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Samar M. Hammad

Title
InstitutionMedical University of South Carolina
DepartmentRegenerative Medicine and Cell Biology
AddressP.O. Box MSC 508
BSB 645
Basic Science Building - 173 Ashley Ave.
Phone843-876-5200
Fax843-792-0664
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    The Hammad laboratory is interested primarily in lipoprotein-related research. Recently, our focus has been on investigating the sphingolipid signaling mechanisms which mediate the survival of foam cells (lipid laden macrophages) and their sustained cell activation in response to modified lipoproteins and lipoprotein-immune complexes. The transformation of macrophages into foam cel ls is a critical event in the development of atherosclerosis and defining mechanisms mediating foam cell formation and determining the role of foam cells in the pathology of atherosclerosis is an area of great clinical relevance. Our goal is to uncover targets in the signaling pathway such as receptors and/or sphingolipids that can have therapeutic implications for blocking cytokine release and prevention of vulnerable atherosclerotic plaques. Macrophages internalize oxidized LDL immune complexes (oxLDL-IC) via the Fc-y receptor and transform into activated foam cells. Our data demonstrated that exposure of human monocytic cells to oxLDL-IC leads to increased cell survival compared to oxLDL alone. We examined the effect of oxLDL-IC on sphingosine kinase 1 (SK1), an enzyme implicated in mediating pro-survival and inflammatory responses through the generation of the signaling molecule sphingosine-1-phosphate (S1P). Intriguingly, oxLDL-IC, but not oxLDL alone, induced an immediate translocation and release of SK1 into the conditioned medium. This finding indicates that S1P may be generated extracellularly in response to modified LDL immune complexes and may therefore promote cell survival and prolong cytokine release by activated macrophages. Our goal is to uncover mechanisms by which oxLDL-IC suppress apoptosis of foam cells, and reveal specific targets in the signaling pathway that can have therapeutic implications for blocking cytokine release and to prevent formation of vulnerable plaques.

    Another area of interest is the role of modified lipoproteins in diabetic vascular complications including nephropathy. We have investigated the effects of hypercholesterolemia on the development of diabetic complications in a genetically modified hypercholesterolemic mouse made diab etic with streptozotocin. The mouse is a double knockout for the LDL receptor and the editing of the apoB mRNA (LDLr-/- Apobec -/-). In this animal model, we found that the combination of hypercholes terolemia and diabetes resulted in a significant lipid accumulation in the tubular basement membrane, which could have contributed to the albuminuria. We also published the first report on the mouse lipoprotein subclass profile using Nuclear Magnetic Resonance (NMR).

    Another area of research, with which I am involved and collaborating with Dr. W.S. Argraves in the department, is the function of the newly discovered HDL receptor, Cubilin, in mediating uptake, degradation and transcytosis/exocytosis of HDL. Cubilin is expressed in the renal proximal tubule, intestine, and yolk sac endoderm. Our goal is to determine the physiological significance of cubilin-mediated renal uptake of filterable forms of HDL to HDL homeostasis. A decreased level of plasma HDL is a major risk factor for coronary atherosclerosis.


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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Kelly CB, Yu JY, Jenkins AJ, Nankervis AJ, Hanssen KF, Garg SK, Scardo JA, Basu A, Hammad SM, Aston CE, Lyons TJ. Haptoglobin phenotype modulates lipoprotein-associated risk for preeclampsia in women with Type 1 diabetes. J Clin Endocrinol Metab. 2019 Jun 20. PMID: 31219590.
      View in: PubMed
    2. Buie JNJ, Hammad SM, Nietert PJ, Magwood G, Adams RJ, Bonilha L, Sims-Robinson C. Differences in plasma levels of long chain and very long chain ceramides between African Americans and whites: An observational study. PLoS One. 2019; 14(5):e0216213. PMID: 31067249.
      View in: PubMed
    3. Lopes-Virella MF, Baker NL, Hunt KJ, Hammad SM, Arthur J, Virella G, Klein RL. Glycosylated sphingolipids and progression to kidney dysfunction in type 1 diabetes. J Clin Lipidol. 2019 May - Jun; 13(3):481-491.e1. PMID: 31043336.
      View in: PubMed
    4. Park KH, Ye ZW, Zhang J, Hammad SM, Townsend DM, Rockey DC, Kim SH. 3-ketodihydrosphingosine reductase mutation induces steatosis and hepatic injury in zebrafish. Sci Rep. 2019 Feb 04; 9(1):1138. PMID: 30718751.
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    5. Iqbal J, Walsh MT, Hammad SM, Cuchel M, Rader DJ, Hussain MM. ATP binding cassette family A protein 1 determines hexosylceramide and sphingomyelin levels in human and mouse plasma. J Lipid Res. 2018 11; 59(11):2084-2097. PMID: 30279221.
      View in: PubMed
    6. Kelly CB, Hookham MB, Yu JY, Jenkins AJ, Nankervis AJ, Hanssen KF, Garg SK, Scardo JA, Hammad SM, Menard MK, Aston CE, Lyons TJ. Response to Comment on Kelly et al. Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes. Diabetes Care 2018;41:120-127. Diabetes Care. 2018 06; 41(6):e102-e103. PMID: 29784706.
      View in: PubMed
    7. Kelly CB, Hookham MB, Yu JY, Jenkins AJ, Nankervis AJ, Hanssen KF, Garg SK, Scardo JA, Hammad SM, Menard MK, Aston CE, Lyons TJ. Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes. Diabetes Care. 2018 01; 41(1):120-127. PMID: 29122892.
      View in: PubMed
    8. Kelly CB, Hookham MB, Yu JY, Lockhart SM, Du M, Jenkins AJ, Nankervis A, Hanssen KF, Henriksen T, Garg SK, Hammad SM, Scardo JA, Aston CE, Patterson CC, Lyons TJ. Circulating adipokines are associated with pre-eclampsia in women with type 1 diabetes. Diabetologia. 2017 12; 60(12):2514-2524. PMID: 28875223.
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    9. Virella G, Wilson K, Elkes J, Hammad SM, Rajab HA, Li Y, Chassereau C, Huang Y, Lopes-Virella M. Immune complexes containing malondialdehyde (MDA) LDL induce apoptosis in human macrophages. Clin Immunol. 2018 02; 187:1-9. PMID: 28689783.
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    10. Iqbal J, Walsh MT, Hammad SM, Hussain MM. Sphingolipids and Lipoproteins in Health and Metabolic Disorders. Trends Endocrinol Metab. 2017 07; 28(7):506-518. PMID: 28462811.
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    11. Lee MH, Appleton KM, El-Shewy HM, Sorci-Thomas MG, Thomas MJ, Lopes-Virella MF, Luttrell LM, Hammad SM, Klein RL. S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization. J Lipid Res. 2017 02; 58(2):325-338. PMID: 27881715.
      View in: PubMed
    12. Fu D, Yu JY, Yang S, Wu M, Hammad SM, Connell AR, Du M, Chen J, Lyons TJ. Survival or death: a dual role for autophagy in stress-induced pericyte loss in diabetic retinopathy. Diabetologia. 2016 10; 59(10):2251-61. PMID: 27475954.
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    13. Hammad SM, Baker NL, El Abiad JM, Spassieva SD, Pierce JS, Rembiesa B, Bielawski J, Lopes-Virella MF, Klein RL. Increased Plasma Levels of Select Deoxy-ceramide and Ceramide Species are Associated with Increased Odds of Diabetic Neuropathy in Type 1 Diabetes: A Pilot Study. Neuromolecular Med. 2017 Mar; 19(1):46-56. PMID: 27388466.
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    14. Iqbal J, Walsh MT, Hammad SM, Cuchel M, Tarugi P, Hegele RA, Davidson NO, Rader DJ, Klein RL, Hussain MM. Microsomal Triglyceride Transfer Protein Transfers and Determines Plasma Concentrations of Ceramide and Sphingomyelin but Not Glycosylceramide. J Biol Chem. 2015 Oct 23; 290(43):25863-75. PMID: 26350457.
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    15. Basu A, Yu JY, Jenkins AJ, Nankervis AJ, Hanssen KF, Henriksen T, Lorentzen B, Garg SK, Menard MK, Hammad SM, Scardo JA, Aston CE, Lyons TJ. Trace elements as predictors of preeclampsia in type 1 diabetic pregnancy. Nutr Res. 2015 May; 35(5):421-30. PMID: 25912764.
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    16. Twal WO, Hammad SM, Guffy SL, Argraves WS. A novel intracellular fibulin-1D variant binds to the cytoplasmic domain of integrin beta 1 subunit. Matrix Biol. 2015 Apr; 43:97-108. PMID: 25661773.
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    17. Al Gadban MM, Alwan MM, Smith KJ, Hammad SM. Accelerated vascular disease in systemic lupus erythematosus: role of macrophage. Clin Immunol. 2015 Apr; 157(2):133-44. PMID: 25638414.
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    18. Shrader S, Mauldin M, Hammad S, Mitcham M, Blue A. Developing a comprehensive faculty development program to promote interprofessional education, practice and research at a free-standing academic health science center. J Interprof Care. 2015 Mar; 29(2):165-7. PMID: 25051084.
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    19. Klein RL, Hammad SM, Baker NL, Hunt KJ, Al Gadban MM, Cleary PA, Virella G, Lopes-Virella MF. Decreased plasma levels of select very long chain ceramide species are associated with the development of nephropathy in type 1 diabetes. Metabolism. 2014 Oct; 63(10):1287-95. PMID: 25088746.
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    20. Du M, Basu A, Fu D, Wu M, Centola M, Jenkins AJ, Hanssen KF, Garg SK, Hammad SM, Scardo JA, Aston CE, Lyons TJ. Serum inflammatory markers and preeclampsia in type 1 diabetes: a prospective study. Diabetes Care. 2013 Jul; 36(7):2054-61. PMID: 23393212.
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    21. Hammad SM, Al Gadban MM, Semler AJ, Klein RL. Sphingosine 1-phosphate distribution in human plasma: associations with lipid profiles. J Lipids. 2012; 2012:180705. PMID: 23209911.
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    22. Fu D, Wu M, Zhang J, Du M, Yang S, Hammad SM, Wilson K, Chen J, Lyons TJ. Mechanisms of modified LDL-induced pericyte loss and retinal injury in diabetic retinopathy. Diabetologia. 2012 Nov; 55(11):3128-40. PMID: 22935961.
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    23. Yu Y, Hanssen KF, Kalyanaraman V, Chirindel A, Jenkins AJ, Nankervis AJ, Torjesen PA, Scholz H, Henriksen T, Lorentzen B, Garg SK, Menard MK, Hammad SM, Scardo JA, Stanley JR, Wu M, Basu A, Aston CE, Lyons TJ. Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes. BJOG. 2012 Nov; 119(12):1512-20. PMID: 22900949.
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    24. Truman JP, Al Gadban MM, Smith KJ, Jenkins RW, Mayroo N, Virella G, Lopes-Virella MF, Bielawska A, Hannun YA, Hammad SM. Differential regulation of acid sphingomyelinase in macrophages stimulated with oxidized low-density lipoprotein (LDL) and oxidized LDL immune complexes: role in phagocytosis and cytokine release. Immunology. 2012 May; 136(1):30-45. PMID: 22236141.
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    25. Al Gadban MM, German J, Truman JP, Soodavar F, Riemer EC, Twal WO, Smith KJ, Heller D, Hofbauer AF, Oates JC, Hammad SM. Lack of nitric oxide synthases increases lipoprotein immune complex deposition in the aorta and elevates plasma sphingolipid levels in lupus. Cell Immunol. 2012 Mar-Apr; 276(1-2):42-51. PMID: 22560558.
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    26. Hammad SM, Truman JP, Al Gadban MM, Smith KJ, Twal WO, Hamner MB. ALTERED BLOOD SPHINGOLIPIDOMICS AND ELEVATED PLASMA INFLAMMATORY CYTOKINES IN COMBAT VETERANS WITH POST-TRAUMATIC STRESS DISORDER. Neurobiol Lipids. 2012 Mar 22; 10:2. PMID: 24403911.
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    27. Basu A, Alaupovic P, Wu M, Jenkins AJ, Yu Y, Nankervis AJ, Hanssen KF, Scholz H, Henriksen T, Lorentzen B, Clausen T, Garg SK, Menard MK, Hammad SM, Scardo JA, Stanley JR, Dashti A, Aston CE, Lyons TJ. Plasma lipoproteins and preeclampsia in women with type 1 diabetes: a prospective study. J Clin Endocrinol Metab. 2012 May; 97(5):1752-62. PMID: 22438226.
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    28. El-Shewy HM, Sohn M, Wilson P, Lee MH, Hammad SM, Luttrell LM, Jaffa AA. Low-density lipoprotein induced expression of connective tissue growth factor via transactivation of sphingosine 1-phosphate receptors in mesangial cells. Mol Endocrinol. 2012 May; 26(5):833-45. PMID: 22422617.
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    29. Truman JP, Al Gadban MM, Smith KJ, Hammad SM. Acid sphingomyelinase in macrophage biology. Cell Mol Life Sci. 2011 Oct; 68(20):3293-305. PMID: 21533981.
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    30. Azar M, Basu A, Jenkins AJ, Nankervis AJ, Hanssen KF, Scholz H, Henriksen T, Garg SK, Hammad SM, Scardo JA, Aston CE, Lyons TJ. Serum carotenoids and fat-soluble vitamins in women with type 1 diabetes and preeclampsia: a longitudinal study. Diabetes Care. 2011 Jun; 34(6):1258-64. PMID: 21498785.
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    31. Hammad SM. Blood sphingolipids in homeostasis and pathobiology. Adv Exp Med Biol. 2011; 721:57-66. PMID: 21910082.
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    32. Al Gadban MM, Smith KJ, Soodavar F, Piansay C, Chassereau C, Twal WO, Klein RL, Virella G, Lopes-Virella MF, Hammad SM. Differential trafficking of oxidized LDL and oxidized LDL immune complexes in macrophages: impact on oxidative stress. PLoS One. 2010 Sep 02; 5(9). PMID: 20824093.
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    33. Hammad SM, Pierce JS, Soodavar F, Smith KJ, Al Gadban MM, Rembiesa B, Klein RL, Hannun YA, Bielawski J, Bielawska A. Blood sphingolipidomics in healthy humans: impact of sample collection methodology. J Lipid Res. 2010 Oct; 51(10):3074-87. PMID: 20660127.
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    34. Lee MH, Hammad SM, Semler AJ, Luttrell LM, Lopes-Virella MF, Klein RL. HDL3, but not HDL2, stimulates plasminogen activator inhibitor-1 release from adipocytes: the role of sphingosine-1-phosphate. J Lipid Res. 2010 Sep; 51(9):2619-28. PMID: 20522601.
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    35. Smith KJ, Twal WO, Soodavar F, Virella G, Lopes-Virella MF, Hammad SM. Heat shock protein 70B' (HSP70B') expression and release in response to human oxidized low density lipoprotein immune complexes in macrophages. J Biol Chem. 2010 May 21; 285(21):15985-93. PMID: 20348092.
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    36. Diffley JM, Wu M, Sohn M, Song W, Hammad SM, Lyons TJ. Apoptosis induction by oxidized glycated LDL in human retinal capillary pericytes is independent of activation of MAPK signaling pathways. Mol Vis. 2009; 15:135-45. PMID: 19158958.
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    37. Yu Y, Jenkins AJ, Nankervis AJ, Hanssen KF, Scholz H, Henriksen T, Lorentzen B, Clausen T, Garg SK, Menard MK, Hammad SM, Scardo JC, Stanley JR, Dashti A, May K, Lu K, Aston CE, Wang JJ, Zhang SX, Ma JX, Lyons TJ. Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women. Diabetologia. 2009 Jan; 52(1):160-8. PMID: 18985316.
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    38. Argraves KM, Gazzolo PJ, Groh EM, Wilkerson BA, Matsuura BS, Twal WO, Hammad SM, Argraves WS. High density lipoprotein-associated sphingosine 1-phosphate promotes endothelial barrier function. J Biol Chem. 2008 Sep 05; 283(36):25074-81. PMID: 18606817.
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    39. Hammad SM, Twal WO, Barth JL, Smith KJ, Saad AF, Virella G, Argraves WS, Lopes-Virella MF. Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells. Atherosclerosis. 2009 Feb; 202(2):394-404. PMID: 18597759.
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    40. Twiner MJ, Ryan JC, Morey JS, Smith KJ, Hammad SM, Van Dolah FM, Hess P, McMahon T, Satake M, Yasumoto T, Doucette GJ. Transcriptional profiling and inhibition of cholesterol biosynthesis in human T lymphocyte cells by the marine toxin azaspiracid. Genomics. 2008 Mar; 91(3):289-300. PMID: 18191373.
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    41. Hammad SM, Crellin HG, Wu BX, Melton J, Anelli V, Obeid LM. Dual and distinct roles for sphingosine kinase 1 and sphingosine 1 phosphate in the response to inflammatory stimuli in RAW macrophages. Prostaglandins Other Lipid Mediat. 2008 Mar; 85(3-4):107-14. PMID: 18166496.
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    42. Hammad SM, Taha TA, Nareika A, Johnson KR, Lopes-Virella MF, Obeid LM. Oxidized LDL immune complexes induce release of sphingosine kinase in human U937 monocytic cells. Prostaglandins Other Lipid Mediat. 2006 Mar; 79(1-2):126-40. PMID: 16516816.
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    43. Hammad SM, Powell-Braxton L, Otvos JD, Eldridge L, Won W, Lyons TJ. Lipoprotein subclass profiles of hyperlipidemic diabetic mice measured by nuclear magnetic resonance spectroscopy. Metabolism. 2003 Jul; 52(7):916-21. PMID: 12870170.
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    44. Hammad SM, Hazen-Martin DJ, Sohn M, Eldridge L, Powell-Braxton L, Won W, Lyons TJ. Nephropathy in a hypercholesterolemic mouse model with streptozotocin-induced diabetes. Kidney Blood Press Res. 2003; 26(5-6):351-61. PMID: 14610340.
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    45. Hammad SM, Barth JL, Knaak C, Argraves WS. Megalin acts in concert with cubilin to mediate endocytosis of high density lipoproteins. J Biol Chem. 2000 Apr 21; 275(16):12003-8. PMID: 10766831.
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    46. Hammad SM, Stefansson S, Twal WO, Drake CJ, Fleming P, Remaley A, Brewer HB, Argraves WS. Cubilin, the endocytic receptor for intrinsic factor-vitamin B(12) complex, mediates high-density lipoprotein holoparticle endocytosis. Proc Natl Acad Sci U S A. 1999 Aug 31; 96(18):10158-63. PMID: 10468579.
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    47. Hammad SM, Siegel HS, Marks HL. Total cholesterol, total triglycerides, and cholesterol distribution among lipoproteins as predictors of atherosclerosis in selected lines of Japanese quail. Comp Biochem Physiol A Mol Integr Physiol. 1998 Feb; 119(2):485-92. PMID: 11248992.
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    48. Hammad SM, Ranganathan S, Loukinova E, Twal WO, Argraves WS. Interaction of apolipoprotein J-amyloid beta-peptide complex with low density lipoprotein receptor-related protein-2/megalin. A mechanism to prevent pathological accumulation of amyloid beta-peptide. J Biol Chem. 1997 Jul 25; 272(30):18644-9. PMID: 9228033.
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    49. Hammad SM, Siegel HS, Marks HL. Dietary cholesterol metabolism in Japanese quail lines selected for plasma cholesterol levels. Proc Soc Exp Biol Med. 1997 Jan; 214(1):62-8. PMID: 9012362.
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    50. Hammad SM, Siegel HS, Marks HL. Dietary cholesterol effects on plasma and yolk cholesterol fractions in selected lines of Japanese quail. Poult Sci. 1996 Jul; 75(7):933-42. PMID: 8966183.
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    51. Siegel HS, Hammad SM, Marks HL. Atherosclerosis in Japanese Quail males selected for high or low plasma cholesterol. Poult Sci. 1995 Oct; 74(10):1712-6. PMID: 8559737.
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    52. Siegel HS, Hammad SM, Leach RM, Barbato GF, Green MH, Marks HL. Dietary cholesterol and fat saturation effects on plasma esterified and unesterified cholesterol in selected lines of Japanese quail females. Poult Sci. 1995 Aug; 74(8):1370-80. PMID: 7479517.
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    53. Hammad S.; Siegel H.S.; Marks H.L.; Barbato G.F. . A fast HPLC analysis of cholesterol and cholesteryl esters in avian plasma. Journal of Liquid Chromatography. 1992; 15(11):2005-2014.
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