The role of histocompatibility matching in bone allografting was studied in two canine bone graft models. In a cancellous ulnar segmental replacement model, frozen bone allografts exchanged between closely matched dogs were significantly better incorporated by radiographic and histologic criteria than were strongly incompatible grafts. Frozen allografts from disparate donors in recipients receiving immunosuppression appeared indistinguishable 6 months later from those in the untreated closely matched groups and from fresh autografts. Fresh vascularized orthotopically placed fibular bone grafts were evaluated by quantitative blood flow assessment, microangiography, and fluorochrome histomorphometry. Revascularized grafts exchanged between untreated closely matched dogs demonstrated preservation of blood flow and a pattern of repair that was delayed but not otherwise different than vascularized autografts. These results suggest that fresh vascularized grafts in the judiciously matched or immunosuppressed recipient offer attractive clinical possibilities.
The genetically alien fetus survives far beyond the time required to reject grafts genetically identical to that fetus. Two strains of animals which mutually reject grafts will nevertheless have normal pregnancies and hybrid offspring without apparent fetal or neonatal immunological disease which could be caused by a maternal response to fetal transplantation antigens. Many theories which could account for this paradox have been reviewed recently (1, 2).The most compelling and provocative of these theories has evolved from data provided by in vitro assays of cell-mediated immunity which have shown that as a consequence of an allogeneic pregnancy maternal lymphocytes respond to paternal but not to third-party antigens (3, 4). These responses are blocked specifically by autologous maternal serum suggesting that maternal humoral factors might inhibit in vivo the potential pathological activity of maternal lymphocytes for fetal tissues which bear transplantation antigens (3, 4). Pregnancy thus becomes a state of immunological enhancement.The development of in vivo models to determine how pregnancy influences the maternal response to paternal antigens has not met with uniform success. Reports (1, 2, 5, 6) suggest that the female, as a consequence of pregnancy, delays rejecting grafts histocompatible with the allogeneic fetus, but there is also evidence suggesting that pregnancy does not alter the rate of rejection of grafts (1, 2, 7). The discrepancies are probably methodological since hosts of different parity, strains of different histocompatibility, and a variety of test grafts were employed.A readily available model to study the influence of pregnancy on the way in which the female responds to transplantation antigens is the pregnancy-induced unresponsiveness to the male-specific transplantation antigen of the mouse, H-Y (6). Virgin female mice of certain strains reject male skin grafts due to the H-Y antigen. Aider many syngeneic pregnancies females show delayed rejection of male skin grafts and often become tolerant of such grafts (6). The pregnancyinduced hyporesponsiveness to male skin grafts is specific for the male antigen since female grafts, histoincompatible at minor antigens, (H-4), do not enjoy prolonged survival on hosts which otherwise would show delayed rejection of syngeneic male skin grafts (8).
In vivo labeling of protein of the hypothalamo-neurohypophysial tract was accomplished by slow infusion of ^S-cysteine into the third ventricle of dehydrated dogs. In shortterm experiments hypothalamo-median eminence tissue was found to contain labeled protein which possessed chemical and serological properties very similar to those of bovine neurophysin. The subcellular distribution of this material paralleled the distribution of vasopressin. When the animals were permitted to survive 10-21 days with free access to water, labeled neurophysin was found in their posterior pituitary glands. When hemilobes of these glands were incubated in vitro and challenged with elevated K + , there occurred a simultaneous increase in the release of radioactive vasopressin and neurophysin into the incubation medium compared with the amounts released during incubation in media containing either low K + or high K + in the presence of Mg ++ . Some evidence was also obtained for simultaneous release in vivo of hormone and carrier protein into the blood stream by comparing the content of radioactive protein in plasma immediately before and after hemorrhage of 2 dogs which had previously received intraventricular infusion of ^S-cysteine. The results presented in this paper, together with the findings of other investigators concerning changes in the levels of neurophysin-like proteins in the posterior lobe, are highly suggestive of simultaneous biosynthesis and release of the hormones of the neurohypophysis and their carrier proteins. The high molecular weight protein fraction which accompanies beef neurophysin prepared by salt fractionation was found to be immunologically unrelated to the hormone-binding proteins.
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