AA Oxidopathy References


Majid Ali, M.D.

Redox regulation in the circulating blood is a dynamic, elaborately integrated complex of diverse energetic-molecular events that involve all plasma and cellular oxidant-antioxidant systems. Changes of redox dysregulation in circulating blood comprise cell erythrocyte membrane damage and cell lysis, zones of plasma congealing, activation of polymorphonuclear leukocytes and monocytes, transformation of monocytes into macrophages, and formation of microclots and microplaques. We designate this broad spectrum of changes as AA oxidopathy. Derangements of the clotting-unclotting equilibrium (CUE), involving both established and as yet unrecognized coagulation pathways, are designated oxidative coagulopathy. Spontaneity of oxidation in the circulating blood assures that oxidative coagulopathy, and fibrinolytic response triggered by it, occurs in health at all times. Oxidatively triggered molecular responses to AA oxidopathy occurring in the endothelial cells, myocytes, and fibroblasts that constitute atherogenesis are regarded as consequences of unrelenting AA oxidopathy.
Plasma cholesterol, a weak antioxidant, initially prevents AA oxidopathy—albeit inadequately—and, once oxidized, feeds the oxidative fires set off by a host of oxidative stressors discussed above. Chronic use of HMG Co-reductase inhibitor statin drugs provides minimal short-term clinical benefits and, as yet undefined, long-term chemical consequences of disruption of lipid metabolism and carcinogenicity. The short-term benefits of statin drugs, in our view, may be largely attributed to their ability to address the single issue of mycotoxicity in the pathogenesis of oxidative coagulopathy.
The AA oxidopathy hypothesis provides a rational explanation of atherogenic mechanisms of risk factors of IHD as well as for the coronary vasospastic events that cause clinical ischemic heart disease without coronary occlusive disease. The proposed hypothesis also calls for a radically different clinical approach to prevention and reversal of ischemic heart disease. Specifically, it requires an integrative approach that addresses all of the following principal categories of chronic oxidant stressors: 1) adrenergic hypervigilence; 2) glucose-insulin dysregulation; 3) fungal and bacterial stress proteins, as well as other types of toxins; and 4) ecologic oxidants. The dominant prevailing approaches to ischemic coronary artery disease—such as angioplasty, coronary bypass and multiple drug therapies that focus on calcium channel and adrenergic blockade—evidently do not address any of the causes of AA oxidopathy, and thus cannot be regarded as optimal therapies.


1. Ali M. Spontaneity of Oxidation in Nature and Aging. Monograph, Teaneck, New Jersey, 1983.
2. Ali M. The agony and death of cell. Syllabus of the Instruction Course of the American Academy of Environmental Medicine, Denver, Colorado, 1985.
3. Ali M. Intravenous Nutrient Protocols in Molecular Medicine. Monograph. Institute of Preventive Medicine, Bloomfield, New Jersey, 1987.
4. Ali M. Molecular basis of cell membrane injury. In: Syllabus of the Instruction Course of the American Academy of Environmental Medicine. Denver, Colorado, 1990.
5. Ali M. Spontaneity of oxidation and molecular basis of environmental illness. In: Syllabus of the 1991 Instruction Course of the American Academy of Environmental Medicine, Denver, Colorado, 1990.
6. Ali M. Spontaneity of oxidation and chronic disease. In: Syllabus of the Instruction Course of the American Academy of Environmental Medicine, Denver, Colorado, 1992.
7. Ali M. Oxidative coagulopaty. In: Syllabus of the Capital University of Integrative Medicine, Washington, D.C., 1997.
8. Ali M. Hypothesis: Chronic fatigue is a state of accelerated oxidative molecular injury. J Advancement in Medicine. 1993;6:83-96.
9. Ali M. Spontaneity of oxidation in nature is the root cause of all illness. In: RDA: Rats, Drugs and Assumption. pp. 199-304. Life Span, Denville, New Jersey, 1995.
10. Ali M. The Canary and Chronic Fatigue. 1994. Life Span, Denville, New Jersey.
11. Ali M. Oxidative plasma membrane injury and magnesium. Environmental Physician. Summer 1992. American Academy of Environmental Medicine, Denver, Colorado.
12. Ali M. Ascorbic acid reverses abnormal erythrocyte morphology in chronic fatigue syndrome. Am J Clin Pathol. 1990;94:515.
13. Ali M. Ascorbic acid prevents platelet aggregations by norepinephrine, collagen, ADP and ristocetin. Am J Clin Pathol. 1991;95:281.
14. Ali M, Prasad PV, Rigolosi et al. Cardiac myocytolysis: pathologic basis of cardiomyopathy in dialysis patients (Abstract). Kidney International 1982;21:161
15. Ali M. Fayemi AO. Cardiac myocytolysis in cardiomyopathy. in The Pathology of Maintenance Hemodialysis. pp 132-8, 1982 Charles C Thomas Publishers, Springfield, Ill.
16. Ali M. Hemosiderosis in hemodialysis patients: an autopsy study of 50 cases. JAMA 1980;244;343.
17. Ali M, Fayemi AO, Rigolosi R et al. Failure of serum ferritin levels to predict bone marrow iron content after intravenous iron-dextran therapy. Lancet 1982; 652
18. Ali M, Fayemi AO, Braun E. Dissociation between hepatosplenic and marrow iron in liver cirrhosis. Arch Pathol Lab Med. 1982;106:200-204.
19. Ali M, Fayemi AO. Arterial and myocardial calcification. In: The Pathology of Maintenance Hemodialysis. pages 130-2. Charles C Thomas, Springfield, Ill., 1982.
20. Fayemi AO, Ali M, Braun E. Oxalosis in hemodialysis patients: a pathologic study of 80 patients. Arch Pathol Lab Med 1979;103:58-62.
21. Ali M, Fayemi AO. Cardiac oxalosis. In: The Pathology of Maintenance of Hemodialysis. pp 146-147. Charles C Thomas, Springfield, Ill., 1982.
22. Ali M, Fayemi AO. Arterial intimal thickening. In: The Pathology of Maintenance Hemodialysis. pp 175-185. Charles C Thomas, Springfield, Ill., 1982.
23. Fayemi AO, Ali M. Intrarenal vascular alterations in hemodialysis patients: a semiquantitative light microscopic study. Human Pathology 1979;10:685-92.
24. Ali M, Fayemi AO. The pathology of end-stage renal disease in hemodialysis patients. Isr J Med Sci 1979;15:901-9.
25. Ali M, Braun E, Laraia S et al. Immunochemical LD assay for myocardial infarction. Am J Clin Pathol. 1981;76:426-429.
26. Ali M, Laraia S, Angeli R, et al. Immunochemical CK-MB assay for myocardial infarction. Am J Clin Pathol. 1982;77:573-579.
27. Ali M. The basic equation of life. pp 225-236. In: The Butterfly and Life Span Nutrition. The Institute of Preventive Medicine Press, Denville, New Jersey. 1992.
28. Ali M. The Ghoraa and Limbic Exercise. The Institute of Preventive Medicine Press, Denville, New Jersey. 1993.
29. Ali M. The Cortical Monkey and Healing. The Institute of Preventive Medicine, Bloomfield, New Jersey. 1989.
30. Ali M. What Do Lions Know About Stress? Life Span, Denville, New Jersey. 1996.
31. Ali M. Healing, Miracles and the Bite of the Gray Dog. Life Span, Denville, New Jersey. 1997.
32. Ali M. Ali O. Fayemi AO et al. Improved myocardial perfusion in patients with advanced ischemic heart disease with an integrative management program including EDTA chelation therapy. J Integrative Medicine 1997;1:81-92.
33. Ali M. Ali O. Fayemi AO. Preliminary experience with improved renal function in patients with renal failure with an integrated management plan including EDTA chelation therapy. J Integrative Medicine. 1997;1:93-104.
34. Ali M, Ali O, Fayemi AO et al. Improved peripheral perfusion in patients with advanced peripheral arterial disease with an integrated management plan including EDTA chelation therapy. J Integrative Medicine. 1997 (in press).
35. Heinecke JW, Baker L, Rosen H et al. Superoxide-mediated modification of low density lipoprotein by arterial smooth muscle cells. J Clin Invest. 1986;77:757-61.
36. Morel DW, Hessler JR, Chisolm GM: Low density lipoprotein cytotoxicity induced by free radical peroxidation of lipid. J Lipid Res 1983;24:1070.
37. Cathcart MK, Morel DW, Chisolm GM. Monocytes and neutrophils oxidize low density lipoprotein making it cytotoxic. J Leuk Biol 1985;38:341-50.
38. Parthasarathy S, Printz DJ, Boyd D, et al. Macrophage oxidation of low density lipoprotein generates a modified form recognized by the scavenger receptor. Arteriosclerosis 1986;6:505-10.
39. Hiramatsu k, Rosen H, Heinecke JW, et al. Superoxide initiates oxidation of low density lipoprotein by human monocytes. Arteriosclerosis 1987;7:55-60.
40. Witztum JL. Role of oxidized low density lipoprotein in atherogeneses. Bri Heart J 1993;69:512-18.
41. Witztum JL. The oxidation hypothesis of atherosclerosis. Lancet 1994;344:793-5.
42. Steinberg D. Metabolism of lipoproteins and their role in the pathogenesis of atherosclerosis. In: Gotto AM Jr., Paoletti R, eds. Atherosclerosis reviews Vol 18. Stokes J III, mancini M, eds. Hypercholesterolemia: clinical and therapeutic implications. New York: Raven Press, 1988:1-23.
43. Witztum JL, Mahoney EM, Branks MJ, et al. Nonenzymatic glucosylation of low density lipoprotein alters its biologic activity. Diabetes 1982;31:283-91.
44. Parthasarathy S, Young SG, Witztum JL, et al. Probucol inhibits oxidative modification of low density lipoprotein. J Clin Invest 1986;77:641-4.
45. Steinberg D, Parthasarathy S, Carew TE et al. Beyond cholesterol: Modification of low-density lipoprotein that increases its atherogenecity. N Eng J Med 1989;320:915-24.
46. Bradford RW, Allen H, Culbert ML. Oxidology: The study of reactive oxygen toxic species (ROTS) and their metabolism in health and disease. 1985. Bradford Research Institute, Chula Visat, CA.
47. Bradford RW, Allen H. Free radical (ROS)-mediated disseminated intravascular coagulation modulated by fungal heat shock proteins and bacterial endotoxins. Monograph 1995. Bradford Research Institute, Chula Vista, CA.
48. Gey KF. On the antioxidant hypothesis with regard to arteriosclerosis. Bibl Nutr Dieta 1986;37:53-91.
49. Gey KF, Brubacher GB, Staehelin HB. Plasma levels of antioxidant vitamins in relation to ischemic heart disease and cancer. Am J Clin Nutr 1987;45:1368-1377.
50. Witztum JL, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 1991;88:1785-92.
51. Kehrer JP. Free radicals as mediators of tissue injury and disease. Critical reviews in toxicology 1993;23(I):21-48
52. Mueller HE et al. Increase of microbial neuraminidase activity by the hydrogen peroxide concentration. Experientia 1972;28:397-8.
53. Hayano S, Tanaka A. Sialidase-loke enzyme produced by group A, B, C, G and L Streptococci and by Streptococcus sanguis. J Bacteriol 1969;97:1328-33.
54. Shacter E, William JA, Levine RL. Oxidative modification of fibrinogen inhibits thrombin-catalyzed clot formation. Free radical Biol Med 1995;18:815-21.
55. Vissers MC et al. Oxidative damage to fibronectin. II. The effect of H2O2 and the hydroxyl radical. Arch Biochem Biophys 1991;285:357.
56. Bradford RW, Allen H. Bradford-Allen coagulative pathway and altered coagulation components in pathology and stress. In Oxidology. Bradford Research Institute, Chula Vista, CA. 1997
57. Maseri A. Ischemic heart disease: a rational basis for clinical practice and clinical research. New York: Churchill Livingstone, 1995:193-301.
58. Maseri A. Inflammation, atherosclerosis, and ischemic events—exploring the hidden side of the moon. N Eng J Med 1997;336:1014-5.
59. Morris JN. Recent history of coronary disease. Lancet 1951;1:1-7,69-73.
60. Finlayson R. Ischaemic heart disease, aortic aneurysms, and atherosclerosis in the City of London, 1868-1982. Med Hist Suppl 1985;5:151-68.
61. Meade TW, Chakrabarti R. Arterial disease research: Observation or intervention? Lancet 1972;2:913-6.
62. Enriquez-Sarano M, Klodas E, Garratt KN, et al. Secular trends in coronary atherosclerosis—and analysis in patients with valvular regurgitation. N Eng J Med 1996;335:316-22.
63. Smith, GD. Secular Trends in coronary atherosclerosis. N Eng J Med 1997;336:224-5 (Letter)
64. Stampfer MJ, Malinow MR. Can lowering homocysteine levels reduce cardiovascular risk? N Eng J Med 1995;332:329-329.
65. Ginsburg GS, Safran C, Pasternak RC. Frequency of low serum HDL in hospitalized patients with “desirable” total cholesterol levels. Am J Cardiol 1991;68:187-192.
66. Miller M, Seidler A, Kwiterovich PO, et al. Long-term predictors of subsequent cardiovascular events with coronary artery disease and “desirable” levels of plasma total choleseterol. Circulation 1992;86:1165-1170.
67. Eaker ED, Packard B, Thom TJ. Epidemiology and risk factors for coronary heart disease in women. Cardiovasc Clin. 1989;19:129-145.
67. Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;334:1383-9.
68. Eliot RS, Bratt GT. The paradox of myocardial ischemia and necrosis in young women with normal coronary arteriogram—relationship to anomalous hemoglobin-oxygen dissociation. Am J Cardiol. 1969;23:633-38.
69. Likoff RS, Segal BL, Kasparian H. Paradox of normal selective coronary arteriogram in patients considered to have unmistakable coronary heart disease. N Eng J Med 1967;276:1063.
70. Dear DH, Russel RO, Jones WB et al. Myocardial infarction in the absence of coronary occlusion. Am J cardiol. 1971;28:718.
71. Sullivan JL. Iron and the sex difference in heart disease risk. Lancet 1981;1:1293-1294.
72. Salonen JT, Nyyssonen K, Korpela H et al. High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish Men. Circulation 1992;86:803-811.
73. Salonen J, Salonen R, Seppanen K, et al. Interactions of serum copper, selenium, and low density lipoprotein cholesterol in atherogenesis. BMJ 1991;302:756-760.
74. Salonen R, Salonen JT, Progression of carotid atherosclerosis and its determinants: a population based ultrasonography study. Atherosclerosis. 1990;81:33-40.
75. Salonen JT, Seppanen K, Nyyssonen K, et al. Intake of mercury from fish, lipid peroxidation, and the risk of myocardial infarction and coronary, cardiovascular, and any death in eastern Finnish men. Circulation 1995;91:645-655.
76. Mattila KJ, Nieminen MS, Valtonen VV, et al. Association between dental health and acute myocardial infarction. BMJ 1989;298:779-781.
77. Salonen JT, Alfthan G, Huttunen JK, Pikkarainen J, Puska P. Association between cardiovascular death and myocardial infarction and serum selenium in a matched-pair longitudinal study. Lancet 1982;2:175-179.
78. Kok FJ, Hofman A, Witteman JC, de Bruijn AM, Kruyssen DH, de Bruin M, Valkenburg HA. Decreased selenium levels in acute myocardial infarction. JAMA 1982;261:1161-1164.
79. Abram AS, Brooks BA, Eylath U. Chromium and cholesterol-induced atherosclerosis in rabbits. Ann Nutr Metab 1991:35:203-207
80. Schroeder HA, Nason AP, Tipton IH. Chromium deficinecy as a factor in atherosclerosis. J Chronic Dis 1970;23:123-142.
81. Enstrom JE, Kanim LE, Klein MA. Vitamin C Intake and Mortality among a sample of the united States population. Epidemiology 1992;3:194-202.
82. Nyyssonen K, Parvianen MT, Salonen R, et al.Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland. BMJ 1997;314:634-638.
83. Stephens NG, Parsons A, Schofield PM, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996;347:781-386.
84. Stampher MJ, Hennekens CH, Manson JH, et al. Vitamin E consumption and the risk of coronary disease in women. N Eng J Med 1993;328:1444-1449.
85. Shaish A, Daugherty A, O’Sullivan, et al. Beta-carotene inhibits atherogenesis in hypercholesterolemic rabbits. J Clin Invest1995;96:2075-82.
86. carotene
87. Folkers K, Littarru GP, Ho L, et al. Evidence for a deficiency of coenzyme Q10 in human heart disease. Inter J Vitamin Nutr Research 1970;4:380-390.
88. Folkers K, Watanabe T, Kaji M. Crtique of coenzyme Q10 in biochemical and biomedical research and in ten years of clinical research in cardiovascular disease. J Mol Med 1977;2:431-460.
89. Keany JF Jr, Xu A, Cunningham D, et al. Dietary probucol preserves endothelial function in cholesterol-fed rabbits by limiting vascular oxidative stress and superoxide generation. J Clin Invest 1995;95:2520-9.
90. Tardif J-C, Cote G, Lesperance J, et al. Probucol and multivitamin in the prevention of restenosis after coronary angioplasty. N Eng J Med 1997;337:365-72.
91. Clark NE, Clark CN, Mosher RE. Treatment of angina pectoris with disodium ethylenediaminetetraacetic acid. Am J Med Sci 1956;December:654-666.
92. Cranton EM, Frackelton JP. Free radical pathology in age-associated diseases: Treatment with EDTA chelation , nutrition and antioxidants. J Holist Med 1984;6:6-37.
93. Hein OH et al. Alcohol consumption, serum low density lipoprotein choleseterol concentration, and risk of ischaemic heart disease:six years follow-up in Copenhagen Male study. British Med J 1996;312:736-741.
94. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J pathol 1969;56:111-28.
95. McCully KS. Homocysteine metabolism in scurvy, growth and arteriosclerosis. Nature 1971;231:391-392.
96. Graham IM, Daly LE, Refsum HM, et al. Plasma homocysteine as a risk factor for vascular disease. The Eurpoean Concerted Action Project. JAMA 1997;277;1775-1781.
97. Munro JM, Cotran RS. The pathogenesis of atherosclerosis: atherogenesis and inflammation. Lab Invest 1988;58:249-6l.
98. Ross R. The pathogenesis of atherosclerosis—an update. N Eng J Med 1986;314:488-500.
99. Ross R. The pathogenesis of atherosclerosis-a prospective for the 1990s. Nature 1993:362:801-9.
100. Berk BC, Weintraub WS, Alexander RW. Elevation od C-reactive protein in “active” coronary artery disease. Am J Cardiol 1990;65:168-72.
101. Alexander RW. Inflammation and coronary artery disease. N Eng J Med 1994;331:468-9.
102. Ridker PM, Cushman M, Stampfer MJ et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Eng J Med 1997;336:973-79.
103. Liuzzo G, Biasucci LM, Gallimore JR, et al. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med 1994;331:417-24.
104. McMurray HF, Parthasarathy S, Steinberg D: Oxidatively modified low density lipoprotein is a chemoattractant for human T-lymphocytes. J Clin Invest 1993;92:1004.
105. van der Wal AC, Das PK, Bentz van de Berg D et al. Atherosclerotic lesions in humans: in situ immunophenotypic analysis suggesting an immune mediated response. Lab Invest 1989;61:166-170.
106. Caliguiri G, Summaria, Liuzzo G, et al. Time course of T-lymphocytes activation and of C-reactive protein in unstable angina: relation to prognosis. Circulation 1996;94:Supplement1:1-571. abstract.
107. Stemme S, Holm J, Hansson GK. T lymphocytes in human atherosclerotic plaques are memory cells expressing CD45RO and the integrin VLA-1. Arterioscler Thromb 1992;12:206-11.
108. Habenicht AJR, Glomset JA, King WC, Nist C, Mitchell CD, Ross R. Early changes in phosphatidylinositol and arachidonic acid metabolism in quiescent Swiss 3T3 cells stimulated to divide by platelet-derived growth factor. J Biol Chem 1981;256:12329-35.
109. van der Wal AC, Becker AE, van der Loos CM et al. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 1994;89:36-44.
110. Palabrica T, Lobb R, Furie BC, Aronovitz M, Benjamin C, Hsu YM, Sajer SA, Furie B. Leukocyte accumulation promoting fibrin deposition in mediated in vivo by P-selectin on adherent platelets. Nature 1992;359:848-851.
111. Gerrity RG, Goss JA, Soby L. Control of monocyte recruitment by chemotactic factor(s) in lesion-prone area of swine aorta. Arteriosclerosis 1985; 5:55-66.
112. DiCorleto PE, de la Motte CA. Characterization of the adhesion of the human monocytic cell line U-937 to cultured endothelial cells. J Clin Invest 1985;75:1153-61.
113. Schwartz SM, Benditt EP. Clustering of replicating cells in aortic endothelium. Proc Natl Acad Sci USA 1976;73:651-3.
114. Tucker RF, Shipley GD, Moses HL, Holley RW. Growth inhibitor from BSC-1 cells closely related to platelet type B transforming growth factor. Science 1974;226:705-7.
115. Walker LN, Bowen-Pope DF, Ross R, Reidy MA. Intimal vascular smooth muscle cells secrete PDGF-like activity. Fed Proc 1985;44:737. abstract.
116. Castellot JJ Jr, Addonzio ML, Rosenberg R, et al. Cultured endothelial cells produce a heparinlike inhibitor of smooth muscle cell growth. J Cell Biol 1981;90:372-9.
117. Renick RE, Ling KLE, Humphries SE, Henney AM. Effect of acetyl-LDL on monocyte/macrophage expression of matrix metaloproteinases. Atherosclerosis 1994;109(suppl):192. Abstract.
118. Jonasson L, Holm J, Skalli O, Bondjers G, Hansson GK. Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis 1986;6:131-138.
119. Rajavashisth TB, Andalibi A, Territo MC, et al: Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low-density lipoproteins. Nature 1990;344:254.
120. Barrett TB, Gajdusek CM, Schwartz SM, McDougall JK, Benditt EP. Expression of the sis gene by endothelial cells in culture and in vivo. Proc Natl Acad Sci USA 1984; 81:6772-4.
121. Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix-metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 1994;94:2493-2503.
122. Henney Am, Wakeley PR, Davies MJ, Foster K, Hembry R, Murphy G, Humphries S. Localization of stromelysin gene expression in atherosclerotic plaques by in situ hybridization. Proc Natl Acad Sci USA 1991;88:8154-8158.
123. Gibbons GH and Dzau VJ. Molecular therapies for vascular disease. Science 1996;272:689-93.
124. Barrett TB, Gajdusek CM, Schwartz SM, McDougall JK, Benditt EP. Expression of the sis gene by endothelial cells in culture and in vivo. Proc Natl Acad Sci USA 1984; 81:6772-4.
125. Davies MJ, Gordon JL, Gearing AJH, Pigott R, Woolf N, Katz D, Kyriakopoulos A. The expression of the adhesion molecules ICAM-1, VCAM-1, PECAM, and E-selectin in human atherosclerosis. J Pathol 1993;171:223-229.
126. Berliner JA, Navab B, Fogelman AM et al. Atherosclerosis: basic mechanisms: oxidation, inflammation, and genetics Circulation 1995;91:2488-2496.
127. Vartianen E, Puska P, Pekkanen J et al. Changes in risk factors explain changes in mortality from ischaemic heart disease. BMJ 1994;309:23-27.
128. Expert Panel on Detection and Treatment of High Blood Cholesterol in adults. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in adults (Adult treatment Panel II). JAMA 1993;269:3015-3023.
129. Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Eng J Med 1990;323:1289-98.
130. Blankenhorn DH, Azen SP, Kramsch DM, et al. Coronary angiographic changes with lovastatin therapy: the Monitored Atherosclerosis Regression Study (MARS). Ann Intern Med 1993;119:969-76.
131. National Heart, Lung and Blood Institute, “The Lipid research Clinics coronary primary prevention trial results. JAMA 1984;251:351-60.
132. Buchwald H, Vargo RL, Matts JP, et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease. N Eng J Med 1990;323:946-55.
133. Physician’s Health Study Research Group, “Final report on the aspirin component of the ongoing Physicians’ Health Study,” N Eng J Med 1989;321:129-135.
134. Smith GD, Song F, Sheldon T. Cholesterol lowering and mortality: the importance of considering initial level of risk. BMJ 1993;306:1367-73.
135. Hulley SB, Walsh JMB, Newman TB. Health policy on blood cholesterol: time to change directions. Circulation 1992;86:1026-9.
136. Frick MH, Elo O, Haapa K et al. “Helsinki Heart Study: Primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia. N Eng J Med 1987;317:1237-1244.
137. Hulley SB, Newman TB. The cholesterol in the elderly: Is it important? JAMA 1994;272:1372-4.
138. Newman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs. JAMA 1996;275:55-60.
139. Huttunen J, Heinonen O, Manninen V, et al.The Helsinki Heart Study: an 8.5 year safety and mortality follow-up. J Intern Med. 1994;235:31-39.
140. Criqui MH. Cholesterol, primary and secondary prevention, and all-cause mortality. Ann Intern Med. 1991;115:973-76.
142. Smith GD, Pekkanen J. Should there be a moratorium on the use cholesterol-lowering drugs? BMJ 1992;304:431-4.
143. Law MR, Thompson SG. Low serum cholesterol and the risk of cancer: an analysis of the published prospective studies. cancer Causes Control. 1991;2:253-61.
144. Law MR, Thompson SG, Wald NJ. Assessing possible hazards of reducing serum cholesterol. BMJ 1994;308:373-9.
145. Kritchevsky SB, Kritchevsky D. Serum cholesterol and cancer risk: an epidemiologic perspective. Annu Rev Nutr. 1992;12:391-416.
146. Sacks FM, Pfeiffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001-9.
147. Jones TW. Observations on some points in the anatomy, physiology, and pathology of the blood. British Foreign Medical reviews. 14:585-9; 1842
148. Virchow R. Gesammelte Abhandlungen zur Wissenschaftichen Medicin. 1856. pg 477.
149. Trousseau A. Phlegmasia alba dolens. Clinique Medicle de L’Hotel-Dieu de Paris 3:94; 1865.
150. Dastre A. Fibrinolyse dans le sang. Arch. Physiol. Norm. Path. 5 Ser. 5:661-63, 1893.
151. Hunter J. Treatise on the Blood, Inflammation and Gun-Shot Wounds. London, Nicoll, 1794.
152. Green JR. Note on the action of sodium chloride in dissolving fibrin. J physiol (London) 8:372-377; 1887.
153. Delezenne C, Pozerski E. Action du serum sanguin sur la gelatine en presence du chloroform. C R Soc Biol. 1903;55:327-9.
154. Opie EL, Barker BI. Leucoprotease and antiprotease of mammals and of birds. J Exp Med. 1907;9:207-221.
155. Tillet WS, Garner RL. The fibrinolytic activity of hemolytic streptococci. J Exp. Med. 1933;58:485-502.
156. Kaplan MH. Nature and role of the lytic factor in hemolytic streptococcal fibrinolysis. Proc Soc Exp Biol 1944;57:40-3
157. McKay DG. Disseminated Intravascular Coagulation: An Intermediary Mechanism of Disease. 1965. New York. Harper & Row.
158. Brick RL. Disseminated intravascular coagulation. Hematology/Oncology Clinics of North America 1993;6:1259-65.
159. Kitchens CS. Concept of hypercoagulability: a review of its development, clinical application, and recent progress. Semin Thromb Hemost 1985;11:293-301.
160. Launder TM, Marlar RA, Adcock DM. Abnormalities in fibrinolysis associated with thrombosis. Thrombosis and Hemostasis. No.TH90-6. 1990;12:1-9.
161. Bachmann F. Fibinolysis. In: Verstraeie M, Vermylen J, Lijnen R, et al. eds. Thrombosis XIth Congress Hemostasis. Leuven, Belgium: International Society on Thrombosis and Haemostasis and Leuven University Press. 1987:227-26.
162. Ingerslev M and Teilum G. Biopsy studies of the liver in pregnancy. 1. Normal histological features of the liver as seen on aspiration. Acta. Obstret. Gyn, Scand. 1946;25:339-51.
163. Corriveau DM, Fristma GA (eds). Hemostasis and thrombosis in the clinical laboratory. Philadelphia, 1988. JP Lippincott.
164. Davies JA. The pre-thrombotic state. Clin Sci 1985;69:641-9.
165. Muller CA, Worthington MG, Thandroyen FT. Antiarrhythmic and metabolic effects of indormin during acute regional ischemia and reperfusion in isolated rat heart. J Cardiovasc Pharmacol. 1990;15:408-12.
166. Vatner SF, Patrick TA, Knight DR et al. Effects of calcium channel blocker on responses of blood flow, function, arrhythmias, and extent of infarction following reperfusion in conscious baboons. Cir Research 1988;62:105-7.
167 Koller PT, Bergmann SR. Reduction of lipid peroxidation in reperfused isolated rabbit hearts b diltiazem. Circ. Res. 1989;65-838-43.
168. Coker SJ. Further evidence that thromboxane exacerbates arrhythmias: Effects of UK38485 during coronary artery occlusion and reperfusion in anaesthetized greyhound. J Mol Cell Cardiol. 1984;16:633-8.
169. Coker SJ, Parratt JR. Prostacyclin—antiarrhythmic or arrhythmogenic? Comparison of the effects of intravenous and intracoronary prostacyclin and ZK36374 during coronary artery occlusion and reperfusion in anesthetized greyhounds. J Cardiovasc Pharmacol.1983;5:557-563.
170. Kukreja RC, Loesser KE, Naseem SA et al. Antioxidant effect of histidine during ischemia/reperfusion injury in rat heart. In Oxidative Processes and Antioxidants: Their Relation to Nutrition and Health Outcomes. Report of the Thirteenth ROSS Conference on Medical Research. 1994. Abbott Laboratories, Columbus, Ohio.
171. Halliwell, B. Reactive oxygen species and the central nervous system. J Neurochemistry 59:1609-23; 1992
172. Genbacev O, Zhou Y, Ludlow JW, et al. Regulation of human placental development by oxygen tension. Science 1997;277:1669-1672
173. Sundaresan M, Yu Z-X, Feranna VJ et al. Requirement gor generation of H2O2 for platelet-derived growth factor signal transduction. Science 1995;270:296-99.
174. Irani K, Xia Y, Zweier JL et al. Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science 1997;275:1649-1651.
175. Halliwell B, Gutteridge JMC. Lipid peroxidation, oxygen radicals, cell damage and antioxidant therapy. Lancet 1984;i:1396-8.
176. Halliwell B, Gutteridhe JMC. Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 1984;219:1-14.
177. Halliwell B. Protection against tissue damage in vivo by desferrioxamine. What is its mechanism of action? Free Radic Biol Med. 1989;7:645-51.
178. Halliwell B, Gutteridge JMC. Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts. Arch Biochem Biophys 1986;246:501-14.
179. Puppo A, Halliwell B. Formation of hydroxyl radicals from hydrogen peroxide in the presence of iron. Is haemoglobin a biological Fenton catalyst? Biochem J 1988;249:185-190.
180. Sadrzadeh SM, Anderson DK, Panters SS et al. Hemoglobin potentiates central nervous system damage. J Clin Invest 1987;79:662-4.
181. Gutteridge JMC. The antioxidant activity of haptoglobin towards haemoglobin-stimulated lipid peroxidation. Biochem Biophys Acta 1987;917:219-223.
182. Gutteridge JMC, Halliwell B. Radical-promoting loosely-bound iron in biological fluids and the bleomycin assay. Life Chem Rep 1987;4:113-142.
183. Kanner J, German JB, Kinsella JE. Initiation of lipid peroxidation in biological systems. CRC Crit Rev Food Sci Nutr 1987;25:317-374.
184. MacDonald RL, Weir BKA. A review of hemoglobin and the pathogenesis of cerebral vasospasm. Stroke 1991;22:971-982.
185. Sambrano GR, Parthosathy S, Steinberg D. Recognition of oxidatively damaged erythrocytes by a macrophage receptor with specificity for oxidized low density lipoprotein. Proc Nat Acad Sci USA 1994;91:3265-69.
186. Lonberg-Holm K, Philipson L. Early interactions between animal viruses and cells. In Monographs in Virology 1974;9:1-149. Eds. Melnik JL. Basel: S. Karger.
187. Maddy AH. The properties of the protein of plasma membrane of ox erythrocytes. Biochemica et Biophysica Acta 1966;117:193-200.
188. Seganti L, Superti F, Mastromarino P et al. Role of carbohydrates on cell membrane receptors for vesicular stomatitis virus . Bollettino dell’Instituto Sieroterapico Milanese 1982;61:294-299.
189. Oda T, Akaike T, Hamamoto T, et al. Oxygen radicals in influenza-induced pathogenesis and treatment with pyran ploymer-conjugated SOD. Science 1989;244:974-977.
190. Halonen PE, Toivanen P, Nikkari T. Non-specific inhibitors of activity of hemagglutinins of rabies and vesicular stomatitis viruses. J gen Viriol. 1974;22:309-31.
191. Bailey CA, Miller DK, Lenard J. Effects of DEAE-dextran on infection and hemolysis by VSV. Evidence that nonspecific electrostatic interactions mediate effective binding of VSV to cell. Virology 1984;133:111-118.
192. Dales S. Early events in cell-animal virus interactions. Bacteriologic Reviews 1973;37:103-135.
193. Mastromarino P, Conti C, Goldini P et al. Characterization of membrane components of the erythrocyte involved in vesicular stomatitis virus attachment and fusion at acidic Ph. J Gen Virol 1987;68:2359-2369.
194. Babior BM, Kipnes RS, Carnutte JT. Biologic defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest. 1973;52:741-744.
195. Babior BM, Curnutte JT, Kipnes RS. Biologic defense mechanisms. Evidence for the participation of superoxide in bacterail killing by xanthine oxidase. J Lab Clin Med. 1975;85:235-244.
196. Babior BM. Oxygen-dependent microbial killing by phagocytes Part I. N Eng J Medicine 1978:298: 659-668.
197. Babior BM. Oxygen-dependent microbial killing by phagocytes. Part II. N Eng J Med 1978: 298:721-26.
198. Weiss SJ. Tissue destruction by neutrophils. N Eng J Med 1989;320:365-76.
199. Havemann K, Janoff A. Neutral proteases of human polymorphonuclear leukocytes. Urban & Schwarzenberg, Baltimore. 1978. PP468).
200. Janoff A, Scherer J. Mediators of inflammation in leukocyte lysosomes. IX. Elastinolytic activity in granules of human polymorphonuclear leukocytes. J Exp Med 1968;128:1137-1155.
201. Del Maestro R, Thaw HH, Bjork J, et al. Free radicals as mediators of tissue injury. Acta Physiol Scan. 1908, Suppl, 492:43-57. (WBC generated oxidizing species increase capillary permeability and enhance polymorphonuclear-endothelium adhesion.)
202. Lazarus GS, Brown RS, Daniels JR, et al. Human granulocyte collagenase. Science 1968;159:1483-1485.)
203. Clark RA, Stone PJ, El Hag A, et al. Myeloperoxidase-catalyzed inactivation of alpha-1-protease inhibitor by human neutrophils. J Biol Chem 1981;256:3348-53.
204. Tanaka H, Sukhova GK, Swanson SJ, et al. Sustained activation of vascular cells and leukocytes in the rabbit aorta after baloon injury. Circulation 1993;88:1788-1803.
205. Baeurle PA, Rupee RA, Pahl HL. Reactive oxygen intermediates as second messengers of a general pathogen response. Pathol Biol (Paris) 1996;44:29-35
206. Collins T, Read MA, Neish AS, et al. Transcriptional regulation of endothelial cell adhesion molecules. FASEB J 1995;9:899-909.
207. Bourcier T, Sukhova G, Libby P. The nuclear factor k-B signalling pathway participates in dysregulation of vascular smooth cells in vitro and in human atherosclerosis. J Biol Chem 1997;272:15817-24.
208. Bevilacqua MP, Pober JS, Wheeler ME, et al. Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest 1985;76:2003-11.
209. Lindner V, Collins T. Expression of NF-kappa B and 1 kappa B-alpha by aortic endothelium i an arterial injury model. Am J Pathol 1996;148:427-38.
210. Witte D, Cornicelli JA. Platelet-derived growth factor stimulates low density lipoprotein receptor activity in cultured human fibroblasts. Proc Natl Acad Sci USA 1980; 77:5962-6.202.
211. Chait A, Ross R, Albers JJ, Bierman EL. Platelet-derived growth factor stimulates activity of low density lipoprotein receptors. Proc Natl Acad Sci USA 1980;77:4084-8.
212. Schwartz CJ, Valente AJ, Sprague EA, et al. The pathogenesis of atherosclerosis: an overview. Clin cardiol 1991;14:Suppl 1:11-116.
213. Freedman JE, Farhat JH, Loscalzo J, et al. a-Tocopherol inhibits aggegation of human platelets by a protein kinase C-dependent mecanism. Circulation 1996;94:2434-40.
214. Grotendorst GR, Chang T, Seppa HEJ, Kleinman HK, Martin GR. Platelet-derived growth factor is a chemoattractant for vascular smooth muscle cells. J Cell Physiol 1982;113:261-6.
215. Huang JS, Huang SS, Deuel TF, Specific covalent binding of platelet-derived growth factor to human plasma a2-macroglobulin. Proc Natl Acad Sci USA 1984;81:342-6.
216. Ross R, Glomset J, Kariya B, Harker L. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci USA 1974;71:1207-10.
217. Kohler N, Lipton A. Platelets as a source of fibroblast growth-promoting activity. Exp Cell Res 1974;87:297-301.
218. Baumgartner HR. Platelet interaction with vascular structures. Thromb Diath Haemorrh 1972; Suppl 51:161-76.
219. Silkworth JB, McLean B, Stehbens WE. The effect of hypercholesterolemia on aortic endothelium studied en face. Atherosclerosis 1975;22:335-48.
220. Castellot JJ Jr, Favreau LV, Karnovsky MJ et al. Inhibitors of vascular smooth muscle cell growth by endothelial-derived heparin: possible role of a platelet endoglycosidase. J Biol Chem 1982;257:11256-60.
221. Grotendorst GR, Chang T, Seppa HEJ, Kleinman HK, Martin GR. Platelet-derived growth factor is a chemoattractant for vascular smooth muscle cells. J Cell Physiol 1982;113:261-6.
222. Gerrity RG, Naito HK, Richardson M, Schwartz CJ. Dietary induced atherogenesis in swine: morphology of the intima in prelesion stages. Am J Pathol 1979;95:775-92.
223. Nathan CF, Murray HW, Cohn ZA. Current concepts: the macrophage as an effector cell. N Engl J Med 1980;303:622-6.
224 Gibbons GH and Dzau VJ. Molecular therapies for vascular disease. Science 1996;272:689-93.
225. Van Furth R. Current view on the mononuclear phagocyte system. Immunobiology 1982;161:178-85.
226. Moncada S, Herman AG, Higgs EA, Vane JR. Differential formation of prostacyclin (PGX or PGI2) by layers of the arterial wall: an explanation for the anti-thrombotic
227. Bowen-Pope DF, Ross R. Is epidermal growth factor present in human blood: Interference with the radioreceptor assay for epidermal growth factor. Biochem Biophys Res Commun 1983;114:1036-41.
227. Oka Y, Orth DN. Human plasma epidermal growth factor/beta-urogastrone is associated with blood platelets. J Clin Invest 1983;72:249-59.
228. Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB. Transforming growth factor-beta in human platelets; identification of a major storage site, purification, and characterization. J Biol Chem 1983;258:7155-60.
229. Ali M. Fungemia and primordial life forms in fibromyalgia and CFS: Oxidative regression to primordial cellular ecology. J Integrative Medicine (in press).
230. Ali M, Ali O, Bradford R. et al Immunostaining of candida organisms in peripheral smears. (Abstract). 1995. American Academy of Otolaryngic Allergy, Spring Meeting, Palm Desert, CA.
231. Ali M. Immunostaining of candida organisms. In RDA: Rats, Drugs and Assumptions. Page 451. 1995 Life Span, Denville, New Jersey.
232. Ali M and Ramanarayanan MP: A computerized micro-ELISA assay for allergen-specific IgE antibodies. Am J Clin Pathol 1984;81:591.
233. Ali M, Ramanarayanan MP, Nalebuff DJ, et al: Serum concentrations of allergen-specific IgG antibodies in inhalant allergy: Effect of specific Immunotherapy. Am J Clin Pathol. 1983;80:290.
234. Ali M. The bloodstream: An Open Ecosystem. In RDA: Rats, Drugs and Assumption. Page 424-435. 1995 Life Span, Denville, New Jersey.
235. Ali M. Naked bacteria, naked yeast. In RDA: Rats, Drugs and Assumptions. Pages 455-457. 1995 Life Span, Denville, New Jersey.
236. Walsh TJ et al. Detection of circulating Candida enolase by immunoassay i patients with cancer and invasive candidiasis. N Eng J Med 1991;324:1026.
237. Myerburg RJ, Conde CA, Sung RJ, et al. Clinical electrophysiologic and hemodynamic profile of patients resusitated from prehospital cardiac arrest. Am J Med 1980;68:568-76.
238. Davies MJ, Thomas A. Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. N Eng J Med 1984;310:1137-40.
239. Friedman M, Rosenman RH. Association of specific overt behavior pattern with blood and cardiovascular findings. JAMA 1959;169:1286).
240. Friedman MD, Thoresen E, Gill JJ, et al. Alteration of type A behavior and its effect on cardiac recurrences in post myocardial infarction patients:summary results of the recurrent coronary prevention project.
241. Mittleman MA, Maclure M. Mental stress during daily life triggers myocardial ischemia. JAMA 1997;277:558-9.
242. Rogers MP,Dubey D, Reich P. The influence of the psyche and the brain on immunity and disease susceptibility. Psychosomatic medicine 1979;41:147-165.
243. Rosenman RH, Brand RJ, Jenkins CD, et al. Coronary artery disease in the Western Collaborative Group Study: final follow-up experience of 8 1/2 years. JAMA 1975;23:872.)
244. Salonen JT, Puska P, Mustaniemi H. Changes in morbidity and mortality during comprehensive community programme to control cardiovascular disease during 1972-79 in North Karelia. BMJ 1979;ii:1178-83.
245. Carruthers ME. Aggression and atheroma. Lancet 1969;2:1170)
246. Blumenthal JA, Williams RB Jr, Kong Y, et al. Type A behavior pattern and coronary atherosclerosis. Circulation 1978;58:634)
247. The Review Panel on Coronary-Prone Behavior and Coronary Artery Disease. A critical review. Circulation 1981;63:1199.)
248. Gullette ECD, Blumenthal JA, Babyak M, et al. Effects of mental stress on myocardial ischemia during daily life. JAMA 1997;277:1521-1526.
249. Jenkins CD. Recent evidence supporting psychological and social risk factors for coronary disease. Part II. N Eng J Med 1976;294:1033).
250. Frasure-Smith N, Lesperance F, Prince R, et al. Montreal Heart Attack Readjustment Trial (M-HART): a randomized trial of psychosocial intervention following MI. J Am Coll Cardiol. 1997;29:(suppl):452A.

251. Ali M. The Limbic-Spiritual State. in Healing Miracles and the Bite of the Gray Dog. 1997. Life Span, Denville, New Jersey pp76-85.
252. Ali, M. A Biochemical profile in the Limbic State. In The Cortical Monkey and Healing. 1990. Institute of Preventive Medicine, Bloomfield, New Jersey pp 207-210.
253. Ali M. The Cortical Monkey and Healing. pp 175-198 IPM 1990, Bloomfield, N.J.
254. Selye H. Stress in Health and Disease. 1973. Butterworth, Boston.
255. Fuller RW. Control of epinephrine synthesis and secretion. Fed Pro. 1973;32:1772-1781)
256. Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxidase dismutase. J Biol Chem 1972;247:3170-3175.
257. Cohen G, Heikkila RE. The generation of hydrogen peroxide, superoxide radical and hydroxyl radical by 6-hydroxydopamine, dialuric acid and related cytotoxic agents. J Biol Chem 1974;249:2447-2452.
258. Singh A. Chemical and biochemical aspects of superoxide radicals and related species of activated oxygen. In Active Oxygen and Medicine (a symposium)). Can J Physiol Pharmacol. Petkau A, Dhalla NS (eds). 1982;60:1330-1345.
259. Hoffer A. Oxidation-reduction in brain. J Orthomolecular Psychiatry. 1983;12:292-301.
260. Levine S, Kidd P. Antioxdant Adaptation: Its Role in Free radical Pathology. 1985. Biocurrent Division, Allergy Research Group, California PP 242-243.
261. Mittleman MA, Maclure M, Tofler GH, et al. Triggering of acute myocardial infarction by heavy exertion: protection against triggering by regular exertion. N Engl J Med 1993;329:1677-1683.
262. Willich SN, Lewis M, Lowell H, et al. Physical exertion as a trigger of acute myocardial infarction. N Engl J Med 1993;329:1684-1690.
263. Muller JE, Mittleman MA, Maclure M, Sherwood JB, Tofler GH, for the Determinants of Myocardial Infarction Onset Study Investigators. Triggering myocardial infarction by sexual activity: low absolute risk and prevention by regular physical exertion. JAMA 1996;275:1405-1409.
264. Siscovick DS, Weiss NS, Hallstrom AP, Inui TS, Peterson DR. Physical activity and primary cardiac arrest. JAMA 1982;248:3113-3117.
265. Ambrose JA, Winters SL, Arora RR, et al. Coronary angiographic morphology in myocardial infarction: a link between the pathogenesis of unstable angina and myocardial infarction. J Am Coll Cardiol 1985;6:1233-8.
266. Black A, Black MM, Gensini G. Exertion and acute coronary artery injury. Angiology 1975;26:759-83.
267. Clampricotti R, el Gamal MI, Bonnier JJ, Relik TH. Myocardial infarction and sudden death after sport: acute coronary angiographic findings. Cathet Cardiovasc Diagn 1989;17:193-7.
268. Daoud AS, Jarmolych J, Jakovic LG, Rosenberg AA, Hedberg RF. Possible relationship of coronary thrombosis and rupture of arteriosclerotic plaque. Lab Invest 1963;12:863.
269. Hammoudeh AJ, Haft JL. Coronary-plaque rupture in acute coronary syndromes triggered by snow shoveling. N Eng J Med 1996;335:2001.
270. Kujala UM. Low LDL oxidation in veterans endurance atheletes. Scandinavian J Medicine Sciene and Sports. 1996;6:303-308.
271. Sue DY, Wasserman K. Impact of integrative cardiopulmonay exercise testing on clinical decision making. Chest 1991;99:981-92.
272. Adner MM, Castelli NP. Elevated high-density lipoprotein levels in marathon runners. JAMA 1980;243:534-6.
273. Weintraub WS, Klein LW, Seelaus PA, et al. Importance of total life consumption of cigarettes as a risk factor for coronary artery disease. Am J Cardiol 1985; 55:660-72.
274. Center for Chronic Disease Prevention and health promotion. Reducing the health consequences of smoking: 25 years of progress: a report of the surgeon general: executive summary. washington, D.C. Government Printing Office, 1989. (DHHS publication no. (CDC) 89:8411.) (ref for 70% reduction)
275. Waters D, Lesperance J, Gladstone P, et al. Effects of cigarette smoking on the angiographic evolution of coronary atherosclerosis: a canadian Coronary Atherosclerosis Intervention Trial (CCAIT) Substudy. Circulation 1996;94:614-21.
276. Ross R. The pathogenesis of atherosclerosis—an update. N Eng J Med 1986;314:488-500.
277. Hasdai D, Garratt KN, Grill DE, et al. Effect of smoking status on the long-term outcome after successful percutaneous coronary revascularization. N Eng J Med 1997;336:755-61.
278. Penn A, Batastini G, Soloman J, et al. Dose-dependent size increases of aortic lesions following chronic exposure to 7,12 dimethylbenzene. Cancer research. 1981;41:588-92.
279. Celermajor DS, Adams MR, Clarkson P et al. Passive smoking and impaired endothelium-dependent arterial dilatation in health young adults. N Eng J Med. 334:150-54; 1996
280. Schwarz KB, Cox J, Sharma S et al. Cigarette smoking is a pro-oxidant in pregnant women regardless of antioxidant nutrient intake. J Nutr Env Med 1995;5:225-34.
281. Folts JD, Bonebrake FC. The effects of cigarette smoking and nicotine on platelet thrombus formation in stenosed dog coronary arteries: Inhibition with phentolamine. Circulation 1982;65:465-70
282. Grines CL, Topol EJ, O’Niell WW, et al. Effect of cigarette smoking on outcome after thrombolytic therapy for myocardial infacrtion. 1995;91:298-303.
283. Cryer PE, Haymond MW, Santiago JV, Shah SD. Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodyhamic and metabolic events. N Engl J Med 1976;295:573.
284. Goldsmith JR. Carbon monoxide and coronary heart disease. Ann Intern Med 1969;71:199.
285. Gerritsen T, Vaughn JG, Waisman HA. The identification of homocystine in the urine. Biochem Biophys Res Commun 1962;9:493-6.
286. Carson NAJ, Neill DW. Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland. Arch Dis Child 1962;37:505-13.
287. Schimke RN, McKusick VA, Huang T, Pollack AD. Homocystinuria: studies of 20 families with 38 affected members. JAMA 1965;193:711-9.
288. Mudd SH, Levy HL, Skovby F. Disorders of transsulfuration. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 7th ed. Vol. 1. New York: McGraw-hill 1995;1279-327.
289. Stamler JS, Slivka A. Biological chemistry of thiols in the vasculature and in vascular-related disease. Nutr Rev 1996;54:1-30.
290. McCully KS, Wilson RB. Homocysteine theory of arteriosclerosis. Atherosclerosis. 1975;22:215-227.
291. McCully KS. Homocystein theory of arteriosclerosis: development and current status. Atheroscler Rev. 1983;11:157-246.
292. Kannel WB. Range of serum cholesterol values in the populaton devloping coronary artery disease. Am J Cardiol 1995;76:69C-77C.
293. Harker LA, Ross R, Slichter SJ, Scott CR. Homocystine-induced arteriosclerosis: the roll of endothelial cell injury and platelet response in its genesis. J Clin Invest 1976;58:731-41.
294. Harker LA, Slichter SJ, Scott CR, Ross R. Homocystinemia: Vascular injury and arterial thrombosis. N Engl J Med 1974;291:537-43.
295. Stampfer MJ, Malinow MR, Willet WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physician. JAMA 1992;268:877-881.
296. Perry IJ, Refsum H, Morris RW, Ebrahim SB, Ueland PM, Shaper AG. Prospective study of serum homocysteine concentration and risk of stroke in middle-aged British men. Lancet 1995;346:1395-8.
297. Verhoef P, Stampfer MJ, Buring JE, et al. Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. Am J Epidemiol 1996;143:845-59.
298. Ueland PM, Refsum H, Brattstorm L. Plasma homocysteine and cardiovascular disease. In:Francis RB Jr, ed. Atherosclerotic cardiovascular disease, hemostasis, and endothelial function. New York:Marcel Dekker, 1992:183-236.
299. Tsai J-C, Perrella MA, Yoshizumi M, et al. Promotion of vascular smoth cell growth by homocysteine: a link to atherosclerosis. Pro Nat Acad Sci USA 1994;91:6369-73.
300. Stamler JS, Osborne JA, Jaraki O, et al. Adverse effects of homocysteine are modulated by endothelium-derived releasing factor and related oxides of nitrogen. J Clin Invest 1993;91:308-18.
301. Mudd SH, Skovby F, Levy HL, et al. The natural history of homocystinuria due to cystathionine B-synthase deficiency. Am J Hum Genet 1985;37:1-31.
302. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. New Engl J Med 1997;337:230-236.
303. Petri M, Roubenoff R, Dallal GE, Nadeau MR, Selhub J, Rosenberg IH. Plasma homocysteine as a risk factor for atherothrombotic events in systemic lupus erythematosus. Lancet 1996;348:1120-4.
304. Stampfer MJ, Malinow MR, Willett WC et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA. 268:877-81; 1992.
305. Arnesen E, Refsum H, Bonaa KH, et al. The Tromso Study: serum total homocysteine and myocardial infarction : a prospective study. Presented at the 3rd International Conference on Preventive Cardiology. Oslo, Nowray, June 27-July 1, 1993. Abstract.
306. Selhub J, Jacques PF, Bostom AG, et al. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N Eng J Med 1995;332:286-91.
307. Bonjour JP. Vitamins and alcholi:III Vitamin B . International Journal for Vitamin and Nutrition Research. 1980, March 1980:215-230.
308. Reynold RD, Natta CL. Depressed plasma pyridoxal phosphate concentrations in adult asthamatics. Am J Clin Nutr 1985;41:684-9.
309. Crane FL, Halefl Y, Lester RL, et al. Isolation of a quinone from te heart mitochondria. Biochem Biophys Acta 1957;25:220-221.
310 DePierre JW, Ernster L. Enzyme topology on intercellular membranes. Rev Biochem 1977;46:201-262.
311. Kamikawa T, Kobayashi A, Yamashita T, et al. Effects of coenzyme Q10 on exercise tolerance in chronic satble angina pectoris. Am J cardiol 1985;56:247-251.
312. Folkers K, Littarru GP, Ho l, et al. Evidence for a deficiency of coenzyme Q10 in human heart disease. Inter J Vitamin Nutr. 1970;40:380-390.
313. Folkers K, Watanabe T, Kaji M, e al. Critique of coenzyme Q in biochemical and biomedical research and in ten years of clinical research in cardiovascular disease. J Mol Med 1977;2:431-460.
314. Kilarrus N, Yamaquchi A, Otaki M, et al. Myocardial tissue level of coenzyme Q in patients with cardiac failure. In: Folkers K, Yamamura Y,eds. Biomedical and clinical aspects of coenzyme Q. Vol 4. Amsterdam. Elsevier/North Holland Biochemical Press. 1984:243-252.
315. Boler J, Farley TM, Scholler J, Folkers K. Deficiency of coenzyme Q10 in the rabbit. Inter J Vitamin Nutr Research 1967;39:281-288.
316. Nayier WG. The use of coenzyme Q10 to protect ischemic heart muscle. In: Yamamure Y, Folkers K, Ito Y. eds. Biomedical and clinical Aspects of Coenzyme Q. Vol. 2. Amsterdam:Elsevier/North Holland Biochemical Press. 1980:409-425.
317. Ohhara H, Kanaids H, Yoshimura R, et al. Effects of coenzyme Q10 on ischemia and reperfusion of the isolated perfused rat heart. J Mol Cell Cardiol 1981; 13:65-74.
318. Arifa M, Kiyosue T, Imanishi S, et al. Electrophysiologic and ionotropic effects of coenzyme Q10 on gunea pig ventricular muscle. Jpn Heart J 1982;23:961-974.
319. Oharra H, Kanakie H, Nakamura M, et al. A protective effect of coenzyme Q on the adriamycin-induced cardiotoxicity in the isolated perfused rat heart. J Mol Cell Cardiol 1981;13:741-752.
320. Langsjoen H, Langsjoen P, Langsjoen P et al. Usefulness of coenzyme Q10 in clinical cardiology:a long-term study. Mol Aspects Med (England) 1994; 15 Suppl:165-75.
321. Mortensen SA. Perspectives on therapy of cardiovascular diseases with coenzyme Q10 (ubiquinone). Clin Investig (Germany). 1993;71(8 Suppl):S116-23.
322. Langsjoen P, Langsjoen P, Willis R, Folkers K. Treatment of essemntial hypertension with coenzyme Q10. Mol Aspects Med (England). 1994;15 Suppl:S265-72.
323. Digiesi V, Cantini F, Oradei A et al. Coenzyme in essential hypertension. Mol Aspects Med (England) 1994;15 Suppl:257-63.
Greenberg S, Frishman WH. Coenzyme Q10: a new drug for cardiovascular disease. J Clin Pharmacol. 1990;30(7):596-608.
324. Sullivan JL. Stored iron as risk factor for ischemic heart disease, in Lauffer RB (ed): Iron and Human Disease. Boca raton, Fla, CRC Press 1992.
325. Sullivan JL. The iron paradigm of ischemic heart disease. Am Heart J 1989;117:1177-1188.
326. Babbs CF. Role of iron ions in the genesis of reperfusion injury following successful cardiopulmonary resusitation: Preliminary data and a biochemical hypothesis. Ann Emerg Med 1985;14:777-783.
327. Gordon T, Kannel WB, Hjortland MC, McNamara PM. Menopause and coronary heart disease: The Framingham Study. Ann Intern Med 1978;89:157-161.
328. Bottiger LE, Carlson LA. Risk factors for ischaemic vascular death for men in the Stockholm Prospective Study. Atherosclerosis 1980;36:389-408.
329. Lauffer RB. Iron stores and the international variation in mortality from coronary artery disease. Med Hypotheses 1991;35:96-102.
330. Murray MJ, Murray AB, Murray NJ. Nutritional iron and copper deficiency may protect against the atherogenesis of high-fat diets. (abstract) Arterioscler Thromb 1991;11:1479a.
331. Halliwell B, Gutteridge JMC. Role of free radicals and catalytic metal ions in human disease: An overview, in Packer L, Glazer AN (eds): Methods in Enzymology, vol 186. San Diego, Academic Press, 1990, pp 1-85.
332. van der Kraaij A, Mostert LJ, van Eijk HG, Koster JF. Iron load increases the susceptibility of rat hearts to oxygen reperfusion damage: Protection by the antioxidant (+)-cyanidanol-3 and deferoxamine. Circulation 1988;78:442-449.
333. McCord JM. Is iron sufficiency a risk factor in ischemic heart disease? Circulation 1991;83:1112-1114.
334. Cross CD, Halliwell B, Borish ET, Pryor WA, Saul RL, McCord JM, Harman D. Oxygen radicals and human disease. Ann Intern Med 1987;107:526-545.
335. Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine, ed 2. Oxford, Clarendon Press, 1989.
336. Williams RE, Zweier JL, Flaherty JT. Treatment with deferoxamine during ischemia improves functional and metabolic recovery and reduces reperfusion-induced oxygen radical generation in rabbit hearts. Circulation 1991;83:1006-1014.
337. Smith C, Mitchinson MJ, Aruoma OI, Halliwell B. Stimulation of lipid peroxidation and nydroxyl radical generation by the contents of human atherosclerotic lesions. Biochem J (in press).
338. Ganther HE. Interactions of vitamin E and selenium with mercury and silver. Ann NY Acad Sci 1980;355:1-372.
339. Jansson G, Harms-Ringdahl M. Stimulating effects of mercuric and silver ions on the superoxicde anion production in human polymorphonuclear leucocytes. Free Rad Res Commun 1993;18:87-98.
340. International Programme on Chemical Safety (IPCS). Environmental Health Criteria 101: Methylmercury. Geneva, Switzerland: World Health Organization; 1990.
341. Wayner DDM, Burton GW, Ingold KU, Barclay LRC, Locke SJ. The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma. Bioochim Biophys Acta 1987;924:408-419.
342. Naganuma A, Koyama Y, Imura N. Behavior of methylmercury in mammalian erythrocytes. Toxicol Appl Pharmacol 1980;54:405-410.
343. Benov LC, Benchev IC, Monovich OH. Thiol antidotes effect on lipid peroxidation in mercury-poisoned rates. Chem Biol Interact 1990;73:321-332.
344. Cuvin-Aralar ML, Furness RW. Mercury and selenium interaction: a review. Ecotoxicol Eviron Safety 1991;21:348-364.
345. Suadicani P, Hein HO, Gyntelberg F. Serum selenium concentration and risk of ischaemic heart disease in a prospective cohort study of 3,000 males. Atherosclerosis. 1992;96:33-42.
346. Salonen JT Association between cardiovascular death and myocardial infarction and serum selenium in a matched-pair longitudinal study. Lancet 1982;2:175-9.
347. Virtamo J. Serum selenium and the risk of coronary heart disease and stroke. Am J Epidemiol. 1985;127:276-82.
348. Anderson RA. Chromium nutrition in the elderly, in RR Watson (ed): The Handbook of Nutrition in the Aged. Boca raton, Fl. CRC 1993, pp385-392.
349. Newman HAI, Leighton RF, Lanese RR, et al. Serum chromium and angiographically determined coronary artery disease. Clin Chem 1978;24:541-544.
350. Simonoff M, Llabador Y, Hamon C, et al. Lower plasma chromium in patients with coronary artery and heart diseases. Biol Trace Elem Res 1984;6:431-439.
351. Schroeder HA, Nason P, Tipton IH. Chromium deficiency as a factor in atherosclerosis. J Chronic Dis 1970;23:123-142.
352. Levine RA, Streeton DHP, Doisy RJ. Effects of oral chromium supplementation on the glucose tolerance of elderly human subjects. Metabolism 1968;17:114-124.
353. Davies S, Howard JM, Hunnisett A, et al. Age-related decreases in chromium levels in 51,665 hair, sweat, and serum samples from 40,872 patients—implications for prevention of cardiovascular disease and type II diabetes mellitus. Metabolism 1997;46:1-4.
354. Glinsman WH, Mertz W. Effects of trivalent chromium on glucose tolerance. Metabolism 1966;15:510-515.
355. Abrahama AS, Brooks BA, Elath U. The effects of chromium supplementation on serum glucose and lipids in patients with and without non-insulin-dependent diabetes. Metabolism 1992;41:768-775.
356. Frei B. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage. Am J Clin Nutr 1991;54:1113-85.
357. Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA 1989;86:6377-81.
358. Frei B, Stocker R, England L, Ames BN. Ascorbate: the most effective antioxidant in human blood plasma. Adv Exp Med Biol 1990;264:155-63.
359. Harats D, Ben-Naim M, Dabach Y, Hollander G, Havivi E, Stein Y. Effect of vitamin C and E susceptibility of plasma lipoproteins to peroxidation induced by acute smoking. Atherosclerosis 1990;85:47-54.
360. Jialal I, Grundy SM. Preservation of the endogenous antioxidants in low density lipoprotein by ascorbate but not probucol during oxidative modification. J Clin Invest 1991;87:597-601.
361. Cheraskin E. Vitamin C and coronary artery atherosclerosis. J Advancement Medicine 9:133; 1996
362. Gey KF, Stahelin HB, Eichholzer M. Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke: Basel prospective study. Clin Invest 1993;71:3-6.
363. Riemersma RA, Wood DA, MacIntyre CCA, et al. Risk of angina pectoris and plasma concentration Vitamins A, C and E and carotene. Lancet 1991;337:1-5.
364. Nyyossonen K, Parvianen M, Salonen R, et al. Vitamin C deficinecy and risk of myocardial infarction: prospective population study of men from eastern Finland. BMJ 1997;314:634-638.
365. Gale CR, Martyn CN, Winter PD, et al. Vitamin C and risk of death from stroke and coronary heart disease in cohort of elderly people. BMJ 1995;310:1563-6.
366. Enstrom JE, Pauling L. Mortality among health-conscious elderly californians. Proc Natl Acad Sci USA 1982;79:6023-6027.
367. Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993;328:1450-6.
368. Retsky KL, Frie B. Vitamin C prevents metal ion-dependent initiation and propogation of lipid peroxidation in human low-density lipoprotein. Biochem Biophys Acta 1995;1257:279-87.
369. Salonen JT. Dietary fats, antioxidants and blood pressure. Ann Med 1991;23:295-8.
370. Knecht P, Reunanen A, Jarvinen R, et al. Antioxidant vitamin intake and coronary mortality in a longitudinal population study. Am J Epidemiol 1994;139:1180-9.
371. Cockcroft J and Chowienczyk P. Beyond cholesterol reduction in coronary heart disease:is vitamin E the answer? Heart 76:293-294; 1996.
372. Jain SK et al. Effects of modest vitamin E supplementation on blood glycated hemoglobin and triglycerides levels and red cell indices in Type I diabetic patients. J Am Coll Nutr. 15(5):458-61; 1996.
373. Stampfer MJ, Hennekens CH, Manson JE, Coditz GA, Rosner B, Willett WC. Vitamin E consumption and risk of coronary disease in women. N Engl Med 1993;328:1444-9.
374. Packer JE, Slater TF, Wilson RL. Direct observaion of a free radical interaction between vitamin E and vitamin C. Nature 1979;278:737-8.
375. Steinburg D. Studies on the mechanisms of action of probucol. Am J Cardiol 1986;57:16H-21H.
376. Setruda M, Inden M, Hiraoka N, et al. Probucol therapy in the prevention of restenosis after successful percutaneous transluminal coronary angioplasty. Clin Ther 1993;15:374-82.
377. Lee YJ, Yamaguchi H, Daida H, et al. Pharmacologic interventions to modify restenosis. Circulation 1991;84:Suppl II:II-299. Abstract.
378. Watanabe K, Sekiya M, Ikeda S, et al. Preventive effects of probucol on restenosis after percutaneous transluminal coronary angioplasty. Am Heart J 1996;132:23-9.
379. Yokoi H, Yamaguchi H, Kuwabara Y. Effectiveness of probucol in preventing restenosis after percutaneous transluminal coronary angioplasty: Probucol Angioplasty Restenosis Restenosis trial (PART). J Am Coll Cardiol 1996;2: Suppl A:391A. Abstract.
380. Carew TE, Schwenke DC, Steinberg D. Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that antioxidant in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Proc Natl Acad Sci USA 1987;84:7725-9.
381. Anderson TJ, Meredith IT, Yeung AC, The effect of cholesterol- lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Eng J Med 1995;332:488-93.
382. Casdorph HR. EDTA chelation therapy: efficacy in arteriosclerotic heart disease. J Holist Med 1981;3:53-59.
383. Casdorph HR. EDTA chelation therapy, II: efficacy in brain disorders. J Holist Med 1981;3:101-117.
384. Chappell LT, Janson M. EDTA chelation therapy in the treatment of vasular disease. J Cardiovas Nurs. 1996;10:78-86.
385. Chappell LT, Stahl JP. EDTA chelation therapy for vascular disease: a meta-analysis using unpublished data. J Adv Med 1994;7:131-42.
386. Chappell LT, Stahl JP. The correlation between EDTA chelation therapy and improvement in cardiovascular function: a meta-analysis. J Adv Med 1993;6:139-160.
387. Hancke C, Flytie K. Benefits of EDTA chelation therapy on arteriosclerosis. J Adv Med 1993;6:161-172.
388. Meltzer LE, Ural E, Kitchell JR. The treatment of coronary artery heart disease with disodium EDTA. In: Seven M, ed. Metal-Binding in Medicine. Philadelphia: JB Lippincott, 1960.
389. Olsewer E, Sabbag FC, Carter JP. A pilot double-blind study of sodium-magnesium EDTA in peripheral vascular disease. J Natl Med Assoc 1990;82:173-174.
390. Rudolph CJ, McDonough EW, Barber RK. A nonsurgical approach to obstructive carotid stensis using EDTA chelation. J Adv Med 1991;4:157-166.
391. Hein OH et al. Alcohol consumption, serum low density lipoprotein cholesterol concentration, and risk of ischaemic heart disease:six years follow-up in Copenhagen Male study. British Med J 1996;312:736-741.
392. Betina V. Mycotoxins. Amsterdam:Elsevier, 1989, pp. 86-95.
393. Butler WH. Mycotoxins. In The Filamentous Fungi. vol. 1, eds. JE Smith and DR Berry, pp. 320-329. London: Edward Arnold.
394. Ciegler A, Bennett JW. Mycotoxins and Mycotoxicosis. Bioscience 1980;30:512-515.
395 Ciegler A, Burmeister HR, Vesonder RF et al. Mycotoxins:Occurrence in the environment. in Mycotoxins and N-Nitroso Compounds:Environmental risks, vol.1,ed. RC Shank, pp.1-50. Boca raton, Fla:CRC Press.
396. Cole RJ, Cox RH. Handbook of Toxic Fungal Metabolites. 1981. New york Academic Press.
397. Hendry KM, Cole EC. A review of mycotoxins in indoor air. J Toxicol Environmental Health 1993;38:183-198.
398. Lewis CW, Smith JE, Anderson JG et al. The presence of mycotoxin-associated fungal spores isolated from the indoor air of the damp domestic environment and cytotoxic to human cell lines. Indoor Environ 1994;3:323-330.
399. Schiefer HB. Mycotoxins in indoor air: A critical toxicological viewpoint. Proc 5th Int Conf on Indoor Air Quality and Climate, 1990 Ottawa, pp. 167-172.
400. Brinton WT, Vastbinder EE, Greene JW et al. An outbreak of organic dust toxic syndrome in a college fraternity. JAMA 1987;248:1210-2.
401. Bu’Lock JD. Mycotoxins as secondary metabolites. 1980. In The Biosynthesis of Mycotoxins, ed. PS Steyn. pp 1-16. New York Academic Press.
402. Kinsman OS. Effect of mammalian steroid hormones and leutinizing hormone on the germination of candida albicans and implication for vaginal candidosis. Mycosis 1988;31:617-421.
403. Landers JP. New Concepts in steroid hormone action: Transcriptio factors, proto-oncogene, and the cascade model for steroid regulation of gene expression. Critical Reviews in Eukaryotic Gene Expression. 1992;2:19-21.
404. Andre AJ. Hormones, puffs and flies. The molecular control of metamorphosis by ecdysone. Trends in Genetics. 1992;8:132-4.
405. Edwards JE. Invasive Candida infections. N Eng J Med 1991;324:1060-64.
406. Klotz SA. A fibronectin receptor on Candida albicans mediates adherence of the fungus to extracellular matrix. J Infectious Dis 1991;163:604-6.
407. Bergstrom JD, Kurtz MM, Rew EJ, Amend AM, Karkas JD, et al. The zaragozic acids. A family of fungal metaboilites that are picomolar competitive inhibitors of squalene synthase. Proc Natl Acad Sci USA 1993;90:80-84.
408. Matossian MK. Effects of natural fungal toxins on fertility and mortality in Connecticut, 1660-1900. J Nutritional & Environmental Medicine 1996;6:285-300.
409. Ellis RJ, et al. Molecular chaperons. Annual Review of Biochemistry 1994;36:1.
410. Picard D, et al. Reduced levels of hsp90 compromise steroid receptor action in vivo. Nature 1990;348:166.
411. Gething MJ, et al. Protein folding in the cell. Nature 1992;355:33.
412. Wiech H, et al. HPs90 chaperons protein folding in vitro. Nature 1992;358:169.
413. Jakob U, et al. Assisting spontaneity: The role of HPs90 and small HsPs as molecular chaperons. Trends in Biochemical Sciences 1994;19:205.
414. Schlesinger MJ. How the cell copes with stress and the function of heat shock proteins. Pediatric Research 1994;19:205.
415. Dawson RF, Farthing JE, Marshall PS, et al. The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. 1. Taxonomy, fermentation, isolation, physico-chemical properties and biological activity. J Antibiot 1992;45:639-47.
416. Matthews R, et al. Cloning of a DNA sequence encoding a major fragment of the 47 kilodalton stress protein homologue of Candida albicans. FEMS Microbiology Letters 1989;51:25.
417. Ness GC, Zhao S, Keller Rk. Effect of squalene synthase inhibition on the expression of hepatic cholesterol biosynthetic enzymes, LDL receptor, and cholesterol 7 a hydroxylase. 1994;311:277-85.
418. Botstein D, Chervitz SA, Cherry JM. Yeast as a model organism. Science 1997;277:1259-1260.
419. Evans RA, et al. Candidiasis-endocrinopathy syndrome with progressive myopathy. Quarterly Journal of Medicine, New Series 1989;70:262.
420. Edwards JE. Invasive Candida Infections. New England Journal of Medicine 1992;324:1060.
421. Matthews R, et al. Autoantibody to heat shock protein 90 can mediate protection against systemic candidiasis. Immunology 1991;74:20.
422. Bergstrom JD, Dufresne C, Bills GF, et al. Discovery, biosynthesis, and mechanism of action of the zaragozic acids: potent inhibitors of squalene synthase. Annu Rev Microbiol 1995;49:607-39.
423. Abe I, Tomessch JC, Wattanasin S, et al. Inhibitors of squalene biosynthesis and metabolism. Nat Prod Rep. 1994;11:279-302.
424. Berg D, Plempel M. Sterol biosynthesis inhibitors. Pharmaceutical and agrochemical aspects. 1988 Chichester, UK:Ellis Horwood. pp 583.
425. Stopka T. , Chicago. Personal communication.
426. Bergstrom JD, Liesch JM, Hensens OK, Onishi JC, Huang L, et al. Antihypercholesterolemics. Eur Patent No. 040812A1 1991.
427. Blows WM, Foster G, Lane SJ, Noble D, Piercey JE, et al. The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. V. Minor Metabolites. J Antibiot 1994;47:740-54.
428. Dreyfuss MM, Chapela IH. Potential of fungi in the discovery of novel, low-molecular weight pharmaceuticals. In: The Discovery of natural Products with Therapeutic Potential, ed. VP Gullo. 1994 pp. 49-80. Boston:Butterworth-Heinmann.
429. Endo A. Monacolin K, a new hypocholesterolemic agent produced by a Monascus species. J Antibiot 1979;32:852-54.
Horie M, Tsuchiya Y, Hayashi M, Iida Y, Iwasawa Y, et al. NB-598: a potent competitive inhibitor of squalene expoxidase. J Biol Chem 1990;265:18075-78.
430. Ackerman MJ, Clapham DE. Ion Channels-Basic Science and Clinical Disease. N Engl J Med 1997;336:1575-86.
431. Keating MT. The long QT syndrome: a review of recent molecular genetic and physiologic discoveries. Medicine (Baltimore)1996;75:1-5.
432. Shimkets RA, Warnock DG, Bositis CM, et al. Liddle’s syndrome: heritable human hypertension caused by mutations in the B subunit of the epithelial sodium channel. Cell 1994;79:407-14.
433. Neyroud N, Tesson F, Denjoy I, et al. A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nat Genet 1997;15:186-9.
434. Hudson AJ, Ebers GC, Bulman DE. The skeletal muscle sodium and chloride channel diseases. Brain 1995;118:547-63
435. Koch MC, Steinmeyer K, Lorenz C, et al. The skeletal muscle chloride channel in dominant and recessive human nyotonia. Science 1992;257:797-800.
436. Ali M. Leaky cell membrane dysfunction. Monograph 1987. Teaneck, New Jersey.
437. Yusuf, S. Calcium antagonists in coronary artery disease and hypertension-Time for reevaluation? Circulation 1995;92:1079-1082.
438. Furberg CD, Psaty BM, Meyer JV. Nifedipine: Dose-related increase in mortality in patients with coronary heart disease. Circulation;92:1326-1331.
439. Boden WE, Schelewaert R, Walters EG. Design of a placebo-controlled clinical trial of long-acting diltiazem and aspirin versus aspirin alone in patients receiving thrombolysis with a first acute myocardial infarction. Am J cardiol 1995;75:1120-1123.
440. Thadani U, Zellner S, Glasser S et al. Double-blind, dose-response, placebo-controlled multicenter study of nisoldipine: a new second-generation calcium channel blocker in angina pectoris. Circulation 1991;84:2398-2408.
442. Vatner SF, Patrick TA, Knight DR, et al. Effects of calcium channel blocker on responses of blood flow, function, arrhythmias, and6extent of infarction following reperfusion in conscious baboons. Cir Res 1988;62:105-8.
443. Muller CA, Worthington MG, Thandroyen FT. Antiarrhythmic and metaboliic effects of indoramin during acute regional ischemia and reperfusion in isolated rat heart”
444. Rassmussen H, Bordier P. The Physiological and Cellular Basis of Metabolic Bone Disease. Williams and Wilkins, Baltimore, 1974.
445. Woods, KL, Fletcher S. Long-term outcome after intravenous magnesium sulphate in suspected acute myocardial infaction: The second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). Lancet 1995;343:816-9.
446. Woods KL, Fletcher S, Roffe C, Haider Y. Intravenous magnesium sulphate in suspected acute myocardial infarction: Results of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). Lancet 1992;339:1553-8.
447. Ali M. Experience with intravenous nutrient therapy for allergic patients with chronic fatigue. Am Acad Otolaryngic Allergy Abstracts Summer 1992;p23.
448. Seelig MS, Elin RJ. Reexamination of magnesium infusions in myocardial infarction. Am J cardiol 1995;76:172-173.
449. Halstead BW. The Scientific Basis of Chelation Therapy. Golden Quill Publishers, Inc. Box 1278, Colton, Ca
450. Inkeles S, Eisenberg D. Hyperlipidemia and coronary atherosclerosis: a review. Medicine (Baltimore) 1971;60:110-23.
451. Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA 1984;251:351-64.
452. Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and treatment of High Blood Cholesterol in adults. Arch Int Med 1988;148:36-69.
453. Brown G, Abers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990;323:1289-98.
454. Vartiainen E, Puska P, Pekkanen T et al. Changes in risk factors explain changes in mortality from ischemic heart disease in Finland. BMJ;309:23-7.
455. Gould AL, Rossouw JE, Santanello NC et al. Cholesterol reduction yields clinical benefits: a new look at old data. Circulation 1995;91:2274-2282.
456. CASS Principal Investigators and their Associates. Myocardial infarction and mortality in the coronary artery surgery Study (CASS) Randomized Trial. N Eng J Med 1984;310:750-8.
457. Rogers S. More on pravastatin and coronary disease. N Eng J Med 1996;335:1239-40.
458. Ali M. Punishing 99 to favor one. In Rats, Drugs and Assumptions. pp 116-7. 1995. Life Span, Denville, New Jersey.
459. Brown MS, Goldstein JL. Receptor-mediated control of cholesterol metabolism. Science 1976;191;150-54.
460. Brown MS, Kovanen PT, Goldstein JL. Regulation of plasma cholesterol by lipoprotein receptors. Science 1981;212:628-35.
461. Goldstein JL, Brown MS. The low-density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem 1977;46:897-930.
462. Brown MS, Goldstein JL. How LDL receptors influence cholesterol and atherosclerosis. Sci Am 1984; 251(5):58-66.
463. Goldstein JL, Brown MS. The low-density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem 1977;46:897-930.
464. Goldstein JL, Kita T, Brown MS. Defective lipoprotein receptors and atherosclerosis: lessons from an animal counterpart of familial hypercholesterolemia. N Engl J Med 1983;309:288-96.
465. Goldstein JL, Ho YK, Basu SK, et al. Binding sites on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Pro Natl Acad Sci USA 1979;76:333-7.
466. Brown MS, Goldstein JL. How LDL receptors influence cholesterol and atherosclerosis. Sci Am 1984; 251(5):58-66.
467. Henricksen t, Mahoney EM, Steinberg D. Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptor for acetylated low density lipoproteins. Proc Natl Acad Sci USA 1981;78:6499-503.
468. Henricksen T, Mahoney EM, Steinberg D: Enhanced macrophage degradation of biologically modified low density lipoprotein. Arteriosclerosis 1983;3:149-159.
469. Heart and Stroke Facts: 1996 Statistics Supplement. American Heart Association, Dallas, Tx 1996.
470. Miller M, Seidler , Kwiterovich PO, et al. Long-term predictors of subsequent cardiovascular events with coronay artery disease and “desirable” levels of plasma total cholesterol. Circulation 1992;86:1165-1170.
471. Rose G. Sick individuals and sick populations. Int J Epidemiology 1985;14:32-38.
472. Mertz W. Chromium occurrence and function in biological systems. Physiol Rev 1969;49:163-239.
473. Newman HAI, Leighton RF, Lanese RR, et al. Serum chromium and angiographically determined coronary artery disease. Clin Chem 1978;24:541-544.
474. Schroeder HA, Nason AP, Tipton IH. Chromium deficiency as a factor in atherogenesis. J Chronic Dis 1970;23:123-142.
475. Davies S, Howard JM, Hunnisett A, et al. Age-related decreases in chromium levels in 51,665 hair, sweat, and serum samples from 40,872 patients(implications for the prevention of cardiovascular disease and type-II diabetes mellitus. Metabolism 1997;46:1-5.
476. Ravnskov U. Cholesterol lowering trials in coronary heart disease: frequency of citation and outcome. BMJ 1992;305:15-19.
477. Jackson RL, Gotto AM Jr. Hypothesis concerning membrane structure, cholesterol, and atherosclerosis. In: Paoletti R, Gotto AM, Jr, eds. Atherosclerosis reviews. Vol. 1. New York:Raven Press, 1976:1-21.
478. Mclean JW, Tomlinson JE, Kuang W-J, et al. cDNA sequence of human apolipoprotein (a) is homologous to plasminogen. Nature. 1987;330:132-137.
479. Loscalzo J, Weinfeld M, Fless GM, et al. Lipoprotein (a), fibrin binding and plasminogen activation. Arteriosclerosis. 1990;10:240-245.
480. Ezratty A, Simon DI, Loscalzo J. Lipoprotein (a) binds to human platelets and attenuates plasmonigen binding and activation. Biochemistry 1993;32:4628-4633.
481. Trieu VN, Zioncheck TF, Lawn RM, et al. Interaction of of apolipoprotein (a) with apoprotein B-containing lipoproteins. J Biol Chem. 1991;266:5480-5485.
482. Smith EB, Cochran . Factors influencing the accumulation in fibrous plaques of lipid derived from low-density lipoprotein: preferential immobilization of lipoprotein (a) (Lp (a). Atherosclerosis 1990;84:173-181.
483. Kleinveld HA, Hak-Lemmers HL, Hectors MP, et al. Vitamin E and fatty acid intervention does not attentuate the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits. Arterioscler Thromb Vasc Biol 1995;15:290-7.
484. Keany JF Jr, Gaziano JM, Xu A, et al. Low-dose a-tocopherol improves and high-dose a-tocopherol worsens endothelial vasodilator function in cholesterol-fed rabbits. J Clin Invest 1994;93:844-51.
485. Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 1993;91:2546-51.
486. Friedman M, van den Bovenkamp GJ. The pathogenesis of a coronary thrombus. Am J Pathol 1966;48:19-44.
487. Falk E. Why do plaques rupture? Circulation 1992;86:Suppl III: III-30(III-42.
488. Brown DL, Hibbs MS, Kearney MN, Looushin C, Isner JM. Identification of 92-kD gelatinase in human coronary atherosclerotic lesions: association of active enzyme synthesis with unstable angina. Circulation 1995;91:2125-2131.
489. Burke JM, Ross R. Synthesis of connective tissue macromolecules by smooth muscle. Intl Rev. Connect Tissue Res 1979;8:119-57.
490. Walker LN, Bowen-Pope DF, Ross R, Reidy MA. Intimal vascular smooth muscle cells secrete PDGF-like activity. Fed Proc 1985;44:737. abstract.
491. Colucci WS, Braunwald E. pathophysiology of heart failure. In: Braunwald E, ed. Heart Disease 5th ed. Philadelphia. WB Saunders, 1997:394-420.
492. Haddad EB, Salmon M, Koto H et al. Ozone induction of cytokine-induced neutrophil chemoattractant (CINC) and nuclear factor-kB in rat lung: Inhibition by corticosteroids. FEBS Lett 1996;379:265-8.
493. Schwartz SM, Benditt EP, Endothelial cell replication. 1. Effects of age and hypertension in rat. Cir Res 1977;41:248-55.
494. Hibbs JB, Westenfelder C, Tainter R, et al. Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy. J Clin Invest 1992;89:867-77.
495. Lerman A, Edwards BS, Hallet JW, et al. Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis. N Eng J Med 1991;325:997-1001.
496. Quinn MT, Parthasarathy S, Steinberg D. Endothelial cell-derived chemotactic activity for mouse peritoneal macrophages and the effects of modified forms of low density lipoprotein. Proc natl Acad Sci USA 1985;82:5949-53.
497. Quinn MT, Parthasarathy S, Fong LG, et al. oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci USA 1987;84:2995-8.
498. Vega GL, Grundy SM. Hypoalphalipoprteinemia (low density lipoprotein) as a risk factor for coronary heart disease. Curr Opin Lipidology 1996;7:209-16.
499. Mensink RP, Katan MB. Effect of dietary fatty acids on serum lipids and lipoproteins: a meta-analysis of 27 trials. Arterioscler Thromb 1992;12:911-9.
500. Sacks FM. Dietary fats and coronary heart disease. J Cardiovasc Risk 1994;1:3-8.
501. Katan MB, Grundy SM, Willett WC. Beyond low-fat diets. N Eng J Med 1997;337:563-566.
502. Mensink RP, Katan MB. Effect of monounsaturated fatty acids versus complex carbohydrates on high-density lipoproteins in healthy men and women. Lancet 1987;1:122-5.
503. Lee-Han H, Cousins M, Beaton M, et al. Compliance in a randomized clinical trial of dietary fat reduction in patients with bresat dysplasia. Am J Clin Nutr 1988;48:575-86.




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