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University Fylicrofilms INFORMATION TO USERS This dissertation was produced from a microfilm copy of the original document. While the most advanced technological means to photograph and reproduce tbjs document have been used, the quality is heavily dependent upon tlty quality of the original submitted. The following explanation of techniques is provided to help you understand markings or patterns which may appear on this reproduction. 1. The sign or "target" for pages apparently lacking from the document photographed is "Missing Page(s)". If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting thru jmage anc| duplicating adjacent pages to insure you complete continuity. 2. When an image on the film is obliterated w ith a large bound black mark, it is an indication that the photographer suspect^ tbat t|ie copy may have moved during exposure and thus caus^ a blurred image. You will find a good image of the page in the adjacent frame. 3. When a map, drawing or chart, etc., was part of the material being photographed the photographer followed a definite method in "sectioning" the material. It is customary to begin phoning at the upper left hand corner of a large sheet and to continue phptoing from left to right in equal sections with a small overlap. If necessary, sectioning is continued again — beginning below the fif'st row and continuing on until complete. 4. The majority of users indicate that the textual content0 f greatestis value, however, a somewhat higher quality reproduction could be made from "photographs" if essential to the understanding o f the dissertation. Silver prints of "photographs" may be ordered at additional charge by writing the Order Departm ent, giving the catalog number, title, author and specific pages you wish reproducecj. University fylicrofilms 300 North Zeeb R^ad Ann Arbor, Michigan 48106 A Xerox E d u catio nCompany 72-27,009 GIDEON, Jr., Leonard Albert, 1943- IMMUNOLOGICAL PARAMETERS OF RENAL TRANSPLANTATION IN THE CANINE. The Ohio State University, Ph.D., 1972 Microbiology ! University Microfilms, A XEROX Company, Ann Arbor, Michigan j .... _ 1 THIS DISSERTATION HAS BEEN MICROFILMED EXACTLY AS RECEIVED IMMUNOLOGICAL PARAMETERS OF RENAL TRANSPLANTATION IN THE CANINE DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University by Leonard Albert Gideon, Jr., B.S., D.V.M., M.S. ***** The Ohio State University 1972 Approved by Advisor epartment of Microbiology 1/ PLEASE NOTE: Some pages may have indistinct print. Filmed as received. University Microfilms, A Xerox Education Company ACKNOWLEDGEMENTS To Dr. John H. Wallace, advisor and friend, I wish to offer my greatest appreciation for his constant encouragement, guidance and sincere interest. Dr. Wallace, you are a rare combination of a thoughtful person and scholar. I wish to thank Drs. Ronald St. Pierre, Matthew Dodd and Frank Chorpenning for serving on the examining committee and offering helpful suggestions in the preparation of the manuscript. An especial appre­ ciation is extended to Dr. St. Pierre for the personal counseling he provided and for the preparation of the mounted slides for histological examination. I wish to thank Drs. James Madura, James Cerilli, Leroy Johnson, Jay Stein, Milton Wyman, Alden Stilson and Alton Wilson for their guidance, encouragement and/or generosity in providing facilities and materials during the course of this research project. I am deeply grateful to the National Institute of Health and Merilyn C. Hiller, Hematology Program Director, National Institute of Arthritis and Metabolic Diseases, for supporting me on a Post Doctoral Fellowship for the past three years. Finally, I wish to thank my wife, and my parents for their encouragement and prayers throughout the years. VITA December 27, 1943 Born, Portland, Oregon 1966 .......... B.S. degree, Texas A and M University, College Station, Texas 1967 .......... D.V.M. degree, Texas A and M University, College Station, Texas 1968-1969 . American Veterinary Medical Assoc. Fellow 1968-1971 . Teaching Associate, Department of Veterinary Surgery, The Ohio State University 1969 .......... M.S. degree, The Ohio State University, Columbus, Ohio 1969-1972 . National Institutes of Health Post Doctoral Fellow PUBLICATIONS 1. Cerilli, G. James and Gideon, Leonard. "Successful Long Term Inhibition of Xenograft Rejection." Surgical Forum, 10, 1969. 2. Cerilli, James, Gideon, Leonard and Hattan, Dorothy. "Effect of Immunosuppression and Cellular Antigen on Xenograft Survival.” Transplantation Proceedings 2, 1970, p. 516. FIELDS OF STUDY Major Field: Veterinary Medicine Veterinary Surgery. Dr. Leroy Johnson Immunology. Dr. John H. Wallace TABLE OF CONTENTS page AC KNOWLEDGE NE NT S ......................................... ii VITA ..................................................... iii LIST OF P L A T E S ........................................... v LIST OF FIGURES ......................................... vii LIST OF TABLES ......................................... ix Introduction ............ 1 Review of the Literature .................. 6 Experimental Procedure .................................. 38 Results ................................................. 60 D i s c u s s i o n ............................................... 139 Summary ................................................. 155 BIBLIOGRAPHY ............................................. 157 LIST OF PLATES Plate Page 1. Rabbit Anti-Coyote Serum Reacted with Dog and Coyote Sera in the Ouchterlony Te s t ............................. 61 2. Rabbit Anti-Dog Serum Reacted with Dog and Coyote Sera in the Ouchterlony T e s t ................................. 62 3. Rabbit Anti-Coyote Serum Reacted with Six Different Coyote Sera in the Ouchterlony T e s t ..................... 63 4. Rabbit Anti-Dog Serum Reacted with Six Different Dog Sera in the Ouchterlony Test ........................... 64 5. Rabbit Anti-Dog Serum Unabsorbed (a) and Absorbed with Dog (b) and Coyote (c) Sera and Reacted with Dog and Coyote Sera in the Ouchterlony T e s t .................... 66 6. Immunoelectrophoresis of Dog and Coyote Sera Reacted with Rabbit Anti-Coyote Serum ........................ 67 7. Immunoelectrophoresis of Dog and Coyote Sera Reacted with Rabbit Anti-Dog Serum .......................... 68 8. Immunofluorescense of Erythrocytes from a C-Antigen Positive Dog .......................................... 123 9. Cortical Biopsy of a Coyote Kidney Showing Normal Parenchyma ............................................ 127 10. Biopsy from a Rejected Coyote Kidney in the No-Treatment G r o u p .................................................. 128 11. Biopsy from a Rejected Coyote Kidney in the No-Treatment G r o u p .................................................. 129 12. Biopsy from a Rejected Dog Kidney in the HADLG-Treated G r o u p .................................................. 131 13. Biopsy from a Rejected Coyote Kidney in the HADLG-Treated Group ......................... 132 v LIST OF PLATES CONTINUED Plate Page 14. Biopsy from a Rejected Coyote Kidney in the HADLG and Antigen-Treated G r o u p .............................. 133.. 15. Biopsy from a Rejected Coyote Kidney in the Antigen- Treated Group ................ .................. 135 16. Biopsy from a Rejected Coyote Kidney in the Homologous ALG-Treated Group ................................... 136 vi LIST OF FIGURES Figure Page 1. Horse Anti-Dog Lymphocyte Serum: Progression of Antibody Titer with Immunization ...................... 70 2. Horse Anti-Dog Lymphocyte Serum: Serum Absorption with Dog Erythrocytes ................................ 71 3. Progression of Lymphocyte Cytotoxic Antibody Production with Immunization .................................... 79 4. Progression of Lymphocyte Cytotoxic Antibody Production with Immunization ......................... 80 5. Dog (75) Leukocyte Response to 3052 Anti-3051 Anti­ lymphocyte Globulin Administration .................... 81 6. Dog (99) Leukocyte Response to 3041 Anti-3049 Anti­ lymphocyte Globulin Administration .................... 82 7. Leukocyte Response of the Dogs in the No-Treatment Group ................................................ 95 8. Leukocyte Response of the Dogs in the HADLG-Treated Group ................................................ 97 9. Leukocyte Response of Dog 9974 to HADLG Treatment and Transplantation with Dog 3049 K i d n e y .............. 102 10. Leukocyte Response of Dog 0P-10 to Homologous ALG Treatment and Transplantation with Coyote 12 Kidney 108 11. Leukocyte Response of Dog A-l to Homologous ALG Treatment and Transplantation with Coyote 12 Kidney 110 vii LIST OF FIGURES CONTINUED Figure Page 12. Leukocyte Response of Dog 3051 to Homologous ALG Treatment and Transplantation with Dog 3052 Kidney . 113 13. Leukocyte Response of the Dogs in the HADLG and Antigen Treatment Group .............................. 115 14. Leukocyte Response of Dog 3044 to Lymphoid Antigen Pretreatment and Transplantation with Coyote 6 Kidney . 118 viii LIST OF TABLES Table Page 1. Horse Antibody Against Dog Lymphocytes: Characteristics of the Ammonium Sulfate Precipitated Product .......... 73 2. Reactivity of Horse Anti-Dog Lymphocyte Serum in the Direct Hemagglution Assay ............................ 74 3. Horse Antiserum Against Dog Lymphocytes ................. 76 4. Rabbit Antisera Against Dog and Coyote Lymphocytes . 77 5. Dog and
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