Peroxyl radicals: inductors of neurodegenerative and other inflammatory diseases. Their origin and how they transform cholesterol, phospholipids, plasmalogens, polyunsaturated fatty acids, sugars, and proteins into deleterious products.
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[1] S. Lovestone. Early diagnosis and the clinical genetics of Alzheimer’s disease , 1999, Journal of Neurology.
[2] L. Marnett,et al. Free radical epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene by hematin and polyunsaturated fatty acid hydroperoxides , 1981 .
[3] J L Witztum,et al. Oxidized phospholipids and isoprostanes in atherosclerosis. , 1998, Current opinion in lipidology.
[4] S. Wright,et al. Polyunsaturated fatty acids are FXR ligands and differentially regulate expression of FXR targets. , 2004, DNA and cell biology.
[5] Guoyao Wu,et al. Linoleic acid-induced endothelial activation: role of calcium and peroxynitrite signaling. , 2004, Journal of lipid research.
[6] L. Marnett. Oxy radicals, lipid peroxidation and DNA damage. , 2002, Toxicology.
[7] E. Stadtman,et al. Conversion of amino acid residues in proteins and amino acid homopolymers to carbonyl derivatives by metal-catalyzed oxidation reactions. , 1989, The Journal of biological chemistry.
[8] T. Osawa,et al. Covalent attachment of 4-hydroxy-2-nonenal to erythrocyte proteins. , 1997, Journal of biochemistry.
[9] P. Stenvinkel,et al. Phospholipid plasmalogen, a surrogate marker of oxidative stress, is associated with increased cardiovascular mortality in patients on renal replacement therapy. , 2004, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.
[10] G. Spiteller. Linoleic acid peroxidation--the dominant lipid peroxidation process in low density lipoprotein--and its relationship to chronic diseases. , 1998, Chemistry and physics of lipids.
[11] Stanley L. Hazen,et al. Identification of &agr;-Chloro Fatty Aldehydes and Unsaturated Lysophosphatidylcholine Molecular Species in Human Atherosclerotic Lesions , 2003 .
[12] W. Jira,et al. Increase in hydroxy fatty acids in human low density lipoproteins with age. , 1996, Chemistry and physics of lipids.
[13] R. G. Salomon,et al. Oxidized phospholipids, isolevuglandins, and atherosclerosis. , 2005, Molecular nutrition & food research.
[14] G. Spiteller,et al. Oxidized phytosterols increase by ageing in photoautotrophic cell cultures of Chenopodium rubrum , 1997 .
[15] Aldons J Lusis,et al. Thematic review series: The Pathogenesis of Atherosclerosis Published, JLR Papers in Press, April 1, 2004. DOI 10.1194/jlr.R400001-JLR200 The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL , 2004, Journal of Lipid Research.
[16] G. Spiteller,et al. Epoxidierung von Kohlenstoff-Kohlenstoff-Doppelbindungen in Terpenen durch Linolsäurehydroperoxide , 1993 .
[17] N. Bogdanovic,et al. The Swedish APP670/671 Alzheimer’s Disease Mutation: The First Evidence for Strikingly Increased Oxidative Injury in the Temporal Inferior Cortex , 2001, Dementia and Geriatric Cognitive Disorders.
[18] Spiteller. Identification of Toxic 2,4-Decadienal in Oxidized, Low-Density Lipoprotein by Solid-Phase Microextraction. , 2000, Angewandte Chemie.
[19] U. Walther,et al. Zur Bildung von Ölsäureepoxid bei der Lagerung technischer Ölsäure , 1993 .
[20] D. Collen,et al. Oxidation of low density lipoproteins in the pathogenesis of atherosclerosis. , 1998, Atherosclerosis.
[21] Catherine M Smart,et al. Gene expression during leaf senescence. , 1994, The New phytologist.
[22] A. C. Nicholson,et al. Herpesvirus in atherosclerosis and thrombosis: etiologic agents or ubiquitous bystanders? , 1998, Arteriosclerosis, thrombosis, and vascular biology.
[23] D. Alkon,et al. Oxidation of Cholesterol by Amyloid Precursor Protein and β-Amyloid Peptide* , 2005, Journal of Biological Chemistry.
[24] B. Hyman,et al. Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the amyloid β-peptide , 2001, Nature Cell Biology.
[25] R. Clark,et al. Oxidation of lysine side-chains of elastin by the myeloperoxidase system and by stimulated human neutrophils. , 1986, Biochemical and biophysical research communications.
[26] R. Schmidt,et al. Specificity of detection of Chlamydia pneumoniae in cardiovascular atheroma: evaluation of the innocent bystander hypothesis. , 1997, The American journal of pathology.
[27] D. Steinberg,et al. Oxidized phospholipids, linked to apolipoprotein B of oxidized LDL, are ligands for macrophage scavenger receptors. , 2000, Journal of lipid research.
[28] S. Lipton,et al. Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures. , 1995, Proceedings of the National Academy of Sciences of the United States of America.
[29] D. Massel,et al. Mediastinal irradiation: A risk factor for atherosclerosis of the internal thoracic arteries. , 1999, The Canadian journal of cardiology.
[30] W. Kern,et al. Synthesis and Properties of Naturally Occurring α- Hydroxyaldehydes. , 1996 .
[31] V. Monnier,et al. Aging of proteins: immunological detection of a glucose-derived pyrrole formed during maillard reaction in vivo. , 1989, The Journal of biological chemistry.
[32] D. Steinberg. Hypercholesterolemia and inflammation in atherogenesis: two sides of the same coin. , 2005, Molecular nutrition & food research.
[33] G. Spiteller. Furan fatty acids: Occurrence, synthesis, and reactions. Are furan fatty acids responsible for the cardioprotective effects of a fish diet? , 2005, Lipids.
[34] S. Genuth,et al. Glycation Products as Markers and Predictors of the Progression of Diabetic Complications , 2005, Annals of the New York Academy of Sciences.
[35] R. Bucala,et al. Advanced glycation end products contribute to amyloidosis in Alzheimer disease. , 1994, Proceedings of the National Academy of Sciences of the United States of America.
[36] E. Brunke,et al. The essential oil of Rhus coriaria L. fruits , 1993 .
[37] G. Besser,et al. Met-enkephalin circulates in human plasma , 1980, Nature.
[38] M. V. van Eden,et al. Deleterious iron-mediated oxidation of biomolecules. , 2002, Free radical biology & medicine.
[39] W. Markesbery,et al. Acrolein is increased in Alzheimer’s disease brain and is toxic to primary hippocampal cultures , 2001, Neurobiology of Aging.
[40] D. Steinberg,et al. The oxidative modification hypothesis of atherosclerosis: does it hold for humans? , 2001, Trends in cardiovascular medicine.
[41] M. Carson,et al. The Push-Me Pull-You of T Cell Activation , 2001, Science.
[42] W. Markesbery,et al. Oxidative Alterations in Alzheimer's Disease , 1999, Brain pathology.
[43] E. Araki,et al. Statins Suppress Oxidized Low Density Lipoprotein-induced Macrophage Proliferation by Inactivation of the Small G Protein-p38 MAPK Pathway* , 2005, Journal of Biological Chemistry.
[44] G. Spiteller,et al. Detection of short-chain alpha-hydroxyaldehydic compounds as pentafluorbenzyloxime derivatives in bovine liver. , 1995, Chemistry and physics of lipids.
[45] D. Butterfield,et al. The critical role of methionine 35 in Alzheimer's amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity. , 2005, Biochimica et biophysica acta.
[46] B. Staels,et al. Peroxisome proliferator-activated receptors (PPARs): nuclear receptors with functions in the vascular wall , 2001, Zeitschrift für Kardiologie.
[47] W. Powell,et al. Increased levels of monohydroxy metabolites of arachidonic acid and linoleic acid in LDL and aorta from atherosclerotic rabbits. , 1991, Biochimica et biophysica acta.
[48] Mark P Mattson,et al. Neuronal and glial calcium signaling in Alzheimer's disease. , 2003, Cell calcium.
[49] C. Napoli,et al. Neurodegenerative diseases: insights into pathogenic mechanisms from atherosclerosis , 2005, Neurobiology of Aging.
[50] J. Vliegenthart,et al. Demonstration by EPR spectroscopy of the functional role of iron in soybean lipoxygenase-1. , 1975, Biochimica et biophysica acta.
[51] R. Griffiths,et al. Benzodiazepine self-administration in humans and laboratory animals – implications for problems of long-term use and abuse , 1997, Psychopharmacology.
[52] H. Shen,et al. Aflatoxin B1-induced lipid peroxidation in rat liver. , 1994, Toxicology and applied pharmacology.
[53] B. Ohlsson,et al. Oxysterols induce interleukin‐1β production in human macrophages , 2002, European journal of clinical investigation.
[54] G. Spiteller,et al. Transformations of 12,13-Epoxy-ll-hydroxy-9-octadecenoic Acid and 4,5-Epoxy-N-acetylsphingosine by Incubation with Liver Homogenate and Liver Microsomes , 2000, Zeitschrift fur Naturforschung. C, Journal of biosciences.
[55] R. Bryant,et al. Altered lipoxygenase metabolism and decreased glutathione peroxidase activity in platelets from selenium-deficient rats. , 1980, Biochemical and biophysical research communications.
[56] R. Ross,et al. Atherosclerosis is an inflammatory disease. , 1998, American heart journal.
[57] F. Mach,et al. Cholesterol-independent effects of statins in inflammation, immunomodulation and atherosclerosis. , 2005, Current drug targets. Cardiovascular & haematological disorders.
[58] C. Glass,et al. Differential recruitment of the coactivator proteins CREB-binding protein and steroid receptor coactivator-1 to peroxisome proliferator-activated receptor gamma/9-cis-retinoic acid receptor heterodimers by ligands present in oxidized low-density lipoprotein. , 2003, The Journal of endocrinology.
[59] Jeffrey K. Yao,et al. Oxidative Damage and Schizophrenia , 2001, CNS drugs.
[60] P. Jenner. Oxidative damage in neurodegenerative disease , 1994, The Lancet.
[61] T. Montine,et al. E-4-hydroxy-2-nonenal is cytotoxic and cross-links cytoskeletal proteins in P19 neuroglial cultures. , 1996, The American journal of pathology.
[62] W. Garvey,et al. The adipocyte lipid binding protein (ALBP/aP2) gene facilitates foam cell formation in human THP-1 macrophages. , 2002, Atherosclerosis.
[63] N. Leitinger. Oxidized phospholipids as modulators of inflammation in atherosclerosis , 2003, Current opinion in lipidology.
[64] V. Monnier,et al. Structure elucidation of a senescence cross-link from human extracellular matrix. Implication of pentoses in the aging process. , 1989, The Journal of biological chemistry.
[65] K. Uchida,et al. Oxidative fragmentation of collagen and prolyl peptide by Cu(II)/H2O2. Conversion of proline residue to 2-pyrrolidone. , 1992, The Journal of biological chemistry.
[66] E. Oliw,et al. Oxygenation of Arachidonic Acid by Cytochromes P‐450 , 1999 .
[67] T. Pedersen,et al. Hyperlipidaemia and aortic valve disease , 2004, Current opinion in lipidology.
[68] G. Spiteller,et al. Increase of Caryophyllene Oxide in Ageing Lemon Balm Leaves (Melissa officinalis L.) -A Consequence of Lipid Peroxidation? , 1996 .
[69] S. Hazen,et al. Isolevuglandin-protein adducts in humans: products of free radical-induced lipid oxidation through the isoprostane pathway. , 2000, Biochimica et biophysica acta.
[70] B. Halliwell,et al. Oxygen radicals and the nervous system , 1985, Trends in Neurosciences.
[71] J. Cazenave,et al. Platelet phospholipids are differentially protected against oxidative degradation by plasmalogens , 2002, Lipids.
[72] M. Cybulsky,et al. NF-κB: pivotal mediator or innocent bystander in atherogenesis? , 2001 .
[73] C. Akoh,et al. Methods for measuring oxidative rancidity in fats and oils. , 2002 .
[74] S. Younkin,et al. Genetic background regulates β-amyloid precursor protein processing and β-amyloid deposition in the mouse , 2003 .
[75] J. Ngeh,et al. Inflammation, infection and antimicrobial therapy in coronary heart disease – where do we currently stand? , 2001, Fundamental & clinical pharmacology.
[76] K. Honn,et al. Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 5 , 2012, Advances in Experimental Medicine and Biology.
[77] I. Sergiev,et al. The effect of drought and ultraviolet radiation on growth and stress markers in pea and wheat , 2001 .
[78] B Chance,et al. The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. , 1973, The Biochemical journal.
[79] J. Vliegenthart,et al. Spectroscopic studies on the active site of hydroperoxide lyase; the influence of detergents on its conformation , 2001, FEBS letters.
[80] I. Björkhem,et al. On the mechanism of oxidation of cholesterol at C-7 in a lipoxygenase system. , 1992, The Journal of biological chemistry.
[81] A. Lupo,et al. Evaluation of Glyoxal and Methylglyoxal Levels in Uremic Patients under Peritoneal Dialysis , 2005, Annals of the New York Academy of Sciences.
[82] E. Niki,et al. Acrolein Is a Product of Lipid Peroxidation Reaction , 1998, The Journal of Biological Chemistry.
[83] K. Wang. Caspases: a drug discovery perspective. , 1999, Current opinion in drug discovery & development.
[84] R. Brigelius-Flohé. Tissue-specific functions of individual glutathione peroxidases. , 1999, Free radical biology & medicine.
[85] G. Stewart,et al. Leukotoxins of gram-negative bacteria. , 2002, Veterinary microbiology.
[86] G. Spiteller. Is Atherosclerosis a Multifactorial Disease or Is It Induced by a Sequence of Lipid Peroxidation Reactions? , 2005, Annals of the New York Academy of Sciences.
[87] M. Reilly,et al. Quantitative high performance liquid chromatography/tandem mass spectrometric analysis of the four classes of F(2)-isoprostanes in human urine. , 1999, Proceedings of the National Academy of Sciences of the United States of America.
[88] Seon-Hwa Lee,et al. Oxidative DNA damage and cardiovascular disease. , 2001, Trends in cardiovascular medicine.
[89] T. Montine,et al. Lipid peroxidation in aging brain and Alzheimer's disease. , 2002, Free radical biology & medicine.
[90] E. Schiffrin,et al. Beyond blood pressure: the endothelium and atherosclerosis progression. , 2002, American journal of hypertension.
[91] L. Horrocks,et al. Plasmalogens, docosahexaenoic acid and neurological disorders. , 2003, Advances in experimental medicine and biology.
[92] R. Pontcharraud,et al. Evidence for the reactivity of fatty aldehydes released from oxidized plasmalogens with phosphatidylethanolamine to form Schiff base adducts in rat brain homogenates. , 2004, Chemistry and physics of lipids.
[93] Andreas Hald,et al. Oxidative stress and inflammation in Parkinson's disease: is there a causal link? , 2005, Experimental Neurology.
[94] J. Hathcock. Evaluation of fao/who pesticide standards in relation to polish and honduran diets , 1983 .
[95] K. Uchida,et al. Identification of oxidized histidine generated at the active site of Cu,Zn-superoxide dismutase exposed to H2O2. Selective generation of 2-oxo-histidine at the histidine 118. , 1994, The Journal of biological chemistry.
[96] P Kouklis,et al. Ca(2+) signalling and PKCalpha activate increased endothelial permeability by disassembly of VE-cadherin junctions. , 2001, The Journal of physiology.
[97] J. Pettegrew,et al. Brain Membrane Phospholipid Alterations in Alzheimer's Disease , 2001, Neurochemical Research.
[98] I. Buttino,et al. Bioactive aldehydes from diatoms block the fertilization current in ascidian oocytes , 2003, Molecular reproduction and development.
[99] H. Kuhn,et al. Sequence determinants for the positional specificity of lipoxygenases. , 2002, Advances in experimental medicine and biology.
[100] O. Witte,et al. Lysophosphatidylcholine as a Ligand for the Immunoregulatory Receptor G2A , 2001, Science.
[101] T. Osawa,et al. Glucosone as a Radical-Generating Intermediate in the Advanced Maillard Reaction , 1996 .
[102] F. Crews. Alcohol and Neurodegeneration , 2006 .
[103] I. Puddey,et al. Fatty acid oxidation products in human atherosclerotic plaque: an analysis of clinical and histopathological correlates. , 2003, Atherosclerosis.
[104] H. Sies. Biochemie des oxidativen Stress , 1986 .
[105] C. Masters,et al. Amyloid plaque core protein in Alzheimer disease and Down syndrome. , 1985, Proceedings of the National Academy of Sciences of the United States of America.
[106] A. Favier,et al. Can malondialdehyde be used as a biological marker of progression in neurodegenerative disease? , 2002, Journal of Neurology.
[107] P. Domingues,et al. Identification of oxidation products and free radicals of tryptophan by mass spectrometry , 2003, Journal of the American Society for Mass Spectrometry.
[108] D. Butterfield,et al. Free radicals and brain aging. , 2004, Clinics in geriatric medicine.
[109] A. Aljada,et al. Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects. , 2003, Diabetes.
[110] C. Sonntag. Free-Radical Reactions of Carbohydrates as Studied by Radiation Techniques , 1980 .
[111] S. Toyokuni,et al. Endogenous Formation of Protein Adducts with Carcinogenic Aldehydes , 2001, The Journal of Biological Chemistry.
[112] Paul J Thornalley,et al. The autoxidation of glyceraldehyde and other simple monosaccharides under physiological conditions catalysed by buffer ions. , 1984 .
[113] H. Hartung,et al. Statins — a cure-all for the brain? , 2005, Nature Reviews Neuroscience.
[114] Barry Halliwell,et al. Reactive Oxygen Species and the Central Nervous System , 1992, Journal of neurochemistry.
[115] D. Steinberg,et al. The oxidative modification hypothesis of atherogenesis: an overview. , 2000, Free radical biology & medicine.
[116] B. Zilinskas,et al. Salt and oxidative stress: similar and specific responses and their relation to salt tolerance in Citrus , 1997, Planta.
[117] G. Spiteller,et al. 9-Hydroxy-10,12-octadecadienoic acid (9-HODE) and 13-hydroxy-9,11-octadecadienoic acid (13-HODE): excellent markers for lipid peroxidation , 1997 .
[118] G. Spiteller,et al. Oxidation of D-(-)-Ribose with H2O2 and Lipid Hydroperoxides , 1996 .
[119] G. Spiteller,et al. Iron Release from the Active Site of Lipoxygenase , 2000 .
[120] G. Poli,et al. 4‐Hydroxynonenal in the Pathomechanisms of Oxidative Stress , 2000, IUBMB life.
[121] J. Trojanowski,et al. Increased 8,12‐iso‐iPF2α‐VI in Alzheimer's disease: Correlation of a noninvasive index of lipid peroxidation with disease severity , 2000, Annals of neurology.
[122] G. Sobue,et al. Lipid peroxidation and advanced glycation end products in the brain in normal aging and in Alzheimer's disease , 2002, Acta Neuropathologica.
[123] F. McArdle,et al. Intracellular generation of reactive oxygen species by contracting skeletal muscle cells. , 2005, Free radical biology & medicine.
[124] T. Montine,et al. Carbonyl toxicology and Alzheimer's disease. , 2002, Toxicology and applied pharmacology.
[125] W. Vogt. Oxidation of methionyl residues in proteins: tools, targets, and reversal. , 1995, Free radical biology & medicine.
[126] Alexander D. MacKerell,et al. Polyunsaturated fatty acids in lipid bilayers: intrinsic and environmental contributions to their unique physical properties. , 2002, Journal of the American Chemical Society.
[127] T. Montine,et al. Reactions of 4-hydroxy-2(E)-nonenal and related aldehydes with proteins studied by carbon-13 nuclear magnetic resonance spectroscopy. , 1998, Chemical research in toxicology.
[128] T. Lyons,et al. Carboxymethylethanolamine, a Biomarker of Phospholipid Modification during the Maillard Reaction in Vivo * , 1997, The Journal of Biological Chemistry.
[129] G. Spiteller,et al. α-Hydroxyaldehyde Derivatives Arising from Oxidation of Plasmalogens† , 1992 .
[130] K. Žarković. 4-hydroxynonenal and neurodegenerative diseases. , 2003, Molecular aspects of medicine.
[131] D. Grant,et al. Linoleic acid epoxide promotes the maintenance of mitochondrial function and active Na+ transport following hypoxia. , 2004, Toxicology letters.
[132] S. Hazen. Myeloperoxidase and plaque vulnerability. , 2004, Arteriosclerosis, thrombosis, and vascular biology.
[133] T. Lyons,et al. Age-dependent accumulation of N epsilon-(carboxymethyl)lysine and N epsilon-(carboxymethyl)hydroxylysine in human skin collagen. , 1991, Biochemistry.
[134] J. Heinecke. Mechanisms of oxidative damage by myeloperoxidase in atherosclerosis and other inflammatory disorders. , 1999, The Journal of laboratory and clinical medicine.
[135] S. Wassall,et al. Docosahexaenoic acid: membrane properties of a unique fatty acid. , 2003, Chemistry and physics of lipids.
[136] K. Uchida. Histidine and lysine as targets of oxidative modification , 2003, Amino Acids.
[137] E. Jeffery,et al. The relationship between nickel chloride-induced peroxidation and DNA strand breakage in rat liver. , 1992, Toxicology and applied pharmacology.
[138] D. Straus,et al. Effects of cyclopentenone prostaglandins and related compounds on insulin-like growth factor-I and Waf1 gene expression. , 1998, Biochimica et biophysica acta.
[139] L. Sayre,et al. Independent Synthesis, Solution Behavior, and Studies on the Mechanism of Formation of a Primary Amine-Derived Fluorophore Representing Cross-linking of Proteins by (E)-4-Hydroxy-2-nonenal , 1999 .
[140] A. Mazel,et al. Induction of cell death in arabidopsis by superoxide in combination with salicylic acid or with protein synthesis inhibitors. , 2001, Free radical biology & medicine.
[141] R. L. Jones,et al. The identification of an epoxy-hydroxy acid as a product from the incubation of arachidonic acid with washed blood platelets. , 1979, Prostaglandins.
[142] N. Voelkel,et al. Leukotoxins and the lung. , 1999, Pulmonary pharmacology & therapeutics.
[143] E. Stadtman,et al. Recent advances in the analysis of oxidized proteins , 2003, Amino Acids.
[144] L. Horrocks,et al. Neural membrane phospholipids in alzheimer disease , 1995, Neurochemical Research.
[145] G. Glenner,et al. Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. , 1984, Biochemical and biophysical research communications.
[146] J. Witztum,et al. C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: Phosphorylcholine of oxidized phospholipids , 2002, Proceedings of the National Academy of Sciences of the United States of America.
[147] L. Weber,et al. Hepatotoxicity and Mechanism of Action of Haloalkanes: Carbon Tetrachloride as a Toxicological Model , 2003, Critical reviews in toxicology.
[148] Wei Liu,et al. 4-hydroxynonenal triggers multistep signal transduction cascades for suppression of cellular functions. , 2003, Molecular aspects of medicine.
[149] T. Montine,et al. Mechanisms of 4-hydroxynonenal-induced neuronal microtubule dysfunction , 2005, Brain Research.
[150] M. Alberghina. Biochemistry of lipids in vascular function. , 2004 .
[151] H. Imai,et al. Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) in mammalian cells. , 2003, Free radical biology & medicine.
[152] J. Oates,et al. Ionophores stimulate prostaglandin and thromboxane biosynthesis. , 1977, Proceedings of the National Academy of Sciences of the United States of America.
[153] T. Osawa,et al. Formation of Nepsilon-(hexanonyl)lysine in protein exposed to lipid hydroperoxide. A plausible marker for lipid hydroperoxide-derived protein modification. , 1999, The Journal of biological chemistry.
[154] H. Sies,et al. Glutathione and its role in cellular functions. , 1999, Free radical biology & medicine.
[155] J. Baynes,et al. Formation of pentosidine during nonenzymatic browning of proteins by glucose. Identification of glucose and other carbohydrates as possible precursors of pentosidine in vivo. , 1991, The Journal of biological chemistry.
[156] V. Calabrese,et al. Vitamin E and Neurodegenerative Disorders Associated with Oxidative Stress , 2002, Nutritional neuroscience.
[157] I. Ifrim,et al. Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response. , 1977, Science.
[158] B. Halliwell,et al. Free radicals in biology and medicine , 1985 .
[159] G. Spiteller,et al. Increase of aldehydic compounds derived from plasmalogens in the brain of aged cattle. , 1996, Chemistry and physics of lipids.
[160] Frank Roels,et al. Peroxisomal Disorders and Regulation of Genes , 2003, Advances in Experimental Medicine and Biology.
[161] Ronald J A Wanders,et al. Functions and biosynthesis of plasmalogens in health and disease. , 2004, Biochimica et biophysica acta.
[162] A. Scanu,et al. Malondialdehyde modification of lipoprotein(a) produces avid uptake by human monocyte-macrophages. , 1992, The Journal of biological chemistry.
[163] T. Vasankari,et al. Baseline diene conjugation in LDL lipids: an indicator of circulating oxidized LDL. , 1999, Free radical biology & medicine.
[164] G. Spiteller,et al. Lipid oxidation products in ischemic porcine heart tissue. , 1996, Chemistry and physics of lipids.
[165] J. Tabet,et al. Identification of 4-hydroxy-2-nonenal-modified peptides within unfractionated digests using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. , 2004, Analytical chemistry.
[166] H. Tohgi,et al. Alterations of 3-nitrotyrosine concentration in the cerebrospinal fluid during aging and in patients with Alzheimer's disease , 1999, Neuroscience Letters.
[167] M. Brown,et al. Regulation of plasma cholesterol by lipoprotein receptors. , 1981, Science.
[168] Mohammad Abdollahi,et al. Pesticides and oxidative stress: a review. , 2004, Medical science monitor : international medical journal of experimental and clinical research.
[169] G. Merényi,et al. Tyrosine Nitration by Simultaneous Generation of ⋅NO and O⨪2 under Physiological Conditions , 2000, The Journal of Biological Chemistry.
[170] F. Ausubel,et al. Programmed cell death in plants: A pathogen-triggered response activated coordinately with multiple defense functions , 1994, Cell.
[171] J. Trojanowski,et al. 12/15-lipoxygenase is increased in Alzheimer's disease: possible involvement in brain oxidative stress. , 2004, The American journal of pathology.
[172] Y. Yamaguchi,et al. Self defensive substances in rice plant against rice blast disease , 1983 .
[173] J. Baynes,et al. Mechanism of autoxidative glycosylation: identification of glyoxal and arabinose as intermediates in the autoxidative modification of proteins by glucose. , 1995, Biochemistry.
[174] S. Avery,et al. Induction of lipid peroxidation during heavy metal stress in Saccharomyces cerevisiae and influence of plasma membrane fatty acid unsaturation , 1997, Applied and environmental microbiology.
[175] R. C. Johnson,et al. Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. , 1995, Proceedings of the National Academy of Sciences of the United States of America.
[176] G. Ulsaker,et al. Gas chromatographic-mass spectrometric identification of four triene monoepoxides of arachidonic acid in human plasma. , 1990, The Analyst.
[177] T. Montine,et al. Suppression of longitudinal increase in CSF F2-isoprostanes in Alzheimer's disease. , 2004, Journal of Alzheimer's disease : JAD.
[178] G. Spiteller. Lipid peroxidation in aging and age-dependent diseases , 2001, Experimental Gerontology.
[179] H. Vlassara. Advanced glycation end-products and atherosclerosis. , 1996, Annals of medicine.
[180] K. Kristensson,et al. Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease , 1991, Lipids.
[181] V. Sridevi,et al. Heat Shock Induced Lipid Changes and Solute Leakage in Germinating Seeds of Pigeonpea , 2002, Biologia Plantarum.
[182] J. Falck,et al. Identification of the 11,14,15- and 11,12,15-Trihydroxyeicosatrienoic Acids as Endothelium-derived Relaxing Factors of Rabbit Aorta* , 1998, The Journal of Biological Chemistry.
[183] J. Arnaud,et al. Lipid peroxides and antioxidant defenses in accelerated transplantation-associated coronary arteriosclerosis. , 1993, American heart journal.
[184] J. Baynes,et al. Identification of N epsilon-carboxymethyllysine as a degradation product of fructoselysine in glycated protein. , 1986, The Journal of biological chemistry.
[185] G. Spiteller,et al. Oxidation of furan fatty acids by soybean lipoxygenase-1 in the presence of linoleic acid. , 1994, Chemistry and physics of lipids.
[186] A. Sidhu,et al. Modulation of D1-like dopamine receptor function by aldehydic products of lipid peroxidation , 2003, Brain Research.
[187] E. Stadtman,et al. Oxidation of methionine residues of proteins: biological consequences. , 2003, Antioxidants & redox signaling.
[188] F. Hayase,et al. Detection and determination of glyceraldehyde‐derived advanced glycation end product , 2004, BioFactors.
[189] Evi Kostenis,et al. A glance at G-protein-coupled receptors for lipid mediators: a growing receptor family with remarkably diverse ligands. , 2004, Pharmacology & therapeutics.
[190] B. Howard,et al. Antioxidant Vitamin Supplements and Cardiovascular Disease , 2004, Circulation.
[191] C. Raetz,et al. Disappearance of plasmalogens from membranes of animal cells subjected to photosensitized oxidation. , 1988, The Journal of biological chemistry.
[192] H. Kühn,et al. The role of lipoxygenase-isoforms in atherogenesis. , 2005, Molecular nutrition & food research.
[193] M. Percival. Human 5-lipoxygenase contains an essential iron. , 1991, The Journal of biological chemistry.
[194] B. Becker,et al. Modeling of risk factors for the degeneration of retinal ganglion cells following ischemia/reperfusion in rats: effects of age, caloric restriction, diabetes, pigmentation, and glaucoma , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.
[195] W. Markesbery,et al. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. , 1991, Proceedings of the National Academy of Sciences of the United States of America.
[196] J. Boyle,et al. Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture. , 2005, Current vascular pharmacology.
[197] M. Cabrini,et al. The insidious effect of diatoms on copepod reproduction , 1999, Nature.
[198] C. Behl,et al. Hydrogen peroxide mediates amyloid β protein toxicity , 1994, Cell.
[199] D. Selkoe,et al. Alzheimer's Disease--Genotypes, Phenotype, and Treatments , 1997, Science.
[200] P. Chang,et al. Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. , 2004, Clinica chimica acta; international journal of clinical chemistry.
[201] S. Horiuchi,et al. Increased production of urea hydrogen peroxide from Maillard reaction and a UHP-Fenton pathway related to glycoxidation damage in chronic renal failure. , 2004, Journal of the American Society of Nephrology : JASN.
[202] M. Glomb,et al. Amides Are Novel Protein Modifications Formed by Physiological Sugars* , 2001, The Journal of Biological Chemistry.
[203] H. Rasmussen,et al. Regulation of cyclic AMP metabolism in the rat erythrocyte during chronicβ-adrenergic stimulation. Evidence for calmodulin-mediated alteration of membrane-bound phosphodiesterase activity , 1981, The Journal of Membrane Biology.
[204] M. Mattson,et al. β-Amyloid Peptide Free Radical Fragments Initiate Synaptosomal Lipoperoxidation in a Sequence-Specific Fashion: Implications to Alzheimer′s Disease , 1994 .
[205] B. Engelmann. Plasmalogens: targets for oxidants and major lipophilic antioxidants. , 2004, Biochemical Society transactions.
[206] A. Jenkins,et al. Pyridoxamine, an Inhibitor of Advanced Glycation Reactions, Also Inhibits Advanced Lipoxidation Reactions , 2000, The Journal of Biological Chemistry.
[207] S. Rapoport,et al. A lipoxygenase in rabbit reticulocytes which attacks phospholipids and intact mitochondria , 1975, FEBS letters.
[208] Mark A. Smith,et al. 4‐Hydroxynonenal‐Derived Advanced Lipid Peroxidation End Products Are Increased in Alzheimer's Disease , 1997, Journal of neurochemistry.
[209] Martin J. Mueller,et al. Formation of isoprostane F(2)-like compounds (phytoprostanes F(1)) from alpha-linolenic acid in plants. , 2000, Free radical biology & medicine.
[210] T. Ozawa,et al. Neutrophil microsomes biosynthesize linoleate epoxide (9,10-epoxy-12-octadecenoate), a biological active substance. , 1988, Biochemical and biophysical research communications.
[211] Spiteller. Oxidation of Linoleic Acid in Low-Density Lipoprotein: An Important Event in Atherogenesis. , 2000, Angewandte Chemie.
[212] C. Bailly,et al. Osmoconditioning reduces physiological and biochemical damage induced by chilling in soybean seeds. , 2001, Physiologia plantarum.
[213] W. Kern,et al. Aldehydic lipid peroxidation products derived from linoleic acid. , 2001, Biochimica et biophysica acta.
[214] L. Lue,et al. Involvement of Microglial Receptor for Advanced Glycation Endproducts (RAGE) in Alzheimer's Disease: Identification of a Cellular Activation Mechanism , 2001, Experimental Neurology.
[215] J. Morrow,et al. Identification of Extremely Reactive γ-Ketoaldehydes (Isolevuglandins) as Products of the Isoprostane Pathway and Characterization of Their Lysyl Protein Adducts* , 1999, The Journal of Biological Chemistry.
[216] B. Ames,et al. Oxidative damage to DNA: relation to species metabolic rate and life span. , 1988, Proceedings of the National Academy of Sciences of the United States of America.
[217] T. Montine,et al. Cerebrospinal fluid F2‐isoprostane levels are increased in Alzheimer's disease , 1998, Annals of neurology.
[218] D. Butterfield,et al. Elevated glutathione as a therapeutic strategy in Alzheimer's disease , 2002 .
[219] E. Stadtman,et al. Michael addition-type 4-hydroxy-2-nonenal adducts in modified low-density lipoproteins: markers for atherosclerosis. , 1994, Biochemistry.
[220] G. Barillari,et al. Nitrotyrosine in peripheral vascular disease , 2003, Journal of thrombosis and haemostasis : JTH.
[221] W. Pryor,et al. Suggested mechanisms for the production of 4-hydroxy-2-nonenal from the autoxidation of polyunsaturated fatty acids. , 1990, Free radical biology & medicine.
[222] J. Valentine,et al. An Alternative Mechanism of Bicarbonate-mediated Peroxidation by Copper-Zinc Superoxide Dismutase , 2003, Journal of Biological Chemistry.
[223] G. Bondjers,et al. Arterial repair and atherosclerosis after mechanical injury , 1971 .
[224] F. Marks,et al. Prostaglandins, leukotrienes, and other eicosanoids : from biogenesis to clinical applications , 1999 .
[225] D. Praticò,et al. Oxidative injury in diseases of the central nervous system: focus on Alzheimer's disease. , 2000, The American journal of medicine.
[226] G. Spiteller,et al. On the cytotoxity of oxidized phytosterols isolated from photoautotrophic cell cultures of Chenopodium rubrum tested on meal-worms Tenebrio molitor , 1998 .
[227] K. Fujimoto,et al. Age-dependent accumulation of phosphatidylcholine hydroperoxide in the brain and liver of the rat , 1993, Lipids.
[228] E. Sigal,et al. Identification of a specific methionine in mammalian 15-lipoxygenase which is oxygenated by the enzyme product 13-HPODE: dissociation of sulfoxide formation from self-inactivation. , 1995, Biochemistry.
[229] V. Preedy,et al. Oxidized products of cholesterol: toxic effects. , 2005 .
[230] H. Ukeda,et al. Spectrophotometric Assay of Superoxide Anion Formed in Maillard Reaction Based on Highly Water-soluble Tetrazolium Salt , 2002, Analytical sciences : the international journal of the Japan Society for Analytical Chemistry.
[231] J. Baynes,et al. Glycoxidation and lipoxidation in atherogenesis. , 2000, Free radical biology & medicine.
[232] S. Clarke. The multi-dimensional regulation of gene expression by fatty acids: polyunsaturated fats as nutrient sensors , 2004, Current opinion in lipidology.
[233] B. Egan,et al. Epoxy-Keto Derivative of Linoleic Acid Stimulates Aldosterone Secretion , 2004, Hypertension.
[234] K. Feingold,et al. Oxidized cholesterol in the diet is a source of oxidized lipoproteins in human serum Published, JLR Papers in Press, February 1, 2003. DOI 10.1194/jlr.M200266-JLR200 , 2003, Journal of Lipid Research.
[235] G. Spiteller,et al. Enzymatic production of hydroperoxides of unsaturated fatty acids by injury of mammalian cells. , 1996, Chemistry and physics of lipids.
[236] Munehiro Yoshida,et al. A simple, rapid, highly sensitive and reproducible quantification method for plasma malondialdehyde by high-performance liquid chromatography. , 1998, Biomedical chromatography : BMC.
[237] S. Orrenius,et al. Different prooxidant levels stimulate growth, trigger apoptosis, or produce necrosis of insulin-secreting RINm5F cells. The role of intracellular polyamines. , 1994, The Journal of biological chemistry.
[238] P. Kovacic. Role of oxidative metabolites of cocaine in toxicity and addiction: oxidative stress and electron transfer. , 2005, Medical hypotheses.
[239] G. Spiteller,et al. Epoxidation — a consequence of cell damage , 1997 .
[240] P. Saikku. Chlamydia pneumoniae and atherosclerosis--an update. , 1997, Scandinavian journal of infectious diseases. Supplementum.
[241] S. Jimi,et al. Appearance of cross linked proteins in human atheroma and rat pre-fibrotic liver detected by a new monoclonal antibody. , 1998, Biochimica et biophysica acta.
[242] I. Feussner,et al. Unprecedented lipoxygenase/hydroperoxide lyase pathways in the moss Physcomitrella patens. , 2004, Angewandte Chemie.
[243] G. Aykaç-toker,et al. An increase in lipoprotein oxidation and endogenous lipid peroxides in serum of obese women , 2003, Clinical and Experimental Medicine.
[244] W. Pryor,et al. Autoxidation of polyunsaturated fatty acids: II. A suggested mechanism for the formation of TBA-reactive materials from prostaglandin-like endoperoxides , 1976, Lipids.
[245] 5-Lipoxygenase as a putative link between cardiovascular and psychiatric disorders. , 2004, Critical reviews in neurobiology.
[246] H. Gardner. Oxygen radical chemistry of polyunsaturated fatty acids. , 1989, Free radical biology & medicine.
[247] P. Libby,et al. Roles of infectious agents in atherosclerosis and restenosis: an assessment of the evidence and need for future research. , 1997, Circulation.
[248] C. Rouzer,et al. Translocation of 5-lipoxygenase to the membrane in human leukocytes challenged with ionophore A23187. , 1988, The Journal of biological chemistry.
[249] Donald E Ingber,et al. Mechanical control of tissue growth: function follows form. , 2005, Proceedings of the National Academy of Sciences of the United States of America.
[250] D. Butterfield,et al. Lipid peroxidation and protein oxidation in Alzheimer's disease brain: Potential causes and consequences involving amyloid β-peptide-associated free radical oxidative stress , 2002 .
[251] J. Baynes,et al. Role of the Maillard Reaction in Aging of Tissue Proteins , 1998, The Journal of Biological Chemistry.
[252] G. Spiteller. Are lipid peroxidation processes induced by changes in the cell wall structure and how are these processes connected with diseases? , 2003, Medical hypotheses.
[253] M. Record,et al. Studies on ether phospholipids. II. Comparative composition of various tissues from human, rat and guinea pig. , 1984, Biochimica et biophysica acta.
[254] S. Arlt,et al. Increased lipoprotein oxidation in Alzheimer's disease. , 2000, Free radical biology & medicine.
[255] P. Edwards,et al. Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages. , 1980, Proceedings of the National Academy of Sciences of the United States of America.
[256] K. Beyreuther,et al. Amyloidogenicity of beta A4 and beta A4-bearing amyloid protein precursor fragments by metal-catalyzed oxidation. , 1992, The Journal of biological chemistry.
[257] D. Silverman,et al. Exchange of 18O in the reaction of peroxynitrite with CO2 , 2005 .
[258] W R Markesbery,et al. Oxidative stress hypothesis in Alzheimer's disease. , 1997, Free radical biology & medicine.
[259] H. Esterbauer,et al. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. , 1991, Free radical biology & medicine.
[260] V. Monnier,et al. Cross‐Linking of the Extracellular Matrix by the Maillard Reaction in Aging and Diabetes: An Update on “a Puzzle Nearing Resolution” , 2005, Annals of the New York Academy of Sciences.
[261] M. Beal. Oxidative Damage in Neurodegenerative Diseases , 1997 .
[262] G. Perry,et al. Advanced Maillard reaction end products are associated with Alzheimer disease pathology. , 1994, Proceedings of the National Academy of Sciences of the United States of America.
[263] U. Diczfalusy. Analysis of cholesterol oxidation products in biological samples. , 2004, Journal of AOAC International.
[264] R. Ross,et al. Atherosclerosis and the Arterial Smooth Muscle Cell , 1973 .
[265] G. Spiteller. The relation of lipid peroxidation processes with atherogenesis: a new theory on atherogenesis. , 2005, Molecular nutrition & food research.
[266] H. Vainio,et al. Styrene oxidation to styrene oxide coupled with arachidonic acid oxidation by soybean lipoxygenase. , 1983, Toxicology letters.
[267] K. Messmer,et al. Early inflammatory response to asbestos exposure in rat and hamster lungs: role of inducible nitric oxide synthase. , 2002, Toxicology and applied pharmacology.
[268] Á. Simonyi,et al. Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases. , 2004, Journal of lipid research.
[269] W. Kern,et al. Synthesis and properties of natural occurring α-hydroxyaldehydes , 1996 .
[270] L. See,et al. Increase of lipid peroxidation by cisplatin in WI38 cells but not in SV40‐transformed WI38 cells , 2003, Journal of biochemical and molecular toxicology.
[271] Y. Hellsten,et al. Formation of hydrogen peroxide and nitric oxide in rat skeletal muscle cells during contractions. , 2003, Free radical biology & medicine.
[272] V. Monnier,et al. Mechanism of Protein Modification by Glyoxal and Glycolaldehyde, Reactive Intermediates of the Maillard Reaction (*) , 1995, The Journal of Biological Chemistry.
[273] J. Beneytout,et al. trans,trans-2,4-decadienal: cytotoxicity and effect on glutathione level in human erythroleukemia (HEL) cells. , 1996, Cancer letters.
[274] Xianlin Han,et al. Plasmalogen deficiency in early Alzheimer's disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry , 2001, Journal of neurochemistry.
[275] E. Blée,et al. Biosynthesis of phytooxylipins: the Peroxygenase pathway , 1998 .
[276] V. Monnier,et al. Mechanism of formation of the Maillard protein cross-link pentosidine. Glucose, fructose, and ascorbate as pentosidine precursors. , 1991, The Journal of biological chemistry.
[277] J. Baynes. Role of Oxidative Stress in Development of Complications in Diabetes , 1991, Diabetes.
[278] I. Kullo,et al. Adenovirus-mediated gene transfer of macrophage colony stimulating factor to the arterial wall in vivo. , 1998, Arteriosclerosis, thrombosis, and vascular biology.
[279] S. Arlt,et al. Use of vitamin C and E in the treatment of Alzheimer's disease , 2002 .
[280] Alexander A Spector,et al. Emergent patterns of growth controlled by multicellular form and mechanics. , 2005, Proceedings of the National Academy of Sciences of the United States of America.
[281] M. Zagorski,et al. Solvent-induced fragmentation of prostaglandin endoperoxides. New aldehyde products from PGH2 and a novel intramolecular 1,2-hydride shift during endoperoxide fragmentation in aqueous solution , 1984 .
[282] P. Touboul,et al. Statins in Stroke Prevention and Carotid Atherosclerosis: Systematic Review and Up-to-Date Meta-Analysis , 2004, Stroke.
[283] M. Lebl,et al. Peptides: The Wave of the Future , 2001, American Peptide Symposia.
[284] B. Wolozin,et al. The cellular biochemistry of cholesterol and statins: insights into the pathophysiology and therapy of Alzheimer's disease. , 2006, CNS drug reviews.
[285] E. Wills. Mechanisms of lipid peroxide formation in animal tissues. , 1966, The Biochemical journal.
[286] A. Nègre-Salvayre,et al. Impairment of the cytotoxic and oxidative activities of 7 beta-hydroxycholesterol and 7-ketocholesterol by esterification with oleate. , 2003, Biochemical and biophysical research communications.
[287] J. Bohl,et al. Immunohistochemical investigation of the brain of aged dogs. I. Detection of neurofibrillary tangles and of 4-hydroxynonenal protein, an oxidative damage product, in senile plaques , 2001, Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis.
[288] S. Hazen,et al. Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy. , 2003, JAMA.
[289] D. Bernlohr,et al. Covalent Modification of Epithelial Fatty Acid-binding Protein by 4-Hydroxynonenal in Vitro and in Vivo , 2002, The Journal of Biological Chemistry.
[290] A. Benedetti,et al. Cytotoxic aldehydes originating from the peroxidation of liver microsomal lipids. Identification of 4,5-dihydroxydecenal. , 1984, Biochimica et biophysica acta.
[291] J. Baynes,et al. Pathways of formation of glycoxidation products during glycation of collagen. , 1995, Biochemistry.
[292] G. Holmquist,et al. Mapping of peroxyl radical induced damage on genomic DNA. , 1999, Biochemistry.
[293] N. Porter. Mechanisms for the autoxidation of polyunsaturated lipids , 1986 .
[294] P. Reaven,et al. Induction of monocyte differentiation and foam cell formation in vitro by 7-ketocholesterol. , 2002, Journal of lipid research.
[295] A. Mally,et al. Glutathione conjugates of 4-hydroxy-2(E)-nonenal as biomarkers of hepatic oxidative stress-induced lipid peroxidation in rats. , 2005, Free radical biology & medicine.
[296] A. Loidl-Stahlhofen,et al. α-Hydroxyaldehydes, products of lipid peroxidation , 1994 .
[297] P. Lantos,et al. Decrease and structural modifications of phosphatidylethanolamine plasmalogen in the brain with Alzheimer disease. , 1999, Journal of neuropathology and experimental neurology.
[298] J. Cravedi,et al. Fate of 4-hydroxynonenal in vivo: disposition and metabolic pathways. , 2003, Molecular aspects of medicine.
[299] W. Frishman,et al. Pathophysiology and pharmacological approaches for prevention of coronary artery restenosis following coronary artery balloon angioplasty and related procedures. , 1997, Progress in cardiovascular diseases.
[300] I. Rahman. Smoking-Induced Inflammation, Injury and Disease: Molecular Mechanisms , 2004 .
[301] P. Riederer,et al. Dramatic increase of α-hydroxyaldehydes derived from plasmalogens in the aged human brain , 1997 .
[302] D. Grant,et al. Defining mechanisms of toxicity for linoleic acid monoepoxides and diols in Sf-21 cells. , 2001, Chemical research in toxicology.
[303] J. Joseph,et al. Nitration of γ-tocopherol and oxidation of α-tocopherol by copper-zinc superoxide dismutase/H2O2/NO2−: Role of nitrogen dioxide free radical , 1998 .
[304] V. A. Folcik,et al. Lipoxygenase contributes to the oxidation of lipids in human atherosclerotic plaques. , 1995, The Journal of clinical investigation.