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The Journal of Clinical Investigation

Published by The Press, New Yorkfor The American Society for Clinical Investigation, Inc. Ajit P. Varki, Editor Associate Editors Dennis A. Carson Paul A. Insel Jerrold M. Olefsky Kenneth R. Chien Martin F. Kagnoff Zaverio M. Ruggeri Mark H. Ginsberg Thomas J. Kipps Peter D. Wagner Donald G. Guiney Fu-Tong Liu Joseph L. Witztum Karl Y. Hostetler Daniel T. O'Connor Michael J. Held, Managing Editor E. Kay Meschko, Assistant Managing Editor Consulting Editors Peter Agre* Robert A. Eisenberg Seymour J. Klebanoff Stephen M. Prescott* R. Wayne Alexander Glen A. Evans Robert A. Klocke Douglas Richman Robert J. Alpern Darrell D. Fanestil Orville Kolterman Alan G. kobinson* David H. Alpers Marilyn G. Farquhar Stuart Kornfeld John Ross, Jr. William P. Arend Jack L. Feldman Stanley J. Korsmeyer* Arthur H. Rubenstein Peter S. Aronson* James R. Feramisco Ira Kurtz Erkki Ruoslahti Bernard M. Babior Alan R. Leff Elizabeth Barrett-Connor Joshua Fierer Robert S. Schwartz* Kurt Benirschke Alan M. Fogelman Peter Libby Stephen M. Schwartz Bruce Beutler* Uta Francke* Dean H. Lockwood William E. Seaman Ernest Beutler Elaine V. Fuchs* Dennis Y. Loh* Sanford J. Shattil* Michael P. Bevilacqua Fred H. Gage David J. Loskutoff Jan J. Sixma J. Michael Bishop Detlev Ganten Eduardo Marban* Dennis J. Slamon Roland C. Blantz Gordon N. Gill John A. McDonald James R. Snapper Jan L. Breslow Henry N. Ginsberg Rodger P. McEver* Roger Spragg Arthur E. Broadus* Laurie H. Glimcher* Shlomo Melmed George Stamatoyannopoulos* Frances M. Brodsky* Stephen L. Gluck* Donald Metcalf Daniel Steinberg Eric J. Brown Jeffrey I. Gordon* Beverly S. Mitchell* Judith L. Swain* Gerard N. Burrow Mehran Goulian Robert L. Modlin Eng M. Tan Webster Cavenee Harry B. Greenberg* Salvador Moncada Palmer W. Taylor Alan Cherrington Bevra H. Hahn Joel Moss* Simeon I. Taylor* William W. Chin* John M. Harlan* Barbara E. Murray* Donald F. Tierney Francis V. Chisari Stephen M. Hedrick Jacob B. Natvig Michael Tuck Charles G. Cochrane Helen H. Hobbs* Eric G. Neilson* Geoffrey M. Wahl Desire Collen Brian B. Hoffman Paul E. Neiman* John H. Walsh Barry S. Coller Alan Hofmann Yale Nemerson Karlman Wasserman James D. Crapo Gerald T. Nepom Stephen Wasserman Philip E. Cryer Jay H. Hoofnagle Elizabeth F. Neufeld David J. Weatherall Linda K. Curtiss Marcus A. Horwitz* Yasutomi Nishizuka Arthur Weiss* Robert J. Desnick* Stephen B. Howell Stuart H. Orkin John B. West Jared M. Diamond Willa A. Hsueh George E. Palade Cornelia Weyand Janice G. Douglas* Charles A. Janeway, Jr. Stephen J. Pandol Raymond L. White Jeffrey M. Drazen C. Ronald Kahn James C. Paulson R. Sanders Williams* Boris Draznin Daniel K. Podolsky Flossie Wong-Staal Richard Dutton Carolyn J. Kelly* Kenneth S. Polonsky Stephen G. Young Walter Eckhart Elliott D. Kieff Jacques Pouyssegur Elizabeth Ziegler * Members of The Editorial Committee, American Society for Clinical Investigation, Inc. Editorial Assistants Kris E. Beaver, Deanna Crabb, Marion I. Froehlich, Stephen J. Shea, and M. Kayle Watts Copy Editing and Production David Itkin, Effie Janulis, and Justine Manser Editorial Offices: University of California at San Diego, School of Medicine and Veterans Affairs Medical Center Abbreviations GP, glycoprotein NS, not significant (material in parentheses GSH, glutathione, reduced OD, optical density for explanation only) h, hour 1,25(OH)2D, 1,25-dihydroxyvitamin D HBSS, Hanks' balanced salt solution 25(OH)D3, 25-hydroxyvitamin D3 A, angstrom (0o-8 cm) HDL, high density lipoprotein osM, osmolar AA, arachidonic acid Hepes, N-2-hydroxyethylpiperazine-N'-2- osmol, osmole(s) ACTH, adrenocorticotropin ethane sulfonic acid P, probability AIDS, acquired immunodeficiency syndrome HIV, human immunodeficiency virus PAGE, polyacrylamide gel electrophoresis ANOVA, analysis of variance HLA, human histocompatibility leukocyte PBL, peripheral blood lymphocyte apo, apolipoprotein (also apo A, apo B, etc.) antigens PBMC, peripheral blood mononuclear cell ATP, adenosine triphosphate (also ADP, HPLC, high performance liquid PBS, phosphate-buffered saline AMP, CTP, UDP, etc.) chromatography PCR, polymerase chain reaction BCG, Calmette-Guerin bacillus HSA, human serum albumin PDGF, platelet-derived growth factor bp, basepair Id, idiotype PG, prostaglandin (also PGE, PGF, etc.) BP, blood pressure ID50, 50% infective dose PHA, phytohemagglutinin BSA, bovine serum albumin IFN, interferon pI, isoelectric point BTU, British thermal unit Ig, immunoglobulin Pipes, piperazine-N, N-bis (2-ethanesulfonic C, complement IGF, insulin-like growth factor acid) 0C, degree Celsius IL, interleukin (e.g., IL-2) PMA, phorbol myristate acetate cAMP, cyclic AMP IU, international unit(s) PMN, polymorphonuclear leukocyte cDNA, complementary DNA °K, degree kelvin PMSF, phenylmethylsuflonyl fluoride CFA, complete Freund's adjuvant kb, kilobase psi, pounds per square inch CFU, colony-forming unit kcal, kilocalorie(s) PTH, parathyroid hormone Ci, curie(s) Kd, dissociation constant r, correlation coefficient CoA, coenzyme A K2, inhibition constant RA, cpm, counts per minute K., Michaelis constant Rf, retardation factor cps, counts per second KRB, Krebs-Ringer bicarbonate buffer RFLP, restriction fragment length CSA, colony-stimulating activity LDso, 50% lethal dose polymorphism d, day(s) LDL, low density lipoprotein RIA, radioimmunoassay d, density liter(s), liter(s) RNA, ribonucleic acid D, dalton ,ul (not X), microliter(s) rpm, revolutions per minute kD, kilodalton ml, milliliter(s) RQ, respiratory quotient DEAE, diethylaminoethyl LPS, s, second(s) DME, Dulbecco's modified Eagle's medium m, meter(s) SD, standard deviation DMSO, dimethylsulfoxide cm3 (not cc), cubic centimeter(s) SDS, sodium dodecyl sulfate DNA, deoxyribonucleic acid ,m or 10-6 m (not 1i), micrometer(s) SEM, standard error of the mean DNP, dinitrophenyl (micron) SLE, systemic erythematosus DTT, dithiothreitol M, molar SOD, superoxide dismutase dyn * s* cm-5, units of peripheral vascular mAb, monoclonal antibody sp act, specific activity resistance MEM, minimum essential medium SSC, standard saline citrate EBV, Epstein-Barr virus Mes, 2-(N-morpholino) ethanesulfonic acid tl/2, half-life ED5o, 50% effective dose Aeq, microequivalent(s) TCA, trichloroacetic acid EDTA, ethylenediaminetetraacetate meq, milliequivalent(s) TGF, transforming growth factor EGF, epidermal growth factor MHC, major histocompatibility complex TLC, thin-layer chromatography EGTA, ethyleneglycol-bis(,B-aminoethyl mmHg, millimeters of mercury TNF, ether)-N,N'-tetraacetic acid mo, month Tris, tris(hydroxymethyl)-aminomethane ELISA, enzyme-linked immunosorbent assay moi, multiplicity of infection TX, thromboxane E/T ratio, effector/target ratio mol, mole(s) U, unit(s) eV, electron volt(s) mol wt, molecular weight Vj volt(s) °F, degree Fahrenheit Mops, 3-(4-Morpholino) propane sulfonic VLDL, very low density lipoprotein FACSO, registered trademark of Becton acid Vml,,-maximum velocity Dickinson and Company for a Mr, relative molecular mass vol, volume(s) fluorescence activated cell sorter mRNA, messenger RNA vWf, von Willebrand factor FBS, fetal bovine serum n, number in study, group W, watt(s) (voltampere) FCS, fetal calf serum N, normal (concentration) kW, kilowatt(s) FFA, free fatty acids NAD, nicotinamide adenine dinucleotide wk, week FITC, fluorescein isothiocyanate (also NADH, NADP, etc.) wt, weight FMLP, formylmethionylleucylphenylalanine NE, norepinephrine yr, year g, unit ofgravity No.(s), number(s) GFR, glomerular filtration rate NP-40, Nonidet P40 GM-CSF, granulocyte macrophage colony- stimulating factor

The Journal ofClinical Investigation (ISSN 0021-9738) is published monthly for $275 per year, individual rate is $130 ifpaid by personal check (postal surcharge in Europe only, $85) by The Rockefeller University Press, 222 East 70th Street, New York, NY 10021. Second-class postage paid at NewYork, NY and additional mailing offices. POSTMASTER: Send address changes to The Journal ofClinical Investigation, Order Service, The Rockefeller University Press, 222 East 7Qth Street, New York, NY 10021. Copyright © 1994, The American Society for Clinical Investigation, Inc. Manuscript Submission Form for The Journal of Clinical Investigation Type All Required Information: A Covering Letter Is Not Necessary (Pleasefollow the Instructions to Auuhors from the most recent January or July issue) Title:

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Courier Service: Regular Mail: Ajit P. Varki, Editor Ajit P. Varki, Editor The Journal ofClinical Investigation The Journal of Clinical Investigation UCSD School of Medicine P. O. Box 85182 VA Medical Center, Room 5142 San Diego, CA 92186-5182 3350 La Jolla Village Drive (Do not use this address for courier service) San Diego, CA 92161 March Author Index Ewart, A. K. . . . . 1071 Inui, K.-...... 1250 Mysler, E...... 1029 Volume93, Number3 Fay,C.T...... 1179 Ishibashi, K. . . . . 1250 Nakajima, K. ... 1250 Ferchal, F...... 1293 Jansson, L...... 1113 Nakamura, T. 1285 Ferrante, A. . ...1063 Jin, W...... 1071 Nakano, T. .. 1266 Figueredo, V. M. 951 Johnson, D. W. 1063 Namikawa, C. 1285 Finke,E.H. . 1312 Joshi, M. A. ... 1257 Nemenoff, R. A.. 1224 Fitzpatrick, L. A. 989 Kagimoto, S. ... 1321 Nessmann, C. . 1149 Abrams, S. A. . . ..1014 Flake, A. W. . 1051 Karachunski, P. 1020 Ngo-Giang-Huong, N. 1293 Aerts, J. M. F. G. ..1288 Flye, M. W. . 1312 Karp, P. H. . . 1307 Ocrant, I...... 1179 Ahern, D...... 1315 Fondacci, C. . 1149 Kashyap, M. L. . . . 1056 O'Keane, J. C. 1257 Alberg, D. G. . ...1315 Forrest, M. J. . 1140 Keating, M. T. 1071 Oksenhendler, E. 1293 Allen, P. M. . . . . 1208 Frank, H. J. L. 1056 Keet, I. P. M.. .. 982 Oldstone, M. B. A. 1332 Alsat, E...... 1149 Frei, B...... 998 Kelly, C. P. ... 1257 Orii, T...... 1035 Antignac, C. . . . . 1195 Frenkel, E. P.. . 958 Kenner, K. A. 1156 Otto, S. A...... 982 Atkinson, D. . . . . 1071 Friedman, S. M. . .1029 Kern, F., Jr. ... 1186 Papadopoulos, S. M. 1339 Awasthi, S...... 958 Froguel, P . . . . .1120 Kihara, Y.. .. 1275 Papapoulos, S. E. 1108 Awasthi, Y. C . 958 Fukao, T...... 1035 Knebelmann, B. 1195 Park, Y.-K. . 989 Bajpai, K. K.. . . . 958 Fuleihan, R. . . . .1315 Koch, A. E. . . 921 Parks, W. C. . 1234 Baker, J. R. . ...1042 Fushimi, K. . .. 1250 Kochera, M. . . . . 1005 Passa, P...... 1120 Bates, E. J...... 1063 Gabriel, R...... 1149 Konieczkowski, M. 1224 Pedram, A. . . . .1056 Becker, ...... 1257 Gaeta, F. C. A. ...1140 Korsgren, O. . . 1113 Pierce, G. F. . . . . 1298 Bell, G. I...... 1120 Garcia-Higuera, I. .. 937 Krammer, P. H. 1029 Pollak, M. R.. . . .1108 Bellido, T...... 944 Geha, R. S. . . . .1315 Krebs, E. G. . . 1266 Polonsky, K. S. . . . 1120 Belshaw, P. J. ... 1315 Gelb, M. H. . . . .1224 Kubota, A...... 1321 Pope, R. M. . . . .921 Bigby, T. D. ... 1042 Gesundheit, N. . . . 1131 Kunkel, S. L. . . . . 921 Pothoulakis, C. 1257 Biltz, R...... 1298 Girard, J...... 1163 Kusari, J...... 1156 Pottratz, S. T. . ..944 Bini, P...... 1029 Goh, D ...... 1063 Kusuoka, H. .. 1216 Poulos, A...... 1063 Blot, Ph...... 1149 Golomb, G. . . . .1243 Kuwahara, M. 1250 Prins, B...... 1056 Bondy, C. A. . ...966 Goss, J. A . . . . .1312 Lacy, P. E . . . . . 1312 Protti, M. P. . . . . 1020 Bornfeldt, K. E. 1266 Granert, C. . . . . 929 Lalouel, J.-M. . ..1285 Pueyo, M. E. . . . .1120 Boulware, S. D. 1131 Graves, L. M.. . . .1266 LaMont, J. T.. .. 1257 Raines, E. W.. . . . 1266 Brandes, R. . . . . 951 Gronich, J...... 1224 Langlade-Demoyen, P. 1293 Ramesh, N. . . . .1315 Brandi, M. L.. . . . 1108 Gros, F...... 1195 Latchman, D. S.. . . 1087 Ramos, P...... 1029 Brown, E. M.. . . . 1108 Grunfeld, J.-P. ...1195 Lee, M.-S...... 1332 Rasmussen, L. M. . .1172 Broxmeyer, H. E. ..919 Gubler, M.-C.. . . .1195 Lefer, A. M. .. 1140 Raud, J...... 929 Broyer, M...... 1195 Guzman, L. A. 1243 Levin, E. R. .. 1056 Reinhardt, R. R. . 966 Buerke, M...... 1140 Haffner, D. . . . .1163 Levy, R. J...... 1243 Remmers, E. F. 1095 Burdick, M. D. 921 Hagenbuch, B. 1326 Lindbom, L. . . 929 Rennert, N. J. 1131 Byrne, M. M. . . 1120 Hagerty, D. T. 1208 Lindquist, L. .. 929 Rice, H...... 1051 Camacho, S. A. 951 Haines, G. K.. . . . 921 Linevsky, J. K. 1257 Richter, E. A.. . . .974 Carrara, F . . . . . 1102 Hardy, S. J. . . . .1063 Longmuir, K. .. 1298 Ristimaki, A. P. . . .1095 Charpie, J. R.. . . . 1339 Harlow, L. A.. . . . 921 Looney, D. J. ... 920 Ritz, E...... 1163 Chen, W...... 1243 Harmon, W. . ...1315 Lutterbaugh, J. . . 1005 Roberts, L. J., II . 998 Cherkes, J. K.. . . . 1179 Harvey, D. P.. . . .1063 Lynch, S. M. . . 998 Robinson, B. S. . 1063 Chin, E...... 966 Hashimoto, T. ...1035 Manolagas, S. C. . 944 Roby, J. D. . 1234 Chou, Y.-H. W. . . . 1108 Hata, A...... 1285 Marban, E. . . 1216 Roos, M. T. L. 982 Chuang, M.-Y. 1056 Haymond, M. W. ..1014 Marber, M. S.. . . . 1087 Ross, R...... 1266 Clarke, B. L. ... 989 He,N.G . ... 958 Mariotti, C. . . . . 1102 Roth, R. A. ... 966 Clement, K. ... 1120 Hedrick, M. . . . .1051 Markowitz, S. D. 1005 Ruoslahti, E. ... 1172 Cohen, D...... 1120 Hendy, G. N . . . .1108 Marumo, F. . 1250 Saito, F...... 1250 Cole, D. E. C. . . ..1108 Henry, R. R. . . . .1156 Marx,S.J. .... 1108 Saito, H...... 1250 Conti-Tronconi, B. M.. 1020 Hespel, P...... 974 Mauras, N...... 1014 Sano, H...... 1095 Cooper, M. J. . . ..1005 Hii, C. S. T. . . . .1063 Mayor, Federico, Jr. 937 Sarvetnick, N. . . .1332 Crabb, D...... 944 Hill, D. E...... 1156 Mazarakis, D. D . 921 Sasaki, M...... 1285 Crofford, L. J. . . . 1095 Hla, T...... 1095 Mecham, R. P . 1234 Sasaki, S...... 1250 Dallapiccola, B. . . 1102 Hoganson, G.. . . .1035 Mehis, O...... 1163 Sasayama, S. . . . .1275 Darmaun, D. . . . . 1014 Hollak, C. E. M.. . .1288 Meier, P. J. ... 1326 Sato, K ...... 1285 Deschenes, G. . ..1195 Horner, A . . . . . 1315 Menko, F. H.. .. 1108 Saxena, M...... 958 Dickey, B. F. . . . . 1257 Hors-Cayla, M.-C. ..1195 Meyaard, L. ... 982 Schaefer, F. ... 1163 DiDonato, S. . . . . 1102 Housley, R. M. . . . 1298 Miedema, F. ... 982 Schreur, K. D. 1339 Ding, L...... 966 Howard, J. F., Jr. ..1020 Mocharla, H. ... 944 Sedor, J. R. .. 1224 Drappa, ...... 1029 Hu, R.-M...... 1056 Moiola, L...... 1020 Seidman, C. E. 1108 Drouot, L...... 1195 Hunziker, E. B. ...1078 Morgan, J. P. 1275 Seidman, J. G. 1108 Durmowicz, A. G. ..1234 Ikeuchi, T...... 1250 Morris, C. A. 1071 Seino, S...... 1321 Elkon, K. B. . . . . 1029 Imamura, M. . ...1321 Morris, C. F. 1298 Seino,Y. . .. 1321 Epps, H. R. . . . . 1095 Imura, H...... 1321 Morrow, J. D. 998 Sharma, R. . . 958 Evain-Brion, D. . . 1149 Ingram, R. T . . . ..989 Munafo, D. A. . . . 1042 Sherwin, R. S. 1131 Evavold, B. D. . . 1208 Inoko, M...... 1275 Myeroff, L. . . . . 1005 Shimatsu, A. . . . . 1321

1345 Shindo, K. . . 1042 Tamborlane, W. V. 1131 Vieira, N. E. . 1014 Xie, X. . . 929 Shizuru, J. . . 1332 Tamura, K. 1285 Villa, A. E. 1243 Yamada, Y. * . 1321 Singh, S. V. . . 958 Tavassoli, M.. . 1051 Vionnet, N. . 1120 Yamaguchi, S. . . 1035 Singhal, S. S. . . 958 Tiranti, V. . 1102 Wagner, J. . 1078 Yellon, D. M.. . . 1087 Smith, J. J. . 1307 Topol, E. J. . 1243 Wakazono, A. . 1035 Yergey, A. L. . . 1014 Srivastava, S. K. . . 958 Traicoff, J. . . 1005 Walker, J. M.. . 1087 Yi, E. S.. . . 1298 Stamenkovic, I. . . 1315 Tryggvason, K. . 1195 Watanabe, T. X.. . 1250 Yin, S. . . 1298 Steinmann, B. . . 1108 Tsuda, K. . 1321 Webb, R. C. 1339 Zachor, D.. . . 1179 Stenmark, K. R. . . 1234 Tuomanen, E. 917 Weiner, M. W. 951 Zanjani, E. D. . . 1051 Stoffel, M. . . . 1120 Uchida, S. . 1250 Welsh, M. J. . 1307 Zapf, J. . . 1078 Strieter, R. M. . . 921 Ulich, T. R. . 1298 Weyrich, A. S. . 1140 Zeviani, M. . . 1102 Sturis, J. . . 1120 van Oers, M. H. J. . 1288 Wilder, R. L. . 1095 Zheng, Z. . . 1140 Suh, K.-I. . . 1156 van Weely, S. . . 1288 Willson, J. K. V. . . 1005 Zhou, J. 966, 1195 Swiriduk, M. . . 1005 Velho, G. . 1120 Wogensen, L. 1332 Ziller, S. A., III . . 958 Takeda, J. . . 1120 Vergauwen, L. 974 Wolf, Y. G. . 1172 Zimniak, P. . . 958

1346 Contents

The Journal of Clinical Investigation March 1994, Volume 93, Number 3

Editorials Identification of a novel exonic mutation at - 13 from 5' splice site causing exon skipping in a girl with mitochondrial acetoacetyl-coenzyme A spoonful of sugar to control ? E. Tuomanen . 917 A thiolase deficiency. T. Fukao, S. Yamaguchi, A. Wakazono, T. Orii, Consequences of human stem cells taking up residence in sheep. G. Hoganson, and T. Hashimoto ...... 1035 H. E. Broxmeyer. 919 Leukotriene A4 hydrolase in human bronchoalveolar lavage fluid. Immune responses to human immunodeficiency virus type 1 in exposed D. A. Munafo, K Shindo, J. R. Baker, and T. D. Bigby ...... 1042 but uninfected individuals: protection or chance? D. J. Looney . 920 Long-term repopulating ability of xenogeneic transplanted human fetal liver hematopoietic stem cells in sheep. E. D. Zanjani, A. W. Flake, Regular Articles H. Rice, M. Hedrick, andM. Tavassoli. 1051 Macrophage inflammatory protein-Ia. A novel chemotactic cytokine for High density lipoproteins stimulate the production and secretion of macrophages in rheumatoid arthritis. A. E. Koch, S. L. Kunkel, endothelin- 1 from cultured bovine aortic endothelial cells. R.-M. Hu, L. A. Harlow, D. D. Mazarakis, G. K Haines, M. D. Burdick, M.-Y. Chuang, B. Prins, M. L. Kashyap, H. J. L. Frank, A. Pedram, R. M. Pope, and R. M. Strieter. 921 andE. R. Levin . 1056 Inhibition of leukocyte rolling with polysaccharide fucoidin prevents Neutrophil migration inhibitory properties of polyunsaturated fatty pleocytosis in experimental meningitis in the rabbit. C. Granert, J. Raud, acids. The role of fatty acid structure, metabolism, and possible second X. Xie, L. Lindquist, and L. Lindbom. 929 messenger systems. A. Ferrante, D. Goh, D. P. Harvey, B. S. Robinson, Rapid desensitization of neonatal rat liver jtadrenergic receptors. A role C. S. T. Hii, E. J. Bates, S. J. Hardy, D. W Johnson, andA. Poulos . 1063 for fl-adrenergic receptor kinase. I. Garcia-Higuera Supravalvular aortic stenosis associated with a deletion disrupting the and Federico Mayor, Jr. . 937 elastin gene. A. K Ewart, W Jin, D. Atkinson, C. A. Morris, 17 f3-Estradiol inhibits expression of human interleukin-6 promoter- andM. T. Keating . 1071 reporter constructs by a receptor-dependent mechanism. S. T. Pottratz, Differential effects of insulin-like growth factor I and growth hormone T. Bellido, H. Mocharla, D. Crabb, and S. C. Manolagas . 944 on developmental stages of rat growth plate chondrocytes in vivo. Ca2" transient decline and myocardial relaxation are slowed during low E. B. Hunziker, J. Wagner, andJ. Zapf ...... 1078 flow ischemia in rat hearts. S. A. Camacho, R. Brandes, Myocardial protection after whole body heat stress in the rabbit is V. M. Figueredo, andM. W. Weiner. 951 dependent on metabolic substrate and is related to the amount of the Adenosine triphosphate-dependent transport of doxorubicin, inducible 70-kD heat stress protein. M. S. Marber, J. M. Walker, daunomycin, and vinblastine in human tissues by a mechanism distinct D. S. Latchman, andD. M. Yellon ...... 1087 from the P-glycoprotein. S. Awasthi, S. S. Singhal, S. K Srivastava, Cyclooxygenase-I and -2 expression in rheumatoid synovial P. Zimniak, K K Bajpai, M. Saxena, R. Sharma, S. A. Ziller III, tissues. Effects of interleukin- I#, phorbol ester, and corticosteroids. E. P. Frenkel, S. V. Singh, N. G. He, and Y. C. Awasthi. 958 L. J. Crofford, R. L. Wilder, A. P. Ristimaki, H. Sano, E. F. Remmers, Cellular distribution of insulin-degrading enzyme gene H. R. Epps, and T. Hla ...... 1095 expression. Comparison with insulin and insulin-like growth factor Defective respiratory capacity and mitochondrial protein synthesis in receptors. C. A. Bondy, J. Zhou, E. Chin, R. R. Reinhardt, L. Ding, transformant cybrids harboring the tRNAI(1tUR) mutation associated and R. A. Roth. 966 with maternally inherited myopathy and cardiomyopathy. C. Mariotti, Adenosine receptors mediate synergistic stimulation of glucose uptake V. Tiranti, F. Carrara, B. Dallapiccola, S. DiDonato, andM. Zeviani 1102 and transport by insulin and by contractions in rat skeletal muscle. Familial hypocalciuric hypercalcemia and neonatal severe L. Vergauwen, P. Hespel, and E. A. Richter . 974 hyperparathyroidism. Effects of mutant gene dosage on phenotype. Programmed death of T cells in human immonodeficiency virus M. R. Pollak, Y.-H. W. Chou, S. J. Marx, B. Steinmann, D. E. C. Cole, infection. No correlation with progression to disease. L. Meyaard, M. L. Brandi, S. E. Papapoulos, F. H. Menko, G. N. Hendy, S. A. Otto, 1. P. M. Keet, M. T. L. Roos, and F. Miedema . 982 E. M. Brown, C. E. Seidman, andJ. G. Seidman ...... 1108 Age- and gender-related changes in the distribution of osteocalcin in the Characterization of mixed syngeneic-allogeneic and syngeneic- extracellular matrix of normal male and female bone. Possible xenogeneic islet-graft rejections in mice. Evidence of functional involvement of osteocalcin in bone remodeling. R. T. Ingram, impairment of the remaining syngeneic islets in xenograft rejections. 989 . . 1113 Y.-K Park, B. L. Clarke, and L. A. Fitzpatrick. 0. Korsgren and L. Jansson ...... Formation of non-cyclooxygenase-derived prostanoids Insulin secretory abnormalities in subjects with hyperglycemia due to (F2-isoprostanes) in plasma and low density lipoprotein exposed to glucokinase mutations. M. M. Byrne, J. Sturis, K Clement, N. Vionnet, oxidative stress in vitro. S. M. Lynch, J. D. Morrow, L. J. Roberts II, M. E. Pueyo, M. Stoffel, J. Takeda, P. Passa, D. Cohen, G. L Bell, and B. Frei. 998 G. Velho, P. Froguel, and K S. Polonsky ...... 1120 A benign cultured colon adenoma bears three genetically altered colon Comparison of the metabolic effects ofrecombinant human insulin-like cancer oncogenes, but progresses to tumorigenicity and transforming growth factor-I and insulin. Dose-response relationships in healthy growth factor-beta independence without inactivating the p35 tumor young and middle-aged adults. S. D. Boulware, W V. Tamborlane, suppressor gene. S. D. Markowitz, L. Myeroff; M. J. Cooper, J. Traicoff N. J. Rennert, N. Gesundheit, andR. S. Sherwin ...... 1131 andJ. K V 1005 M. Kochera, J. Lutterbaugh, M. Swiriduk, Willson Sialyl lewis-containing oligosaccharide attenuates myocardial Calcium and protein kinetics in prepubertal boys. Positive effects of reperfusion injury in cats. M. Buerke, A. S. Weyrich, Z. Zheng, testosterone. N. Mauras, M. W Haymond, D. Darmaun, N. E. Vieira, F. C. A. Gaeta, M. J. Forrest, andA. M. Lefer . 1140 1014 S. A. Abrams, andA. L. Yergey. Alterations of human placental epidermal growth factor receptor in Epitopes on the , subunit of human muscle acetylcholine receptor intrauterine growth retardation. C. Fondacci, E. Alsat, R. Gabriel, recognized by CD4' cells of myasthenia gravis patients and healthy Ph. Blot, C. Nessmann, and D. Evain-Brion . 1149 subjects. L. Moiola, P. Karachunski, M. P. Protti, J. F. Howard, Jr., 1020 Skeletal muscle protein tyrosine phosphatase activity and tyrosine and B. M. Conti-Tronconi ...... phosphatase I B protein content are associated with insulin action and The apoptosis-l/Fas protein in human systemic lupus erythematosus. resistance. J. Kusari, K A. Kenner, K-I. Suh, D. E. Hill, E. Mysler, P. Bini, J. Drappa, P. Ramos, S. M. Friedman, and R. R. Henry. 1156 P. H. Krammer, and K B. Elkon ...... 1029 Metabolic clearance of recombinant human growth hormone in health Rapid Publications and chronic renal failure. D. Haffner, F. Schaefer, J. Girard, E. Ritz, and 0. Mehis. 1163 Angiotensinogen as a risk factor for essential hypertension in Japan. A. Hata, C Namikawa, M. K T K Antibodies against transforming growth factor-,6l suppress intimal Sasaki, Sato, Nakamura, Tamura, and J.-M. Lalouel ...... hyperplasia in a rat model. Y. G. Wolf; L. M. Rasmussen, 1285 and E. Ruoslahti. 1172 Marked elevation Of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. E. M. S. van M. H. Cocaine differentially inhibits neuronal differentiation and C. Hollak, Weely, J. van Oers, proliferation and M. G. Aerts in vitro. D. Zachor, J. K Cherkes, C. T. Fay, and . Ocrant. 1179, I ,r, J. F...... 1288 Human immunodeficiency virus (HIV) cytotoxic T Effects ofdietary cholesterol on cholesterol and bile acid homeostasis in nef-specific lymphocytes in noninfected heterosexual contact of patients with cholesterol gallstones. F. Jr. 1186 HIV-infected Kern, patients. P. Langlade-Demoyen, N. Ngo-Giang-Huong, F. Ferchal, Deletions in the COL4A5 collagen gene in X-linked alport and E. Oksenhendler ...... 1293 syndrome. Characterization of the pathological in nonrenal transcripts factor is a factor for cells and correlation with disease Keratinocyte growth growth type II pneumocytes in expression. C. Antignac, vivo. T. R. Ulich, E. S. Yi, K Longmuir, S. Yin, R. Biltz, C. F. B. Knebelmann, L. Drouot, F. Gros, G. Deschbzes, M.-C. Hors-Cayla, Morris, R. M. Housley, and G. F. Pierce ...... J. Zhou, K Tryggvason, J.-P. Grunfeld, M. Broyer, andM.-C. Gubler 1195 1298 Defective fluid transport by cystic fibrosis airway epithelia. J. J. Smith, Regulation ofthe costimulator B7, not class II major histocompatibility P. H. Karp, and M. J. Welsh ...... 1307 complex, restricts the ability of murine kidney tubule cells to stimulate Induction ofimmune unresponsiveness to concordant islet xenografts by CD4' T cells. D. T. Hagerty, B. D. Evavold, and P. M. Allen . 1208 intrahepatic preimmunization and transient immunosuppression. Mechanism of the diastolic dysfunction induced by glycolytic J. A. Goss, E. H. Finke, M. W. Flye, and P. E. Lacy ...... 1312 inhibition. Does adenosine triphosphate derived from glycolysis play a favored role in cellular Ca2" homeostasis in ferret myocardium? Cyclosporin A inhibits CD40 ligand expression in T lymphocytes. R. H. Kusuoka and E. Marban ...... 1216 Fuleihan, N. Ramesh, A. Homer, D. Ahern, P. J. Be/shaw, D. G. Alberg, I. Stamenkovic, W. Harmon, and R. S. Geha . . . . . 1315 Interleukin la causes rapid activation of cytosolic phospholipase A2 by phosphorylation in rat mesangial cells. J. Gronich, M. Konieczkowski, Identification of somatostatin receptor subtypes and an implication for M. H. Gelb, R. A. Nemenoff; and J. R. Sedor 1224 the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors. A. Kubota, Y. Yamada, S. Kagimoto, Persistence of the fetal of in severe pattern tropoelastin gene expression A. Shimatsu, M. Imamura, K. Tsuda, H. Imura, S. Seino, and Y. Seino 1321 neonatal bovine pulmonary hypertension. K R. Stenmark, A. G. Durmowicz, J. D. Roby, R. P. Mecham, and W. C Parks 1234 Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter. Local delivery of dexamethasone for prevention of neointimal B. Hagenbuch and P. J. Meier ...... 1326 proliferation in a rat model of balloon angioplasty. A. E. Villa, L. A. Guzman, W. Chen, G. Golomb, R. J. Levy, and E. J. Topol 1243 Pancreatic islet production of murine interleukin-10 does not inhibit immune-mediated tissue destruction. M.-S. Lee, L. Wogensen, Cloning, characterization, and chromosomal mapping of human J. Shizuru, M. B. A. Oldstone, and N. Sarvetnick ...... 1332 aquaporin of collecting duct. S. Sasaki, K. Fushimi, H. Saito, F. Saito, S. Uchida, K Ishibashi, M. Kuwahara, T. Ikeuchi, K-i. Inui, Endothelium dependency of contractile activity differs in infant and adult vertebral arteries. J. R. Charpie, K. D. Schreur, K Nakajima, T. X. Watanabe, and F. Marumo . 1250 S. M. Papadopoulos, and R. C. Webb ...... 1339 Neutrophil recruitment in Clostridium difficile toxin A enteritis in the rabbit. C P. Kelly, S. Becker, J. K Linevsky, M. A. Joshi, J. C O'Keane, March Author Index ...... 1345 B. F. Dickey, J. T. LaMont, and C. Pothoulakis ...... 1257 Correction ...... 1347

Insulin-like growth factor-I and platelet-derived growth factor-BB induce Correction ...... 1349 directed migration ofhuman arterial smooth muscle cells via signaling pathways that are distinct from those of proliferation. K E. Bornfeldt, E. W. Raines, T. Nakano, L. M. Graves, E. G. Krebs, and R. Ross 1266 Sodium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium. Evidence from aequorin-loaded ferret ventricular muscles. Y. Kihara, S. Sasayama, M. Inoko, and J. P. Morgan ...... 1275 Differential effects of insulin-like growth factor I and growth hormone Adenosine receptors mediate synergistic stimulation of glucose uptake on developmental stages of rat growth plate chondrocytes in vivo. and transport by insulin and by contractions in rat skeletal muscle. E. B. Hunziker, J. Wagner, andJ. Zapf ...... 1078 L. Vergauwen, P. Hespel, and E. A. Richter ...... 974 Characterization of mixed syngeneic-allogeneic and syngeneic- Myocardial protection after whole body heat stress in the rabbit is xenogeneic islet-graft rejections in mice. Evidence of functional dependent on metabolic substrate and is related to the amount of the impairment of the remaining syngeneic islets in xenograft rejections. inducible 70-kD heat stress protein. M. S. Marber, J. M. Walker, 0. Korsgren and L. Jansson. 1113 D. S. Latchman, and D. M. Yellon ...... 1087 Comparison ofthe metabolic effects ofrecombinant human insulin-like Mechanism of the diastolic dysfunction induced by glycolytic growth factor-I and insulin. Dose-response relationships in healthy inhibition. Does adenosine triphosphate derived from glycolysis play a young and middle-aged adults. S. D. Boulware, W. V. Tamborlane, favored role in cellular Ca2" homeostasis in ferret myocardium? N. J. Rennert, N. Gesundheit, and R. S. Sherwin. I H. Kusuoka and E. Marban. 1216 Alterations of human placental epidermal growth factor receptor in Cloning, characterization, and chromosomal mapping of human intrauterine growth retardation. C. Fondacci, E. Alsat, R. Gabriel, aquaporin of collecting duct. S. Sasaki, K Fushimi, H. Saito, F. Saito, Ph. Blot, C. Nessmann, and D. Evain-Brion . S. Uchida, K Ishibashi, M. Kuwahara, T Ikeuchi, K-i. Inui, Metabolic clearance of recombinant human growth hormone in health K Nakajima, T. X. Watanabe, and F. Marumo. 1250 and chronic renal failure. D. Haffner, F. Schaefer, J. Girard, E. Ritz, Sodium/calcium exchange modulates intracellular calcium overload and 0. Mehis. 1163 during posthypoxic reoxygenation in mammalian working Antibodies against transforming growth factor-fil suppress intimal myocardium. Evidence from aequorin-loaded ferret ventricular muscles. hyperplasia in a rat model. Y. G. Wolf; L. M. Rasmussen, Y. Kihara, S. Sasayama, M. Inoko, andJ. P. Morgan ...... 1275 and E. Ruoslahti. 1172 t Molecular cloning, chromosomal localization, and functional Interleukin la causes rapid activation of cytosolic phospholipase A2 by characterization of a human liver Na+/bile acid cotransporter. phosphorylation in rat mesangial cells. J. Gronich, M. Konieczkowski, B. Hagenbuch and P. J. Meier. 1326 M. H. Gelb, R. A. Nemenoff; and J. R. Sedor. 1224 * Endothelium dependency of contractile activity differs in infant and Insulin-like growth factor-I and platelet-derived growth factor-BB induce adult vertebral arteries. J. R. Charpie, K D. Schreur, directed migration ofhuman arterial smooth muscle cells via signaling S. M. Papadopoulos, and R. C. Webb. 1339 pathways that are distinct from those of proliferation. K E. Bornfeldt, * Atherosclerosis Thrombosis Metabolism E. W Raines, T. Nakano, L. M. Graves, E. G. Krebs, and R. Ross / / * Induction ofimmune unresponsiveness to concordant islet xenografts by Formation of non-cyclooxygenase-derived prostanoids intrahepatic preimmunization and transient immunosuppression. (F2-isoprostanes) in plasma and low density lipoprotein exposed to J. A. Goss, E. H. Finke, M. W. Flye, and P. E. Lacy . oxidative stress in vitro. S. M. Lynch, J. D. Morrow, L. J. Roberts II, and B. Frei. 998 N Cell Growth and Differentiation High density lipoproteins stimulate the production and secretion of Long-term repopulating ability of xenogeneic transplanted human fetal endothelin-l from cultured bovine aortic endothelial cells. R.-M. Hu, liver hematopoietic stem cells in sheep. E. D. Zanjani, A. W Flake, M.-Y. Chuang, B. Prins, M. L. Kashyap, H. J. L. Frank, A. Pedram, and E. R. Levin . 1056 H. Rice, M. Hedrick, andM. Tavassoli ...... 1051 Cocaine differentially inhibits neuronal differentiation and proliferation Skeletal muscle protein tyrosine phosphatase activity and tyrosine phosphatase IB protein content are associated with insulin action and in vitro. D. Zachor, J. K Cherkes, C. T. Fay, and . Ocrant . . . . . 1179 resistance. J. Kusari, K A. Kenner, K-I. Suh, D. E. Hill, Persistence of the fetal pattern oftropoelastin gene expression in severe and R. R. Henry. 1156 neonatal bovine pulmonary hypertension. K R. Stenmark, A. G. Durmowicz, J. D. Roby, R. P. Mecham, and W. C. Parks . 1234 Effects ofdietary cholesterol on cholesterol and bile acid homeostasis in patients with cholesterol gallstones. F. Kern, Jr. 1186 t Keratinocyte growth factor is a growth factor for type II pneumocytes in vivo. T. R. Ulich, E. S. Yi, K Longmuir, S. Yin, R. Biltz, C. F. Morris, Local delivery of dexamethasone for prevention of neointimal proliferation in a rat model of balloon angioplasty. A. E. Villa, R. M. Housley, and G. F. Pierce ...... 1298 L. A. Guzman, W. Chen, G. Golomb, R. J. Levy, and E. J. Topol 1243 * Transport and Cellular, Organ March Author Index. . . 1345 Ca2+ transient decline and myocardial relaxation are slowed during low Correction ...... 1347 flow ischemia in rat hearts. S. A. Camacho, R. Brandes, Correction ...... 1349 V. M. Figueredo, and M. W Weiner. 951 Adenosine triphosphate-dependent transport of doxorubicin, daunomycin, and vinblastine in human tissues by a mechanism distinct from the P-glycoprotein. S. Awasthi, S. S. Singhal, S. K. Srivastava, P. Zimniak, K K Bajpai, M. Saxena, R. Sharma, S. A. Ziller III, * Perspectives article E. P. Frenkel, S. V. Singh, N. G. He, and Y. C Awasthi. 958 t Rapid Publication

Coverpicture: Immunohistochemical staining ofosteopontin, osteonectin, osteocalcin, and decorin (clockwise from bottom left) in adjacent sections ofnormal human cortical bone (X 100). See related article in this issue by Ingram R. T., Y. K. Park, B. L. Clarke, and L. R. Fitzpatrick, pp. 989-997.