Showing papers on "Transplantation published in 1993"
TL;DR: Captopril protects against deterioration in renal function in insulin-dependent diabetic nephropathy and is significantly more effective than blood-pressure control alone.
Abstract: Background Renal function declines progressively in patients who have diabetic nephropathy, and the decline may be slowed by antihypertensive drugs The purpose of this study was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy Methods We performed a randomized, controlled trial comparing captopril with placebo in patients with insulin-dependent diabetes mellitus in whom urinary protein excretion was > or = 500 mg per day and the serum creatinine concentration was Results Two hundred seven patients received captopril, and 202 placebo Serum creatinine concentrations doubled in 25 patients in the captopril group, as compared with 43 patients in the placebo group (P = 0007) The associated reductions in risk of a doubling of the serum creatinine concentration were 48 percent in the captopril group as a whole, 76 percent in the subgroup with a baseline serum creatinine concentration of 20 mg per deciliter (177 mumol per liter), 55 percent in the subgroup with a concentration of 15 mg per deciliter (133 mumol per liter), and 17 percent in the subgroup with a concentration of 10 mg per deciliter (884 mumol per liter) The mean (+/- SD) rate of decline in creatinine clearance was 11 +/- 21 percent per year in the captopril group and 17 +/- 20 percent per year in the placebo group (P = 003) Among the patients whose base-line serum creatinine concentration was > or = 15 mg per deciliter, creatinine clearance declined at a rate of 23 +/- 25 percent per year in the captopril group and at a rate of 37 +/- 25 percent per year in the placebo group (P = 001) Captopril treatment was associated with a 50 percent reduction in the risk of the combined end points of death, dialysis, and transplantation that was independent of the small disparity in blood pressure between the groups Conclusions Captopril protects against deterioration in renal function in insulin-dependent diabetic nephropathy and is significantly more effective than blood-pressure control alone
4,772 citations
TL;DR: A schema for international standardization of nomenclature and criteria for the histologic diagnosis of renal allograft rejection was developed in Banff, Canada on August 2-4, 1991 and validated by the circulation of sets of slides for scoring by participant pathologists.
1,345 citations
TL;DR: In patients with idiopathic dilated cardiomyopathy, treatment with metoprolol prevented clinical deterioration, improved symptoms and cardiac function, and was well tolerated.
1,126 citations
TL;DR: The clinical impression is that the current incidence of VOD at the institution is much higher than the 21% rate reported 9 years ago and that more patients have severe liver disease, which may explain the apparent increased incidence and severity of this complication.
Abstract: Objective: To determine the incidence and clinical course of veno-occlusive disease of the liver (VOD) after bone marrow transplantation and to analyze risk factors for severe VOD. Design: Cohort s...
1,120 citations
TL;DR: The progressive increase in strength was correlated with the degree of bone ingrowth, mineralization, and maturation of the healing tissue, noted histologically.
Abstract: Our study evaluated tendon-to-bone healing in a dog model. Twenty adult mongrel dogs had a transplantation of the long digital extensor tendon into a 4.8-millimeter drill-hole in the proximal tibial metaphysis. Four dogs were killed at each of five time-periods (two, four, eight, twelve, and twenty-six weeks after the transplantation), and the histological and biomechanical characteristics of the tendon-bone interface were evaluated. Serial histological analysis revealed progressive reestablishment of collagen-fiber continuity between the bone and the tendon. A layer of cellular, fibrous tissue was noted between the tendon and the bone, along the length of the bone tunnel; this layer progressively matured and reorganized during the healing process. The collagen fibers that attached the tendon to the bone resembled Sharpey fibers. High-resolution radiographs showed remodeling of the trabecular bone that surrounded the tendon. At the two, four, and eight-week time-periods, all specimens had failed by pull-out of the tendon from the bone tunnel. The strength of the interface was noted to have significantly and progressively increased between the second and the twelfth week after the transplantation. At the twelve and twenty-six-week time-periods, all specimens had failed by pull-out of the tendon from the clamp or by mid-substance rupture of the tendon. The progressive increase in strength was correlated with the degree of bone ingrowth, mineralization, and maturation of the healing tissue, noted histologically.
1,022 citations
TL;DR: A randomised comparison of high-dose chemotherapy plus ABMT with the same drugs at lower doses not requiring bone-marrow rescue in patients with active Hodgkin's disease found that high doses facilitated by ABMT can lead to better disease-free survival.
973 citations
TL;DR: In this retrospective study of HBsAg-positive patients, liver transplantation had better results in those who had fulminant hepatitis or delta virus superinfection and reduced mortality.
Abstract: Background The role of liver transplantation in patients positive for the hepatitis B surface antigen (HBsAg) is controversial because of the high rate of recurrent hepatitis B virus (HBV) infection. It has not been determined whether this risk is greater for certain patients and whether the administration of anti-hepatitis B surface antigen (anti-HBs) immune globulin is beneficial. Methods We conducted a retrospective study at 17 European centers of 372 consecutive HBsAg-positive patients who underwent liver transplantation between 1977 and 1990. Recurrence of HBV infection was defined as the reappearance of HBsAg in serum. Results For all 334 patients with follow-up data, the mean (±SE) three-year actuarial risk of recurrence of HBV was 50 ±3 percent. The risk was 67 ±4 percent among 163 patients with HBV-related cirrhosis, 32 ±5 percent among 110 patients with cirrhosis related to hepatitis delta virus, 40 ±16 percent among 14 patients with fulminant hepatitis delta infection, and 17 ±7 percent among 3...
969 citations
TL;DR: Routine donor liver biopsies are recommended to decrease the rate of IPF and PNF, and the combination of risk factors shown to be significant for PDF should be avoided--and the only variable that can be controlled, the preservation time, should be kept as short as possible.
Abstract: In a retrospective analysis on 323 orthotopic liver transplant procedures performed between July 1984 and October 1991 the incidence of two forms of primary dysfunction (PDF) of the liver: primary nonfunction (PNF), and initial poor function (IPF) were studied. The incidence of PDF was 22% (73/323) with 6% PNF (20/323) and 16% IPF (53/323), while 78% (250/323) had immediate function (IF). Occurrence of both IPF and PNF resulted in a higher graft failure rate (P 3 days), older donor age (> 49 years), extended preservation times (> 18 hr), and fatty changes in the donor liver biopsy, as well as reduced-size livers, younger recipient age, and renal insufficiency prior to OLTx, significantly affected the incidence of IPF and PNF. Multivariate analysis of potential risk factors showed that reduced-size liver (P = 0.0001), fatty changes on donor liver biopsy (P = 0.001), older donor age (P = 0.009), retransplantation (P = 0.01), renal insufficiency (P = 0.02), and prolonged cold ischemia times (P = 0.02) were independently associated with a higher incidence of IPF and PNF. No statistical correlation was found between PDF and etiology of ESLD, nutritional status of the recipient, UNOS status, and Child-Pugh classification in this study. We conclude that PNF and IPF are both separate clinical entities that have a significant effect on outcome after OLTx. Routine donor liver biopsies are recommended to decrease the rate of IPF and PNF. The combination of risk factors shown to be significant for PDF should be avoided--and, if that is not possible, the only variable that can be controlled, the preservation time, should be kept as short as possible.
969 citations
TL;DR: Transfer of the neomycin-resistance gene into bone-marrow cells harvested from children with acute myeloid leukaemia in remission should enable the development of better marrow purging strategies.
955 citations
TL;DR: This process of "infectious" tolerance explains why no further immunosuppression was needed to maintain long-term transplantation tolerance in adult mice.
Abstract: The maintenance of transplantation tolerance induced in adult mice after short-term treatment with nonlytic monoclonal antibodies to CD4 and CD8 was investigated. CD4+ T cells from tolerant mice disabled naive lymphocytes so that they too could not reject the graft. The naive lymphocytes that had been so disabled also became tolerant and, in turn, developed the capacity to specifically disable other naive lymphocytes. This process of "infectious" tolerance explains why no further immunosuppression was needed to maintain long-term transplantation tolerance.
884 citations
TL;DR: The best indication for transplantation seems to be patients with small and uninodular or binodular tumors; until now, these patients were considered to be the best candidates for resection.
Abstract: OBJECTIVE: Currently, there is considerable controversy about the place of transplantation in the treatment of hepatocellular carcinoma (HCC). This study compared resection to transplantation in cirrhotic patients with HCC in order to determine reasonable indications of each treatment. SUMMARY BACKGROUND DATA: The usual procedure is to resect when feasible and to transplant in other cases. METHODS: Three-year survival with and without recurrence was analyzed in 60 patients who underwent resection and 60 who underwent transplantation. Several prognostic factors, such as size, number of nodules, portal thrombus, and histologic form, were studied. RESULTS: In terms of overall survival rates, resection and transplantation yield the same results (50% vs. 47%, respectively, at 3 years). For transplantation, however, the rate for survival without recurrence is better than that for resection (46% vs. 27%, respectively; p 3 cm, or presence of portal thrombus). CONCLUSIONS: The best indication for transplantation seems to be patients with small and uninodular or binodular tumors; until now, these patients were considered to be the best candidates for resection. Patients undergoing transplantation for unresectable, large, multinodular or diffuse tumors seem to represent bad indications for transplantation. These results could help define reasonable indications for transplantation in an era with a shortage of liver grafts.
Memorial Sloan Kettering Cancer Center1, University of Minnesota2, Medical College of Wisconsin3, University of Utah4, University of Texas at Austin5, University of California, Los Angeles6, Fred Hutchinson Cancer Research Center7, University of Kentucky8, Gulf Coast Regional Blood Center9, University of British Columbia10, Stanford University11
TL;DR: The National Marrow Donor Program has benefited a substantial number of patients in need of marrow transplants from closely HLA-matched unrelated donors and has facilitated the recruitment of unrelated donors into the donor pool and the access to suitable marrow.
Abstract: Background and Methods Allogeneic bone marrow transplantation is curative in a substantial number of patients with hematologic cancers, marrow-failure disorders, immunodeficiency syndromes, and certain metabolic diseases. Unfortunately, only 25 to 30 percent of potential recipients have HLA-identical siblings who can act as donors. In 1986 the National Marrow Donor Program was created in the United States to facilitate the finding and procurement of suitable marrow from unrelated donors for patients lacking related donors. Results During the first four years of the program, 462 patients with acquired and congenital lymphohematopoietic disorders or metabolic diseases received marrow transplants from unrelated donors. The probability of engraftment by 100 days after transplantation was 94 percent, although 8 percent of patients later had secondary graft failure. The probability of grade II, III, or IV acute graft-versus-host disease was 64 percent, and the probability of chronic graft-versus-host disease at...
TL;DR: Information is provided on how to identify the wood of several species common to the Northern Hemisphere using a hand-magnifying lens.
Abstract: INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1 7 CYTOKINES AND EFFECTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1 8 Cell Sources and Stimuli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1 8 Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320 Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321 REGULA TORS AND EFFECTORS OF CYTOKINE EFFECTS . . . . . . . . . . . . 322 Factors that Enhance Effects of TNF . . . . . . . . . . . . . . . . . . . . . . . . . . . 322 Factors that Suppress Effects of TNF . . . . . . . . . . . . . . . . . . . . . . . . . . . 323 Secondary Mediators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325 Locations of Production in Tissues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326 Development of Tolerance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327 CYTOKINES AND DISEASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329 Shock and Tissue Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329 Cachexia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330 Insulin Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332 Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332 Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332 HlV Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333 Adult Respiratory Distress Syndrome and Reperfusion Injury . . . . . . . . . . . . . 333 Diseases of Central Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334 FUTURE OF CYTOKINES IN THE BIOLOGY OF DISEASE . . . . . . . . . . . . . 335
Book•
01 May 1993
TL;DR: This poster presents a probabilistic procedure to characterize the response of the immune system to the presence of carbon dioxide in the airway of an invalid person.
Abstract: CONTENTS: Atmosphere Anatomy Elasticity Flow Control Pulmonary ventilation Pulmonary circulation Distribution Diffusion Carbon dioxide Oxygen Non-Respiratory functions Exercise Sleep High altitude Diving Drowning Neonates Smoking Anaesthesia Ventilatory failure Artificial ventilation Extra-Corporeal respiration Transplantation Anaemia Pulmonary oedema Col/ Atel Embolus ARDS Hypercap Hypoxia Hyperoxia
TL;DR: The expression of cell adhesion molecules is an important element in the inflammatory component of atherosclerosis and contributes to both monocyte and lymphocyte activation and recruitment from advential vessels and the arterial lumen.
Abstract: The expression of PECAM, ICAM-1, VCAM-1, and E-selectin was studied in 64 samples of human coronary arteries taken from 15 explanted hearts obtained within 5 min of transplantation. Normal artery (n = 12), predominantly fibrous plaques (n = 23), and plaques containing extracellular lipid (n = 26) and three segments showing recanalization channels were studied. All endothelial cells strongly and equally expressed PECAM; positive staining was used to check that artefactual denudation of the endothelial surface had not occurred. PECAM was also present in some lipid-filled macrophages. Normal arteries showed no VCAM-1 staining but focal segments of the endothelium were positive for ICAM-1 and E-selectin. ICAM-1 was strongly and constantly expressed by the endothelium over all types of plaques and in macrophages. E-selectin expression was confined to endothelial cells and occurred on the surface in 35 per cent of fibrous and 22 per cent of lipid-containing plaques. VCAM-1 staining of surface endothelium occurred in 39 per cent of fibrous and 20 per cent of lipid-containing plaques. A population of spindle-shaped cells of macrophage type (positive for EMB11 antigen) expressed VCAM-1 in lipid-containing plaques. Adventitial vessels adjacent to plaques showed endothelial expression of ICAM-1 and E-selectin. VCAM-1 staining of adventitial vessel endothelium was associated with local lymphoid aggregation. In conclusion, the expression of cell adhesion molecules is an important element in the inflammatory component of atherosclerosis and contributes to both monocyte and lymphocyte activation and recruitment from adventitial vessels and the arterial lumen.
TL;DR: It is proposed recently that the exchange of migratory leukocytes between the transplant and the recipient with consequent long-term cellular chimerism in both is the basis for acceptance of all whole-organ allografts and xenograftS.
Journal Article•
TL;DR: A clinically applicable, standardized method for assessing functional results after lung transplantation is required to evaluate factors that may affect long-term outcome, to permit comparison of results from different centers, and to evaluate results of clinical trials.
Abstract: A clinically applicable, standardized method for assessing functional results after lung transplantation is required to evaluate factors that may affect long-term outcome, to permit comparison of results from different centers, and to evaluate results of clinical trials An ad hoc working group was established under the auspices of the International Society for Heart and Lung Transplantation for the purpose of developing such a clinically applicable system Chronic allograft dysfunction is often associated with pathologic findings of obliterative bronchiolitis, the cause of which has not been defined Physiologically, such dysfunction is associated with obstructive airways disease The group concluded that the forced expiratory volume in 1 second was the most reliable and consistent indicator of graft dysfunction, excluding other identifiable causes The term bronchiolitis obliterans syndrome was adopted to describe such dysfunction, recognizing that there may or may not be pathologic evidence of bronchiolitis obliterans present Four stages of bronchiolitis obliterans syndrome were defined, each with two subcategories to indicate whether pathologic evidence of obliterative bronchiolitis had been identified This working formulation will require reappraisal in the future to reassess its practical application and to make such adjustments as may seem appropriate
TL;DR: Action potential prolongation in severe heart failure may partially be explained by a reduction in current densities of the inward rectifier K+ current and of the transient outward K+Current, which may have a significant effect on cardiac relaxation.
Abstract: Prolongation of the action potential has been postulated to be a major reason for the altered diastolic relaxation of the heart in patients with severe heart failure. To investigate the electrophysiological basis for this action potential prolongation in terminal heart failure, K+ currents were recorded in single ventricular myocytes isolated from 16 explanted hearts of patients undergoing transplantation. Results from diseased hearts were compared with ventricular cells isolated from six undiseased donor hearts. Action potential duration was significantly prolonged in cells from patients with heart failure. A delayed rectifier K+ current was hardly detectable in most cells, and if it could be recorded, it was very small in both diseased and undiseased cells. When currents were normalized for cell surface area, the average current density of the inward rectifier K+ current was significantly reduced in diseased cells when compared with normal control cells (hyperpolarization at -100 mV, -15.9 +/- 2.2 vs -9.0 +/- 1.2 microA/cm2; P < .01). In addition, a large transient outward K+ current could be recorded in human myocytes. The average current density of the time-dependent component of this transient outward K+ current was significantly reduced in heart failure (depolarization at +40 mV, 9.1 +/- 1.0 vs 5.8 +/- 0.64 microA/cm2; P < .01). Action potential prolongation in severe heart failure may partially be explained by a reduction in current densities of the inward rectifier K+ current and of the transient outward K+ current. These alterations may thereby have a significant effect on cardiac relaxation.
TL;DR: The overall mortality risk following renal transplantation was initially increased, but there was a long-term survival benefit compared with similar patients on dialysis.
Abstract: Objective. —To compare mortality risk among cadaveric renal transplant recipients vs transplant candidates on dialysis in the cyclosporine era. Setting. —Patient mortality risk was analyzed by treatment modality for a completed statewide patient population. Patients. —All Michigan residents younger than age 65 years who started end-stage renal disease (ESRD) therapy between January 1,1984, and December 31, 1989, were included. Patients were followed up from ESRD onset (n=5020), to wait-listing for renal transplant (n=1569), to receiving a cadaveric first transplant (n=799), and to December 31, 1989. Main Outcome Measure. —Mortality rates. Results. —Using a time-dependent variable based on the waiting time from date of wait-listing to transplantation and adjusting for age, sex, race, and primary cause of ESRD, the relative risk (RR) of dying was increased early after transplantation and then decreased to a beneficial long-term effect, given survival to 365 days after transplantation (RR, 0.36;P .05). Overall, the estimated times from transplantation to equal mortality risk was 117±28 days and to equal cumulative mortality was 325±91 days. Conclusions. —The overall mortality risk following renal transplantation was initially increased, but there was a long-term survival benefit compared with similar patients on dialysis. These analyses allow improved description of comparative mortality risks for dialysis and transplant patients and allow advising patients regarding comparative survival outcomes. (JAMA. 1993;270:1339-1343)
TL;DR: Recent discoveries that organs and tissues can be regenerated and reconstructed, using cells cultured on synthetic biodegradable polymers, renders this method useful in creating polymer-cell graft for use in cell transplantation.
TL;DR: In this article, the authors found that acute rejection, CsA dosage < 5 mg/kg/day at 1 year, and infection are the major risk factors for the development of chronic rejection.
Abstract: Chronic rejection is a major barrier to long-term renal allograft survival. Cyclosporine, though effective at reducing graft loss to acute rejection, has had little impact on the incidence of chronic rejection. Between June 2, 1986 and January 22, 1991, 587 kidney-alone transplants (566 patients) were performed, and had been entered into our renal transplant database and had at least 1 year of follow-up: 103 with biopsy-proven chronic rejection (37 living-related donor, 66 cadaver) and 484 without chronic rejection (236 LRD 248 CAD). The 5-year patient survival was 84% for recipients with biopsy-proven chronic rejection vs. 89% without (P = .08). The 5-year graft survival was 31% for recipients with biopsy-proven chronic rejection vs. 81% without (P 50 years), gender, human leukocyte antigen matching, peak and transplant panel-reactive antibody, acute rejection episodes, infections (including cytomegalovirus, viral, and bacterial), donor age, and CsA dosage at 1 year ( or = 5 mg/kg). Logistic regression models were fit to the data using a forward stepwise selection procedure. In this analysis, risk factors included an acute rejection episode (P < .001), CsA dosage < 5 mg/kg/day at 1 year (P = .007), infection (P = .023), female gender (P = .042), and retransplant (P = .103). Individual analyses were done for CAD and LRD recipients. For both groups, important variables were acute rejection, infection, CsA dosage at 1 year, and age at transplant. In conclusion, acute rejection, CsA dosage < 5 mg/kg/day at 1 year, and infection are the major risk factors for the development of chronic rejection, suggesting that chronic rejection may be the result of inadequate immunosuppression (acute rejection episodes and low CsA dosage) or the production of inflammatory cytokines (infections).
TL;DR: Uri Galili argues that the interaction between anti-Gal in the serum and alpha-galactosyl epitopes on cells of nonprimate grafts may act as an immunological barrier which prevents xenotransplantation.
TL;DR: It is suggested that the risk of NHL is related to the aggressiveness of the immunosuppressive regimen, and in patients who received rejection prophylaxis with antilymphocyte antibodies there were significant increases in risk.
TL;DR: A novel method was developed to prepare three-dimensional structures with desired shapes used as templates for cell transplantation that are highly porous with large surface/volume and provide the necessary space for attachment and proliferation of the transplanted cells.
Abstract: A novel method was developed to prepare three-dimensional structures with desired shapes used as templates for cell transplantation. The produced biomaterials are highly porous with large surface/volume and provide the necessary space for attachment and proliferation of the transplanted cells. The processing technique calls for the formation of a composite material with nonbonded fibers embedded in a matrix followed by thermal treatment and the selective dissolution of the matrix. To evaluate the technique, poly(glycolic acid) (PGA) fiber meshes were bonded using poly(L-lactic acid) (PLLA) as a matrix. The bonded structures were highly porous with values of porosity up to 0.81 and area/volume ratios as high as 0.05 micron-1.
TL;DR: It is reported here that soil-borne diseases may contribute to the succession of foredune plant species and the different sensitivities of plant species for the soil-bourne pathogens could be an evolutionary response to selection pressures of the succession stage.
Abstract: ECOLOGICAL study of the role of soil microorganisms in vegetation succession has focused mainly on organisms affecting plant nutrition, such as mycorrhiza and nitrogen-fixing bacteria. But, soil-borne diseases are involved in the degeneration of Ammophila arenaria (Marram grass) and Hippophae rhamnoides (Sea buckthorn), two plant species that dominate the coastal foredunes of Europe and are widely planted for sand stabilization. We have used reciprocal transplantation and report here that soil-borne diseases may contribute to the succession of foredune plant species. In pot experiments, plant species that succeed A. arenaria were tolerant of the soil-borne diseases of this species. Plant species that were grown in soils from both previous and later succession stages were reduced most in soils from the later stages. During foredune succession, therefore, plants disappear from sites where the soil has become colonized with specific growth-depressing microorganisms. The soil-borne diseases must have considerable importance for the outcome of interspecific competition and may be involved in patterns of clonal growth. The different sensitivities of plant species for the soil-borne pathogens could be an evolutionary response to selection pressures of the succession stage to which a species is confined by the combined effect of local abiotic and biotic environmental factors.
TL;DR: It is shown that most of human IgM antibodies present in the serum of healthy donors and reactive with pig cells react with galactose in an (alpha 1-3) linkage with Galactose--i.e., Gal(alpha 1,3)Gal.
Abstract: A major problem with pig-to-human-tissue xenograft studies is that humans have natural antibodies to pig cells; these antibodies would cause hyperacute rejection if pig tissues were xenografted to humans. Here we show that most of human IgM antibodies present in the serum of healthy donors and reactive with pig cells react with galactose in an (alpha 1-3) linkage with galactose--i.e., Gal(alpha 1-3)Gal. Absorption studies demonstrated that the antibodies detected the same or similar epitopes on the surface of pig erythrocytes, blood and splenic lymphocytes, and aortic endothelial cells (EC). The antibodies were sensitive to 2-mercaptoethanol (2ME) treatment, did not bind to protein A or G, and were present in the high molecular weight fraction of serum; they are clearly IgM antibodies. Further, the antibodies did not react with human ABO blood group substances and are not related to human blood group A or B, which carry a terminal galactose. The reaction of human serum with pig erythrocytes was specifically inhibited by mono- and disaccharides: D-galactose, melibiose, stachyose, methyl-alpha-D-galactopyranoside, and D-galactosamine but not by D-glucose or methyl-beta-D-galactopyranoside; demonstrating that the reaction is with galactose in an alpha and not a beta linkage. A cDNA clone encoding the murine alpha-1,3-galactosyltransferase (which transfers a terminal galactose residue with an (alpha 1-3) linkage to a subterminal galactose) was isolated by polymerase chain reaction (PCR), cloned, and transfected into COS cells, which are of Old World monkey origin and, like humans, do not express Gal(alpha 1-3)Gal. After transfection, COS cells became strongly reactive with human serum and with IB4 lectin [which reacts only with Gal(alpha 1-3)Gal]; this reactivity could be removed by absorption with pig erythrocytes. As most of the antibody reacting with pig cells can be removed by absorption with either melibiose or Gal(alpha 1-3)Gal+ COS cells, most of these react with Gal(alpha 1-3)Gal. These findings provide the basis for genetic manipulation of the pig alpha-1,3-galactosyltransferase for future transplantation studies.
TL;DR: The data indicate that peritransplant use of DST followed by subsequent treatment with CTLA4Ig can induce prolonged, often indefinite, cardiac allograft acceptance, and may be clinically applicable for cadaveric organ and tissue transplantation in humans.
Abstract: Allograft rejection is a T cell-dependent process. Productive T cell activation by antigen requires antigen engagement of the T cell receptor as well as costimulatory signals delivered through other T cell surface molecules such as CD28. Engagement of CD28 by its natural ligand B7 can be blocked using a soluble recombinant fusion protein, CTLA4Ig. Administration of CTLA4Ig blocks antigen-specific immune responses in vitro and in vivo, and we have shown that treatment of rats with a 7-d course of CTLA4Ig at the time of transplantation leads to prolonged survival of cardiac allografts (median 30 d), although most grafts are eventually rejected. Here, we have explored additional strategies employing CTLA4Ig in order to achieve long-term allograft survival. Our data indicate that donor-specific transfusion (DST) plus CTLA4Ig can provide effective antigen-specific immunosuppression. When DST is administered at the time of transplantation followed by a single dose of CTLA4Ig 2 d later, all animals had long-term graft survival (> 60 d). These animals had delayed responses to donor-type skin transplants, compared with normal rejection responses to third-party skin transplants. Furthermore, donor-matched second cardiac allografts were well tolerated with minimal histologic evidence of rejection. These data indicate that peritransplant use of DST followed by subsequent treatment with CTLA4Ig can induce prolonged, often indefinite, cardiac allograft acceptance. These results may be clinically applicable for cadaveric organ and tissue transplantation in humans.
TL;DR: It is suggested that the meticulous management of surgical factors at each stage of the LRLT procedure is crucial for successful outcome and may be regarded as an independent modality to supplement cadaver donation.
Abstract: The authors successfully performed a series of 33 living related liver transplantations (LRLT) on children (15 males and 18 females, ranging from 7 months to 15 years of age) from June 1990 to May 1992, with the informed consent of their parents and the approval of the Ethics Committee of Kyoto University. Before operation, six of the children required intensive care, another 14 were hospitalized, and 13 were homebound. Donors (12 paternal and 21 maternal) were selected solely from the parents of the recipients on the basis of ABO blood group and graft/recipient size matching determined by computed tomography scanning. Procurement of graft was performed using ultrasonic aspirator and bipolar electrocautery without blood vessel clamping and without graft manipulation. All donors subsequently had normal liver function and returned to normal life. The left lateral segment (16 cases), left lobe (16 cases), or right lobe (one case) were used as grafts. The partial liver graft was transplanted into the recipient who underwent total hepatectomy with preservation of the inferior vena cava using a vascular side clamp. Twenty-seven of 33 recipients are alive and well with the original graft and have normal liver function. The patient survival rate was 89% (24/27) in elective cases and 50% (3/6) in emergent cases. The other six recipients had functioning grafts but died of extrahepatic complications. Complications of the graft were minimal in all cases. Hepatic vein stenosis, which occurred three times in two cases, was successfully treated by balloon dilatation. In cases with sclerotic portal vein, the authors anastomosed the portal vein of the graft to the confluence of the splenic vein and the superior mesenteric vein without a vascular graft, after experiencing a case of vascular graft thrombosis. After hepatic artery thrombosis occurred in one of the initial seven recipients whose arterial anastomosis was done with surgical loupe, microsurgery was introduced for hepatic artery reconstruction. There has been no occurrence of thrombosis since then. The current results with LRLT suggested that the meticulous management of surgical factors at each stage of the LRLT procedure is crucial for successful outcome. Living related liver transplantation is a promising option for resolving the graft shortage in pediatric liver transplantation and may be regarded as an independent modality to supplement cadaver donation.
TL;DR: The intraocular injection of CNTF, BDNF, and ScN-derived medium, which retard the process of lesion-induced RGC degeneration, may be successfully used as a subsidiary strategy in transplatation protocols to result in larger populations of RGC which can be recruited to regenerate their axons and provide a basis for functional recovery.
TL;DR: Liver transplantation does have important benefits in FAP during the first 2 years after surgery, Neurological decline is halted and amyloid deposits can be mobilised.