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Publicatie lijst dr

PUBLICATIONS Dr. R.A. De Abreu (until April- 2006)
1. Berns AW, De Abreu RA, Kraaikamp M van, Benedetti EL, Bloemendal H. Synthesis of
lens protein in vitro. V. Isolation of messenger-like RNA from lens by high resolution zonal centrifugation. FEBS letters 1971; 18: 159-163. 2. Lommen EJP, De Abreu RA, Trijbels JMF and Schretlen EDAM. The IMP dehydrogena- se catalysed reaction in erythrocytes of normal individuals and patients with hypoxanthine guanine phosphoribosyltransferase deficiency. Acta Paediatr 1974; 64: 140-142. 3. Bresters TW, De Abreu RA, Kok A de, Visser J, Veeger C. The pyruvate-dehydrogenase complex from Azotobacter Vinelandii. 1. Purification and properties. Eur J Biochem 1975; 59: 335-345. 4. Grande HJ, Bresters TW, De Abreu RA, Kok A de, Visser J, Veeger C. The pyruvate- dehydrogenase complex from Azotobacter Vinelandii. 3. Stoichiometry and function of the individual components. Eur J Biochem 1975; 59: 355-363. 5. Veeger C, Visser AJWG, Krul J, Grande HJ, De Abreu RA, Kok A de. Fluorescence studies on lipoamide dehydrogenase, pyruvate dehydrogenase complexes and transhydro-genase. In: Flavins and Flavoproteins. Proc 4th Int Conf. Singer TP ed, Elsevier Publ Co, Amsterdam, 1976; 500-505. 6. De Abreu RA, Kok A de, Graaf-Hess AC de, Veeger C. Transformation of the 4- component pyruvate dehydrogenase complex from Azotobacter Vinelandii into a 3-component complex. FEBS letters 1977; 82: 89-92. 7. De Abreu RA, Kok A de, Graaf-Hess AC de, Veeger C. Determination of the chain stoichiometries from the number of reactive sulfhydryl groups in the pyruvate dehydroge-nase complexes of Azotobacter Vinelandii and Escherichia Coli. Eur J Biochem 1977; 81: 357-364. 8. De Abreu RA, Vries J de, Kok A de, Veeger C. Crosslinking studies with th pyruvate dehydrogenase complexes from Azotobacter vinelandii and Escherichia coli. Eur J Biochem 1979; 79 379-387. 9. Veeger C, Visser AJWG, Eweg J-K, Grande HJ, De Abreu RA, Graaf-Hess AC de, Müller F. Fluorescence of oxidized and reduced flavins and flavoproteins. In: Flavins and Flavoproteins. Proc Int 6th Conf. Yagi K and Yamano T eds, Jap Scient Soc Press, 1980. 10. De Abreu RA, Baal JM van , Bakkeren JAJM, Bruyn CHMM de, Schretlen EDAM. A high-performance liquid chromatographic assay for identification and quantification of nucleotides in lymphocytes and malignant lymphoblasts. J Chromatogr 1982; 227: 45-52. 11. De Abreu RA, Baal JM van, Schouten TJ, Schretlen EDAM, Bruyn CHMM de. High- performance liquid chromatographic determination of plasma 6-mercaptopurine in clinically relevant concentrations. J Chromatogr Biomed Appl 1982; 227: 526-533. 12. De Abreu RA, Baal JM van, Bruyn CHMM de, Bakkeren JAJM, Schretlen EDAM. High- performance liquid chromatographic determination of purine and pyrimidine bases, ribonucleosides, deoxyribonucleosides and cyclic ribonucleoties in biological fluids. J Chromatogr 1982; 229: 67-75. 13. Smits MG, Gabreëls FJM, Froeling PGA, De Abreu RA, Thyssen HOM. Calcium- phosphate metabolism in autosomal recessive idiopathic strio-pallido-dentate calcinosis and Cockayne's syndrome. Clin Neurol Neurosurg 1983; 85: 145-153. 14. Smits MG, De Abreu RA, Froeling PGA, Gabreëls FJM. Presence of cerebral parathyroid hormone-responsive adenylcyclase in humans. Ann Neurol 1983; 14: 348-349. 15. Peters GJ, De Abreu RA, Oosterhof A, Veerkamp JH. Concentration of nucleotides and deoxynucleotides in peripheral and phytohemagglutinin-stimulated mammalian lymphocytes. Biochim Biophys Acta 1983; 759: 7-15. 16. De Abreu RA, Peters GJ, Veerkamp JH. Concentration of Nucleotides in peripheral blood lymphocytes of various mamalian species. In: Purine and pyrimidine metabolism in man IVB: Biochemical, Immunological, and Cancer Research, Bruyn de CHMM, Simmonds HA and Müller MM eds, Plenum Press, New York/London, 1984; 125-128. 17. Schouten TJ, De Abreu RA, Bruyn CHMM de, Kleyn E van der, Oosterbaan MJM, Schretlen EDAM, Vaan GAM de. 6-Mercaptopurine: Pharmacokinetics in animals and preliminary results in children. In: Purine and pyrimidine metabolism in man IVB: Biochemical, Immunological, and Cancer Research, Bruyn CHMM de, Simmonds HA and Müller MM eds, Plenum Press, New York/London, 1984: 367-370. 18. Bakkeren JAJM, De Abreu RA, Sengers RCA, Gabreëls FJM, Maas JM, Renier WO. Elevated urine, blood and cerebrospinal fluid levels of uracil and thymine in a child with dihydrothymine dehydrogenase deficiency. Clin Chim Acta 1984; 140: 247-256. 19. Bökkerink JPM, Schouten TJ, De Abreu Ra, Lippens RJJ, Vaan GAM de, Bruyn CHMM de, Laarhoven JPRM van. 6-Mercaptopurine en methotrexaat, zicht op een rationeel gebruik na 35 jaar? Tijdschr Kindergeneesk 1984; 52: 118-123. 20. Baal JM van, Leeuwen MB van, Schouten TJ, De Abreu RA. Sensitive high-performance liquid chromatographic determination of 6-mercaptopurine, 6-thioguanine, 6-mercaptopu-rineriboside and 6-thioguanosine in biological fluids. J Chromatogr 1984; 336: 422-428. 21. De Abreu RA, Peters GJ, Bakkeren JAJM, Veerkamp JH. Discrepancies in ribonucleotide concentrations in human lymphocytes isolated from heparinized and defibrinized blood. Clin Chim Acta 1985; 145: 349-355. 22. Janssen JThP, Baal JM van, Vierwinden G, De Abreu RA. Determination of nucleotide content in splenic lymphocytes from patients with Hodgkin's disease and controls. In Thesis: J.Th.P. Janssen, Characteristics of Lymphocytes in Hodgkin's Disease. 1985; chapter 9: 105-111. 23. Schouten TJ, De Abreu RA, Schretlen EDAM, Leeuwen MB, Baal JM van, Vaan GAM de. 6-Thioguanine: High-dose 2-H infusions in Goats. J Cancer Res Clin Oncol 1985; 110: 115-118. 24. Kraan PM van der, De Abreu RA, Laarhoven JPRM van, Bruyn CHMM de. Mogelijkhe- den van enzymgerichte chemotherapie bij leukemie. Kanker 1985; 3: 30-31. 25. Schouten TJ, De Abreu RA, Schretlen EDAM, Bruyn CHMM de, Kleyn E van der, Oosterbaan MJM, Vaan GAM de. 6-Mercaptopurine: Oral administration and i.v. bolus injections in dogs. Eur J Paediatr Haematol Oncol 1985; 2: 93-98. 26. Schouten TJ, De Abreu RA, Schretlen EDAM, Baal JM van, Leeuwen MB van, Vaan GAM de. 6-Mercaptopurine: High dose 24-hours infusion in goats. J Cancer Res Clin Oncol 1986; 112: 61-66. 27. Schouten TJ, De Abreu RA, Schretlen EDAM, Vaan GAM de, Kleyn E van der. 6- Mercaptopurine: Total body autoradiograms and plasma concentration-time curves of 6MP and metabolites from Marmoset monkeys. Pediat Hematol Oncol 1986; 3: 159-165. 28. De Abreu RA, Bakkeren JAJM, Braakhekke J, Gabreëls FJM, Maas JM, Sengers RCA. Dihydrothymine dehydrogenase deficiency in a family, leading to elevated levels of uracil of uracil and thymine. In: Purine and pyrimidine metabolism in man VA: Clinical Aspects including Molecular Genetics, Nyhan WL and Seegmiller JE eds, Plenum Press, New York/London, 1986; 77-80. 29. De Abreu RA, Bökkerink JPM, Bakker MAH, Hulscher TW, Baal JM van, Bruyn CHMM de, Schretlen EDAM. Influence of methotrexate on purine and pyrimidine pools and on cell phase distribution of cultured human lymphoblasts. In: Purine and pyrimidine metabolism in man VB: Basic Science Aspects, Nyhan WL and Seegmiller JE eds, Plenum Press, New York/London, 1986; 105-111. 30. De Abreu RA, Bökkerink JPM, Bakker MAH, Hulscher TW, Vaan GAM de, Bruyn CHMM de, Schretlen EDAM. Synergy of methotrexate and 6-mercaptopurine on cell-growth and clonogenicity of cultured human T-lymphoblasts. In: Purine and pyrimidine metabolism in man VB: Basic Science Aspects, Nyhan WL and Seegmiller JE eds, Plenum Press, New York/London, 1986; 129-134. 31. Bökkerink JPM, De Abreu RA, Laarhoven JPRM van, Bakker MAH, Hulscher TW, Schretlen EDAM, Bruyn CHMM de. Increased availability of phosphoribosylpyrophosp-hate as the basis for enhanced 6-mercaptopurine incorporation by methotrexate, in cultured human lymphoblasts. In: Purine and pyrimidine metabolism in man VB: Basic Science Aspects, Nyhan WL and Seegmiller JE eds, Plenum Press, New York/London, 1986; 135-139. 32. Kraan PM van der, Zandvoort PM van, De Abreu RA, Bakkeren JAJM, Laarhoven JPRM van, Bruyn CHMM de. Inhibition of 3H thymidine incorporation by guanosine and deoxyguanosine in human peripheral lymphocytes and malignant lymphoid cell lines. In: Purine and pyrimidine metabolism in man VA: Clinical Aspects including Molecular Genetics, Nyhan WL, Thompson LF and Watts RWE eds, Plenum Press, New York/Lon-don, 1986; 547-551. 33. Kraan PM van der, Zandvoort PM van, De Abreu RA, Bakkeren JAJM, Laarhoven JPRM van Bruyn CHMM de. Biphasic effects of adenosine on cell growth and cell cycle of human lymphoid cell lines. In: Purine and pyrimidine metabolism in Man VA: Clinical Aspects including Molecular Genetics, Nyhan WL, Thompson LF and Watts RWE eds, Plenum Press, New York/London, 1986; 553-559. 34. Kraan PM van der, Zandvoort PM van, De Abreu RA, Bakkeren JAJM, Laarhoven JPRM van, Bruyn CHMM de. Inhibition of 3H thymidine incorporation by adenosine and deoxyadenosine in human peripheral lymphocytes and malignant lymphoid cell lines. In: Purine and pyrimidine metabolism in man VB: Basic Science Aspects, Nyhan WL and Seegmiller JE eds, Plenum Press, New York/London, 1986; 213-219. 35. Bökkerink JPM, Bakker MAH, Hulscher TW, De Abreu RA, Schretlen EDAM, Laarho- ven JPRM van, Bruyn CHMM de. Sequence-, time- and dose-dependent synergism of methotrexate and 6-mercaptopurine in human malignant lymphoblasts. Biochem Pharma-col 1986; 35: 3549-3555. 36. Bökkerink JPM, De Abreu RA, Bakker MAH, Hulscher TW, Baal JM van, Vaan GAM de. Dose related effects of methotrexate on purine and pyrimidine nucleotides and on cell kinetic parameters in Molt-4 malignant T-lymphoblasts. Biochem Pharmacol 1986; 35: 3557-3564. 37. Peters WHM, Jansen PLM, Cuypers HTM, De Abreu RA, Nauta H. Deconjugation of glucuronides catalysed by UDP-glucuronyl transferase. Biochim Biophys Acta 1986; 873: 252-259. 38. Kraan PM van der, Zandvoort PM van, De Abreu RA, Baal JM van, Bakkeren JAJM. Inhibition of lymphoid cell growth by adenine ribonucleotide accumulation. The role of PRPP-depletion induced pyrimidine starvation. Biochim Biophys Acta 1987; 927: 213-221. 39. Bökkerink JPM, De Abreu RA, Bakker MAH, Hulscher TW. Potentiation of 6-mercapto- purine after time and dose dependent pretreatment with methotrexate in malignant human T- and B-lymphoblasts. In: The Role of pharmacology in pediatric oncology. Poplack PG, Massimo L and Cornaglia-Ferraris P eds, Dordrecht: Martinus Nijhoff Publishers, 1987: 185-191. 40. De Abreu RA, Bökkerink JPM, Bakker MAH, Hulscher TW, Baal JM van. The effect of methotrexate on purine and pyrimidine deoxyribo-nucleoside triphosphate pools and on cell viability and cell phase distribution in malignant human T- and B- lymphoblasts. In: The Role of pharmacology in pediatric oncology. Poplack PG, Massimo L, Cornaglia-Ferraris P eds, Dordrecht: Martinus Nijhoff Publishers, 1987: 191-195. 41. De Abreu RA, Bökkerink JPM, Vaan GAM de. Synergisme van methotrexaat an 6- mercaptopurine: In vitro studies aan humane maligne lymphoblastaire cellijnen. Tijdschr NKCV 1987; 12: 54-57.
42. Braakhekke JP, Renier WO, Gabreëls FJM, De Abreu RA, Bakkeren JPM, Sengers RCA.
Dihydrothymine dehydrogenase deficiency: a cause of cerebral dysfunction ? In: Verhandlungen de Deutschen Geselschaft für Neurologie 4. Poeck K, Hacke W and Schneider R eds, Berlin: Springer Verlag, 1987: 306-307. 43. Braakhekke JP, Renier WO, Gabreëls FJM, De Abreu RA, Bakkeren JAJM, Sengers RCA. Dihydrothymine dehydrogenase deficiency. Neurological aspects. J Neurol Sci 1987; 78: 71-77. 44. Salemans J, Hoitsma AJ, De Abreu RA, Vos D de, Koene RAP. Pharmacokinetics of azathioprine and 6-mercaptopurine after oral administration of azathioprine. Clin Trans-plant 1987; 1: 217-221. 45. Smits P, Boekema P, De Abreu R, Thien T, Laar A van 't. Evidence for antagonistism between caffeine and adenosine in the cardiovascular system in man. J Cardiovasc Pharmacol 1987; 10: 136-143. 46. Widdershoven J, Munster P van, De Abreu R, Bosman H, Lith Th van, Putten-van Meyel M van der, Motohara K, Matsuda I. Four methods compared for measuring descarboxy-prothrombin (PIVKA-II). Clin Chem 1987; 33: 2074-2078. 47. Bökkerink JPM, Bakker MAH, Hulscher TW, De Abreu RA, Schretlen EDAM. Purine de novo synthesis as the basis of synergism of methotrexate and 6-mercaptopurine in human malignant lymphoblasts of different lineages. Biochem Pharmacol 1988; 37: 2321-2327. 48. Bökkerink JPM, De Abreu RA, Bakker MAH, Hulscher TW, Baal JM van, Schretlen EDAM. Effects of methotrexate on purine and pyrimidine metabolism and cell kinetic parameters in human malignant lymphoblasts of different lineages. Biochem Pharmacol 1988; 37: 2329-2338. 49. Bökkerink JPM, De Abreu RA, Lippens RJJ, Schouten TJ, Vaan GAM de. Biochemische en klinisch-farmacologische aspecten van antimetabolieten bij de behandeling van leukemie. Tijdschr Kindergeneesk 1988; 56: 56-60. 50. Kraan PM van der, Zandvoort PM van, De Abreu RA, Bakkeren JAJM. Effects of 8- aminoguanosine on the toxicity of guanosine and deoxyguanosine for malignant and normal lymphoid cells. J Leuk Biol 1988; 44: 46-50. 51. Gerrits GPJM, Haagen AAM, De Abreu RA, Monnens LAH, Gabreëls FJM, Trijbels FJM, Theeuwes ALM and Baal van JM. Reference values of nucleosides and nucleobases in cerebrospinal fluid of children. Clin Chem 1988; 34: 1439-1442 52. Gerrits GP, Trijbels FJ, Monnens LA, Gabreëls FJ, De Abreu RA, Teeuwes AG, Raaij- Selten van B. Reference values for amino acids in cerebrospinal fluid of children determined using ion-exchange chromatography with fluorimetric detection. Clin Chem Acta 1989; 182: 75-94. 53. Bökkerink JPM, Damen FJM, Hulscher TW, Bakker MAH, De Abreu RA. Biochemical evidence for synergistic combination treatment with methotrexate and 6-mercaptopurine in acute lymphoblastic leukemia. In: Haematology and Blood Transfusion vol 33, Acute Leukemias II, Prognostic Factors and Treatment Strategies. Büchner T, Schellong G, Hiddemann W and Ritter J eds, Springer Verlag, Heidelberg, 1990: 110-117. 54. Raemakers-Franken PC, De Abreu RA, Willems JG, Drift C van der, Vogels GD. In vitro inhibition of cell growth of Molt-4 malignant human T-lymphoblasts by coenzyme F420. Biochem Pharmacol 1991; 41: 561-566. 55. De Abreu RA. In: Urate Deposition in Man and its Clinical Consequences. Acute renal insufficiency: Which mechanisms are involved? Gresser U and Zöllner N, eds. Springer-Verlag, Berlin, 1991: 78-79. 56. Gerrits GPJM, Monnens LAH, De Abreu RA, Schröder CH, Trijbels JMF, Gabreëls FJM. Disturbances of cerebral purine and pyrimidine metabolism in young children with chronic renal failure. Nephron 1991; 58: 310-314. 57. Cornelissen M, Smeets D, Merckx G, De Abreu R. Kolée L, Monnens L. Analysis of chromosome aberations and sister chromatid exchanges in peripheral blood lymphocytes of newborns after vitamine K prophylaxis at birth. Pediatr Res 1991; 30: 550-553. 58. Trueworthy RC, De Abreu RA, Lambooy LHJ, Bökkerink JPM, Stet EH. Action and sequence dependent interaction of acivicin and 6-thioguanine in human derived malignant T-ALL and CALLA+ cell lines. In: Purine and pyrimidine metabolism in man VIIA: Chemotherapy, ATP depletion, and Gout. Harkness RA, Elion GB and Zöllner N eds, Plenum Press, New York/London, 1991: 25-28. 59. Stet EH, De Abreu RA, Janssen YPG, Bökkerink JPM, Trijbels JMF. 6-Mercaptopurine metabolism in two leukemic cell lines. In: Purine and pyrimidine metabolism in man VIIA: Chemotherapy, ATP depletion, and Gout. Harkness RA, Elion GB and Zöllner N eds, Plenum Press, New York/London, 1991: 83-86. 60. De Abreu RA, Strien F van, Lambooy LHJ, Bökkerink JPM. Synergistic interaction of methotrexate and 6-mercaptopurine in human derived malignant T-ALL and CALLA+ cell lines. In: Purine and pyrimidine metabolism in man VIIA: Chemotherapy, ATP depletion, and Gout. Harkness RA, Elion GB and Zöllner N eds, Plenum Press, New York/London; 1991: 87-91. 61. Blom HJ, Engelen DPE, Boers GHJ, Stadhouders AM, Sengers RCA, De Abreu RA, Te Poele-Pothoff, Trijbels JMF. Lipid peroxidation in homocysteinaemia. J.Inher.Metab.Dis. 1992; 15: 419-422. 62. Bökkerink JPM, De Abreu RA, Stet EH, Damen FJM. Cell-kinetics and biochemical pharmacology of methotrexate and 6-mercaptopurine in human malignant T-lymphoblasts. Klin. Pädiatr 1992; 204: 293-298. 63. Kuypers KC, Dongen van JJM, Burg van der P, Roos MTh, Vonk J, De Abreu R, Korte de D, Noesel van CJM, Weening RS, Lier RAW. A combined immunodeficiency with oligoclonal CD8+, Vß3-Expressing, cytotoxic T lymphocytes in the peripheral blood. J.Immunol. 1992; 149: 3403-3410. 64. Stet EH, De Abreu RA, Janssen YPG, Bökkerink JPM, Trijbels JMF. A biochemical basis for synergism of 6-mercaptopurine and mycophenolic acid in MOLT F4, a human lymphoblastic T-cell line. Biochim. Biophys. Acta 1993; 1180: 277-282 65. Bökkerink JPM, De Abreu RA, Stet EH, Damen FJM, Hulscher TW, Bakker MAH, van Baal JM. 6-Mercaptopurine, cytotoxicity and biochemical pharmacology in human malignant T-lymphoblasts. Biochem. Pharmacol. 1993; 45: 1455-1463 66. Gerrits GPJM, Gabreëls FJM, Monnens LAH, De Abreu RA, van Raaij-Selten B., Niezen- Koning KE, Trijbels JMF. Argininosuccinic aciduria: clinical and biochemical findings in three children with the late onset form, with special emphasis on cerebrospinal fluid findings of amino acids and pyrimidines. Neuropediatr. 1993;24: 15-18 67. Cornelissen EAM, Kollée LAA, De Abreu RA. van Baal JM, Motohara K, Verbruggen B, Monnens LAH. Effects of oral versus intramuscular vitamin K prophylaxis on vitamin K1, PIVKA-II and clotting factors in breast-fed infants. Arch.Dis.Child 1993;67: 1250-1254 68. Vogt MHJ, Stet EH, De Abreu RA, Bökkerink JPM, Lambooy LHJ, Trijbels FJM. The importance of methylthio-IMP for methylmercaptopurine ribonucleotide (Me-MPR) cytoxicity in MOLT F4 human malignant T-lymphoblasts. Biochim. Biophys. Acta 1993; 1181: 189-194. 69. Cornelissen EAM, Kolée LAA, De Abreu RA, Motohara K, Monnens LAH. Prevention of Vitamin K deficiency in infancy by weekly administration of vitamin K. Acta Pediatr. 1993; 82: 656-659. 70. Cornelissen EAM, Steegers-Theunissen RPM, Kolée LAA, Eskens TKAB, Vogels- Mentink G, Motohara K, De Abreu RA, Monnens LAH. Increased incidence of neonatal vitamin K deficiency due to maternal anticonvulsant therapy. Am.J.Obstet.Gynaec. 1993; 168: 923-928 71. Stet EH, De Abreu RA, Bökkerink JPM, Lambooy LHJ, Vogels-Mentink TM, Trijbels JMF. Reversal of 6-mercaptopurine and methylmercaptopurine cytotoxicity by amino imidazole carboxamide riboside. Biochem. Biochem. Pharmacol. 1993; 46: 547-550 72. De Abreu RA. Dihydropyrimidine dehydrogenase deficiency: biochemical and genetic basis. In: Molecular genetics,biochemistry and clinical aspects of inherited disorders of purine and pyrimidine metabolism. Springer-Verlag Berlin Heidelberg New York. U.Gresser ed. 1993: 176-182. 73. Gerrits P, Monnens L, Gabreëls F, De Abreu R, Koster A, Trijbels F. CSF as a tool in the diagnosis of metabolic brain diseases. J.Inh.Met.Dis. 1993; 16: 670-675 74. Kerstens PJSM, Stolk JN, Hilbrands LB, van de Putte LBA, De Abreu RA, Boerbooms AMT. 5-nucleotidase and azathioprine-related bone-marrow toxicity. The Lancet 1993; 342: 1245-1246. 75. Stet EH, De Abreu RA, Bökkerink JPM, Lambooy LHJ, Vogels-Mentink TM, Keizer- Garritsen JJ, Trijbels FJM. Inhibition of IMP-dehydrogenase by mycophenolic acid in MOLT-F4 human malignant lymphoblasts. Ann. Clin. Biochem. 1994; 31: 174-180 76. Kerstens PJM, Stolk JN, Boerbooms AMT, Lambooy LHJ, de Graaf R, De Abreu RA, van de Putte LBA. Purine enzymes in rheumatoid arthritis: Possible association with response to azathioprine. A pilot study. Ann. Rheum. Dis. 1994; 53: 608-611. 77. Stet EH, De Abreu RA, Bökkerink JPM, Blom HJ, Lambooy LHJ, Vogels-Mentink TM, de Graaf-Hess AC, van Raay-Selten B, Trijbels FJM. Decrease in s-adenosylmethionine synthesis by 6-mercaptopurine and methylmercaptopurine ribonucleoside in Molt F4 human malignant lymphoblasts. Biochem. J. 1994; 304: 163-168. 78. van Aerts LAGJM, Blom HJ, De Abreu RA, Trijbels FJM, Eskes TKAB, Copius Peereboom-Stegeman JHJ, Noordhoek J. Prevention of Neural Tubel Defects by and Toxicity of L-Homocyteine in Cultured Postimplantation Rat Embryos. Teratology 1994; 50: 348-360. 79. Kerstens PJSM, Stolk JN, Boerbooms AMT, De Abreu RA, Van de Putte LBA. Purine enzymes in rheumatoid arthritis. A clue to the prediction of the response to azathioprine? Review and hypothesis. Clin.Exp.Rheum. 1995; 13: 107-111. 80. Kerstens PJSM, Stolk JN, De Abreu RA, Lambooy LHJ, van de Putte LBA, Boerbooms AAMT. Azathioprine-related bone marrow toxicity and low activities of purine enzymes in patients with rheumatoid arthritis. Arthritis Rheum. 1995; 1: 142-145. 81. Keuzenkamp-Jansen CW, Bökkerink JPM, Trijbels JMF, De Abreu RA, Van der Heyden MAH. Intracellular pharmacology and biochemistry of methotrexate and 6-mercaptopurine in childhood acute lymphoblastic leukemia. In Purine and Pyrimidine metabolism in man VIII (Eds. A. Sahota, MW Taylor), Plenum Publishing Corp., New York 1995; 115-118. 82. De Abreu RA. Nucleotide Metabolism: Mode of Action of Thiopurines in Leukemia. In Purine and Pyrimidine Metabolism in Man VIII (Eds. A. Sahota, MW Taylor), Plenum Publishing Corp., New York 1995; 195-200. 83. Griesmacher A, De Abreu RA, Muller MM. Influence of purines on endothelial high energy phosphates. In Purine and Pyrimidine metabolism in man VIII (Eds. A. Sahota, MW Taylor), Plenum Publishing Corp., New York 1995; 527 - 530 84. Rongen GA, Smits P, Ver Donck K, Willemsen JJ, De Abreu RA, van Belle H, Thien Th. Hemodynamic and Neurohumoral Effects of Various Grades of Selective Adenosine Transport Inhibition in Humans. Implications for its Future Role in Cardioprotection. J. Clin. Invest. 1995; 95: 658-668. 85. Stet EH, De Abreu RA, Bökkerink JPM, Lambooy LHJ, Vogels-Mentink TM, Keizer- Garritsen JJ, Trijbels FJM. Reversal of methylmercaptopurine ribonucleoside cytotoxicity by purine ribonucleosides and adenine. Biochem. Pharmacol. 1995; 49: 49-56. 86. Wevers RA, Engelke U, Abeling NGGM, De Abreu RA, van den Berg GB, Heerschap A. 1H-NMR Spectroscopie in lichaamsvloeistoffen en leucocyten. Ned. Tijdschr. Klin. Chem. 1995; 20: 3-9. 87. Stolk JN, De Abreu RA, Boerbooms AMTh, de Koning DGM, de Graaf R, Kerstens PJSM, van de Putte LBA. Purine enzyme activities in peripheral blood mononuclear cells: comparison of a new non-radiochemical high-performance liquid chromatography procedure and a radiochemical thin-layer chromatography procedure. J. Chromatogr. Biomed Appl. 1995; 666: 33-44. 88. De Abreu RA, Lambooy L, Stet EH, Vogels-Mentink T, van den Heuvel L. Thiopurine induced disturbance of DNA methylation in human malignant cells. Advan. Enzyme Regul. 1995; 35: 251-263. 89. Van Aerts LAGJM, Poirot CM, Herberts CA, Blom HJ, De Abreu RA, Trijbels JMF, Eskes TKAB, Copius Peereboom-Stegeman JHJ, Noordhoek J. Development of methioni-ne synthase and s-adenosyl-homocysteine hydrolase during gestation in rats. J. Reprod. Fert. 1995; 103: 227-232. 90. Tavenier M, Skladanowski AC, De Abreu RA, de Jong JW. Kinetics of adenylate metabolism in human and rat myocardium. Biochem. Biophys. Acta 1995;1244:351-356. 91. Keuzenkamp-Jansen CW, Bökkerink JPM, De Abreu RA, Trijbels JMF. High-dose 6- mercaptopurine infusions and tumor lysis syndrome. Leukemia Res. 1995; 19: 989-990 92. Keuzenkamp-Jansen CW, De Abreu RA, Bökkerink JPM, Trijbels JMF. Determination of extracellular and intracellular thiopurines and methylthiopurines with HPLC. J. Chroma-togr. Biomed. Appl. 1995; 672:53-61. 93. Van den Berg AA, Mooyer PA, van Lenthe H, Stet EH, De Abreu RA, van Kuilenburg AB, van Gennip AH. The IMP dehydrogenase inhibitor mycophenolic acid antagonizes the CTP synthetase inhibitor 3-deazauridine in Molt-3 human leukemia cells: a central role for phosphoribosyl pyrophosphate. Biochem. Pharmacol. 1995; 50: 1095-1098. 94. Keuzenkamp-Jansen CW, De Abreu RA, Blom HJ, Bökkerink JP, Trijbels J.M. Effects on transmethylation by methotrexate and 6-mercaptopurine infusions during the consolidation treatment of acute lymphoblastic leukemia. Biochem. Pharmacol. 1996; 51: 1165-1171. 95. Keuzenkamp-Jansen C.W., van Baal JM, De Abreu RA, de Jong JGN, Zuiderent R, Trijbels JMF. Detection and Identification of 6-methylmercato-8-hydroxy-purine: a major metabolite of 6-mercaptopurine in plasma during intraveneous administration. Clin.Chem. 1996; 42: 380-386. 96. Keuzenkamp-Jansen CW, Leegwater P.A.J, De Abreu RA, Lambooy MAH, Bökkerink JPM, Trijbels JMF. Thiopurine methyltransferase: a review and a clinical pilot study. J. Chromatogr. Biomed. Appl. 1996; 678: 15-22. 97. Wevers RA, Engelke U, Abeling NGGM, De Abreu RA, van den Berg GB, Heerschap A. 1H-NMR spectroscopy in body fluids and leucocytes: a view on metabolism. Klin.Biochem.Metab. 1996; 4: 91-98. 98. Vreken P, Van Kuilenburg AB, Meinsma R; Smit GP, Bakker HD, De Abreu RA, van Gennip AH. A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency. J. Inherit. Metab. Dis. 1996; 19: 645-654. 99. de Jong DJ, Assmann KJ, De Abreu RA, Monnens LA, van Liebergen FJ, Dijkman HB, Huysmans FT. 2,8-Dihydroxyadenine stone formation in a renal transplant recipient due to adenine phosphoribosyltransferase deficiency. J.Urol. 1996; 156: 1754-1755. Stolk JN, Boerbooms AM, De Abreu RA, Kerstens PJ, de Koning DG, de Graaf R, Mulder J, van de Putte LB. Purine enzyme activities in recent onset rheumatoid arthritis: are there differences between patients and healthy controls? Ann. Rheum. Dis. 1996; 55: 733-738. Vreken P, Van Kuilenburg AB, Meinsma R, De Abreu RA, Van Gennip AH. Identification of a four-base deletion (delTCAT296-299) in the dihydropyrimidine dehydrogenase gene with variable clinical expression. Hum. Genet. 1997; 100: 263-265. Putman CW, Rotteveel JJ, Wevers RA, van Gennip AH, Bakkeren JA, De Abreu RA. Dihydropyrimidinase deficiency, a progressive neurological disorder? Neuropediatrics. 1997; 28: 106-110. Leegwater PA, Lambooy LH, De Abreu RA, Bökkerink JP, van den Heuvel LP. DNA methylation patterns in the calcitonin gene region at first diagnosis and at relapse of acute lymphoblastic leukemia (ALL). Leukemia. 1997; 11: 971-978. van Gennip AH, De Abreu RA, van Lenthe H, Bakkeren J, Rotteveel J, Vreken P, van Kuilenburg AB. Dihydropyrimidinase deficiency: confirmation of the enzyme defect in dihydropyrimidinuria. J. Inherit. Metab. Dis. 1997; 20: 339-342. Wevers RA, Engelke U, Rotteveel JJ, Heerschap A, de Jong JG, Abeling NG, van Gennip AH, De Abreu RA. 1H NMR spectroscopy of body fluids in patients with inborn errors of purine and pyrimidine metabolism. J. Inherit. Metab. Dis. 1997; 20: 345-350. Van Kuilenburg AB, Vreken P, Beex LV, Meinsma R, Van Lenthe H, De Abreu RA; van Gennip AH. Heterozygosity for a point mutation in an invariant splice donor site of dihydropyrimidine dehydrogenase and severe 5-fluorouracil related toxicity. Eur. J. Cancer. 1997; 33: 2258-2264. De Abreu RA, Bökkerink JP, Keuzenkamp-Jansen CW, Stet EH, Trijbels JF. Thiopurine treatment in childhood leukemia. Metabolic aspects and sensitivity. Adv. Exp. Med. Biol. 1998; 431: 687-692. Stolk JN, Boerbooms AM, De Abreu RA, van de Putte LB. Azathioprine treatment and thiopurine metabolism in rheumatic diseases. Introduction and first results of investigation. Adv. Exp. Med. Biol. 1998; 431: 487-493. Van Kuilenburg AB, Vreken P, Beex LV, Meinsma R, Van Lenthe H, De Abreu RA, Van Gennip AH Heterozygosity for a point mutation in an invariant splice donor site of dihydropyrimidine dehydrogenase and severe 5-fluorouracil related toxicity. Adv. Exp. Med. Biol. 1998; 431: 293-298. Van Gennip AH, De Abreu RA, Vreken P, Van Kuilenburg AB. Clinical and biochemical aspects of dihydropyrimidinase deficiency. Adv. Exp. Med. Biol. 1998; 431: 125-128. Van Ede AE, Laan RF, Blom HJ, De Abreu RA, van de Putte LB. Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity. Semin. Arthritis. Rheum. 1998; 27: 277-292. Lambooy LH, Leegwater PA, van den Heuvel LP, Bökkerink JP; De Abreu RA Inhibition of DNA methylation in malignant MOLT F4 lymphoblasts by 6-mercaptopurine. Clin. Chem. 1998; 44: 556-559. Leegwater PA, De Abreu RA, Albertioni F. Analysis of DNA methylation of the 5' region of the deoxycytidine kinase gene in CCRF-CEM-sensitive and cladribine (CdA)- and 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine (CAFdA)-resistant cells. Cancer. Lett. 1998; 130: 169-73. Wijmenga C, van de Heuvel LP, Strengman E, Luyten JA, van der Burgt IJ, de Groot R, Smeets DF, Draaisma JM, van Dongen JJ, De Abreu RA; Pearson PL, Sandkuijl LA, Weemaes CM. Localization of the ICF syndrome to chromosome 20 by homozygosity mapping. Am J Hum Genet 1998; 63: 803-809. Hamajima N, Kouwaki M, Vreken P, Matsuda K, Sumi S, Imaeda M, Ohba S, Kidouchi K, Nonaka M, Sasaki M, Tamaki N, Endo Y, De Abreu R, Rotteveel J; van Kuilenburg A, van Gennip A, Togari H, Wada Y. Dihydropyrimidinase deficiency: structural organization, chromosomal localization, and mutation analysis of the human dihydropyrimidinase gene. Am J Hum Genet 1998; 63: 717-726. Stolk JN, Boerbooms AM, De Abreu RA, de Koning DG, van Beusekom HJ, Muller WH, van de Putte LB. Reduced thiopurine methyltransferase activity and development of side effects of azathioprine treatment in patients with rheumatoid arthritis. Arthritis Rheum. 1998; 41: 1858-1866. Van Kuilenburg AB, Vreken P, Beex LV, De Abreu RA, van Gennip AH. Severe 5- fluorouracil toxicity caused by reduced dihydropyrimidine dehydrogenase activity due to heterozygosity for a G-->A point mutation. J. Inherit. Metab. Dis. 1998; 21: 280-284. Van Kuilenburg AB, Vreken P, Abeling NG, Bakker HD, Meinsma R, Van Lenthe H; De Abreu RA, Smeitink JA, Kayserili H, Apak MY, Christensen E, Holopainen I, Pulkki K, Riva D, Botteon G, Holme E, Tulinius M, Kleijer WJ, Beemer FA, Duran M, Niezen- Koning KE, Smit GP, Jakobs C, Smit LM, Van Gennip AH, et-al. Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Hum.Genet. 1999; 104: 1-9. Wevers RA, Engelke UFH, Moolenaar SH, Bräutigam Christa, de Jong JGN, Duran R, De Abreu RA, van Gennip AH. 1H-NMR Spectroscopy of body fluids: Inborn errors of purine and pyrimidine metabolism. Clin. Chem. 1999; 45: 539 - 548. Weigel G, Griesmacher A, De Abreu RA, Wolner E, Müller MM. Azathioprine and 6- mercaptopurine alter the nucleotide balance in endothelial Cells. Thrombosis Res. 1999; 94: 87-94. Stolk JN, de Koning DG, Pennings AH, De Abreu RA, van de Putte LB, Boerbooms AM. Reduced purine 5'-nucleotidase activity in lymphocytes of patients with systemic lupus erythematosus: results of a pilot study. Ann. Rheum. Dis. 1999; 58: 122-125. De Abreu RA, Lambooy LH, Ahment K, Brouwer C, Keizer-Garritsen JJ, Bokkerink JP, Trijbels FJ. 6-mercaptopurine: efficacy and bone marrow toxicity in childhood acute lymphoblastic leukemia. Association with low (thio)purine enzyme activity. Adv Exp Med Biol. 2000; 486: 271-275. van Kuilenburg AB, Haasjes J, Richel DJ, Zoetekouw L, Van Lenthe H, De Abreu RA, Maring JG, Vreken P, van Gennip AH. Clinical implications of dihydropyrimidine dehydrogenase (DPD) deficiency in patients with severe 5-fluorouracil-associated toxicity: identification of new mutations in the DPD gene. Clin Cancer Res. 2000; 6: 4705-4712. Brouwer C, Keizer-Garritsen JJ, Lambooy LH, Ament K, Ter Riet PG, De Abreu RA, Bokkerink JP, Van Wering ER, Van Der Does-Van Den Berg A, Veerman AJ, Trijbels JP. Thiopurine methyl transferase: activity and genotyping in patients with acute lymphoblastic leukemia. Adv Exp Med Biol. 2000; 486: 327-331. Deng L, Yang M, Frund S, Wessel T, De Abreu RA, Tischfield JA, Sahota A. 2,8- Dihydroxyadenine urolithiasis in a patient with considerable residual adenine phosphoribosyltransferase activity in cell extracts but with mutations in both copies of APRT. Mol Genet Metab. 2001; 72: 260-264. Heunks LM, Machiels HA, de Abreu R, Zhu XP, van der Heijden HF, Dekhuijzen PN. Free radicals in hypoxic rat diaphragm contractility: no role for xanthine oxidase. Am J Physiol Lung Cell Mol Physiol. 2001;281: L1402-1412. Brouwer C, Marinaki AM, Lambooy LH, Duley JA, Shobowale-Bakre M, De Abreu RA. Pitfalls in the determination of mutant alleles of the thiopurine methyltransferase gene. Leukemia. 2001; 15:1792-1793. Van Cappellen Van Walsum AM, Jongsma HW, Wevers RA, Nijhuis JG, Crevels J, Engelke UF, De Abreu RA, Moolenaar SH, Oeseburg B, Nijland R. 1H-NMR spectroscopy of cerebrospinal fluid of fetal sheep during hypoxia-induced acidemia and recovery. Pediatr Res. 2002; 52: 56-63. Sumi S, Marinaki AM, Arenas M, Fairbanks L, Shobowale-Bakre M, Rees DC, Thein SL, Ansari A, Sanderson J, De Abreu RA, Simmonds HA, Duley JA. Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency. Hum Genet. 2002; 111: 360-367. van Ede AE, Laan RF, De Abreu RA, Stegeman AB, van de Putte LB. Purine enzymes in patients with rheumatoid arthritis treated with methotrexate. Ann Rheum Dis. 2002; 61: 1060-1064. Wielinga PR, Reid G, Challa EE, van der Heijden I, van Deemter L, de Haas M, Mol C, Kuil AJ, Groeneveld E, Schuetz JD, Brouwer C, De Abreu RA, Wijnholds J, Beijnen JH, Borst P. Thiopurine metabolism and identification of the thiopurine metabolites transported by MRP4 and MRP5 overexpressed in human embryonic kidney cells. Mol Pharmacol. 2002; 62: 1321-1331. Van Kuilenburg AB, De Abreu RA, Van Gennip AH. Pharmacogenetic and clinical aspects of dihydropyrimidine dehydrogenase deficiency. Ann Clin Biochem. 2003; 40: 41-45. De Abreu RA, Trueworthy RC, Van Kuilenburg AB, Vogels-Mentink TM, Lambooy LH, Van Gennip AH. Combination therapy in childhood leukaemia: in vitro studies of thiopurines and inhibitors of purine metabolism on apoptosis. Ann Clin Biochem. 2003; 40: 70-74. Keizer-Garritsen JJ, Brouwer C, Lambooy LH, Ter Riet P, Bokkerink JP, Trijbels FJ, De Abreu RA. Measurement of thiopurine S-methyltransferase activity in human blood samples based on high-performance liquid chromatography: reference values in erythrocytes from children. Ann Clin Biochem. 2003; 40: 86-93. Ruitenbeek W, Kobayashi K, Iijima M, Smeitink JA, Engelke UF, De Abreu RA, Kwast HT, Saheki T, Boelen CA, De Jong JG, Wevers RA. Moderate citrullinaemia without hyperammonaemia in a child with mutated and deficient argininosuccinate synthetase. Ann Clin Biochem. 2003; 40: 102-107. Lambooy LH, Gidding CE, Van Den Heuvel LP, Hulsbergen-Van De Kaa CA, Ligtenberg M, Bokkerink JP, De Abreu RA. Real-time analysis of tyrosine hydroxylase gene expression: a sensitive and semiquantitative marker for minimal residual disease detection of neuroblastoma. Clin Cancer Res. 2003; 9: 812-819.137. Larovere LE, de Kremer. RD, Lambooy LH, De Abreu RA. Genetic polymorphism of thiopurine S-methyltransferase in Argentina. Ann Clin Biochem. 2003; 40: 388-393. van Os S, De Abreu R, Hopman J, Wethly K, Liem D, van de Bor M. Purine and pyrimidine metabolism and electrocortical brain activity during hypoxemia in near-term lambs. Pediatr Res. 2004; 55:1018-1025. Peters GJ, van Kuilenburg AB, De Abreu RA. Purine and pyrimidine metabolism: new challenges. Nucleosides Nucleotides Nucleic Acids. 2004; 23: 1077-1079. de Graaf AO, van den Heuvel LP, Dijkman HB, De Abreu RA, Birkenkamp KU, de Witte T, van der Reijden BA, Smeitink JA, Jansen JH. Bcl-2 prevents loss of mitochondria in CCCP-induced apoptosis. Exp Cell Res. 2004; 299: 533-540. Brouwer C, De Abreu RA, Keizer-Garritsen JJ, Lambooy LH, Ament K, Ter Riet PG, van Wering ER, Trijbels FJ, Veerman AJ, Hoogerbrugge PM, Bökkerink JP. Thiopurine methyltransferase in acute lymphoblastic leukaemia: biochemical and molecular biological aspects. Eur J Cancer. 2005; 41: 613-623. Brouwer C, Vogels-Mentink TM, Keizer-Garritsen JJ, Trijbels FJ, Bökkerink JP, Hoogerbrugge PM, van Wering ER, Veerman AJ, De Abreu RA. Role of 5'-nucleotidase in thiopurine metabolism: Enzyme kinetic profile and association with thio-GMP levels in patients with acute lymphoblastic leukemia during 6-mercaptopurine treatment. Clin Chim Acta. 2005; 361: 95-103. Van Os S, De Abreu R, Hopman J, Wethly K, van der Bor M. Purine and Pyrimidine Metabolism and Electrocortical Brain Activity during Hypotension in Near-Term Lambs. Biol Neonate. 2005 ; 89: 35-41. Brouwer C, Vermunt-de Koning DG, Trueworthy RC, Ter Riet PG, Duley JA, Trijbels FJ, Hoogerbrugge PM, Bökkerink JP, van WeringER, De Abreu RA. Monitoring of inosine monophosphate dehydrogenase activity in mononuclear cells of children with acute lymphoblastic leukemia: enzymological and clinical aspects. Pediatric Blood Cancer 2006; 46: 434-438.

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SPECIFIC TARGETING OF INHALED STEROIDS TO SMALL AIRWAYS IN CHILDREN WITH PROBLEMATIC SEVERE ASTHMA USING THE AKITA: A CASE SERIES H.M. Janssens MD PhD, J.L. Overweel-Uyterlinde Department of Pediatric Pulmonology, Erasmus MC- Sophia Children's Hospital, Rotterdam, The Netherlands. INTRODUCTION Asthma is an inflammatory disease affecting the small airways. Small airways are a dif

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