Genetic control of variability in responses to class-I-antigen-disparate thyroid grafts

Thyroid graft transplantation was performed between mice of congenic strains that differ in the K or the D region. Five donor-recipient pairs of different strains were tested in each combination, and the contributions of the K and the D region gene products to thyroid graft rejection were compared. We found that thyroid cells express immunogenic H-2K and H-2D molecules, as measured by their ability to induce strong graft rejection responses. Great variability in the percentage of grafts rejected was found, however, among different pairs of congenic mice. Across D region disparities, for example, the results varied from acute thyroid graft rejection in all B10 (Db) recipients transplanted with B10.HTI (Dd) thyroid grafts, to prolonged survival of all thyroid grafts of B10.S (Ds) donors transplanted into B10.S(26R) (Db) recipient mice. To test the involvement of different genes in regulation of the immune response against class-I-disparate thyroid grafts, a D region disparity was chosen. A minimum of three different genes were found to affect the response. These genes include a non-H-2 background gene and two genes in the K/I and the D regions of the H-2 complex. The possible mechanisms by which structural and regulatory genes might affect the rejection of class-I-disparate thyroid grafts are discussed.     

Overexpression of heme oxygenase-1 protects allogeneic thyroid grafts from rejection in naive mice

BACKGROUND: Endocrine allografts are an option for the treatment of endocrine failure. METHODS: One lobe of the thyroid was transplanted under the kidney capsule. RESULTS: C57BL/10 (H2(b)) thyroids were rejected in naive CBA (H2(k)) mice within 14 days after transplantation. When mice were treated with anti-CD4 monoclonal antibodies (mAb), all grafts survived for more than 60 days. The first grafts still survived after second C57BL/10 or Balb/c (H2(d)) thyroid grafts that were transplanted into the same recipients were rejected acutely, which suggests that the primary grafts were modified under anti-CD4 mAb treatment. To confirm this hypothesis, C57BL/10 thyroid grafts from anti-CD4 mAb-treated mice were retransplanted. All grafts survived in naive mice; this correlated with the overexpression of heme oxygenase-1 (HO-1) in the grafts. Next, an inhibitor of HO-1 (zinc protoporphyrin) or control compound (copper protoporphyrin) was injected intraperitoneally after transplantation of C57BL/10 thyroid grafts into the primary CBA recipients that had been treated with anti-CD4 mAb. The grafts in mice that had been treated with zinc protoporphyrin, but not copper protoporphyrin, were rejected when retransplanted to naive recipients. CONCLUSIONS: Overexpression of HO-1 correlated with the protection of fully allogeneic thyroid grafts from rejection when retransplanted into naive recipients.     

A comparison of the effects of hyperbaric oxygen culture on survival of murine and canine thyroid gland grafts

Canine thyroid tissue (CTy) was subjected to hyperbaric oxygen culture (HOC) under conditions that affect immunoalteration in murine thyroid tissue (MTy). Survival of autografts and allografts implanted under the kidney capsule was determined after 21 days by ¹²⁵I uptake and histology. Unlike MTy, autograft CTy subjected to normothermic HOC (95% O₂, 5% CO₂; 1.76kg/cm²) for 48 h did not survive (0/8) whereas decrease of culture duration to 24 h resulted in autograft CTy survival (3/3). Under hypothermia (5°C), HOC could be extended to 7 days with autograft CTy survival (3/3 after 4 days and 3/3 after 7 days). Allograft CTy after 24 h of normothermic HOC and 7 days of hypothermic HOC was rejected. Indicators of oxygen free radical injury were determined: catalase activity was comparable in MTy and CTy (means 14.82 and 6.3–10.8 mm/mg protein, respectively) but superoxide dismutase activity was low in CTy (means 0.01–0.29 and 4.75 U/mg protein, respectively). Malondialdehyde content after 48 h of normothermic HOC was higher in CTy than in MTy (means 2215 and 1275 nmol/g, respectively). The results show that CTy is injured by HOC under conditions tolerated by MTy, and that this difference is related to the greater sensitivity of CTy to oxygen free radical injury.     

A comparison of the effects of hyperbaric oxygen culture on survival of murine and canine thyroid gland grafts

Abstract. Canine thyroid tissue (CTy) was subjected to hyperbaric oxygen culture (HOC) under conditions that affect immunoalteration in murine thyroid tissue (MTy). Survival of autografts and allografts implanted under the kidney capsule was determined after 21 days by ¹²⁵I uptake and histology. Unlike MTy, autograft CTy subjected to normothermic HOC (95% O₂,5% CO₂; 1.76kg/cm²) for 48 h did not survive (0/8) whereas decrease of culture duration to 24 h resulted in autograft CTy survival (3/3). Under hypothermia (5"C), HOC could be extended to 7 days with autograft CTy survival (3/3 after 4 days and 3/3 after 7 days). Allograft CTy after 24 h of normothermic HOC and 7 days of hypothermic HOC was rejected. Indicators of oxygen free radical injury were determined: catalase activity was comparable in MTy and CTy (means 14.82 and 6.3–10.8 mm/mg protein, respectively) butsuperoxide dismutase activity was low in CTy (means 0.01–0.29 and 4.75 U/mg protein, respectively). Malondialdehyde content after 48 h of normothermic HOC was higher in CTy than in MTy (means 2215 and 1275 nmol/g, respectively). The results show that CTy is injured by HOC under conditions tolerated by MTy, and that this difference is related to the greater sensitivity of CTy to oxygen free radical injury.     

Endovascular grafts

The clinical application of endovascular grafts began with the work of Parodi in 1990, which fused intravascular stent and prosthetic graft technologies. These less invasive devices have been applied to the treatment of arterial aneurysm, long segment occlusive disease, and traumatic vascular injuries. A host of different systems have been developed that exploit the unique properties of balloon, superelastic metal, and vascular graft devices.     

Femorofemoral grafts for unilateral occlusion of aortic bifurcation grafts.

Femorofemoral bypass grafts were performed in 10 patients who developed thrombosis of one of the limbs of previously placed aortoiliac or aortofemoral bifurcation grafts. There were no operative deaths or significant postoperative morbidity, and no amputations had to be performed following the bypass. Nine of the 10 patients have patent grafts from 5 to 70 months (average 33 months) following operation. Of these nine, eight are asymptomatic and one has mild claudication on the side of the unoccluded limb. Because of its simplicity, low operative risk, and encouraging late success rate, we feel that femorofemoral bypass grafting for late unilateral occlusion of a prosthetic bifurcation graft is the procedure of choice.     

Vascularised nerve grafts

Since Taylor (1976) successfully performed the first vascularised free nerve graft, experimental and clinical data have not provided conclusive support for the superiority of this method of repairing loss of nerve substance.Experimental work yields conflicting results. Histologic results are in favour of vascularised grafts but non-vascularised fascicular grafts placed in a healthy bed recover sufficient neovascularisation within a short period of time (four to six days).In the field of brachial plexus repair, vascularised grafts give consistent results. However, if thrombosis of the anastomoses occurs, the grafts fail completely.In our experience, vascularised nerve grafts used for repairing digital nerves and arteries, have a high rate of thrombosis.There are few potential donor sites. A nerve graft cannot be considered to be physiologically vacularised if it relies only on an artery or on an arterialised vein. Given the present state of immunosuppressant treatments, vascularised allografts are not yet appropriate.Therefore, vascularised nerve grafts have limited applications. In general it is preferable to repair the tissue bed so as to promote revascularisation of conventional nerve grafts.