhibition of Thymidylate Synthase in Patients with Colon Cancer....Pages 131-134 A Novel Xanthine Dehydrogenase Inhibitor (BOF-4272)....Pages 135-138 Changes Caused by Ethanol Intake on Metabolism of Hypouricemic Agents (Combination of Allopurinol and Benzbromarone)....Pages 139-142 Allopurinol in Breast Milk....Pages 143-145 Pharmacokinetics of Benzbromarone: Evidence for a Biliary-Intestinal-Biliary Recirculation....Pages 147-150 Analysis of Uric Acid Transport in Renal Tubules Using Benzbromarone and Pyrazinamide....Pages 151-155 Deficient Benzbromarone Elimination from Plasma: Evidence for a New Genetically Determined Polymorphism with an Autosomal Recessive Inheritance....Pages 157-160 Urate Transport in the Proximal Tubule of Human Kidney....Pages 177-180 The Genetics of Renal Excretion of Urate in Man....Pages 181-183 What is the Pathogenesis of Familial Gouty Nephropathy?....Pages 185-189 Renal Urate Hypoexcretion Preceding Renal Disease in a New Kindred with Familial Juvenile Gouty Nephropathy (FJGN)....Pages 191-194 Familial Nephropathy and Gout: Which Comes First?....Pages 195-198 Does Allopurinol Affect the Progression of Familial Juvenile Gouty Nephropathy?....Pages 199-202 Congenital Chloride Losing Enteropathy Associated with Tophaceous Gouty Arthritis....Pages 203-208 The Role of Lead in Gout Nephropathy Reviewed: Pathogenic or Associated Factor?....Pages 209-212 Myogenic Hyperuricemia in Hypoparathyroidism....Pages 213-216 Lipoprotein Metabolism in Primary Gout - Influence of Alcohol Intake and Body Weight....Pages 217-221 Serum Urate and Uric Acid Excretion....Pages 223-226 Gout and Main Rheumatic Diseases in Man....Pages 227-230 Importance of the Confounding Factors Age and Sex in the Correlation of Serum Uric Acid, Cholesterol and Triglyceride Levels....Pages 231-234 Changes in Urate Metabolism After Castration of Patients Suffering from Carcinoma of the Prostate....Pages 235-238 Renal Hypouricemia Associated with Hyperoxypurinemia due to Decreased Renal Excretion of Oxypurines: a New Defect in Renal Purine Transport....Pages 239-242 Significance of Hypouricemia....Pages 243-245 Organic Distribution and Interrelationships of Lesions Occurring in Laying Hens Suffering from Gout and Urolithiasis....Pages 247-250 A Biochemical Investigation on Chicken Gout Observed in the Marmara Region in Turkey....Pages 251-254 Production of Uric Acid and Allantoin in Perfused Rat Liver....Pages 255-257 Dynamics in the Purine Nucleotides of Liver During Various Periods of Hypoxia/Ischaemia and Reoxygenation....Pages 259-264 Adenosine: Origin and Clinical Roles....Pages 265-270 Oxypurines in Extracellular Fluids from Piglets During Hypoxemia and Reoxygenation....Pages 271-274 Regulation of Adenosine Concentrations by Acadesine (Aica-Riboside) in Human B-Lymphoblasts....Pages 275-278 Preservation of Adenine Nucleotides Following Ischemia and Reperfusion: Correlation with Functional Recovery....Pages 279-284 An Alternative Pathway of Adenylate and ATP Synthesis....Pages 285-288 Preservation of Nucleotide Pool During Heart Transplantation and Evaluation of Adenylate Catabolic Pathways in the Human Heart....Pages 289-292 The Influence of Acetate on Adenine Nucleotides in Rat Liver....Pages 293-296 Purine Nucleotide Catabolism in Rat Liver After Castration....Pages 297-300 Adenine Nucleotide Metabolism in Liver Ischemia: Effect of Allopurinol....Pages 301-304 Effects of Pulsed Electromagnetic Fields on the Adenine Nucleotide Pool and Energy Charge in Cells in Culture....Pages 305-308 Mechanisms Accounting for Changes of Adenine Nucleotide Content in Mitochondria at Ischemia....Pages 309-312 New Aspects of Purine Nucleotide Metabolism: Formation of ADP from Inorganic Phosphate During Degradation of AMP....Pages 313-316 Phosphorylation of Adenosine by an Exchange Reaction Between AMP and Adenosine in Anoxic Hepatocytes....Pages 317-320 Hypoxanthine and Inosine Metabolism in Cultured Rat Cardiomyocytes....Pages 321-325 The Mechanism of Conversion of Xanthine Dehydrogenase to Oxidase and the Role of the Enzyme in Reperfusion Injury....Pages 327-333 Purification of Xanthine Oxidase from Human Milk....Pages 335-338 Mechanisms of Protection of Hepatocytes at Anoxia and Reoxygenation by the Xanthine Oxidase Inhibitor Oxypurinol....Pages 339-342 Oxypurinol Reduces Ischemic Brain Injury in the Gerbil and Rat....Pages 343-346 Acadesine (Aica Riboside) Attenuates Reperfusion Injury and Oxidant-Induced Damage of the Heart....Pages 347-347 Effects of H 2 O 2 and CHPO on ATP-, CP-Content and 14C-HX-Uptake by Huvecs....Pages 349-352 Absence of Xanthine Oxidoreductase Activity in Human Myocardium....Pages 353-356 Lower Xanthine Oxidoreductase Activity in Isolated Perfused Hearts if Xanthine Replaces Hypoxanthine as Substrate....Pages 357-360 Evidence from in vitro Studies that Dihydroorotate Dehydrogenase may be a Source of Toxic Oxygen Species....Pages 361-364 Influence of Oxypurinol on Colitis Induced in Rat Colon by Trinitrobenzene Sulfonic Acid Treatment....Pages 365-368 A Xanthinuric Family - The Proposita Having Immunologically Reactive Xanthine Oxidase but no Xanthine Oxidase Activity....Pages 369-372 Human Hepatic Peroxisomes with Crystalloid Cores Associated with Urate Oxidase Activity....Pages 373-376 Structural Analysis of the Rat Uricase Gene and Evidence that Lysine 164 is Involved in the Substrate-Binding Site of the Enzyme....Pages 377-381 Study of DNA Repair in the Peripheral Blood Lymphocytes of Patients with Rheumatic Diseases Under Going Treatment....Pages 383-385 Nucleoside Transport in Lymphocytes from Alcoholics and Non-Alcoholics....Pages 387-390 Initial Rate Measurements of Cellular Nucleoside Transport: Time Course, Initial Curvature of Time Curves and Metabolism....Pages 391-394 Relationships Between Metabolic Enzymes and the Nucleoside Transport....Pages 395-398 Active Transport of Adenosine into Primary Cultures of Brain Cells and its Methodological Consequences....Pages 399-402 Intestinal Transport and Metabolism of Purine and Pyrimidine Nucleosides....Pages 403-406 Guanine Uptake by Human Erythrocytes....Pages 407-410 Radioligand Binding Studies on the Nucleoside Transport Protein....Pages 411-414 Nucleoside Transport in Guinea-Pig Myocardium....Pages 415-418 Comparison of the Existing Nucleoside Transport Inhibitors: in vitro and in vivo Data....Pages 419-422 Effect of Membrane Lipid Composition on the Functional Activity of a Reconstituted Nucleoside Transporter Derived from Ehrlich Ascites Cells....Pages 423-426 Antibodies and Proteases as Probes of the Structures of Mammalian Nucleoside Transporters....Pages 427-430 Expression of Sodium-Dependent Nucleoside Transporters in Xenopus Oocytes....Pages 431-434 Control of Nucleoside Transport in Neural Cells Effect of Protein Kinase C Activation....Pages 435-438 Isolation of Nucleoside Permeases from Escherichia Coli ....Pages 439-442 Murine Erythroleukemia Cells Resistant to Periodate-Oxidized Adenosine Have Lowered Levels of Nucleoside Transporter....Pages 443-446 Effect of Ischaemia on Cardiac Adenosine Binding Sites....Pages 447-450 A Ferritin-Cyclohexyladenosine Probe for Electron Microscope Localization of A 1 Adenosine Receptor....Pages 451-454 Effect of Adenosine on the Membrane Potential Changes of Human Neutrophils Triggered by the Tripeptide F-Met-Leu-Phe....Pages 455-458 A 2 Adenosine Receptors in Neutrophils from Health Volunteers and Patients with Rheumatic Disease....Pages 459-462 Back Matter....Pages 463-473 Proceedings of the Seventh International/Third Joint Symposium held in Bournemouth, UK, June 30-July 5, 1991