Crevicular tissues as donor tissue for free gingival grafts. Limited human histologic observations.
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Epithelial Cells↗
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Aphakic keratoplasty. Determining donor tissue size to avoid elevated intraocular pressure.
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Aphakia, Postcataract↗
Refractive variation and donor tissue size in aphakic keratoplasty. A prospective randomized study.
Forty-six patients were examined in a prospective, randomized clinical study to compare the use of the same size trephine on both donor and recipient with the use of a 0.5-mm larger trephine on the donor in aphakic keratoplasty and in keratoplasty combined with lens extraction. The results showed no statistically significant difference in refractive error, either in spherical equivalents or in astigmatism. The larger donor tissue may have some value in reducing high plus-refractive error and in reducing intraocular pressure after surgery.
Aphakia↗
Kidney transplantatability across a positive cross-match. Cross-match assays and distribution of B lymphocytes in donor tissues.
Lymphocyte subpopulations were determined in peripheral blood, abdominal lymph-nodes, and spleens from renal allograft donors. Percentages of B lymphocytes were low in peripheral blood (mean +/- S.E., 10-0 +/- 1-0%), variable in lymph-nodes (28-8 +/- 3-8), and high in spleens (41-4 +/- 2-1). Microlym-phocytotoxicity cross-match assays in which sera with B-cell-specific antibody were used were invariably negative with peripheral-blood lymphocytes but positive with lymph-node or spleen preparations. Four renal allografts were transplanted when the standard cross-match was positive with spleen or lymph-node but negative with blood. No hyperacute or accelerated rejection was observed. Potential recipients are often denied allografts because of a positive cross-match with either lymph-node or splenic preparations, and this could be avoided in some cases if cross-matches were performed on peripheral blood or B-lymphocyte-depleted splenic or lymph-node preparations. These results accord with those of other workers who found that B-cell pre-sensitisation is not a contraindication to transplantation.
Antibodies↗
[Conjunctival grafting. Experiences with lyophylized donor-tissue (author's transl)].
Firstly the different methods of surgical replacement of the conjunctiva are discussed. Despite certain disadvantages buccal mucosa is often transplanted. More useful and easier is the use of lyophilized human donor conjunctiva. In 10 years we have operated on 110 eyes in 76 patients according to this method. In some eyes conjunctiva of different donors was used, often the whole conjunctival sack had to be reestablished. A brief description is given of winning the donor material, or surgical grafting technique and results, and one of the case histories of the patients is given. No transplant rejection occured, probably because there are no specific proteins or enzyme activities in the lyophilized tissue. Sometimes in pemphigus and similar diseases the tissue will again be included into areas of contracture. After chemical injuries and burns the end of inflammatory signs should be awaited before grafting.
Conjunctiva↗
Specific unresponsiveness to skin allografts in mice. V. Synergy between donor tissue extract, procarbazine hydrochloride, and antilymphocyte serum in creating a long-lasting unresponsiveness mediated by suppressor T cells.
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Animals↗
The influence of the degree of maturation of donor tissue on the reconstruction of elastic cartilage by isolated chondrocytes.
Chondrocytes isolated from auricular cartilage of 1-, 14-, 28- and 56-day-old rabbits were injected intrasmuscularly as auto- or allogeneic transplants, and the development of the reconstructed cartilage was compared to that of intact tissue. Chondrocytes in cartilage of 1- and 14-day-old rabbits (younger group) were relatively uniform in size. During further development in situ (28 and 56 days) central cells increased considerably and many of them became binucleated. Cartilage reconstructed by chondrocytes from the younger group of animals displayed regular arrangement of cells, i.e. smaller cells at the periphery and larger in the centre. Transplantation of chondrocytes from 28 or 56-day-old rabbits (older group) led to the reconstruction of cartilage with irregular distribution of cells, i.e. some large cells were located at its periphery, while in the centre smaller and larger cells were intermingled in a haphazard manner. Elastic fibres were scanty and thin in cartilage of 1-day-old animals, but their number and size increased with time and they displayed a characteristic pattern. Formation and maturation of these fibres proceeded in cartilage reconstructed by chondrocytes from the younger gorup of animals similarly as in the intact tissue. Chondrocytes from the older group of rabbits reconstructed cartilage in which the number of elastic fibres was reduced and their arrangement appeared irregular.
Age Factors↗
A natural resource. Prevalence of cadaver organs for transplantation and research.
To determine the prevalence of potential cadaver kidney, eye, and research-tissue donors in a tertiary referral hospital, the charts of 718 patients who died were studied. We found a potential kidney-donor rate of 2.4 per 100 hospital deaths, a potential eye-donor rate of 45.4 per 100 deaths, and a potential pancreas-donor rate of 26.5 per 100 deaths. In the study year, 20 potential cadaver kidney donors were projected, theoretically meeting the needs of the transplantation center. Recognized potential eye and pancreas donors were remarkably numerous. Effective education, surveillance, and procurement programs are necessary to salvage these potential donor tissues.
Adolescent↗
Stable chimerism induced in noninbred rabbits by neonatal injection of spleen cells from allotype-suppressed adult donors. I. Replacement of hemopoietic tissue by donor cells.
In the course of experiments designed to demonstrate an active mechanism of allotype suppression in rabbits, spleen cells from adult donors were transferred to newborn recipients. Among 23 rabbits that received injections, 4 stable chimeras were formed, as determined by the production of serum immunoglobulins marked with light and heavy chain allotypes. The other rabbits that survived the immediate postinjection period displayed a temporary chimeric state lasting up to several weeks, after which they either succumbed to graft-versus-host disease or rejected the donor cells. One chimeric animal was apparently repopulated by the hemopoietic cells of the donor's spleen. Insofar as could be determined, the recipient's blood cells became phenotypically identical to those of the donor. This condition manifested itself as a loss of the recipient gene products associated with both lymphocyte and erythrocytes, accompanied by a seemingly total replacement with those of the donor.
Aging↗
Anti-donor immune responses in prediction of transplant rejection.
We assessed various immune responses against donor tissue to determine their value in the diagnosis and prediction of clinical rejection episodes. Twenty-six consecutive clinical renal-transplant recipients were examined. Cell-mediated lymphocytotoxicity preceded and accompanied 41 of 45 rejection episodes (P less than 0.001). Complement-dependent antibody was present in 12 of 15 rejections (P less than 0.002)--four not accompanied by, and eight in association with, cell-mediated lymphocytotoxicity. Mixed lymphocyte reactivity or nonreactivity and inhibition by autologous serum occurred equally often in rejection and quiescence. Lymphocyte-dependent antibody occurred during both rejection episodes and quiescent phases, with a greater frequency during quiescence (P = 0.05). Cell-mediated lymphocytotoxicity was the best predictor of rejection (P less than 0.05). Cell-mediated lymphocytotoxicity was the best predictor of rejection (P less than 0.001), and was more easily suppressed by standard immunosuppressive therapy, than complement-dependent antibody. If specific cell-mediated lymphocytotoxicity, with or without antibody, recurred after rejection therapy, the graft underwent further rejection.
Antigen-Antibody Reactions↗
Effect of parity on recovery of inapparent nodule-transformed mammary gland cells in vivo.
Inapparent nodule-transformed cells were recovered from five late-pregnant, first-pregnancy BALB/cfC3H females 4 months of age and from five late-pregnant multiparous females 6 to 7 months of age. Mammary tissues were removed from each donor and dissociated by means of the enzyme collagenase (0.1%), hyaluronidase (0.1%), and pronase (1.25%). Aliquots of 100,000 viable cells in 0.01 ml of media were injected into the gland-free mammary fat pads of 3-week-old syngeneic host mice. Ten weeks after the injection the outgrowths were classified as ductal, nodule, tumor, or combinations of these types of outgrowths. The recovery of nodule outgrowths indicated the presence of nodule-transformed cells in the cell suspension that was injected. All donors yielded nodule outgrowths, and the percentage of outgrowths was significantly greater than was the percentage recovered from virgin BALB/cfC3H females of the same age groups. The latent period for the emergence of nodules and tumors was reduced from 8 to 9 months in virgin females to 4 months in parous females. The incidence of both nodules and tumors was greatly increased. The data suggest that parity significantly increases the numbers of nodule-transformed cells in donor tissue, decreases the time required for the emergence of nodules and tumors, and increases the number of overt nodules and tumors.
Age Factors↗
The endothelium of clear corneal transplants.
The endothelium of 36 clear penetrating keratoplasties, performed 1 to 19 years previously, was examined and photographed with the clinical specular microscope. There were fewer central endothelial cells in the transplants than in normal corneas. There was no significant correlation between graft endothelial cell density and corneal thickness, rejection episodes, the disease necessitating kertoplasty, or the method of donor tissue preservation. Corneas transplanted from younger donors to younger recipients had significantly more central endothelial cells. Transplanted corneas appeared to lose endothelial cells over a period of time, just as normal corneas do.
Adolescent↗
Motif-Centered Analyses Reveal Universal and Tissue-Specific Mutagenic Mechanisms Operating in the Human Body.
Somatic mutations are inevitable in human genomes and can lead to tumorigenesis, yet baseline mutagenesis in non-cancerous normal cells remain poorly understood. Here, we analyzed the mutation profiles of 11,949 normal samples across 25 tissues obtained from whole-genome and whole-exome sequencing datasets. We applied stringent statistical hypothesis for detecting enrichment and enrichment-adjusted Minimal Estimate of Mutation Load (MEML) in trinucleotide motifs preferred by known mutagenic processes. We found several cancer-associated mutational motifs in cancer-free tissues. Samples enriched with C→T mutations in nCg motif associated with clock-like spontaneous meCpG deamination were detected across all tissues. We revealed another clock-like motif, T→C substitutions in aTn motif associated with exposure to small epoxides and other SN2 electrophiles, in several tissues. Donors with several non-cancerous diseases showed significantly higher, age-independent, and concordant accumulation of aTn and nCg motifs compared to healthy donors. Motifs associated with chemical exposures showed sporadic, tissue and disease-specific mutagenesis. APOBEC-induced C→T and C→G mutations in tCw motif were enriched in bladder, lung, small intestine, liver, and breast with preference for APOBEC3A-like mutagenesis in most. Together, our analyses elucidated several ongoing mutagenic processes in normal human tissues and provided a robust analytical framework for identifying mutagenic sources from somatic mutation catalogues.
Journal Article↗
DL-ethionine treatment of adult pancreatic donors. Amelioration of diabetes in multiple recipients withe tissue from a single donor.
Transplantation of adult rat pancreatic islet tissue as a free graft requires the separation of islet from exocrine tissue to avoid host injury or graft destruction by digestive enzymes. The poor yield from islet isolation techniques currently necessitates the use of multiple donors to ameliorate diabetes in a single recipient. DL-ethionine (DLE) is an agent selectively toxic to the exocrine pancreas. We examined the effect of DLE administration on pancreatic digestive enzyme content and islet mass in adult Lewis rats and the ability of such pancreatic tissue dispersed by collagenase digestion without specific islet isolation to ameliorate diabetes when transplanted to the portal vein of syngeneic rats with streptozotocin induced diabetes. Rats fed normal chow supplemented with 0.5% DLE for 14-20 days showed a logarithmic loss of pancreatic mass. Total pancreatic amylase content declined to 0.3 + 0.1 mg, less than 3% of control values (14.3 +/- 1.0 mg). Total insulin content in DLE treated rats was 87 +/- 8 microg, not significantly different from control rats (101 +/- 7 microg). Histological examination confirmed the selective atrophy of exocrine tissue in DLE treated rats. Fresh pancreatic tissue prepared from a single DLE treated donor ameliorated diabetes 75% of the time when transplanted to one or two recipients and 65% of the time when divided between three of four recipients. Tissue prepared from a single DLE treated donor and stored for 24-48 hours ameliorated diabetes 91% of the time when divided between one or two recipients. Only four of 31 diabetic rats transplanted with fresh pancreatic tissue from untreated adult donors became normoglycemic. Pretreatment of adult rats with DLE induces selective exocrine atrophy, permits dispersed pancreatic tissue from a single donor to ameliorate experimental diabetes in up to four recipients, and allows tissue to be preserved by culture for up to 48 hours without specific islet isolation.
Amylases↗
The origin and mechanism of the allograft reaction.
Previous explanations for the allograft reaction have been based on the concept that antigen causes immunocyte activation, following engagement of the immunocyte's specific receptor. This notion lead to the concept of immune surveillance, the idea that the evolutionary pressure responsible for the development of the vertebrate immune system involved in allograft rejection was a need to recognize and destroy tumor cells that carried novel antigens. Allografts were rejected because they were, in effect, mistaken for tumor cells. At the practical level, these ideas suggested that a solution to the allograft problem required treatment of the recipient in a way that would reduce or eliminate the recipient's immune response to the grafted tissue. We have rejected these ideas on the grounds that the basic premise, the notion that antigen alone drives T cell differentiation, is invalid. To explain the origin of the allograft response, we have developed a theory of allogeneic reactivity based on the concept that a stimulator cell is required for the activation of blood cells involved in both nonspecific inflammatory reactions and specific cellular immunity. This theory provides a conceptual link between invertebrate and vertebrate alloreactivity and explains why the MHC and factors controlling the expression of T cell activity map in the same region of the genome. According to this theory, it is blood cells carried within the transplanted tissue and not transplantation antigen on the surface of graft parenchymal cells, that constitute the major barrier to allotransplantation. Experimentally we have presented evidence for a two-signal mechanism for T cell activation. Both antigen and an inductive stimulus are required for T cell activation, and neither factor alone induces detectable T cell activation. Organ culture of thyroid tissue for 4 weeks renders it non-immunogenic without altering its antigenic composition. Furthermore, cyclophosphamide pretreatment of the thyroid donor, a procedure that does not destroy the vascular bed of the donor tissue, also reduces its immunogenicity. These findings are of both theoretical and practical importance. They show that transplantation antigen carried on the parenchymal cells of a transplant do not constitute the major barrier to allotransplantation and, at least in the case of thyroid and parathyroid transplantation, indefinite allograft survival can be achieved by treatments directed at the transplanted tissue and not the recipient.
Animals↗
Glycerokinase in rat and human adipose tissue: response to hormonal and dietary stimuli.
Glycerokinase activity was measured in homogenates of rat and human adipocytes. Human adipocyte glycerokinase activity was not altered by various dietary and hormonal treatments. In contrast, glycerokinase activity in rat adipocytes was decreased by fasting 48 hr and returned toward normal levels after refeeding for 36 hr. This increase in enzyme activity during refeeding was blocked by prior administration of uromycin. Glycerokinase activity was also significantly increased following prolonged incubation of rat adipocytes with dexamethasone in vitro. This stimulation of glycerokinase was further augmented by the simultaneous addition of insulin. Glycerokinase activity in rat and human adipocytes was also dependent on the body weight of the respective tissue donor. Other data presented indicate that glycerokinase is not involved in the "anti-lipolytic" action of insulin. The possible metabolic significance of glycerokinase in adipose tissue is discussed.
Adipose Tissue↗
Chronologic and physiologic age affect replicative life-span of fibroblasts from diabetic, prediabetic, and normal donors.
Cultured skin fibroblasts from subjects with clinically apparent diabetes mellitus and from subjects genetically predisposed to diabetes have a replicative lifespan that is inversely related to donor age. Fibroblasts from carefully defined normal subjects not predisposed to diabetes fail to show this correlation. The data support the idea that physiologic status of the tissue donor is a more precise determinant of fibroblast replicative lifespan than chronologic age.
Adolescent↗
Effect of organ culture on the survival of thyroid allografts in mice.
Mouse thyroid can be maintained in organ culture for 4 weeks. Uncultured BALB/c thyroid is rejected 10-15 days after transplantation under the kidney capsule of H-2 disparate recipients (C57BL, CBA). Organ culture of thyroid tissue prior to transplantation prolongs allograft survival. This prolongation of graft survival increases with increasing time in culture and 80-90% of BALB/c thyroids maintained in culture for 26 days survive in allogeneic CBA recipients for a 60- to 70-day test period. These allografts show normal function as measured by 125I uptake, and show no histological evidence of chronic rejection. Cultured allografts can be rejected if the host's immune system is stimulated with viable leukocytes of donor origin. Host animals carrying a functioning allograft are not tolerant of donor tissues and will reject a second uncultured allograft from the same donor strain.
Animals↗