Cheryl L. Laffer, Ph.D., M.D.

Professor

cheryl.l.laffer@vanderbilt.edu
Faculty Appointments
Professor of Medicine
Education
M.D., Medicine, University of Miami, Miller School of Medicine, Miami, FloridaPh.D., Genetics, University of Wisconsin, Madison, WisconsinB.S., California Institute of Technology, Pasadena, California
Office Address
Division of Clinical Pharmacology
536 RRB
2200 Pierce Ave
Nashville, TN 37232-6602
Research Keywords
salt sensitivity of blood pressure eicosanoids
Publications
Saleem M, Rahman S, Elijovich F, Laffer CL, Ertuglu LA, Masenga SK, Kirabo A. Sox6, A Potential Target for MicroRNAs in Cardiometabolic Disease. Curr Hypertens Rep [print-electronic]. 2022 Feb 2/5/2022; PMID: 35124768, PII: 10.1007/s11906-022-01175-8, DOI: 10.1007/s11906-022-01175-8, ISSN: 1534-3111.

Laffer CL, Elijovich F. Is clonidine contraindicated for the treatment of hypertensive urgencies in hospitalized patients? [editorial]. Am J Hypertens [print-electronic]. 2022 Feb 2/4/2022; PMID: 35134819, PII: 6522825, DOI: 10.1093/ajh/hpac015, ISSN: 1941-7225.

Sahinoz M, Elijovich F, Ertuglu LA, Ishimwe J, Pitzer A, Saleem M, Mwesigwa N, Kleyman TR, Laffer CL, Kirabo A. Salt Sensitivity of Blood Pressure in Blacks and Women: A Role of Inflammation, Oxidative Stress, and Epithelial Na+ Channel. Antioxid Redox Signal. 2021 Dec 12/20/2021; 35(18): 1477-93. PMID: 34569287, PMCID: PMC8713266, DOI: 10.1089/ars.2021.0212, ISSN: 1557-7716.

Elijovich F, Kleyman TR, Laffer CL, Kirabo A. Immune Mechanisms of Dietary Salt-Induced Hypertension and Kidney Disease: Harry Goldblatt Award for Early Career Investigators 2020. Hypertension [print-electronic]. 2021 Aug; 78(2): 252-60. PMID: 34232678, PMCID: PMC8437138, DOI: 10.1161/HYPERTENSIONAHA.121.16495, ISSN: 1524-4563.

Elijovich F, Laffer CL. Why is salt-sensitivity of blood pressure, a known cardiovascular risk factor, not treated?. Int J Cardiol Hypertens. 2021 Jun; 9: 100096. PMID: 34159311, PMCID: PMC8193348, PII: S2590-0862(21)00015-X, DOI: 10.1016/j.ijchy.2021.100096, ISSN: 2590-0862.

Ruggeri Barbaro N, Van Beusecum J, Xiao L, do Carmo L, Pitzer A, Loperena R, Foss JD, Elijovich F, Laffer CL, Montaniel KR, Galindo CL, Chen W, Ao M, Mernaugh RL, Alsouqi A, Ikizler TA, Fogo AB, Moreno H, Zhao S, Davies SS, Harrison DG, Kirabo A. Sodium activates human monocytes via the NADPH oxidase and isolevuglandin formation. Cardiovasc Res. 2021 Apr 4/23/2021; 117(5): 1358-71. PMID: 33038226, PMCID: PMC8064439, PII: 5872525, DOI: 10.1093/cvr/cvaa207, ISSN: 1755-3245.

Madhur MS, Elijovich F, Alexander MR, Pitzer A, Ishimwe J, Van Beusecum JP, Patrick DM, Smart CD, Kleyman TR, Kingery J, Peck RN, Laffer CL, Kirabo A. Hypertension: Do Inflammation and Immunity Hold the Key to Solving this Epidemic?. Circ Res [print-electronic]. 2021 Apr 4/2/2021; 128(7): 908-33. PMID: 33793336, PMCID: PMC8023750, DOI: 10.1161/CIRCRESAHA.121.318052, ISSN: 1524-4571.

Ertuglu LA, Elijovich F, Laffer CL, Kirabo A. Salt-Sensitivity of Blood Pressure and Insulin Resistance. Front Physiol. 2021; 12: 793924. PMID: 34966295, PMCID: PMC8711096, DOI: 10.3389/fphys.2021.793924, ISSN: 1664-042X.

Elijovich F, Kirabo A, Laffer CL. Hypothesis: Unrecognized actions of ENaC blockade in improving refractory-resistant hypertension and residual cardiovascular risk. Int J Cardiol Hypertens. 2020 Dec; 7: 100048. PMID: 33447773, PMCID: PMC7803029, PII: S2590-0862(20)30025-2, DOI: 10.1016/j.ijchy.2020.100048, ISSN: 2590-0862.

Masenga SK, Elijovich F, Koethe JR, Hamooya BM, Heimburger DC, Munsaka SM, Laffer CL, Kirabo A. Hypertension and Metabolic Syndrome in Persons with HIV. Curr Hypertens Rep. 2020 Sep 9/3/2020; 22(10): 78. PMID: 32880756, PMCID: PMC7467859, PII: 10.1007/s11906-020-01089-3, DOI: 10.1007/s11906-020-01089-3, ISSN: 1534-3111.

Elijovich F, Laffer CL, Sahinoz M, Pitzer A, Ferguson JF, Kirabo A. The Gut Microbiome, Inflammation, and Salt-Sensitive Hypertension. Curr Hypertens Rep. 2020 Sep 9/3/2020; 22(10): 79. PMID: 32880753, PMCID: PMC7471100, PII: 10.1007/s11906-020-01091-9, DOI: 10.1007/s11906-020-01091-9, ISSN: 1534-3111.

Elijovich F, Laffer CL. What Kind of Evidence Is Needed to Dictate Practice Regarding Inhibitors of the Renin-Angiotensin System in COVID-19? [editorial]. Hypertension [print-electronic]. 2020 Sep; 76(3): 665-9. PMID: 32783759, DOI: 10.1161/HYPERTENSIONAHA.120.15712, ISSN: 1524-4563.

Laffer CL, Elijovich F, Sahinoz M, Pitzer A, Kirabo A. New Insights Into the Renin-Angiotensin System in Chronic Kidney Disease [editorial]. Circ Res [print-electronic]. 2020 Aug 8/14/2020; 127(5): 607-9. PMID: 32790525, PMCID: PMC7430039, DOI: 10.1161/CIRCRESAHA.120.317624, ISSN: 1524-4571.

Elijovich F, Laffer CL. Measurement of sodium intake or measurement of the detrimental effects of sodium on health in individual subjects? [letter]. J Clin Hypertens (Greenwich) [print-electronic]. 2020 Feb; 22(2): 303. PMID: 31913540, PMCID: PMC8030029, DOI: 10.1111/jch.13786, ISSN: 1751-7176.

Biaggioni I, Shibao CA, Diedrich A, Muldowney JAS, Laffer CL, Jordan J. Blood Pressure Management in Afferent Baroreflex Failure: JACC Review Topic of the Week. J Am Coll Cardiol. 2019 Dec 12/10/2019; 74(23): 2939-47. PMID: 31806138, PMCID: PMC6939863, PII: S0735-1097(19)38169-0, DOI: 10.1016/j.jacc.2019.10.027, ISSN: 1558-3597.

Alexander MR, Norlander AE, Elijovich F, Atreya RV, Gaye A, Gnecco JS, Laffer CL, Galindo CL, Madhur MS. Human monocyte transcriptional profiling identifies IL-18 receptor accessory protein and lactoferrin as novel immune targets in hypertension. Br J Pharmacol [print-electronic]. 2019 Jun; 176(12): 2015-27. PMID: 29774543, PMCID: PMC6534784, DOI: 10.1111/bph.14364, ISSN: 1476-5381.

Elijovich F, Laffer CL. Urinary sodium excretion measures and health outcomes [letter]. Lancet. 2019 Mar 3/30/2019; 393(10178): 1295. PMID: 30938311, PII: S0140-6736(19)30695-6, DOI: 10.1016/S0140-6736(19)30695-6, ISSN: 1474-547X.

Loperena R, Van Beusecum JP, Itani HA, Engel N, Laroumanie F, Xiao L, Elijovich F, Laffer CL, Gnecco JS, Noonan J, Maffia P, Jasiewicz-Honkisz B, Czesnikiewicz-Guzik M, Mikolajczyk T, Sliwa T, Dikalov S, Weyand CM, Guzik TJ, Harrison DG. Hypertension and increased endothelial mechanical stretch promote monocyte differentiation and activation: roles of STAT3, interleukin 6 and hydrogen peroxide. Cardiovasc Res. 2018 Sep 9/1/2018; 114(11): 1547-63. PMID: 29800237, PMCID: PMC6106108, PII: 5001804, DOI: 10.1093/cvr/cvy112, ISSN: 1755-3245.

Bursztyn M, Touyz RM, Laffer CL, Carey RM, Dominiczak AF. Case of Severe Hypertension and Nephrotic Range Proteinuria. Hypertension [print-electronic]. 2018 Jun; 71(6): 956-61. PMID: 29610267, PII: HYPERTENSIONAHA.118.11045, DOI: 10.1161/HYPERTENSIONAHA.118.11045, ISSN: 1524-4563.

Laffer CL, Elijovich F. Mechanisms of salt sensitivity of blood pressure: an unbiased approach to skinning a cat. J Hypertens. 2018 Mar; 36(3): 702-3. PMID: 29384990, PII: 00004872-201803000-00034, DOI: 10.1097/HJH.0000000000001636, ISSN: 1473-5598.

Elijovich F, Milne GL, Brown NJ, Laniado-Schwartzman M, Laffer CL. Two Pools of Epoxyeicosatrienoic Acids in Humans: Alterations in Salt-Sensitive Normotensive Subjects. Hypertension [print-electronic]. 2018 Feb; 71(2): 346-55. PMID: 29279315, PMCID: PMC5764817, PII: HYPERTENSIONAHA.117.10392, DOI: 10.1161/HYPERTENSIONAHA.117.10392, ISSN: 1524-4563.

Elijovich F, Laffer CL. Discontinuation of Therapy in Hypertension Research: Value, Ethics, Risk, and Role in Renal Denervation Trials [editorial]. Hypertension [print-electronic]. 2017 May; 69(5): 795-7. PMID: 28373585, PII: HYPERTENSIONAHA.117.08884, DOI: 10.1161/HYPERTENSIONAHA.117.08884, ISSN: 1524-4563.

Miller-Hodges E, Dominiczak AF, Jennings GL, Oparil S, Batlle DC, Elijovich F, Basile JN, Laffer CL, Oliveras A, Dhaun N. Hypertension and Its Complications in a Young Man With Autoimmune Disease. Hypertension [print-electronic]. 2017 Apr; 69(4): 536-44. PMID: 28242716, PII: HYPERTENSIONAHA.117.09036, DOI: 10.1161/HYPERTENSIONAHA.117.09036, ISSN: 1524-4563.

Elijovich Fernando, Weinberger Myron H, Anderson Cheryl AM, Appel Lawrence J, Bursztyn Michael, Cook Nancy R, Dart Richard A, Newton-Cheh Christopher H, Sacks Frank M, Laffer Cheryl L. Salt sensitivity of blood pressure: a scientific statement from the American Heart Association. Hypertension. 2016 Sep 9/1/2016; 68(3): e7-e46. DOI: 10.1161/HYP.0000000000000047.

Laffer CL, Scott RC, Titze JM, Luft FC, Elijovich F. Hemodynamics and Salt-and-Water Balance Link Sodium Storage and Vascular Dysfunction in Salt-Sensitive Subjects. Hypertension [print-electronic]. 2016 Jul; 68(1): 195-203. PMID: 27160204, PMCID: PMC4900938, PII: HYPERTENSIONAHA.116.07289, DOI: 10.1161/HYPERTENSIONAHA.116.07289, ISSN: 1524-4563.

Fudim M, Groom KL, Laffer CL, Netterville JL, Robertson D, Elijovich F. Effects of carotid body tumor resection on the blood pressure of essential hypertensive patients. J Am Soc Hypertens [print-electronic]. 2015 Jun; 9(6): 435-42. PMID: 26051925, PII: S1933-1711(15)00109-6, DOI: 10.1016/j.jash.2015.03.006, ISSN: 1878-7436.

Fudim M, Ely EW, Laffer CL, Elijovich F. Diagnosis of pheochromocytoma on physical examination. Eur. Heart J [print-electronic]. 2014 Jul; 35(26): 1705. PMID: 24334718, PII: eht536, DOI: 10.1093/eurheartj/eht536, ISSN: 1522-9645.

Laffer CL, Elijovich F, Eckert GJ, Tu W, Pratt JH, Brown NJ. Genetic variation in CYP4A11 and blood pressure response to mineralocorticoid receptor antagonism or ENaC inhibition: an exploratory pilot study in African Americans. J Am Soc Hypertens [print-electronic]. 2014 Jul; 8(7): 475-80. PMID: 25064769, PMCID: PMC4115247, PII: S1933-1711(14)00546-4, DOI: 10.1016/j.jash.2014.04.011, ISSN: 1878-7436.

Kirabo A, Fontana V, de Faria APC, Loperena R, Galindo CL, Wu J, Bikineyeva AT, Dikalov S, Liang X, Chen W, Saleh MA, Trott DW, Itani HA, Vinh A, Amarnath V, Amarnath K, Guzik TJ, Bernstein KE, Shen XZ, Shyr Y, Chen S, Mernaugh RL, Laffer CL, Elijovich F, Davies SS, Moreno LH, Madhur MS, Roberts J II, Harrison DG. Dendritic cell isoketal-modified proteins activate T cells and promote hypertension. 2014.

Elijovich F, Laffer CL. The issue of African ancestry in Caribbean Hispanics and salt sensitivity of blood pressure [letter]. J Am Soc Hypertens [print-electronic]. 2014 Jan; 8(1): 71. PMID: 23731653, PII: S1933-1711(13)00088-0, DOI: 10.1016/j.jash.2013.04.012, ISSN: 1878-7436.

Elijovich F, Laffer CL. A cautious view of the relationship between ambulatory blood pressure monitoring data and salt-sensitivity of blood pressure [letter]. J. Hypertens. 2013 Sep; 31(9): 1909. PMID: 24107666, PII: 00004872-201309000-00022, DOI: 10.1097/HJH.0b013e328363525f, ISSN: 1473-5598.

Laffer CL, Elijovich F. Differential predictors of insulin resistance in nondiabetic salt-resistant and salt-sensitive subjects. Hypertension [print-electronic]. 2013 Mar; 61(3): 707-15. PMID: 23283360, PMCID: PMC3591466, PII: HYPERTENSIONAHA.111.00423, DOI: 10.1161/HYPERTENSIONAHA.111.00423, ISSN: 1524-4563.

Nichols J, Elijovich F, Laffer CL. Lack of validation of a same-day outpatient protocol for determination of salt sensitivity of blood pressure. Hypertension [print-electronic]. 2012 Feb; 59(2): 390-4. PMID: 22184320, PII: HYPERTENSIONAHA.111.185835, DOI: 10.1161/HYPERTENSIONAHA.111.185835, ISSN: 1524-4563.

Elijovich F, Laffer CL. Detrimental effects of dual ACEI-ARB therapy: is the (pro)renin receptor the culprit?. Kidney Int. 2011 Nov; 80(9): 911-4. PMID: 21997507, PII: ki2011264, DOI: 10.1038/ki.2011.264, ISSN: 1523-1755.

Laffer CL, Elijovich F. A critical appraisal of the clinical effectiveness of a fixed combination of valsartan, amlodipine, and hydrochlorothiazide in achieving blood pressure goals. Integr Blood Press Control [print-electronic]. 2011; 4: 1-5. PMID: 21949633, PMCID: PMC3172079, PII: ibpc-4-001, DOI: 10.2147/IBPC.S6562, ISSN: 1178-7104.

Elijovich F, Laffer CL. Acute stroke: lower blood pressure looks better and better [editorial]. Hypertension [print-electronic]. 2010 Nov; 56(5): 808-10. PMID: 20823376, PII: HYPERTENSIONAHA.110.159038, DOI: 10.1161/HYPERTENSIONAHA.110.159038, ISSN: 1524-4563.

Laffer CL, Elijovich F. Inflammation and therapy for hypertension. Curr. Hypertens. Rep. 2010 Aug; 12(4): 233-42. PMID: 20524088, DOI: 10.1007/s11906-010-0125-3, ISSN: 1534-3111.

Elijovich F, Laffer C. A role for single-pill triple therapy in hypertension. Ther Adv Cardiovasc Dis. 2009; 3: 231-40.

Murphy LJ, Laffer C, Brown, NJ. CYP4A118590 CC genotype is associated with an increased aldosterone-renin ratio. Hypertension. 2009; 54.

Elijovich F, Laffer CL. The relationship between CYP4A11 and human hypertension [letter]. J. Hypertens. 2008 Aug; 26(8): 1712-4. PMID: 18622255, PII: 00004872-200808000-00034, DOI: 10.1097/HJH.0b013e3283000504, ISSN: 0263-6352.

Laffer CL, Gainer JV, Waterman MR, Capdevila JH, Laniado-Schwartzman M, Nasjletti A, Brown NJ, Elijovich F. The T8590C polymorphism of CYP4A11 and 20-hydroxyeicosatetraenoic acid in essential hypertension. Hypertension [print-electronic]. 2008 Mar; 51(3): 767-72. PMID: 18227405, PMCID: PMC2365894, PII: HYPERTENSIONAHA.107.102921, DOI: 10.1161/HYPERTENSIONAHA.107.102921, ISSN: 1524-4563.

Laffer CL, Bolterman RJ, Romero JC, Elijovich F. Effect of salt on isoprostanes in salt-sensitive essential hypertension. Hypertension [print-electronic]. 2006 Mar; 47(3): 434-40. PMID: 16432053, PII: 01.HYP.0000202480.06735.82, DOI: 10.1161/01.HYP.0000202480.06735.82, ISSN: 1524-4563.

Elijovich F, Laffer CL. Masked hypertension: a clinical entity or statistical gymnastics? [editorial]. Clin. Auton. Res. 2004 Jun; 14(3): 140-2. PMID: 15241640, DOI: 10.1007/s10286-004-0189-8, ISSN: 0959-9851.

Laffer CL. Is sodium restriction important to hypertension? The argument for. J Clin Hypertens (Greenwich). 2004 Jun; 6(6): 335-7. PMID: 15187496, ISSN: 1524-6175.

Elijovich F, Laffer CL, Schiffrin EL, Gavras H, Amador E. Endothelin-aldosterone interaction and proteinuria in low-renin hypertension. J. Hypertens. 2004 Mar; 22(3): 573-82. PMID: 15076164, PII: 00004872-200403000-00021, ISSN: 0263-6352.

Laffer CL, Laniado-Schwartzman M, Nasjletti A, Elijovich F. 20-HETE and circulating insulin in essential hypertension with obesity. Hypertension [print-electronic]. 2004 Feb; 43(2): 388-92. PMID: 14707157, PII: 01.HYP.0000112224.87290.3a, DOI: 10.1161/01.HYP.0000112224.87290.3a, ISSN: 1524-4563.

Laffer C, Zhao HW, Schwartzman ML, Nasjletti A, and Elijovich F. Urine 20-HETE and hypertension in the rat. J Hypertens. 2004; 22((Suppl 1)): S14.

Laffer CL, Laniado-Schwartzman M, Wang MH, Nasjletti A, Elijovich F. 20-HETE and furosemide-induced natriuresis in salt-sensitive essential hypertension. Hypertension [print-electronic]. 2003 Mar; 41(3 Pt 2): 703-8. PMID: 12623983, PII: 01.HYP.0000051888.91497.47, DOI: 10.1161/01.HYP.0000051888.91497.47, ISSN: 1524-4563.

Laffer CL, Laniado-Schwartzman M, Wang MH, Nasjletti A, Elijovich F. Differential regulation of natriuresis by 20-hydroxyeicosatetraenoic Acid in human salt-sensitive versus salt-resistant hypertension. Circulation. 2003 Feb 2/4/2003; 107(4): 574-8. PMID: 12566369, ISSN: 1524-4539.

Laffer CL, Elijovich F. Essential hypertension of Caribbean Hispanics: sodium, renin, and response to therapy. J Clin Hypertens (Greenwich). 2002 Jul; 4(4): 266-73. PMID: 12147929, ISSN: 1524-6175.

Elijovich F, Laffer CL. Participation of renal and circulating endothelin in salt-sensitive essential hypertension. J Hum Hypertens. 2002 Jul; 16(7): 459-67. PMID: 12080429, DOI: 10.1038/sj.jhh.1001419, ISSN: 0950-9240.

Elijovich F, Laffer CL, Amador E, Gavras H, Bresnahan MR, Schiffrin EL. Regulation of plasma endothelin by salt in salt-sensitive hypertension. Circulation. 2001 Jan 1/16/2001; 103(2): 263-8. PMID: 11208687, ISSN: 0009-7322.

Laffer CL, Elijovich F. Three Angiotensin paradigms in one patient : etiology of hypertension, glomerular hemodynamics, and long-term glomerular protection. Methods Mol. Med. 2001; 51: 23-37. PMID: 21331707, DOI: 10.1385/1-59259-087-X:23, ISSN: 1543-1894.

Laffer CL, Schiffrin EL, Gavras H, Elijovich F. Variability of plasma endothelin within a hypertensive sibpair is less than that between a group of sibpairs. J Hypertens. 2000; 18((Suppl 4)): S224.

Laffer CL, Schiffrin EL, Gavras H, Elijovich F. Plasma endothelin of sibpairs: variability, inheritance, and linkage to obesity in essential hypertension. Hypertension. 2000; 36: 725.

Baima J, Nicolaou M, Schwartz F, DeStefano AL, Manolis A, Gavras I, Laffer C, Elijovich F, Farrer L, Baldwin CT, Gavras H. Evidence for linkage between essential hypertension and a putative locus on human chromosome 17. Hypertension. 1999; 34: 4-7.

Elijovich F, Laffer CL, Schiffrin EL. The effects of atenolol and zofenopril on plasma atrial natriuretic peptide are due to their interactions with target organ damage of essential hypertensive patients. J Hum Hypertens. 1997 May; 11(5): 313-9. PMID: 9205939, ISSN: 0950-9240.

Elijovich F, Zhao HW, Laffer CL, Du Y, DiPette DJ, Inagami T, Wang DH. Regulation of growth of the adrenal gland in DOC-salt hypertension. Role of angiotensin II receptor subtypes. Hypertension. 1997 Jan; 29(1 Pt 2): 408-13. PMID: 9039135, ISSN: 0194-911X.

Elijovich F, Brown MD, Laffer CL, Lell J, Wallace DC. Native-American and African matrilineal gene pools and essential hypertension of Caribbean Hispanics. J Hypertens. 1996; 14((Suppl 1)): S30.

Laffer CL, Elijovich F. Suboptimal outcome of management of metabolic cardiovascular risk factors in Hispanic patients with essential hypertension. Hypertension. 1995; 26: 1079-84.

Brown MD, Lell J, Elijovich F, Laffer CL, Wallace DC. Estimation of female genetic contribution to modern Caribbean populations using continent-specific mitochondrial DNA polymorphisms. Am J Human Genetics. 1995; 57: 912.

Laffer CL, Elijovich F. Predictors of the pressor response to the clinic visit in essential hypertensives with and without diabetes mellitus. Clinical Autonomic Research. 1994; 4: 323-9.

Elijovich F, Laffer CL. Bayesian analysis supports use of ambulatory blood pressure monitors for screening. Hypertension. 1992; 19((Suppl II)).

Elijovich F, Laffer C, Schiffrin EL, Thornton JC. Volume-related clinical characteristics, not age or other correlates, explain plasma ANF of essential hypertensives in a multivariate model. Hypertension. 1991; 17: 415.

Elijovich F, Laffer CL. Magnitude, reproducibility and components of the pressor response to the clinic. Hypertension. 1990; 15((Suppl II)).

Elijovich F, Laffer C, Goldman M, Schiffrin EL. Plasma ANF of essential hypertensives reflects left atrial emptying, not LVH. J Hypertens. 1990; 8((Suppl 3)): S48.

Jan LY, Barbel S, Timpe L, Laffer C, Salkoff L, O'Farrell P, Jan YN. Studies of Shaker mutations affecting a K+ channel in Drosophila. Current Topics in Membranes and Transport. 1985; 23: 67-77.

Jan LY, Barbel S, Timpe L, Laffer C, Salkoff L, O'Farrell P, Jan YN. Mutating a gene for a potassium channel by hybrid dysgenesis: an approach to the cloning of the Shaker locus in Drosophila. Cold Spring Harbor Symposium on Quantitative Biology. 1983; 48: 233-45.

Shusterman CL, Thiede EW, Kung C. K-resistant mutants and "adaptation" in Paramecium. Proceedings of the National Academy of Science USA. 1978; 75: 5645-9.