ADVANCES IN SWINE IN BIOMEDICAL RESEARCH

Volume 2

ADVANCES IN SWINE IN BIOMEDICAL RESEARCH

Volume 2

Edited by

Mike E. T umbleson University of Illinois

Urbana, J1Jinois

ond

Lawrence B. Schook University of Minnesota

SI. Paul, Minnesota

Springer Science+Business Media, LLC

Library of Congress Cataloging in Publication Data

Advances in swine in biomedical research / edited by Mike E. Thmbleson and Lawrence B. Schook.

p. cm. "Proceedings of an International Symposium on Swine in Biomedical Research, held De­

tober 22-25, 1995, at the University of Maryland, University College Park, Maryland"-T.p. versa.

Inc\udes bibliographical references and index. ISBN 978-1-4613-7699-6 ISBN 978-1-4615-5885-9 (eBook) DOI 10.1007/978-1-4615-5885-9 1. Diseases-Animal models-O>ngresses. 2. Swine as laboratory animals-Congresses. 1.

Thmbleson, M. E. (Mike E.) II. Schook, Lawrence B. III. International Symposium on Swine in Biomedical Research (1995: University of Maryland)

[DNLM: 1. Disease Models, Animal-congresses. 2. Swine-physiology-congresses. 3. Genetic Engineering-congresses. QY 6O.S8 A244 1996] RBl25.A36 1996 619'.9-DC20 DNLM/DLC for Library of Congress

96-38650 CIP

Proceedings of an International Symposium an Swine in Biomedical Research, held October 22-25, 1995, atthe University 01 Maryland, University College Park, Maryland

ISBN 978-1-4613-7699-6

© 1996 Springer Science+Business Media New York

Originally published by Plenum Press, New York in 1996

Softcover reprint of the hardcover 1 st edition 1996

AII rights reserved

10987654321

No part 01 this book may be reproduced, stored in a retrieval system, ar transmitted in any lorm or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise,

without written permission lrom the Publisher

We wish to give special thanks to

Jenny Malakowsky and

Treena Schmidt

for their assistance in preparing this publication

PREFACE

Similarities in structure and function between pigs and human beings include size, feeding patterns, digestive physiology, dietary habits, kidney structure and function, pulmo­nary vascular bed structure, coronary artery distribution, propensity to obesity, respiratory rates, tidal volumes and social behaviors. Since the pig is an omnivore, it provides an adaptable model to evaluate chronic and acute exposures to xenobiotics such as alcohoL caffeine, tobacco, food additives and environmental pollutants. Swine have been used successfully as models to evaluate alcoholism, diabetes, absorption, digestion, total paren­teral nutrition, organ transplantation, atherosclerosis, exercise, hypertension. hemorrhagic hypotension, melanoma, gingivitis, obstructive and reflux nephropathy. osteochondrosis. dermal healing and septic shock.

A severe and worsening shortage of organs and tissues for transplantation in patients with severe organ failure has encouraged the consideration of inter species or xenotransplan­tation. In developing programs toward this end, the pig generally is viewed as the preferred donor because of its size, physiology and availability. The pig harbors relatively few diseases which could be transmitted inadvertently to human patients. The ability to genetically modify swine to ameliorate the consequences of the human immune response offers a further significant advantage.

Another important consideration for an animal model is that basic biologic back­ground information be available for investigators to design future prospective studies. Animal models should accurately and precisely emulate human conditions; survive sufficient time to be functional; provide for multiple and serial samples; and have a gestation period adequate for intervention. When considering human fetal research. one must appraise the ethical implications; therefore. it is paramount that an animal model be developed.

Limitations on the development of animal biotechnologic advances may restrict opportunities for improving human health. With respect to biologic interactions. interrela­tionships between human health and animal biotechnology are symbiotic as well as syner­gistic. The relationship of bioscience and biotechnology to developing countries is not so much one of aggressive impact and doubtful benefits, but of indispensability.

Mike Tumbleson, University of Illinois Larry Schook, University of Minnesota

vii

ACKNOWLEDGMENTS

The coeditors wish to extend appreciation to members ofthe organizing and scientific committees. They provided assistance in developing the sound technical program, as well as aiding in peer review of the submitted papers. Participating individuals were:

• Craig Beattie, USDA/ARS/MARC • Richard Binns, The Babraham Institute • David Brown, University of Minnesota • Harold Gonyou, Prairie Swine Centre • Eric Johnson, University of Minnesota • Charles Louis, University of Minnesota • Arthur Matas, University of Minnesota • James Mickelson, University of Minnesota • Thomas Molitor, University of Minnesota • Nancy Monteiro-Riviere, North Carolina State University • Michael Murtaugh, University of Minnesota • Jack Odie, North Carolina State University • Reinhard Pabst, Hannover Medical School • Linda Panepinto. Panepinto & Associates • Victor Perman, University of Minnesota • Jeffrey Platt, Duke University • Peter Reeds, USDAI ARS/CNRC • Mark Rutherford, University of Minnesota • Gail Scherba, University of Illinois • Steve Squinto, Alexion Pharmaceutical • Bert Stromberg, University of Minnesota • James Terris, Uniformed Services University • Matthew Wheeler, University of Illinois • Federico Zuckermann, University of Illinois

ix

CONTENTS

Volume 2

Methods and Techniques

37. Swine Research Breeds, Methods, and Biomedical Models .................. 423 Michael P. Murtaugh, Nancy A. Monteiro-Riviere, and Linda Panepinto

38. The Pig as a Model for Cutaneous Pharmacology and Toxicology Research .... 425 Nancy A. Monteiro-Riviere and Jim Riviere

39. An in vitro Pig Skin Model for Predicting Human Skin Penetration and Irritation Potential .............................................. 459

William G. Reifenrath, Barbara W. Kemppainen, and Winifred G. Palmer

40. Swine Liver Usage in Extracorporeal Detoxification ....................... 475 Vyacheslav E. Ryabinin

41. Pig Behavior and Biomedical Research: Suitable Subjects and Experimental Models ............................................ ' ........... 485

Harold W. Gonyou

42. Current Status of in vitro Production of Porcine Embryos ................... 491 Hiroaki Funahashi and Billy N. Day

43. Reproductive Physiology in Chinese Meishan Pigs: A University of Illinois Perspective .................................................... 503

Brett R. White, JoElla Barnes, and Matthew B. Wheeler

44. Selection for Extremes in Serum FSH Concentrations Results in Reduced Testis Size and Fertility in Meishan and White Composite Boars ......... 523

Donald D. Lunstra, J. Joe Ford, and Thomas H. Wise

45. Reproductive Characteristics in Sinclair Miniature Swine ................... 533 Guy F. Bouchard, Ronald M. McLaughlin, Mark R. Ellersieck,

Gary F. Krause, Craig Franklin, and Chada S. Reddy

xi

xii Contents

46. A Comparison of Physiological and Biochemical Parameters in Fully Conscious Hormel-Hanford and Yucatan Strains of Miniature Pig ........ 543

George 1. Ikeda, Theodore C. Michel, Dennis W. Gaines, Vira L. Olivito, Philip P. Sapienza, Leonard Friedman, Curtis N. Barton, and Michael W. O'Donnell

47. Biochemical Indices of Stress Associated with Short-Term Restraint in Hormel and Yucatan Miniature Swine ..................................... 557

Leonard Friedman, Linda Panepinto, Dennis W. Gaines, Ruey Chi, Robert C. Braunberg, and James Terris

48. The Minipig as a Model for the Study of Aging in Humans: Selective Responses of Hormones Involved in Carbohydrate and Lipid Metabolism in Different Sexes .............................................. 571

Sam 1. Bhathena, Elliott Berlin, and Wesley A. Johnson

49. Aging and Miniature Swine Heart and Liver Plasma Membranes ............. 581 Elliott Berlin, Melanie A. Banks, Sam 1. Bhathena, Renee C. Peters, and

Wesley A. Johnson

50. Comparing Porcine Models of Coronary Restenosis ....................... 595 Robert N. Willette, Hong Zhang, Calvert Louden and Robert K. Jackson

51. Sinclair Miniature Swine Melanoma as a Model for Evaluating Novel Lymphography Contrast Agents ................................... 607

David K. Johnson, Erik R. Wisner, Stephen M. Griffey, Adele R. Vessey, and Patrick J. Haley

52. The Yucatan Miniature Pig Model of Ventricular Septal Defect ............... 613 M. Michael Swindle, Robert P. Thompson, Alison C. Smith,

George B. Keech, Blase A. Carabello, Wolfgang Radtke, Derek Fyfe and Paul C. Gillette

53. An External Thoracic Duct Venous Shunt to Allow for Long Term Collection of Lymph and Blood in the Conscious Pig ........................... 621

H. Vince Mendenhall, Christopher Horvath, Marek Piechowiak, Lisa Johnson, and Kim Bayer

54. Pregnant Yucatan Miniature Swine as a Model for Investigating Fetal Drug Therapy ...................................................... 629

Donald B. Wiest, M. Michael Swindle, Sandra S. Gamer, Alison C. Smith, Paul C. Gillette

55. A Swine Model for Determining the Bioavailability of Lead From Contaminated Media ............................................ 637

Stan W. Casteel, Ross P. Cowart, Christopher P. Weis, Gerry M. Henningsen, Eva Hoffman, William J. Brattin, Matthew F. Starost, John T. Payne, Steven L. Stockham, Stephen V. Becker, and James R. Turk

Contents xiii

56. Evaluation of Sinclair Miniature Swine as an Osteopenia Model ............. 647

Guy F. Bouchard, Rogely W. Boyce, Carol L. Paddock, Edward Durham, and Chada S. Reddy

57. Neovascularization of the Ischemic Myocardium by Cardiomyoplasty: Its Study Using the Casting Method and Selective Acute Myocardial Infarction in Swine ............................................. 653

Jose M. Borrego, Antonio Ordonez, Ana Hernandez, and Jose Perez

58. Vaccination Study with the Sinclair Miniature Swine-Effect of Vaccine Dose and Litter ..................................................... 663

Guy Bouchard, Edward Durham, Boh Chang Lin, Susan Turnquist, and Chada Reddy

59. Early Characterization of Panepinto Micro/Miniature Swine for Use as Transgenic Animal Models ....................................... 671

Victoria Hampshire, John Bacher, Melvin Dennis, Axel Wolff, and Melissa Yarko

60. Miniature Swine Breeds Used Worldwide in Research ...................... 681 Linda M. Panepinto

61. The Siberian Miniature Pig, Its Development, Genetics, and Use in Biomedical

Research ...................................................... 693

Vilen Tikhonov

Nutrition

62. Pigs as Models for Nutrient Functional Interaction ........................ 709 Peter Reeds and Jack Odie

63. A Piglet Model for Neonatal Amino Acid Metabolism during Total Parenteral Nutrition ...................................................... 713

Ronald O. Ball, James D. House, Linda 1. Wykes, and Paul B. Pencharz

64. The Neonatal Piglet as a Model to Study Insulin Like Growth Factor Mediated Intestinal Growth and Function ................................... 733

Sharon M. Donovan, Vicki M. Houle, Marcia H. Monaco, Elizabeth A. Schroeder, Yookyoung Park, and Jack OdIe

65. The Perinatal Pig in Pediatric Gastroenterology ........................... 745 Per. T. Sangild, Marian Silver, Mette Schmidt, and Abigail L. Fowden

66. Prenatal and Perinatal Development ofIntestinal Transport and Brush Border Hydrolases in Pigs .............................................. 757

Randal K. Buddington, Christiane Malo, and Hongzheng Zhang

xiv Contents

67. Changes in Pig Intestinal Structure and Functions and Resident Microbiota Induced by Acute Secretory Diarrhea ............................... 769

Gayatri Chandra, Monika Oli, Bryon W. Petschow, and Randal K. Buddington

68. Helicobacter Pylori Infection in Gnotobiotic Piglets: A Model of Human Gastric Bacterial Disease ........................................ 779

Steven Krakowka and Kathryn A. Eaton

69. An Experimental Rotaviral Enteritis Model with Neonatal Pigs .............. 811 Guillermo G. Gomez, Edward 1. Rozhon, Richard A. Goforth, and

Oulayvanh Thirakoune

70. Influence of Dietary Protein and Fat Sources on the Levels of Blood Homocysteine in a Pig Model: Preliminary Observations ............... 821

Ghulam Sarwar, Nimal Ratnayake, Robert W. Peace, and Herbert G. Botting

71. Lung Eicosanoid Production in Neonatal Pigs Fed Formula Supplemented with N-3 and N-6 Fatty Acids ......................................... 829

Margaret C. Craig-Schmidt and Meng-Chuan Huang

72. Genetically Diverse Pig Models in Nutrition Research Related to Lipoprotein and Cholesterol Metabolism ...................................... 843

Wilson G. Pond and Harry 1. Mersmann

73. Glucose and Fatty Acid Metabolism in the Newborn Pig .................... 865 Pierre-Henri Duee, Jean-Paul Pegorier, Beatrice Darcy-Vrillon, and

Jean Girard2

Author Index ........................................................... 885

Subject Index ........................................................... 889

Contents

CONTENTS

Volume 1

Overview

1. Advances in Swine in Biomedical Research ............................. . Mike E. Tumbleson and Lawrence B. Schook

General

2. Swine in Physiological and Pathophysiological Research David R. Brown and James M. Terris

3. Swine as a Model in Cardiovascular Research Jack E. McKenzie

xv

5

7

4. Porcine Endotoxemia: Chemical Mediators and Therapeutic Interventions ..... 19 Neil C. Olson

5. Bronchial Function in the Porcine Lung-From the Fetus to the Adult. . . . . . . . .. 33 Malcolm P. Sparrow

6. The Pig as a Model for Studying the Pathobiology ofIntestinal Transport in Infectious Enteric Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 45

Robert A. Argenzio

7. Developments in Breeding G6ttingen Minipigs ........................... 59 Peter 1. A. Bollen and Lars Ellegaard

8. Evaluation of the Mechanism of Cyclosporine A Nephrotoxicity ............. 67 David A. Calvert and James M. Terris

xvi Contents

9. Functional Modulation of the Porcine Small Intestine: Effects ofOpioids and Characteristics of Enteric Opioid Receptors ......................... 79

David R. Brown, Mark A. Osinski, Teresa R. Kowalski, Sutthasinee Poonyachoti, Mary S. Pampusch, and Michael P. Murtaugh

10. Ultrastructure of the Liver From Piglets Fed Dietary Oils ... . . . . . . . . . . . . . . .. 89 Amreek Singh, Cornelia Gilroy, and Esmail Shahidi

II. Effects of Fumonisins in Swine: Implications for Biomedical Research . . . . . . .. 99 Wanda M. Haschek, Laura A. Gumprecht, Geoffrey W. Smith,

Helen M. Parker, Val R. Beasley, and Mike E. Tumbleson

12. Artificial Surfactant as a Vehicle for Endotracheal Epinephrine in Pediatric Porcine Cardiopulmonary Arrest .................................. 113

Melinda S. Jasani, Vinay M. Nadkarni, Michael Szatkowski, John Stefano. Patricia Resnik, Gerald A. Mandell, and Steven K. Salzman

13. Age-Related Cardiovascular Responses to Phenyl Biguanide in Piglets ........ 123 Shiwei Tong, Isaac D. Frasier, Susan Ingenito, Anthony L. Sica,

Norman Gootman, and Phyllis M. Gootman

14. Differential Effects of Left and Right Cardiac Sympathetic Denervation on Ventricular Fibrillation Threshold in Developing Swine ................ 131

Shiwei Tong, Susan Ingenito, Isaac D. Frasier, Norman Gootman, and Phyllis M. Gootman

Transgenics

15. Transplantation and Genetic Manipulation in Porcine Systems ............... 141 Mark S. Rutherford

16. Immunologic Advances Towards Clinical Xenotransplantation ............... 147 Shu S. Lin and Jeffrey L. Platt

17. Assessment of Public Health Aspects of Porcine Xenotransplantation ......... 163 Peter J. Matthews and George W. Beran

18. Porcine Model of Orthotopic Liver Transplantation for Chronic Studies: Results of Initial Two Week Investigations of Biochemical Parameters and Hepatic Hemodynamics ...................................... 171

Mohammed Sika, James G. Drougas, Yolanda T. Becker, William C. Chapman, 1. Kelly Wright, Kevin L. Donovan, Volker I. Striepe, David B. Van Buren, Kathy A. Stokes, Sue Ellen Barnard, Kimberly Taylor Blair, Kareem Jabbour, Phillip E. Williams, and C. Wright Pinson

19. Genetic Engineering of Swine ......................................... 189 Vernon G. Pursel, Morse B. Solomon, and Robert 1. Wall

Contents xvii

20. Development of Swine Embryonic Stem (ES) Cells ........................ 207 Laurie A. Rund, Gregory T. Bleck, Melissa M. Izard, Linda R. Grum,

Raymond W. Gerfen, and Matthew B. Wheeler

21. PCR-RFLP Genotyping ofSLA-DQB and SLA-DRB Alleles ................ 223 Mark S. Rutherford, Xuexian Zhang, and Lawrence B. Schook

22. Identifying Tumor Initiator/Suppressor and Penetrance Associated Genes by Gene Mapping ............................................. 239

Timothy P. L. Smith and Craig W. Beattie

Immunology and Infectious Diseases

23. Immunology and Infectious Diseases of Swine ........................... 251 Reinhard Pabst and Gail Scherba

24. The Functional Structure of the Pig's Immune System, Resting, and Activated .. 253 Richard M. Binns and Reinhard Pabst

25. Immunological Functions of the Intestinal Lamina Propria .................. 267 Mick Bailey, Karen Haverson, and Christopher R. Stokes

26. Soluble Effector and Regulatory Functions in the Porcine Immune System ..... 277 Michael P. Murtaugh, John E. Butler, and Bernard Charley

27. Swine Have a Single JH, <20 VH Genes and No IgD: Are They Suitable Immunological Models for Humans? ............................... 291

John E. Butler, Jishan Sun, and Pedro Navarro

28. Cellular Immune Responses Controlling Infectious Diseases ................ 307 Joan Lunney, Armin Saalmueller, Thomas Pauly. Patricia Boyd,

Sarah Hyatt. David Strom, Stephen Martin. and Federico Zuckermann

29. Spontaneous Regression of Sinclair Swine Cutaneous Malignant Melanoma .... 319 Max S. Amoss, Jr., Valerie A. Fadok, Asha S. Muitani, Sen Pathak,

John F. Greene, Jr. , John W. Measel, Jr., and Clinton D. Morgan

30. The Human and Swine CD4/CD8 Double Positive T Lymphocyte ............ 331 Federico A. Zuckermann and Robert 1. Husmann

31. Defining the Isoforms of Porcine CD45 ................................. 345 William M. Schnitzlein and Federico A. Zuckermann

32. Associations between Stress-Susceptibility and Immune Status in Pigs ........ 359 K. Zhuchaev, S. Knyazev, V Hart, and N. Ephanova

33. Pathogenesis of Enteric Bacterial Infections .............................. 365 Richard E. Isaacson

xviii Contents

34. Aujeszky's Disease (Pseudorabies); A Natural Host-Virus Model of Human Herpesviral Diseases ............................................ 385

Gail Scherba and Federico A. Zuckermann

35. Establishment of Latency in the Natural Host Animal by Aujeszky's Disease (Pseudorabies) Virus Lacking the Putative LAT Gene Promoter .......... 395

Ling Jin, William M. Schnitzlein, and Gail Scherba

36. Pathogenesis of Viral Infections ....................................... 409 Richard C. Wardley, Stephen Martin, and Linda 1. Saif

Author Index ......................................... . . . . . . . . . . . . . . . . .. XIX

Subject Index .......................................................... xxiii