Impact of molecular medicine on pathophysiology, medical practice, and medical education

Croatian Medical Journal

Volumn 44, Issue 4, 2003, Pages 374-385

  Gamulin, Stjepan ^a,b  

^a CROATIAN ACADEMY OF SCIENCES AND ARTS   (Croatia)

^b NONE   (Croatia)

Author keywords

Education, medical; Genetic screening; Genomics; Molecular biology; Pharmacogenomics

Indexed keywords

CLINICAL PRACTICE; CONTINUING EDUCATION; CURRICULUM; EVIDENCE BASED MEDICINE; HEALTH CARE QUALITY; MEDICAL EDUCATION; MEDICAL PRACTICE; MEDICAL PROFESSION; MOLECULAR GENETICS; PATHOPHYSIOLOGY; PHARMACOGENOMICS; REVIEW;

EDUCATION, MEDICAL; EVIDENCE-BASED MEDICINE; FORECASTING; GENETICS, MEDICAL; HUMANS; MOLECULAR BIOLOGY; PHARMACOGENETICS;

EID: 0042839486     PISSN: 03539504     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (110)

1. Pauling L, Itano HA, Singer SJ, Wells JS. Sickle cell anemia: a molecular disease. Science 1949;110:543-8.
2. Strasser BJ. Perspectives: molecular medicine. "Sickle cell anemia, a molecular disease". Science 1999;286:1488-90.
3. Lorentz CP, Wieben ED, Tefferi A, Whiteman DA, Dewald GW. Primer on medical genomics part I: history of genetics and sequencing of the human genome. Mayo Clin Proc 2002;77:773-82.
4. Weatherall DJ. Molecular medicine at the bedside. Br Med J (Clin Res Ed) 1986;292:1505-8.
5. Forget BG. Molecular genetics of human hemoglobin synthesis. Ann Intern Med 1979;91:605-16.
6. Online Mendelian Inheritance in Man. OMIM statistics for March 8, 2003. Available from: www.nebi.nim.nih.gov/Omim/Stats/mimstats.htlm. Accessed: April 14, 2003.
7. White R, Caskey CT. The human as an experimental system in molecular genetics. Science 1988;240:1483-8.
8. Orkin SH. Reverse genetics and human disease. Cell 1986;47:845-50.
9. Lander ES, Linton LM, Birren B. Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature 2001;409:860-921.
10. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. The sequence of the human genome. Science 2001;291:1304-51.
11. Pardanani A, Wieben ED, Spelsberg TC, Tefferi A. Primer on medical genomics. Part IV: expression proteomics. Mayo Clin Proc 2002;77:1185-96.
12. Collins FS. Shattuck lecture - medical and societal consequences of the Human Genome Project. N Engl J Med 1999;341:28-37.
13. Emilien G, Ponchon M, Caldas C, Isacson O, Maloteaux JM. Impact of genomics on drug discovery and clinical medicine. QJM 2000;93:391-423.
14. Subramanian G, Adams MD, Venter JC, Broder S. Implications of the human genome for understanding human biology and medicine. JAMA 2001;286:2296-307.
15. Guttmacher AE, Collins FS. Genomic medicine - a primer. N Engl J Med 2002;347:1512-20.
16. McKusick VA. The anatomy of the human genome: a neo-Vesalian basis for medicine in the 21st century. JAMA 2001;286:2289-95.
17. Peltonen L, McKusick VA. Genomics and medicine. Dissecting human disease in the postgenomic era. Science 2001;291:1224-9.
18. Holtzman NA, Marteau TM. Will genetics revolutionize medicine? N Engl J Med 2000;343:141-4.
19. Sabatini S. Mapping of the human genome: what does it mean for our patients? Am J Med Sci 2001;322:175-8.
20. Weinshilboum RM. The genomic revolution and medicine. Mayo Clin Proc 2002;77:745-6.
21. Gamulin S. Disorders of DNA structure and function [in Croatian]. In: Gamulin S, Marušić M, Kovač Z, editors. Patofiziologija. 5th rev. ed. Zagreb: Medicinska naklada; 2002. p. 46-59.
22. Gamulin S. Disorders of gene expression [in Croatian]. In: Gamulin S, Marušić M, Kovač Z, editors. Patofiziologija. 5th rev. ed. Zagreb: Medicinska naklada; 2002. p. 68-73.
23. Gamulin S. Disorders of protein synthesis and degradation [in Croatian]. In: Gamulin S, Marušić M, Kovač Z, editors. Patofiziologija. 5th rev. ed. Zagreb: Medicinska naklada; 2002. p. 73-9.
24. Blois MS. Medicine and the nature of vertical reasoning. N Engl J Med 1988;318:847-51.
25. Gamulin S, Kovač Z. The principles of pathogenetic mechanisms [in Croatian]. In: Gamulin S, Marušić M, Kovač Z, editors. Patofiziologija. 5th rev. ed. Zagreb: Medicinska naklada; 2002. p. 46-59.
26. van Ommen GJ, Bakker E, den Dunnen JT. The human genome project and the future of diagnostics, treatment, and prevention. Lancet 1999;354 Suppl 1:S15-10.
27. Wetherall DJ The new genetics and clinical practice. Oxford: Oxford University Press; 1991.
28. Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science 1986;232:34-47.
29. Johnson C, Primorac D, McKinstry M, McNeil J, Rowe D, Lawrence JB. Tracking COL1A1 RNA in osteogenesis imperfecta: splice-defective transcripts initiate transport from the gene but are retained within the SC35 domain. J Cell Biol 2000;150:417-32.
30. Owen MC, Brennan SO, Lewis JH, Carrell RW. Mutation of antitrypsin to antithrombin: alpha 1-antitrypsin Pittsburgh (358 Met→Arg), a fatal bleeding disorder. N Engl J Med 1983;309:694-8.
31. White PC, New MI. Genetic basis of endocrine disease 2: congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 1992;74:6-11.
32. Summers KM. Relationship between genotype and phenotype in monogenic diseases: relevance to polygenic diseases. Hum Mutat 1996;7:283-93.
33. Primorac D, Rowe DW, Mottes M, Barišić I, Antičević D, Mirandola S, et al Osteogenesis imperfecta at the beginning of bone and join decade. Croat Med J 2001;42:393-415.
34. Beckmann JS. Disease taxonomy - monogenic muscular dystrophy. Br Med Bull 1999;55:340-57.
35. Young SG. Recent progress in understanding apolipoprotein B. Circulation 1990;82:1574-94.
36. Acton JD, Wilmott RW. Phenotype of CF and the effects of possible modifier genes. Pediatr Respir Rev 2001;2:332-9.
37. Harris CC. The 1995 Walter Hubert lecture - molecular epidemiology of human cancer: insights from the mutational analysis of the p53 tumor-suppressor gene. Br J Cancer 1996;73:261-9.
38. Herrmann SM, Paul M. Studying genotype-phenotype relationships: cardiovascular disease as an example. J Mol Med 2002;80:282-9.
39. Scriver CR. Diets and genes: euphenic nutrition. N Engl J Med 1977;297:202-3.
40. Cooke GS, Hill AV. Genetics of susceptibility to human infectious disease. Nat Rev Genet 2001;2:967-77.
41. Abreu MT, Taylor KD, Lin YC, Hang T, Gaiennie J, Landers CJ, et al. Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease. Gastroenterology 2000;123:679-88.
42. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:57-70.
43. Weatherall DJ. Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias. Nat Rev Genet 2001;2:245-55.
44. Wolf U. Identical mutations and phenotypic variation. Hum Genet 1997;100:305-21.
45. Maquat LE, Carmichael GG. Quality control of mRNA fu nction. Cell 2001;104:173-6.
46. Chang JC, Temple GF, Trecartin RF, Kan YW. Suppression of the nonsense mutation in homozygous β0 thalassaemia. Nature 1979;281:602-3.
47. Kovač Z. Pathophysiological principles of disease and syndrome inheritance [in Croatian]. In: Gamulin S, Marušić M, Kovač Z, editors. Patofiziologija. 5th rev. ed. Zagreb: Medicinska naklada; 2002. p. 79-82.
48. Peters RJ, Boekholdt SM. Gene polymorphisms and the risk of myocardial infraction - an emerging relation. N Engl J Med 2002;347:1963-5.
49. Kenney FT, Lee KL, Barker KL. Hormonal mechanism in regulation of gene expression. Basic Life Sci 1973;1:487-502.
50. Mendell JT, Dietz HC. When the message goes awry: disease-producing mutations that influence mRNA content and performance. Cell 2001;107:411-4.
51. Attwood JT, Yung RL, Richardson BC. DNA methylation and the regulation of gene transcription. Cell Mol Life Sci 2002;59:241-57.
52. Hemann MT, Fridman JS, Zilfou JT, Hernando E, Paddison PJ, Cordon-Cardo C, et al. An epi-allelic series of p53 hypomorphs created by stable RNAi produces distinct tumor phenotypes in vivo. Nat Genet 2003;33:396-400.
53. Aso T, Shilatifard A, Conaway JW, Conaway RC. Transcription syndromes and the role of RNA polymerase II general transcription factors in human disease. J Clin Invest 1996;97:1561-9.
54. Morwenna S, Ratcliffe WP. Mammalian oxygen sensing and hypoxia inducible factor-1. Int J Biochem Cell Biol 1997;29:1419-32.
55. Gamulin S. NF-κB - the central mediator of inflammatory and immune response. Neurol Croat 1998;47 Suppl 1:89-93.
56. Hunter T. Oncoprotein network. Cell 1997;88:333-46.
57. van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002;347:1999-2009.
58. O'Brien RM, Granner DK. Regulation of gene expression by insulin. Physiol Rev 1996;76:1109-61.
59. Ambros V. Development. Dicing up RNAs. Science 2001;293:811-2.
60. Yelin R. Dahary D, Sorek R, Levanon EY, Goldstein O, Shoshan A, et al. Widespread occurrence of antisense transcription in the human genome. Nat Biotechnol 2003;21:379-86.
61. Wilda M, Fuchs U, Wössmann W, Borkhardt A. Killing of leukemic cells with a BRC/ABL fusion gene by RNA interference (RNAi). Oncogene 2002;21:5716-24.
62. Brivanlou AH, Darnell JE. Signal transduction and the control of gene expression. Science 2002;295:813-8.
63. Hunter T. Signaling - 2000 and beyond. Cell 2000;100:113-27.
64. Meerson FZ. Intensity of function of structures of the differentiated cell as a determinant of activity of its genetic apparatus. Nature 1965;206:483-4.
65. Cooper G 4th. Basic determinants of myocardial hypertrophy: a review of molecular mechanisms. Annu Rev Med 1997;48:13-23.
66. Tarazi RC, Fouad FM. Reversal of cardiac hypertrophy by medical treatment. Annu Rev Med 1985;36:407-14.
67. Ulovec Z, Narancsik P, Gamulin S. The effects of hypoglycemia on rat brain polyribosome sedimentation pattern. J Neurochem 1985;45:352-4.
68. Norman M, Gamulin S, Clark K. The distribution of ribosomes between different functional states in livers of fed and starved mice. Biochem J 1973;134:387-98.
69. Pleština S, Gamulin S. Kidney ischaemia-reperfusion injury and polyribosome structure. Nephron 2001;89:201-7.
70. Hilt W, Wolf DH. Proteasomes: destruction as a programme. Trends Biochem Sci 1996;21:96-102.
71. Mitch WE, Goldberg AL. Mechanism of muscle wasting. The role of the ubiquitin-proteasome pathway. N Engl J Med 1996;335:1897-905.
72. Aridor M, Balch WE. Integration of endoplasmic reticulum signaling in health and disease. Nat Med 1999;5:745-51.
73. Furie B, Furie BC. Molecular and cellular biology of blood coagulation. N Engl J Med 1992;326:800-6.
74. Handin RI. Disorders of coagulation and thrombosis. In: Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, et al, editors. Harrison's principles of internal medicine. 14th ed. New York (NY): McGraw-Hill Professional; 1998. p. 736-47.
75. Gamulin S. Disorders of the pancres exocrine function [in Croatian]. In: Gamulin S, Marušić M, Kovač Z, editors. Patofiziologija. 5th rev. ed. Zagreb: Medicinska naklada; 2002. p. 909-10.
76. Brownlee M, Cerami A, Vlassara H. Advanced glycosilation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 1988;318:1315-21.
77. Stadtman ER. Protein oxidation and ageing. Science 1992;257:1220-4.
78. Raufman JP. Cholera. Am J Med 1998;104:386-94.
79. Pope CN. Organophosphorus pesticides: do they all have the same mechanism of toxicity? J Toxicol Environ Health B Crit Rev 1999;2:161-81.
80. Gamulin S. Alteration of functional distribution of ribosomes in various pathological conditions. Period Biol 1980;82:223-8.
81. Paschen W, Doutheil J. Disturbance of the functioning of endoplasmic reticulum: a key mechanism underlying neuronal cell injury. J Cereb Blood Flow Metab 1999;19:1-18.
82. Burke W. Genetic testing. N Engl J Med 2002;347:1867-75.
83. Handyside AH, Lesko JG, Tarin JJ, Winston RM, Hughes MR. Birth of a normal girl after in vitro fertilization and preimplantation diagnostic testing for cystic fibrosis. N Engl J Med 1992;327:905-9.
84. Hartmann LC, Schaid DJ, Woods JE, Myers JL, Arnold PG, Petty PM, et al. Efficacy of bilateral prophyactic mastectomy in women with a family history of breast cancer. N Engl J Med 1999;340:77-84.
85. Eisen A, Weber BL. Prophylactic mastectomy - the price of fear. N Engl J Med 1999;340:137-8.
86. Liu ET. From the molecule to public health. N Engl J Med 1993;395:2028-9.
87. Bustin SA, Dorudi S. Molecular assessment of tumor stage and disease recurrence using PCR-based assays. Mol Med Today 1998;4:389-96.
88. Brugarolas J, Haynes BF, Nevins JR. Towards a genomic-based diagnosis. Lancet 2001;357:249-50.
89. Jensen EV, Block GE, Smith S, Kyser K, DeSombre ER. Estrogen receptors and breast cancer response to adrenalectomy. Natl Cancer Inst Monogr 1971;34:55-70.
90. Gamulin S, Romić-Stojković R. Oestrogen and progesterone receptors in primary breast cancer: a population study. Eur J Cancer 1991;27:491-5.
91. Mirza AN, Mirza NQ, Vlastos G, Singletary SE. Prognostic factors in node-negative breast cancer: a review of studies with sample size more than 200 and follow-up more than 5 years. Ann Surg 2002;235:10-26.
92. Razumović JJ, Stojković RR, Petrovečki M, Gamulin S. Correlation of two methods for determination of cathepsin D in breast carcinoma (immunohistochemistry and ELISA in cytosol). Breast Cancer Res Treat 1997;43:117-22.
93. Jakić-Razumović J, Petrovečki M, Užarević B, Gamulin S. Mutual predictive value of c-erbB-2 over-expression and various prognostic factors in ductal invasive breast carcinoma patients. Tumori 2000;86:30-6.
94. Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro VA, Steinberg SM, et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet 2002;359:572-7.
95. Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W. Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA 2001;286:2270-9.
96. Jordan VC. Targeted antiestrogens to prevent breast cancer. Trends Endocrinol Metab 1999;10:312-7.
97. Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, et al. Multinational study of the efficacy and safety of humanized ant-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999;17:2639-48.
98. Druker BJ, Lydon NB. Lessons learned from the development of an Abl tyrosin kinase inhibitor for chronic myelogenous leukemia. J Clin Invest 2000;105:3-7.
99. Smith AE. Gene therapy - where are we? Lancet 1999;354 Suppl 1:SI1-4.
100. Noguchi P. Risks and benefits of gene therapy. N Engl J Med 2003;348:193-4.
101. Clancy JP, Bebok Z, Ruiz F, King C, Jones J, Walker L, et al. Evidence that systemic gentamicin suppresses premature stop mutations in patients with cystic fibrosis. Am J Respir Crit Care Med 2001;163:1683-92.
102. Kaji EH, Leiden JM. Gene and stem cell therapies. JAMA 2001;285:545-50.
103. Thomas SM. Genomics: the implications for ethics and education. Br Med Bull 1999;55:429-45.
104. Collins FS, McKusick VA. Implications of the Human Genome Project for medical science. JAMA 2001;285:540-4.
105. Varmus H. Getting ready for gene-based medicine. N Engl J Med 2002;347:1526-7.
106. Fears R, Weatherall D, Poste G. The impact of genetics on medical education and training. Br Med Bull 1999;55:460-70.
107. Robertson D, Tung CS. Linking molecular and bedside research: designing a clinical research infrastructure. J Mol Med 2001;79:686-94.
108. Birmingham K. What is translational research? Nat Med 2002;8:647.
109. Stanford University School of Medicine, Beckman Center. Programs we support - translational research. Available at: http://www.beckman.stanford.edu/programs/research. Accessed: April 11, 2003.
110. Wolfsberg TG, Makalowska I, Makalowski W. Web alert. Genetics of disease. Curr Opin Genet Dev 2001;11:237-8.