Illinois Junior Academy of Science - Yearbook (Urbana, IL)

Page 35 text:

Science Proiecfs Exposition: 1966

Page 34 text:

sutured to dark mice. The same medication was given to the control group that was given to the experimental group. All grafts in the control group were rejected. In the experimental group results were favorable. Fifty experi- mental mice were used. Forty of these were used for skin grafts. The seven mice that died were not counted as failures since the deaths were before or during formation of a para- biotic union. One mouse died after grafting. However, the death was caused by infection at a site other than that of the graft. Also, the graft had not been rejected at this time nor did it show any signs of rejection. Therefore, this sub- ject was not called a failure though it was not counted as a successful graft. Rejection of a graft is the only factor indicative of failure, just as the acceptance of a graft is the only indication' of success. All thirty-two of the other mice used for skin grafting survived. However, each mouse which survived operative procedures died by the seventeenth post- operative day, on an average. These mice met apparently violent deaths as attested to by these observations: nasal hemorrhage, flexion of forepaws, hind paws, and neck, pre- ceded by clonic movement of the body. Ten of the experi- mental mice received tail transplants and skin transplants. All of these survived operative procedures. However, on the seventeenth day post-operative, on an average, these mice, too, met apparently violent deaths, as did the mouse used to test the reason for tail atrophy seen in these mice before their death. Rejection of a graft is caused by death of its cells. Dead cells are sloughed off by the host animal. Cells of a donor animal die when grafted to the host because of either mechanical or chemical interference with cell metabolism. Mechanical difficulties which may arise are poor blood sup- ply or infection. Either of these is capable of killing cells. These factors are overcome by using sterile technique and developing an adequate circulation of blood between the graft and its host before transplantation. Though no rejection by mechanical means took place during my experimentation, the transplanted tails were atrophied. Since no infection was present, the atrophy was thought to be due to insufficient blood supply. To check this hypothesis a pair of mice were united parabiotically using skin flaps. After one week of para- biosis, the tail of one mouse was partially amputated., The cut surface was sutured to an incision on the back of the host mouse. In this manner, the tail received nourishment from the donor mouse while circulatory connection with the host mouse was being established. After seven days, when sufficient vascular anastomosis was assumed to be estab- lished, the tail was completely amputated from its donor? It was then sutured to an extension of the incision that was previously cut on the host's back. The tail graft did not atrophy in this case, and it is assumed to be established that insufficient blood supply was the cause of the inanation atrophy in the other tails. CThis last test mouse was not in- cluded in results.l Cells foreign to the host may also be killed by anti- bodies which are formed in the blood serum of the host when the host is subjected to foreign substances, notably proteins or carbohydrates. The principle behind using para- biosis to offset rejection must now be explained. When parabiotic union of host and donor is established, there is a free exchange of blood and substances in the blood between parabiotic union of host and donor is established, there is a antibodies, the alien tissue when introduced in gradually increasing amounts, conditions the mice to tissue from their parabiotic partners. In this way tolerance is built and the immunological mechanism of the mice no longer recognizes the donor cells as foreignf' According to the data I have gathered, the inhibition of the immunological mechanism in parabiotic partners for each other's cells is not permanent. The length of time of inhibition of antibody production for a seven day parabiotic union of host and donor is twenty- four days, on an average, for both skin and tail transplants. These time intervals include the period of parabiotic union since cells foreign to an animal were being introduced into the animals at this time. The use of parabiosis to overcome rejection of tissue transplants was first developed in 1936 on inbred, litter-mate white mice' Success with homotransplants using parabio- sis among inbred strains of mice was reported by Eichwald and Silmser in 1955.6 Unsuccessful attempts at transplanting skin homografts in non litter-mate rats were carried out by Gifford and Crossfield in 1957.' Only in recent years have successful homotransplants using parabiosis been made between unrelated animals. I have found no experimental study which parallels mine. However, related studies show a similar incidence of success in both formation of parabiotic unions though in actual acceptance of skin grafts data is not similar to my own. Results other than my own, relating to tail grafting could not be found. In conclusion, parabiotic union of mice preceding homo- transplants of mouse tissue favorably influences the accept- ance of grafts both at the sight of union' and also at other sites. Tolerance of parabionts to each other's tissue results in temporary inhibition of antibody synthesis, and, thereforeg conditional acceptance of homotransplants. Systematic error is inherent in all animal experimenta- tion. The behavior of any living thing is always unpredict- able to a certain degree. Other error might occur because of the dependence on visual observation in some aspects of experimentation, such as the appearance of a scab preceding rejection. Bibliography 1. Shwind, J. V., personal correspondence, The Sansum Research Foundation, February 2, 1965. 2. Martinez, C., F. Shapiro, and R. A. Good, Essential Duration of Parabiosis and Development of Toler- ance to Skin Homografts in Mice, Proceedings Soc. Exptl. Biol. Med., vol. 104, 1960, pp. 256-269. 3. Shwind, J. V., Homotransplantation of Extremities by Parabiosis, Annals of New York Academy of Science, vol. 99, article 3, October 24, 1962, pp. 933-942. 4. Gifford, H. and J. H. Crossfield, The Effect of Con- tinued Parabiosis on Switch Homotransplants in Rats, Stanford Medical Bulletin, vol. 15, Feb- ruary 1957, pp. 28-32. 5. Eichwald, E. and C. R. Silmser, Transp. Bulletin, vol. 2, 1955, p. 148. 6. Shwind, J. V., Successful Transplantation of a Leg in Albino Rats with Reestablishment of Muscular Control, Science, vol. 84, October 16, 1936, p. 355. 7. Billingham, R. D., P. L. Krohn, and P. B. Medawn, Effect of Cortisone of the Survival of Skin Homo- grafts in Rabbits, British Medical Journal, vol. 1, 1951, pp. 1157-1163. 8. Calne, R. Y., The Rejection of Renal Homografts In- hibition in Dogs by 6-Mercaptopurinef' Lancet, vol. 1. 1960. pp. 417-418. 9. Dammin, G. J., N. D. Couch, and J. E. Murray, Pro- longed Survival of Skin Homografts in Uremic Patients, Annals of the New York Academy of Science, vol. 64, 1957. p. 967. 10. Haurowitz, Feliz, The Template Theory of Antibody Formation, pp. 22-31. 11. Main, J. M. and R. T. Prehn, Successful Skin Homo- grafts after the Administration of High Dosage X-irradiation and Homologous Bone Marrow, Journal Nat'l. Cancer Inst., vol 15, 1955, p. 1023. 12. Marianne, T. C. Martinez, J. M. Smith, and R. A. Good, Induction of Immunological Tolerance to Male Skin Isografts Subsequent to Neonatal Period, Proceedings Soc. Exptl. Biol. Med., vol. 101, 1959, pp. 596-599. 13. Raffel, Sidney, Immunity, Appleton-Century-Croft, Inc., New York, copyright 1953. 14. Woodruff, M. F. A. and B. Lennox, Reciprocal Skin Grafts in a Pair of Twins Showing Blood Chimer- ism, Lancet, vol. 2, 1959, pp. 476-478. ,I ,Q X N ' s ,f lu-1-mnunnxmaun m-xnmumnummnuhx

Page 36 text:

I..l'x 'Q' 42 ii Q A' S Q ,,, K, -5 'QS' -2 1 'lvf 5, in ' ff T its FF' ,Qi J ' EQ' 5 gl-Y.:.hgi.fQg' W . I M- me wa l ' 1 t -- 1,44 E , ,X 3 A U . 71 'wa' f i if '59 . ,Iva '71 ' fix, A 1 . ' : J 4 iii I Es' V Q Q in V , Q I I ,..- I , ,A 74. , 4 .5 ,lr-1 ' - 'EEF '. ' ' T U-' Q - .lr V 7 ' 1 -,,- , , ,V 5, .- 1 , . 1 1 .X ,I . - , . ' '