W. Gray (Jay) Jerome, Ph.D.
Associate Professor of Pathology and Cancer Biology
Vanderbilt University Medical Center
U-2206 MCN, 1161 21st Ave . S.
Nashville, TN 37232
Vascular biology and how changes in the vasculature can affect heart disease, stroke, and cancer.
Research in the laboratory is focused on vascular biology and how changes in the vasculature can affect heart disease, stroke, and cancer. The studies correlate microscopy and biochemistry evidence to determine what changes occur and how these changes affect the disease process. Currently, three interrelated studies are ongoing.
In the first, we are trying to learn why in atherosclerosis the lysosomes of macrophages and smooth muscle cells in the artery wall become bloated with cholesterol. To do this, we use cultured macrophages and look at the uptake and processing of cholesterol. The cholesterol is delivered to the cells within modified lipoproteins. This is similar to what occurs in vivo. We compare quantitative microscopic observations on the uptake and fate of the lipoproteins with measures of key biochemical pathways in cholesterol metabolism. In this way we are beginning to dissect why lysosomes cannot clear their cholesterol load. To relate these tissue culture experiments to the disease process, we also compare the appearance of these tissue culture cells to that exhibited by cells during various stages of atherosclerosis. This is also allowing us to investigate the effect this bloating has on progression of the disease. Among our findings, we have shown that lysosomal cholesterol accumulation occurs in two stages. In the initial stage, cholesteryl esters delivered by lipoproteins are broken down in th lysosome but the resulting unesterified cholesterol cannot escape the lysosome. In later stages, and perhaps related to the free cholesterol accumulation, hydrolysis of the cholesteryl esters is inhibited. This produces lysosomes rich in both free and esterified cholesterol.
In the second set of studies, we are exploring how triglycerides can alter intracellular cholesterol metabolism. We have found that triglycerides significantly increase the rate of cholesterol metabolism and cellular clearance of cholesterol. We are now trying to define the mechanisms by which this occurs.
In a new line of investigation in the laboratory, we are investigating how inhibition of cholesterol use can effect cell proliferation. Under conditions where cholesterol is scarce, cell proliferation, such as that seen in tumors, is slowed. The cell can acquire cholesterol exogenously or synthesize it internally. Each pool of cholesterol appears to have a slight different trafficking mechanism within the cells. It is still not clear whether an inhibition of use of one pool can be compensated by use of cholesterol from the other pool. Cholesterol restriction is a potential means of slowing some tumor growth. However, to fully understand the potential, much more knowledge of cholesterol trafficking and utilization within different cell types is required. . . .
- Yu, SS, Lau, CM, Thomas, SN, Jerome, WG, Maron, DJ, Dickerson, JH, Hubbell, JA, Giorgio, TD Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages. Int J Nanomedicine, 7799-813, 2012.
- Deng, X, Morris, J, Dressmen, J, Tubb, MR, Tso, P, Jerome, WG, Davidson, WS, Thompson, TB The Structure of Dimeric Apolipoprotein A-IV and Its Mechanism of Self-Association. Structure, 20(5), 767-79, 2012.
- Huang, R, Silva, RA, Jerome, WG, Kontush, A, Chapman, MJ, Curtiss, LK, Hodges, TJ, Davidson, WS Apolipoprotein A-I structural organization in high-density lipoproteins isolated from human plasma. Nat Struct Mol Biol, 18(4), 416-22, 2011.
- Weibel, GL, Joshi, MR, Jerome, WG, Bates, SR, Yu, KJ, Phillips, MC, Rothblat, GH Cytoskeleton disruption in J774 macrophages: Consequences for lipid droplet formation and cholesterol flux. Biochim Biophys Acta, 2011.
- Jiang, M, Jerome, WG, Hayward, SW Autophagy in nuclear receptor PPARgamma-deficient mouse prostatic carcinogenesis. Autophagy, 6(1), 175-6, 2010.
- Vaezi, MF, Slaughter, JC, Smith, BS, Washington, MK, Jerome, WG, Garrett, CG, Hagaman, D, Goutte, M Dilated intercellular space in chronic laryngitis and gastro-oesophageal reflux disease: at baseline and post-lansoprazole therapy. Aliment Pharmacol Ther, 32(7), 916-24, 2010.
- Jiang, M, Fernandez, S, Jerome, WG, He, Y, Yu, X, Cai, H, Boone, B, Yi, Y, Magnuson, MA, Roy-Burman, P, Matusik, RJ, Shappell, SB, Hayward, SW Disruption of PPARgamma signaling results in mouse prostatic intraepithelial neoplasia involving active autophagy. Cell Death Differ, 17(3), 469-81, 2010.
- Jerome, WG Lysosomes, cholesterol and atherosclerosis. Clin Lipidol, 5(6), 853-865, 2010.
- Gauthamadasa, K, Rosales, C, Pownall, HJ, Macha, S, Jerome, WG, Huang, R, Silva, RA Speciated human high-density lipoprotein protein proximity profiles. Biochemistry, 49(50), 10656-65, 2010.
- Gu, F, Jones, MK, Chen, J, Patterson, JC, Catte, A, Jerome, WG, Li, L, Segrest, JP Structures of discoidal high density lipoproteins: a combined computational-experimental approach. J Biol Chem, 285(7), 4652-65, 2010.
- Chen, B, Ren, X, Neville, T, Jerome, WG, Hoyt, DW, Sparks, D, Ren, G, Wang, J Apolipoprotein AI tertiary structures determine stability and phospholipid-binding activity of discoidal high-density lipoprotein particles of different sizes. Protein Sci, 18(5), 921-35, 2009.
- Sun, Y, Ishibashi, M, Seimon, T, Lee, M, Sharma, SM, Fitzgerald, KA, Samokhin, AO, Wang, Y, Sayers, S, Aikawa, M, Jerome, WG, Ostrowski, MC, Bromme, D, Libby, P, Tabas, IA, Welch, CL, Tall, AR Free cholesterol accumulation in macrophage membranes activates Toll-like receptors and p38 mitogen-activated protein kinase and induces cathepsin K. Circ Res, 104(4), 455-65, 2009.
- Ullery-Ricewick, JC, Cox, BE, Griffin, EE, Jerome, WG Triglyceride alters lysosomal cholesterol metabolism in cholesteryl ester-laden macrophage foam cells. J Lipid Res, 2009.
- Jerome, WG, Cox, BE, Griffin, EE, Ullery, JC Lysosomal cholesterol accumulation inhibits subsequent hydrolysis of lipoprotein cholesteryl ester. Microsc Microanal, 14(2), 138-49, 2008.
- Silva, RA, Huang, R, Morris, J, Fang, J, Gracheva, EO, Ren, G, Kontush, A, Jerome, WG, Rye, KA, Davidson, WS Structure of apolipoprotein A-I in spherical high density lipoproteins of different sizes. Proc Natl Acad Sci U S A, 105(34), 12176-81, 2008.
- Cao, Z, Li, C, Higginbotham, JN, Franklin, JL, Tabb, DL, Graves-Deal, R, Hill, S, Cheek, K, Jerome, WG, Lapierre, LA, Goldenring, JR, Ham, AJ, Coffey, RJ Use of fluorescence-activated vesicle sorting for isolation of Naked2-associated, basolaterally targeted exocytic vesicles for proteomics analysis. Mol Cell Proteomics, 7(9), 1651-67, 2008.
- Zhang, Y, Vasudevan, S, Sojitrawala, R, Zhao, W, Cui, C, Xu, C, Fan, D, Newhouse, Y, Balestra, R, Jerome, WG, Weisgraber, K, Li, Q, Wang, J A monomeric, biologically active, full-length human apolipoprotein E. Biochemistry, 46(37), 10722-32, 2007.
- Cox, BE, Griffin, EE, Ullery, JC, Jerome, WG Effects of cellular cholesterol loading on macrophage foam cell lysosome acidification. J Lipid Res, 48(5), 1012-21, 2007.
- Fan, D, Qiu, S, Overton, CD, Yancey, PG, Swift, LL, Jerome, WG, Linton, MF, Fazio, S Impaired secretion of apolipoprotein E2 from macrophages. J Biol Chem, 282(18), 13746-53, 2007.
- Yancey, PG, Jerome, WG, Yu, H, Griffin, EE, Cox, BE, Babaev, VR, Fazio, S, Linton, MF Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI. J Lipid Res, 48(5), 1140-9, 2007.
- Jerome, WG Advanced atherosclerotic foam cell formation has features of an acquired lysosomal storage disorder. Rejuvenation Res, 9(2), 245-55, 2006.
- Catte, A, Patterson, JC, Jones, MK, Jerome, WG, Bashtovyy, D, Su, Z, Gu, F, Chen, J, Aliste, MP, Harvey, SC, Li, L, Weinstein, G, Segrest, JP Novel changes in discoidal high density lipoprotein morphology: a molecular dynamics study. Biophys J, 90(12), 4345-60, 2006.
- Brissova, M, Shostak, A, Shiota, M, Wiebe, PO, Poffenberger, G, Kantz, J, Chen, Z, Carr, C, Jerome, WG, Chen, J, Baldwin, HS, Nicholson, W, Bader, DM, Jetton, T, Gannon, M, Powers, AC Pancreatic islet production of vascular endothelial growth factor--a is essential for islet vascularization, revascularization, and function. Diabetes, 55(11), 2974-85, 2006.
- Dove, DE, Su, YR, Zhang, W, Jerome, WG, Swift, LL, Linton, MF, Fazio, S ACAT1 deficiency disrupts cholesterol efflux and alters cellular morphology in macrophages. Arterioscler Thromb Vasc Biol, 25(1), 128-34, 2005.
- Griffin, EE, Ullery, JC, Cox, BE, Jerome, WG Aggregated LDL and lipid dispersions induce lysosomal cholesteryl ester accumulation in macrophage foam cells. J Lipid Res, 2005.
- Settle, SH, Washington, K, Lind, C, Itzkowitz, S, Fiske, WH, Burdick, JS, Jerome, WG, Ray, M, Weinstein, W, Coffey, RJ Chronic treatment of MÃ©nÃ©trier''s disease with Erbitux: clinical efficacy and insight into pathophysiology. Clin Gastroenterol Hepatol, 3(7), 654-9, 2005.
- Wilkinson, M, Cline, M, Jerome, WG Cytopathic herpesvirus infection in a green iguana (Iguana iguana). J Zoo Wildl Med, 36(4), 724-6, 2005.
- W. Gray Jerome, Stefan Handt, Roy R. Hantgan "Endothelial Cells Organize Fibrin Clots into Structures That Are More Resistant to Lysis." Microscopy and Microanalysis, 11(3), 268-277, 2005.
- Jerome, WG, Handt, S, Hantgan, RR Endothelial cells organize fibrin clots into structures that are more resistant to lysis. Microsc Microanal, 11(3), 268-77, 2005.
- Ren, X, Zhao, L, Sivashanmugam, A, Miao, Y, Korando, L, Yang, Z, Reardon, CA, Getz, GS, Brouillette, CG, Jerome, WG, Wang, J Engineering mouse apolipoprotein A-I into a monomeric, active protein useful for structural determination. Biochemistry, 44(45), 14907-19, 2005.
- de Grey, AD, Alvarez, PJ, Brady, RO, Cuervo, AM, Jerome, WG, McCarty, PL, Nixon, RA, Rittmann, BE, Sparrow, JR Medical bioremediation: prospects for the application of microbial catabolic diversity to aging and several major age-related diseases. Ageing Res Rev, 4(3), 315-38, 2005.
- Swift, LL, Kakkad, B, Boone, C, Jovanovska, A, Jerome, WG, Mohler, PJ, Ong, DE Microsomal triglyceride transfer protein expression in adipocytes: a new component in fat metabolism. FEBS Lett, 579(14), 3183-9, 2005.
- Fan, Daping, Li, Qianqian, Korando, Leslie, Jerome, W Gray, Wang, Jianjun A monomeric human apolipoprotein E carboxyl-terminal domain. Biochemistry, 43(17), 5055-64, 2004.
- Prentice, Erik, Jerome, W Gray, Yoshimori, Tamotsu, Mizushima, Noboru, Denison, Mark R Coronavirus replication complex formation utilizes components of cellular autophagy. J Biol Chem, 279(11), 10136-41, 2004.
- Li, Cunxi, Franklin, Jeffrey L, Graves-Deal, Ramona, Jerome, W Gray, Cao, Zheng, Coffey, Robert J Myristoylated Naked2 escorts transforming growth factor alpha to the basolateral plasma membrane of polarized epithelial cells. Proc Natl Acad Sci U S A, 101(15), 5571-6, 2004.
- Swift, Larry L, Zhu, Mei-Ying, Kakkad, Bharati, Jovanovska, Aneta, Neely, M Diana, Valyi-Nagy, Klara, Roberts, Richard L, Ong, David E, Jerome, W Gray Subcellular localization of microsomal triglyceride transfer protein. J Lipid Res, 44(10), 1841-9, 2003.
- Jerome, W Gray, Yancey, Patricia G The role of microscopy in understanding atherosclerotic lysosomal lipid metabolism. Microsc Microanal, 9(1), 54-67, 2003.
- Grant, Kenneth, Jerome, W Gray Laser capture microdissection as an aid to ultrastructural analysis. Microsc Microanal, 8(3), 170-5, 2002.
- Hantgan, Roy R, Stahle, Mary C, Jerome, W Gray, Nagaswami, Chandrasekaran, Weisel, John W Tirofiban blocks platelet adhesion to fibrin with minimal perturbation of GpIIb/IIIa structure. Thromb Haemost, 87(5), 910-7, 2002.
- Yancey, Patricia G, Miles, Stacia, Schwegel, Jennifer, Jerome, W Gray Uptake and trafficking of mildly oxidized LDL and acetylated LDL in THP-1 cells does not explain the differences in lysosomal metabolism of these two lipoproteins. Microsc Microanal, 8(2), 81-93, 2002.
- Hantgan, R R, Stahle, M, Del Gaizo, V, Adams, M, Lasher, T, Jerome, W G, McKenzie, M, Lyles, D S AlphaIIb's cytoplasmic domain is not required for ligand-induced clustering of integrin alphaIIbbeta3. Biochim Biophys Acta, 1540(1), 82-95, 2001.
- Yancey PG, Jerome WG "Lysosomal cholesterol derived from mildly oxidized low density lipoprotein is resistant to efflux." J Lipid Res, 42317-327, 2001.
- Yancey, P G, Jerome, W G Lysosomal cholesterol derived from mildly oxidized low density lipoprotein is resistant to efflux. J Lipid Res, 42(3), 317-27, 2001.
- Bonnefoy, A, Liu, Q, Jerome, W G, Legrand, C, Frojmovic, M M Platelets in suspension require preactivation to adhere to immobilized fibrinogen. Ann N Y Acad Sci, 936459-63, 2001.
- Stokes, A H, Lewis, D Y, Lash, L H, Jerome, W G, Grant, K W, Aschner, M, Vrana, K E Dopamine toxicity in neuroblastoma cells: role of glutathione depletion by L-BSO and apoptosis. Brain Res, 858(1), 1-8, 2000.
- Cashell, A W, Jerome, W G, Flores, E Signet ring stromal tumor of the ovary occurring in conjunction with brenner tumor. Gynecol Oncol, 77(2), 323-6, 2000.
- Avart, S J, Bernard, D W, Jerome, W G, Glick, J M Cholesteryl ester hydrolysis in J774 macrophages occurs in the cytoplasm and lysosomes. J Lipid Res, 40(3), 405-14, 1999.
- Kellner-Weibel G, Yancey PG, Jerome WG, Walser T, Mason RP, Phillips MC,Rothblat GH "Crystallization of free cholesterol in model macrophage foam cells." Arterioscler Thromb Vasc Biol, 191891-8, 1999.
- Kellner-Weibel, G, Yancey, P G, Jerome, W G, Walser, T, Mason, R P, Phillips, M C, Rothblat, G H Crystallization of free cholesterol in model macrophage foam cells. Arterioscler Thromb Vasc Biol, 19(8), 1891-8, 1999.
- Kellner-Weibel, G, Jerome, W G, Small, D M, Warner, G J, Stoltenborg, J K, Kearney, M A, Corjay, M H, Phillips, M C, Rothblat, G H Effects of intracellular free cholesterol accumulation on macrophage viability: a model for foam cell death. Arterioscler Thromb Vasc Biol, 18(3), 423-31, 1998.
- Jerome, W G, Cash, C, Webber, R, Horton, R, Yancey, P G Lysosomal lipid accumulation from oxidized low density lipoprotein is correlated with hypertrophy of the Golgi apparatus and trans-Golgi network. J Lipid Res, 39(7), 1362-71, 1998.
- Yancey, P G, Jerome, W G Lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different species. J Lipid Res, 39(7), 1349-61, 1998.
- Hantgan, R R, Jerome, W G, Hursting, M J No effect of clot age or thrombolysis on argatroban's inhibition of thrombin. Blood, 92(6), 2064-74, 1998.
- Hantgan RR, Jerome WG, Handt S "Platelets and endothelial cells act in concert to delay thrombolysis--evidence from an in vitro model of the human occlusive thrombus." Thromb Haemost, 79602-8, 1998.
- Hantgan, R R, Jerome, W G, Handt, S Platelets and endothelial cells act in concert to delay thrombolysis--evidence from an in vitro model of the human occlusive thrombus. Thromb Haemost, 79(3), 602-8, 1998.
- Jerome, W G, Lewis, J C Cellular dynamics in early atherosclerotic lesion progression in white carneau pigeons. Spatial and temporal analysis of monocyte and smooth muscle invasion of the intima. Arterioscler Thromb Vasc Biol, 17(4), 654-64, 1997.
- Carlson, C S, O'Sullivan, M G, Jayo, M J, Anderson, D K, Harber, E S, Jerome, W G, Bullock, B C, Heberling, R L Fatal disseminated cercopithecine herpesvirus 1 (herpes B infection in cynomolgus monkeys (Macaca fascicularis). Vet Pathol, 34(5), 405-14, 1997.
- Tansey, J T, Thuren, T Y, Jerome, W G, Hantgan, R R, Grant, K, Waite, M Hydrolysis of phosphatidylcholine by hepatic lipase in discoidal and spheroidal recombinant high-density lipoprotein. Biochemistry, 36(40), 12227-34, 1997.
- Lyles, D S, McKenzie, M O, Kaptur, P E, Grant, K W, Jerome, W G Complementation of M gene mutants of vesicular stomatitis virus by plasmid-derived M protein converts spherical extracellular particles into native bullet shapes. Virology, 217(1), 76-87, 1996.
- Handt, S, Jerome, W G, Tietze, L, Hantgan, R R Plasminogen activator inhibitor-1 secretion of endothelial cells increases fibrinolytic resistance of an in vitro fibrin clot: evidence for a key role of endothelial cells in thrombolytic resistance. Blood, 87(10), 4204-13, 1996.
- Endenburg, S C, Hantgan, R R, Lindeboom-Blokzijl, L, Lankhof, H, Jerome, W G, Lewis, J C, Sixma, J J, de Groot, P G On the role of von Willebrand factor in promoting platelet adhesion to fibrin in flowing blood. Blood, 86(11), 4158-65, 1995.
- Tangirala, R K, Jerome, W G, Jones, N L, Small, D M, Johnson, W J, Glick, J M, Mahlberg, F H, Rothblat, G H Formation of cholesterol monohydrate crystals in macrophage-derived foam cells. J Lipid Res, 35(1), 93-104, 1994.
- Lantz, P E, Jerome, W G, Jaworski, J A Radiopaque deposits surrounding a contact small-caliber gunshot wound. Am J Forensic Med Pathol, 15(1), 10-3, 1994.
- Jerome, WL The scientific method. Br Dent J, 177(11-12), 401, 1994.
- Braaten, J V, Jerome, W G, Hantgan, R R Uncoupling fibrin from integrin receptors hastens fibrinolysis at the platelet-fibrin interface. Blood, 83(4), 982-93, 1994.
- Tangirala, R K, Mahlberg, F H, Glick, J M, Jerome, W G, Rothblat, G H Lysosomal accumulation of unesterified cholesterol in model macrophage foam cells. J Biol Chem, 268(13), 9653-60, 1993.
- Braaten, J V, Handt, S, Jerome, W G, Kirkpatrick, J, Lewis, J C, Hantgan, R R Regulation of fibrinolysis by platelet-released plasminogen activator inhibitor 1: light scattering and ultrastructural examination of lysis of a model platelet-fibrin thrombus. Blood, 81(5), 1290-9, 1993.
- Loeser, R, Carlson, C S, Tulli, H, Jerome, W G, Miller, L, Wallin, R Articular-cartilage matrix gamma-carboxyglutamic acid-containing protein. Characterization and immunolocalization. Biochem J, 282 ( Pt 1)1-6, 1992.
- Moyer, C F, Jerome, W G, Taylor, R, Tulli, H, Reinisch, C L Autoimmune vasculitis in MRL/Mp-lpr/lpr mice: orthochromatic basophils participate in the development of delayed-type hypersensitivity angiitis. Autoimmunity, 12(3), 159-65, 1992.
- Jerome, WL Mercury from dental amalgam. Br Dent J, 173(7), 227-8, 1992.
- Thomas, M J, Hedrick, C C, Smith, S, Pang, J, Jerome, W G, Willard, A S, Shirley, P S Superoxide generation by the human polymorphonuclear leukocyte in response to latex beads. J Leukoc Biol, 51(6), 591-6, 1992.
- Taylor, R G, Jerome, W G, Lewis, J C Ultrastructural localization of peroxidase in atherosclerotic lesions of pigeons. Exp Mol Pathol, 57(3), 167-79, 1992.
- Minor, L K, Mahlberg, F H, Jerome, W G, Lewis, J C, Rothblat, G H, Glick, J M Lysosomal hydrolysis of lipids in a cell culture model of smooth muscle foam cells. Exp Mol Pathol, 54(2), 159-71, 1991.
- Jerome, W G, Minor, L K, Glick, J M, Rothblat, G H, Lewis, J C Lysosomal lipid accumulation in vascular smooth muscle cells. Exp Mol Pathol, 54(2), 144-58, 1991.
- Barr, D A, Jerome, W G, Lewis, J C Morphologic characteristics of naturally occurring atherosclerosis in the brachiocephalic artery of the pigeon. Exp Mol Pathol, 54(2), 99-111, 1991.
- Jones, N L, Jerome, W G, Lewis, J C Pigeon monocyte/macrophage lysosomes during beta VLDL uptake. Induction of acid phosphatase activity. A model for complex arterial lysosomes. Am J Pathol, 139(2), 383-92, 1991.
- Jerome, W G, Lewis, J C Early atherogenesis in White Carneau pigeons: effect of a short-term regression diet. Exp Mol Pathol, 53(3), 223-38, 1990.
- Mahlberg, F H, Glick, J M, Jerome, W G, Rothblat, G H Metabolism of cholesteryl ester lipid droplets in a J774 macrophage foam cell model. Biochim Biophys Acta, 1045(3), 291-8, 1990.
- Taylor, R G, Jerome, W G, Lewis, J C Ultrastructural events associated with endothelial cell changes during the initiation and early progression of atherosclerosis. Adv Exp Med Biol, 27389-93, 1990.
- Noseda, A, White, J G, Godwin, P L, Jerome, W G, Modest, E J Membrane damage in leukemic cells induced by ether and ester lipids: an electron microscopic study. Exp Mol Pathol, 50(1), 69-83, 1989.
- Jerome, W G, Lewis, J C Early atherogenesis in the White Carneau pigeon. III. Lipid accumulation in nascent foam cells. Am J Pathol, 128(2), 253-64, 1987.
- Jerome, W G, Lewis, J C Early atherogenesis in White Carneau pigeons. II. Ultrastructural and cytochemical observations. Am J Pathol, 119(2), 210-22, 1985.
- Lewis, J C, Taylor, R G, Jerome, W G Foam cell characteristics in coronary arteries and aortas of White Carneau pigeons with moderate hypercholesterolemia. Ann N Y Acad Sci, 45491-100, 1985.
- Jerome, W G, Lewis, J C Early atherogenesis in White Carneau pigeons. I. Leukocyte margination and endothelial alterations at the celiac bifurcation. Am J Pathol, 116(1), 56-68, 1984.
- Jerome, W G, Lewis, J C, Taylor, R G, White, M S Concurrent endothelial cell turnover and leukocyte margination in early atherosclerosis. Scan Electron Microsc, (Pt 3), 1453-9, 1983.
- Jerome, W G, Cardell, R R Observations on the role of smooth endoplasmic reticulumin glucocorticoid-induced hepatic glycogen deposition. Tissue Cell, 15(5), 711-27, 1983.
- Jerome, W G Medical electron microscopy. Invest Urol, 19(3), 131-5, 1981.