Showing papers on "Transplantation published in 1969"

Malignant lymphomas in transplantation patients.

Abstract: Malignant lymphomas developed in 5 renal homograft recipients treated at 3 widely separated transplantation centers. The development of these tumors appears to be an indirect complication of organ transplantation and/or the measures taken to prevent rejection.

Rate of Calcium Binding and Uptake in Normal Animal and Failing Human Cardiac Muscle

Abstract: Cardiac relaxing system (CRS) and mitochondria were isolated by a modified rapid procedure from human, rabbit, and dog. Relaxing system (sarcoplasmic reticulum) was also isolated from white and red skeletal muscles for comparative purposes. Rapid kinetic measurements were made with a dualbeam spectrophotometric assay procedure. Maximum calcium binding (absence of oxalate), expressed as nmoles calcium/mg protein in 5 minutes at 25°C, for rabbit heart and red and white skeletal muscles were approximately 40, 58 and 170, respectively. The calcium binding constant for rabbit CRS was 2 X 10 (i M~'. The estimated initial binding rates (nmoles calcium/mg protein/minute) of cardiac, white and red skeletal muscle relaxing systems were 256, 1440 and 182, respectively. The rate constant (M~> sec1 ) of CRS was about 2400, which falls between white and red skeletal muscle preparations. Human cardiac muscle from recipients obtained at the time of transplantation yielded CRS with slower rates of accumulation of calcium and very little calcium release, compared to normal animal heart preparations. ATP was the most effective of four nucleoside triphosphates in supporting calcium binding and uptake. Calcium binding and release and calcium uptake of CRS were temperature-sensitive. The energies of activation of binding and uptake were 10.5 kcal mole" 1 and 22.5 kcal mole" 1 , respectively. Under specific conditions, heart mitochondria accumulated calcium at a rate faster than CRS. Mitochondria could also release accumulated calcium.

Rate of Calcium Binding and Uptake in Normal Animal and Failing Human Cardiac Muscle: MEMBRANE VESICLES (RELAXING SYSTEM) AND MITOCHONDRIA

Abstract: Cardiac relaxing system (CRS) and mitochondria were isolated by a modified rapid procedure from human, rabbit, and dog. Relaxing system (sarcoplasmic reticulum) was also isolated from white and red skeletal muscles for comparative purposes. Rapid kinetic measurements were made with a dual-beam spectrophotometric assay procedure. Maximum calcium binding (absence of oxalate), expressed as nmoles calcium/mg protein in 5 minutes at 25°C, for rabbit heart and red and white skeletal muscles were approximately 40, 58 and 170, respectively. The calcium binding constant for rabbit CRS was 2 x 106 M-1. The estimated initial binding rates (nmoles calcium/mg protein/minute) of cardiac, white and red skeletal muscle relaxing systems were 256, 1440 and 182, respectively. The rate constant (M-1 sec-1) of CRS was about 2400, which falls between white and red skeletal muscle preparations. Human cardiac muscle from recipients obtained at the time of transplantation yielded CRS with slower rates of accumulation of calcium and very little calcium release, compared to normal animal heart preparations. ATP was the most effective of four nucleoside triphosphates in supporting calcium binding and uptake. Calcium binding and release and calcium uptake of CRS were temperature-sensitive. The energies of activation of binding and uptake were 10.5 kcal mole-1 and 22.5 kcal mole-1, respectively. Under specific conditions, heart mitochondria accumulated calcium at a rate faster than CRS. Mitochondria could also release accumulated calcium.

Cellular immunity against tumor antigens.

Abstract: Publisher Summary This chapter summarizes the evidence that tumors possess tumor-specific transplantation antigens (TSTA). Virtually all animal neoplasms contain TSTA. Immune reactions against the specific antigens of syngeneic tumors are similar to allograft reactions by which transplanted normal and tumor cells are rejected if they contain isoantigens that are foreign to the recipients. They are to a large extent mediated by immunologically competent cells—that is, lymphocytes and macrophages. The chapter describes several techniques by which cellular immunity to transplantation antigens can be demonstrated, along with a review of different systems in which such techniques were used to detect lymphocyte-mediated immune reactions to TSTA. TSTA are macromolecules present in tumor cells and absent in the normal cells of the same individual and against which immune reactions can be demonstrated with transplantation techniques. The transplantation methods used to demonstrate TSTA can involve the immunization of recipient animals with tumor cells that have been rendered incapable of multiplication (X-irradiation) or that are inoculated in subthreshold doses. Immunization can be also achieved by the inoculation of living tumor cells and excision of the subsequent tumor nodule. The possible role of cellular immunity to TSTA is also discussed in the chapter. The demonstration of cellular immunity to TSTA implies that autochthonous neoplasms appear in the presence of immune lymph node cells, which can destroy their cells at least in vitro . The chapter reviews the phenomenon of allogeneic inhibition. This phenomenon has been postulated to operate in parallel to the immunological mechanisms as part of the organism's defense against antigenic neoplastic cells.

Physical separation of hemopoietic stem cells from cells forming colonies in culture.

Abstract: Mouse bone marrow cells in suspension were separated into a number of fractions on the basis of cell density by equilibrium density gradient centrifugation, or on the basis of cell size by velocity sedimentation. After each type of separation, the cells from the various fractions were assayed for their ability to form macroscopic spleen colonies in irradiated recipient mice, and for their ability to form colonies in a cell culture system. The results from either separation technique demonstrate that cells in some fractions formed more colonies in vivo than in the culture system, while cells in other fractions formed more colonies in culture than in the spleen. The results of control experiments indicate that this separation of the two types of colony-forming cells was not an artifact of the separation procedures. From these experiments it was concluded that the population of cells which form colonies in culture under the conditions used is not identical to the population of cells detected by the spleen colony assay.

Soft-Tissue Calcification in Uremia

Abstract: The association between soft-tissue calcification (STC) and uremia has been recognized for more than 100 years, 1 but it is only since the widespread use of regular dialysis and transplantation that this has become an important problem. 2 Virchow 1 surmised that calcium salts dissolved from bone were carried in the blood and deposited at some distant site to form "calcium metastases," a process analogous to the dissemination of cells from a primary neoplasm. In a review of 88 patients, " the underlying cause of metastatic calcification was nonmetabolic bone disease in 35, uremia in 23, primary hyperparathyroidism in 21, and vitamin D intoxication in 9. The lesions typically occur in the kidneys, stomach, lungs, and the left side of the heart, supposedly because of relative local alkalinity. 4 The essential feature of metastatic calcification is its occurrence in previously normal tissue exposed to an abnormal chemical environment, in contrast to dystrophic calcification which occurs in

Human C′3: Evidence for the Liver as the Primary Site of Synthesis

Abstract: The liver is the primary, if not sole, site of synthesis of the third component of human complement, as shown by a change in the recipient from C'3 FS(0.6) to C'3 SS, the donor type, following homotransplantation of the liver.

Orthotopic cardiac prosthesis for two-staged cardiac replacement

Abstract: Clinical experience with cardiac transplantation has evidenced the feasibility of cardiac replacement in man but has made apparent the need for a mechanical device that will provide circulation and sustain life in emergency conditions while a suitable allograft is obtained. The cardiac prosthesis used in a 47 year old man consisted of two reciprocating pumps constructed entirely of synthetic materials and activated pneumatically in the orthotopic position by a control console connected by tubes passed through the patient's chest wall. The device supported the patient's circulation for 64 hours while a donor for cardiac transplantation was obtained. Death of the recipient from Pseudomonas pneumonia occurred 32 hours after the allografting. The first successful prolonged use of a total mechanical substitute for the human heart is recorded.

Thymus and Antigen‐Reactive Cells

Abstract: Neonatal thymectomy severely limits the ability of some rodents to engage in certain immune responses, particularly cell-mediated immunities such as delayed hypersensitivity and the homograft reaction (reviewed in Miller & Osoba 1967). Many antigens apparently elicit normal humoral antibody responses in thymectomized animals but some, such as heterologous erythrocytes and serum proteins, do not. To account for the immune defects following thymectomy, it was originally postulated that the thymus produced 'the originators of immunologically competent cells' which migrate to other sites (Miller 1961). The simplest relationship between the thymus and the cells taking part in immunity would be that, in response to antigenic stimulation, thymus-derived immunologically competent cells generate the effector cells which actually carry out the response. Recent experiments in our laboratory have attempted to examine this hypothesis in order to define more precisely the cellular basis of the immune defects in thymectomized mice. The purpose of this article is to summarize this work without reviewing the entire literature in the field.

Caclium, phosphorus, and bone in renal disease and transplantation.

Abstract: Calcium-phosphate-bone interrelationships become disrupted progressively in advancing renal disease. Parathyroid hormone (PTH) release, normally attuned to calcium homeostasis requirements, becomes dominated by alterations in phosphate balance. With each wave of nephron destruction, there is believed to occur transient hyperphosphatemia, transient hypocalcemia, and a step-wise rise in PTH levels. When the glomerular filtration rate falls below 25 to 30 ml per minute, hyperphosphatemia persists, hypocalcemia tends to persist, and the stimulus to PTH release is exaggerated. Vitamin D resistance contributes both to hypocalcemia (thus to accelerated PTH secretion) and to osteomalacia. In patients receiving long-term hemodialysis, if hyperphosphatemia and hypocalcemia persist, PTH levels may remain high and osteitis fibrosa may progress. Successful renal transplantation typically leads to regression of hyperparathyroidism and restoration of vitamin D sensitivity; however, hyperparathyroidism may regress slowly, and severe hypercalcemia must be guarded against. True autonomy of PTH release apparently occurs rarely in chronic renal disease.

Immunologic Complementation between Thymus and Marrow Cells—A Model for the Two‐Cell Theory of Immunocompetence

Abstract: Antibody production is a complex series of events beginning with the introduction of the antigen and ending with the production of specific antibody. In recent years, a mountain of information has been gathered concerning the events of antibody production. If one looks at the immune process as a sequence, it is clear that some phases are understood better than others. In particular, the terminal events appear to have been well worked out, such as the structure and specificity of the antibodies and the immunoglobulin classes to which they belong. Looking at somewhat earlier events, we recognize that the cells making those antibodies belong to the lymphoid system. The precise nature of these cells, however, is not known, although recent studies have implicated the small lymphocyte and its descendants, including the plasma cell (Gowans & McGregor 1965). Still earlier events in the immune response are even less well understood, including the mode of action of antigen perhaps the crucial problem.

Transmissible Feline Fibrosarcoma

Abstract: SEVERAL transmissible neoplasms, including avian1 and murine2 sarcomas and feline leukaemia3–5, have been found to be associated with, and probably caused by, “C”-type viral particles. Our preliminary studies with a feline fibrosarcoma indicate that it is also transmissible and is associated with “C”-type viral particles.

Transplantation and Rejection of Individual Cell Layers of the Cornea

Abstract: Techniques have been developed for the transplantation of allografts of pure rabbit corneal epithelium and of endothelium with Descemet's membrane and only minimal amounts of adherent donor stroma. By appropriately inducing vascularization of the donor graft, the recipient becomes sensitized to and ultimately rejects the pure epithelial graft. The epithelium is rejected as a moving front of infiltrated and dying donor cells, with the rapidly regenerating recipient epithelium effecting immediate repair of the defect. The entire epithelial rejection process takes place in the absence of persisting stromal edema and cloudiness. Sensitization by, and rejection of, pure corneal stromal allografts were also studied. Rejection is characterized by a diffuse band of leukocytic infiltrate which sweeps across the donor tissue, leaving dead keratocytes in its wake. Endothelial allografts also lead to sensitization of the recipient and to graft rejection, again when appropriate vascularization is induced. Like epithelium, the rejection of corneal endothelium is associated with an advancing front of densely infiltrated and dying cells. In this instance, however, repair of the defect by recipient endothelium is so slow that edema and cloudiness of the overlying stroma develop and persist for long periods of time. Endothelial regeneration in the rabbit is associated with substantial recovery of corneal clarity.

The influence of the gonads and adrenal glands on the immune response to skin grafts.

Abstract: Summary The congenic strain pair C57BL/10Sn and BIO-129 (12M) differ from one another at the histocompatibility-12 (H-12) locus. Earlier work has shown that in this strain pair females reject allografts more consistently and more rapidly than males. This study is concerned with the effects of gonadectomy and adrenalectomy on the rejection by preimmunized B10-129(12M) mice of C57BL/10Sn skin allotransplants. Immunized unoperated or sham operated females showed, as expected, a higher per cent of rejections and a shorter rejection time than the comparable male group. Oonadectomy, adrenalectomy, and combined orchiectomy-adrenalectomy substantially increased the strength of rejection of males and, to a lesser extent, the strength of rejection of females. Adrenaleetomizcd and gonadectomized- adrenalectomized males and females showed essentially similar rejection patterns. Following gonadectomy alone, the per cent of rejections by females was higher than the corresponding male group, but the rejection rate was slower. Transplanting testes into oophorcctomized females had a greater effect than transplanting ovaries into orchiectomized males. Oophorectomized females with transplanted testes showed a significantly smaller rejection per cent than oophorectomized females without transplants. In contrast, orchiectomized males receiving transplanted ovaries showed a per cent of rejection not significantly different from orchiectomized males without transplants, although the rejection pattern of the rejecting portion was significantly slower than that of the male orehieetomy group

Increased survival in mice inoculated with tumor cells and treated with interferon preparations

Abstract: Repeated administration of potent mouse interferon preparations increased the survival of Balb/c and C 57/B1(6) mice inoculated with 2,000-3,000 RC(19) and EL(4) tumor cells. Only 7/188 (3.7%) untreated mice (or mice treated with control preparations) survived more than 22 days after intraperitoneal inoculation of RC(19) tumor cells. None survived more than 60 days. In contrast, 101/103 (98%) interferon-treated mice survived beyond 22 days, and sixteen (15%) survived more than 60 days. None of these 16 surviving mice show any sign of tumor at present. Three mice (of the 16) from an early experiment are alive ten months after inoculation of RC(19) tumor cells. Mouse interferon preparations derived from three different tissue sources- brain, serum, and monolayer cell cultures (with Newcastle disease virus and West Nile virus as interferon-inducing agents)-all proved effective. A purified preparation of mouse brain interferon was as effective as crude brain interferon. Human amniotic membrane interferon and control tissue preparations were without effect. These findings suggest that interferon itself (or a factor closely associated with interferon) is the active moiety in these preparations.

Transplantable mouse tumor line induced by injection of SV40‐transformed mouse kidney cells

Abstract: A transplantable tumor of inbred mice was obtained by inoculating BALB/c mice subcutaneously with SV40-transformed mouse kidney (mKS-A) cells. Tumors were produced by mKS-A cells in the 71st cell culture passage, but not by cells in the 26th passage. The tumor line has been serially passed in BALB/c mice 14 times. In vitro cell culture lines were derived from tumors after 1, 2, 8, 10 and 12 passages in mice. The tumors, as well as the In vitro tumor cell lines, contained SV40 T-antigen, and sera from the tumor-bearing mice contained antibodies to the SV40 T-antigen. SV40 was rescued from the In vitro tumor cell lines after fusion with green monkey kidney (CV-1) cells in the presence of UV-irradiated Sendai virus. The In vitro tumor cell lines derived from mouse passages 8, 10 and 12 were used as SV40 virus; 2) SV40-transformed cell lines; 3) primary mouse (BALB/c or Yale Swiss) kidney cells, or 4) primary mouse (BALB/c or Yale Swiss) embryo cells. These results showed that the tumor line and the In vitro tumor cell lines have the transplantation antigen.

Transplantation of pluripotential nuclei from triploid frog tumors.

Abstract: Renal tumors were produced by injection of a cell fraction of a tumor into triploid tadpoles of Rana pipiens before they began feeding. Triploid tumor cells were dissociated and transplanted into activated and enucleated eggs. Pluripotency of the implanted nuclei was evidenced by the formation of swimming triploid tadpoles.

Secondary hyperparathyroidism in chronic renal failure. The clinical spectrum in uremia, during hemodialysis, and after renal transplantation.

Abstract: Hyperplasia of the parathyroid glands and high levels of circulating parathyroid hormone are common in patients with chronic renal failure,1and even in those with mild impairment of renal function.2However, the syndrome of overt hyperparathyroidism is not frequently seen in these patients. With the prolongation of the life of patients with chronic renal failure, overt hyperparathyroidism is being observed with increasing frequency. The exact pathogenetic factors which underlie the dynamics of the processes leading to hyperplasia and hyperactivity of the parathyroid glands, the reasons why overt hyperparathyroidism is not always present, the clinical and biochemical criteria of this entity, and the functional characteristics of the parathyroid glands in patients with chronic uremia during hemodialysis and after renal transplant are as yet not clearly delineated.3,4 In this report, the term hyperparathyroidism is used to indicate a syndrome with certain clinical, roentgenographic, and biochemical manifestations which are observed

Physical separation of hemopoietic stem cells differing in their capacity for self-renewal.

Abstract: Bone marrow cells in suspension were separated into a number of fractions on the basis of cell size by sedimentation at unit gravity through gradients of fetal calf serum. The colony forming units (CFU) from the various fractions were tested for their self-renewal capacity using a double transplantation technique. The results indicate that the CFU in the fractions containing slowly sedimenting cells have an increased capacity for self-renewal in comparison with CFU in fractions containing rapidly sedimenting cells. In addition, a culture method was used to select populations containing CFU with increased self-renewal capacity, and these CFU were shown to sediment slowly in comparison with CFU of lower self-renewal capacity obtained from control cultures. It may be concluded that at least part of the heterogeneity observed in the CFU content of individual spleen colonies arises from the composition of the initial cell suspension, probably from intrinsic differences between the stem cells themselves.

The Mechanism of Action of Adrenocorticotropic Hormone

Abstract: Publisher Summary This chapter discusses the relationship of the structure of adrenocorticotropic hormone (ACTH) to its function and the pathway of adrenal cortical biosynthesis. A series of remarkable achievements in protein chemistry have led to the isolation and purification of ACTH, the determination of its primary structure, and its synthesis. The biochemical synthesis of adrenal corticosteroids with its many complexities is explained in the chapter. The influence of ACTH on the adrenal cortex is not limited to the stimulation of corticosteroid production; the maintenance of the structure of the adrenal cortex is also dependent upon this hormone. The removal of the pituitary gland from rats resulted in the atrophy of the adrenal cortex and that the transplantation of the pituitary to hypophysectomized animals caused a return of adrenal cortical weight toward normal. The synthesis of glucocorticoids in the adrenal cortex is accomplished by a series of enzymes situated in different organelles. The evidence indicates that the first substrate, cholesterol, enters the mitochondrion where it is transformed into pregnenolone. Pregnenolone leaves the mitochondrion and is converted into progesterone in the cytoplasm. Progesterone, in turn, is transformed into deoxycorticosterone by an enzyme system in the microsomal fraction of the cell. Corticosterone is produced finally from deoxycorticosterone that has reentered the mitochondrion.

Blocking of the lymphocyte receptor site for cell mediated hypersensitivity and transplantation reactions by anti-light chain sera.

Abstract: Blocking of the Lymphocyte Receptor Site for Cell Mediated Hypersensitivity and Transplantation Reactions by Anti-light Chain Sera

Cardiac transplantation in man

Abstract: The primary surgical aspects of cardiac transplantation in nine patients are presented. Most organ donors required vasopressor support prior to transplantation and in three reversible cardiac arrest occurred. Postoperative complications of wound healing have necessitated modification of cannulation technics for cardiopulmonary bypass to avoid peripheral incisions. Postoperative disturbances in cardiac rhythm may be minimized by appropriate tailoring of the right atrium of the donor. In all cases satisfactory myocardial preservation has been achieved with local hypothermia alone. In the immediate postoperative period management has included the use of right ventricular pacing, isoproterenol, and intravenous digitalization in most recipients. Postoperative complications have included immediate failure of the homograft in one patient, requiring retransplantation six hours postoperatively. Infectious complications have been most frequent and contributed directly to death in four patients. At the present time three patients survive at five and a half, four, and three months postoperatively.