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.

Inhalt

Biochemical Approach to New Medications.- Antimetabolites in Cancer Chemotherapy.- 2-Chlorodeoxyadenosine Chemotherapy Triggers Programmed Cell Death in Normal and Malignant Lymphocytes.- ICI D1694, an Inhibitor of Thymidylate Synthase for Clinical Study.- Action and Sequence Dependent Interaction of Acivicin and 6-Thioguanine in the Human Derived Maligant T-ALL and CALLA+ Cell Lines.- Conversion of Acyclic Nucleoside Phosphonates to their Diphosphate Derivatives by 5-Phosphoribosyl-1-Pyrophosphate (PRPP) Synthetase.- Derivation of New Drugs for Therapy of AIDS.- Biochemical and Pharmacological Properties of C1-972, a Novel 9-Deazaguanine Analog Purine Nucleoside Phosphorylase (PNP) Inhibitor.- Pyrrolo[3,2-D]pyrimidines, a New Class of Purine Nucleoside Phosphyorylase (PNP) Inhibitors as Potential T-cell Selective Immunosuppressive Agents.- Modulation of Metabolism and Anti-HIV-1 Activity of Purine 2?,3?-Dideoxynucleosides by IMP Dehydrogenase Inhibitors.- Acadesine (AICA Riboside) Inhibits Platelet Aggregation in Human Whole Blood.- Concentration and Time Dependent Growth Inhibition and Metabolism in Vitro by 2?, 2?-Difluoro-deoyxcytidine (Gemcitabine).- Thiopurine Methyltransferase Activity and Efficacy of Azathioprine Immunosuppresion in Transplant Recipients.- Increase in 2?,5?-Oligoadenylate Synthetase Caused by Deoxycoformycin in Hairy Cell Leukaemia.- A Dual Anti-Tumour Effect of a Combination of Interferon-? and 5-Fluorouracil or 2-Chlorodeoxyadenosine on Natural Killer (NK) Cell Mediated Cytotoxicity.- The Effect of Methotrexate on the Folate Coenzyme Pools in Human Hepatoma Cells in Culture.- Purine Nucleotide Biosynthesis in Leukemic Promyelocytes Treated with Retinoids.- 6-Mercaptopurine Metabolism in Two Leukemic Cell Lines.- Synergistic Interaction of Methotrexate and 6-Mercaptopurine in Human Derived Malignant T-and CALLA+ Cell Lines.- 6-Thioguanine Metabolism in Human Erythrocytes.- The Impact of Selected Nucleosides on the Cytotoxicity of ARA-C in HL60 Cells.- Effect of Chloroadenosine on the Phosphoinosotide Turnover in Human T Lymphoblasts Activated through the T-cell Receptor/CD3 Complex.- Isolated Liver Perfusion versus Hepatic Artery Infusion with 5-Fluorouracil in a Rat Model; Effects on Thymidylate Synthase.- Changes of Purine Nucleotide Metabolism of Ehrlich Ascites Cells during the Transition of Tumour Growth.- Purine Nucleotides, Nucleosides and Nucleobases of Liver, Skeletal Muscle, Blood and Tumour Cells during the Growth of Ehrlich Ascites Tumour in Mice.- Uridine Fluxes in Healthy Proliferating T-Lymphocytes, MOLT-3 T-ALL Cell-Line Cells and Differentiated MOLT-3 Cells.- Some Aspects of Purine Nucleotide Metabolism in Human Lymphocytes: Nucleotide Content in Human Lymphoblastoid Lines, Transfected with HIV.- Metabolism and Action of 2?, 2?-Difluoro-deoxycytidine: Self Potentiation of Cytotoxicity.- Effect of Leucovorin on 5-Fluorouracil Induced Inhibition of Thymidylate Synthase in Patients with Colon Cancer.- A Novel Xanthine Dehydrogenase Inhibitor (BOF-4272).- Changes Caused by Ethanol Intake on Metabolism of Hypouricemic Agents (Combination of Allopurinol and Benzobromarone).- Allopurinol in Breast Milk.- Pharmacokinetics of Benzbromarone: Evidence for a Biliary-Intestinal Biliary-Recirculation.- Analysis of Uric Acid Transport in Renal Tubules Using Benzbromarone and Pyrazinamide.- Deficient Benzbromarone Elimination from Plasma: Evidence for a New Genetically Determined Polymorphism with an Autosomal Inheritance.- Nucleotide Status in Erythrocytes of Rats Infected with Plasmodium berghei.- Hypoxanthine Depletion Induced by Xanthine Oxidase Inhibits Malaria Parasite Growth in Vitro.- New Nucleoside Transport Pathways Induced in the Host Erythrocyte Membrane of Malaria and Babesia Infected Cells.- Effect of Polyethylene Glycol-Modfied Adenosine Deaminase (PEG-ADA) Therapy in Two ADA-Deficient Children: Measurement of Erythrocyte Deoxyadenosine Triphosphate as a Useful Tool.- Urate Transport in the Proximal Tubule of Human Kidney.- The Genetics of Renal Excretion of Urate in Man.- What is the Pathogenesis of Familial Juvenile Gouty Nephropathy?.- Renal Urate Hypoexcretion Preceding Renal Disease in a New Kindred with Familial Gouty Nephropathy (FJGN).- Familial Nephropathy and Gout: Which Comes First?.- Does Allopurinol Affect the Progression in Familial Juvenile Gouty Nephropathy?.- Congenital Chloride Losing Enteropathy Associated with Tophaceous Gouty Arthritis.- The Role of Lead in Gout Nephropathy Reviewed: Pathogpenic or Associated Factor?.- Myogenic Hyperuricemia in Hypoparathyroidism.- Lipoprotein Metabolism in Primary Gout Influence of Alcohol Intake and Body Weight.- Serum Urate and Uric Acid Excretion.- Gout and Main Rheumatic Diseases in Man.- Importance of Confounding Factors Age and Sex in the Correlation of Serum Uric Acid, Cholesterol and Triglyceride Levels.- Changes in Urate Metabolism after Castration of Patients Suffering from Carcinoma of the Prostate.- Renal Hypouricemia Associated with Hyperoxypurinemia due to Decreased Renal Excretion of Oxypurines: A New Defect in Renal Purine Transport.- Significance of Hypouricemia.- Organic Distribution and Interrelationships of Lesions Occuring in Laying Hens Suffering from Gout and Urolithiasis.- Biochemical Investigations on Chicken Gout Observed in the Marmara Region in Turkey.- Production of Uric Acid and Allantoin in Perfused Rat Liver.- Dynamics in the Purine Nucleotides of Liver during Various Periods of Hypoxia/Ischaemia and Reoxygenation.- Adenosine Origin and Clinical Roles.- Oxypurines in Extracellular Fluids from Piglets during Hypoxemia and Reoxygenation.- Regulation of Adenosine Concentrations by Acadesine (AICA-Riboside) in Human B-Lymphoblasts.- Preservation of Adenine Nucleotides following Ischemia and Reperfusion: Correlation with Functional Recovery.- An Alternative Pathway of Adenylate and ATP Synthesis.- Preservation of Nucleotide Pool during Heart Transplantation and Evaluation of Adenylate Catabolic Pathways in the Human Heart.- The Influence of Acetate on Adenine Nucleotides in Rat Liver.- Purine Nucleotide Catabolism in Rat Liver after Castration.- Adenine Nucleotide Metabolism in Liver Ischemia: Effect of Allopurinol.- Effect of Pulsed Electromagnetic Fields on the Adenine Nucleotide Pool and Energy Charge in Cells in Culture.- Mechanism Accounting for Changes of Adenine Nucleotide Content in Mitochondria at Ischemia.- New Aspects …