Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since 1981, more and more transplant centres collaborating within the Eurotransplant Organization started to use Cyclosporin-A (CsA) as part of their immunosuppressive protocols. Although these protocols differ from centre to centre it was felt important to study the clinical significance of CsA on renal allograft survival, especially with regard to other relevant but more constant factors such as HLA-A, -B and -DR matching, pretransplant blood transfusions, ischemia times, etc. This study encompasses 3150 transfused kidney transplant recipients of whom 765 have received CsA. Analysis shows that the group of CsA treated patients had a significantly better graft survival as compared to the non-CsA treated patients i.e., 71% versus 62% at 2 years respectively. The best kidney graft survival was obtained in the HLA-DR well matched donor-recipients combinations even when CsA was used (79% at 2 years). A significant adverse effect of prolonged cold ischemia times was observed when CsA was administered.
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PMID:Cyclosporin-A experience in Eurotransplant--preliminary data. 391 69

Because few HLA-DR-positive cells are present in the fetal spleen and liver, full HLA typing cannot be performed. However, B lymphocyte precursors can be transformed with Epstein-Barr virus to produce lymphoblastoid cells which express HLA-A, B, and DR antigens. Successful transformation was achieved, usually with spleen and liver, in nine fetuses aged from 15 to 18 weeks, mostly within 7 to 14 days of initiation of the cultures. Spleen-derived lymphoblasts were more suitable for typing because of their greater homogeneity and higher viability. Tissues from two 13-week fetuses from prostaglandin-induced abortions and from a spontaneously aborted 22-week fetus could not be transformed. This is probably attributable to prolonged ischemia before the tissues were obtained but, in the 13-week fetuses, absence of B lymphocyte precursors was not excluded. HLA-DR typing may be useful in obtaining well matched donor-recipient pairs in fetal pancreatic islet transplantation.
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PMID:HLA-DR typing of fetal human spleen and liver lymphoblastoid cells transformed by Epstein-Barr virus. 628 97

A total of 23,607 cases transplanted in 1975-1982 were analyzed for proportion and survival trends within eleven classification variables. Increases of up to 2% of total cases per year in proportions of registered transplants over the eight years are found in the following subcategories (with corresponding decreases in complementary subcategories): first grafts, cadaver donors, recipients with diabetes mellitus, and kidneys shipped more than 50 miles. Larger proportional increases of 3-7% per year are found for HLA-DR matching, cold ischemia times greater than 24 hr, cold storage, and pretransplant transfusions. Recipient population cross-sections are unchanged for age, race, HLA-A,B matching, and cytotoxic antibodies at transplant. Only the pretransplant transfusion classification has no increased graft survival in any subcategory; all other variables have one or more categories with increasing graft survival. It appears likely that the marked shift in transfusion policy nationwide has been the primary factor in increasing graft survival rates overall.
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PMID:Kidney transplantation trends from UCLA registry Data, 1975-1982. 636 42

Biopsies from 46 kidneys that were subsequently transplanted were examined with monoclonal antibodies and the peroxidase-antiperoxidase technique to localize HLA-ABC and DR antigens. There was no variation in the expression of HLA-ABC which was present on all cells of the renal parenchyma. HLA-DR was found consistently on the endothelium of glomeruli and of intertubular capillaries but was only weakly expressed, or not expressed at all, on the endothelium of large vessels. The mesangium of glomeruli also stained for HLA-DR. But there was a striking variation in the expression of HLA-DR by proximal renal tubular cells in the 46 kidneys. HLA-DR was absent from tubules in 11 of 46 kidneys (23%) and probably absent or very weakly expressed in a further 8 kidneys (17%). The expression of HLA-DR in tubular epithelium was not related to the donor's age, sex, blood group, or ischemia times. However, the frequency of HLA-DR3 increased (55%) in donors of kidneys with tubular DR-negative kidneys, as compared with a frequency of 15% in donors of tubular DR-positive kidneys. Although this difference was not significant after a correction for the number of comparisons made, it suggests a genetic influence on the expression of tubular DR. The survival of tubular DR-negative kidneys was better at 1 year than that of tubular DR-positive kidneys (70% vs. 57%--not significant), and tubular DR-positive grafts may have had a higher rate of delayed function when transplanted in cases with a donor-specific positive B cell crossmatch. There was no obvious variation in the number of dendritic cells stained with antibodies to HLA-DR and the leukocyte common antigen despite prior administration of high doses of steroids to some donors before nephrectomy.
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PMID:Localization of major histocompatibility complex (HLA-ABC and DR) antigens in 46 kidneys. Differences in HLA-DR staining of tubules among kidneys. 657 52

Pancreas graft survival is influenced by various donor and recipient factors. Factors that have posed serious problems to pancreas transplantation have included the limited cold ischemia time, early graft thrombosis, and rejection. A limited cold ischemia time not only causes problems in terms of logistics but also implies limitations with regard to HLA matching and organ exchange. Between August 1988 and August 1989 we performed a prospective, nonrandomized European multicenter study to evaluate the effect of University of Wisconsin (UW) solution on pancreas graft survival. In addition, donor and recipient factors were collected and their influence on graft survival analyzed. Overall pancreas graft survival at 1 and 4 years was 67% and 59%, respectively (n = 62). When only simultaneous pancreas and kidney transplants were included, the graft survival was 70% and 63% at 1 and 4 years, respectively. The incidence of pancreas graft thrombosis was 8%. Cold ischemia time was not found to significantly influence pancreas graft survival even when it exceeded 12 h. Factors that did were HLA-DR matching, simultaneous pancreas and kidney transplantation versus pancreas transplantation alone, and ABO blood group matching. We feel that the use of UW solution for pancreas preservation has contributed to improved pancreas graft survival and has reduced early graft thrombosis despite much longer cold ischemia times of over 12 h. Given this and the significant effect of HLA and blood group matching, we conclude that more attention should be paid to preoperative matching and organ exchange in order to further improve pancreas graft survival.
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PMID:Effect of blood group and HLA matching on pancreas graft survival with the use of UW solution. 757 18

Chronic rejection of renal allografts is a major cause of late graft loss. However, time of onset, relation with acute early rejection episodes, and risk factors are largely unknown. We undertook a cohort study of 482 consecutive patients from a single center who received a cadaveric renal allograft between January 1983 and April 1991. During the first 3 months after transplantation, 76 (15.8%) patients developed vascular rejection and 115 (23.9%) developed interstitial rejection. One-year graft survival of patients without rejection, with interstitial rejection, and with vascular rejection was 87.8%, 87%, and 48.7%, respectively. Five-year graft survival was 73.5% for the group without rejection, 71.4% for patients with interstitial rejection, and 34.3% for patients with vascular rejection. The adjusted relative risk of graft loss was 4.92 (95% CI 3.25-7.43) for patients with vascular rejection and 1.27 (95% CI 0.80-2.02) for patients with interstitial rejection compared with patients without early rejection, taking the time dependency of the rejection events and prognostic factors into account. The incidence of vascular rejection was increased in patients with primary nonfunction (RR 1.69, 95% CI 1.01-2.84), with 1 HLA-DR mismatch (RR 2.38, 95% CI 1.44-3.93), with 2 HLA-DR mismatches (RR 3.24, 95% CI 1.25-8.42), with a prolonged cold ischemia time (RR 1.03, 95% CI 1.00-1.06 per hr), and with 1 or more previous transplantations (RR 1.76, 95% CI 1.01-3.07). Risk of developing vascular rejection was decreased in patients using CsA as compared with azathioprine (RR 0.41, 95% CI 0.24-0.67). Early vascular rejection, occurring within 3 months after transplantation, is the most important predicting variable of both early and late graft loss. Use of CsA, less HLA-DR mismatching, and a cold ischemia time of short duration possibly prevent the development of vascular rejection.
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PMID:The relation between acute vascular and interstitial renal allograft rejection and subsequent chronic rejection. 776 62

We previously reported the late onset reduction of muscarinic acetylcholine receptors (LORMAR) which begins 7 days after a 5-min period of experimentally induced forebrain ischemia in the gerbil hippocampus. This study demonstrated that post-ischemic administration of cyclosporin A (CsA) reduced LORMAR 10 days after 5 min of forebrain ischemia in the gerbil hippocampus, suggesting that immunosuppression by CsA may reduce damage to the cholinergic system after ischemia. Microglia positive for HLA-DR class II antigen which presented in the hippocampal CA1 area, the region most vulnerable to ischemia, were also reduced by CsA. CsA may suppress microglial activation especially with regard to the antigen-presenting function, and LORMAR may be attenuated by this modulation of microglial function.
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PMID:Cyclosporin A prevents ischemia-induced reduction of muscarinic acetylcholine receptors with suppression of microglial activation in gerbil hippocampus. 779 77

To determine if cardiac allograft outcome is improved among patients with fewer HLA-DR mismatches with their donors, we studied 132 recipients of a primary cardiac allograft who were transplanted between December 1985 and December 1991. These recipients and their donors all had high-confidence-level serological HLA-DR typing, previously shown to correlate highly with DNA DR typing. Patients were divided in two groups based on the HLA-DR mismatch with their donors. Group I consisted of 78 patients with 1 or zero DR mismatch and group II of 54 patients with 2 DR mismatches. Allograft outcome measurements included incidence of moderate rejection, incidence of allograft vasculopathy at 12 months, cardiac function measured as left ventricular ejection fraction (LVEF) and cardiac index (CI), and actuarial graft survival up to 7 years. Groups I and group II were not different with regard to recipient age, donor age, ischemia time, pulmonary vascular resistance, sex, or PRA greater than 0%. Group II had a higher incidence of moderate rejection on the first-week biopsy (47% vs. 25%, P = 0.019), and during the first month (84% vs. 58%, P = 0.006), but no difference was found in frequency of rejection from months 2 to 12. LVEF was not different in the groups at any point. CI was better in group I at 12 months (2.76 vs. 2.5, P = 0.03). No statistically significant difference was found in incidence of allograft vasculopathy (17% vs. 26%, P = 0.204). Actual graft survival at 1 year was better for group I (91% vs. 74%, P = 0.008), and actuarial graft survival at 6 years also favored group I (76% vs. 56%, P = 0.04). Using high-confidence-level serological HLA-DR typing assignments we demonstrated that HLA-DR mismatching correlates highly with cardiac allograft outcome. Implications are that heart transplant survival could be improved if prospective matching were feasible and prioritized or if immunosuppression were tailored to the HLA-DR match.
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PMID:HLA-DR mismatching correlates with early cardiac allograft rejection, incidence, and graft survival when high-confidence-level serological DR typing is used. 811 51

We propose that tissue-specific alloantigens are of importance in interstitial and vascular rejection. To study this hypothesis we took the following approaches: multivariate analysis on our database (N = 482) was performed, the specificity of T cells cultured from kidneys with rejection was analyzed, and non-anti-HLA antibodies reactive with endothelium were studied. First we observed that in a cohort study of 482 patients receiving a cadaveric renal allograft 76 (15.8%) patients developed vascular rejection and 115 (23.9%) developed interstitial rejection. The incidence of vascular rejection was increased in patients with delayed graft function, HLA-DR mismatches, a prolonged cold ischemia period, and previous transplantations. Next we examined 40 graft infiltrating cell (GIC) lines cultured from renal biopsies taken during rejection episodes. Thirteen GIC lines reacted in a donor-specific fashion to proximal tubular cells (PTEC) but not to donor splenocytes. These GIC recognize polymorphic tissue-specific peptides in the context of allo-MHC Class I. Finally, we studied if non-conventional allo-antigen systems on endothelial cells could be the target of the humoral immune response during vascular rejection. We found the endothelial monocyte (EM) system, and another system that is present on endothelial cells and platelets, which can be tested in an antibody-dependent cellular cytotoxicity assay (ADCC).
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PMID:Tissue antigens in tubulointerstitial and vascular rejection. 858 71

Univariate and multivariate analyses have been performed on donor an d recipient variables to determine possible effects on the outcome of 516 primary cadaveric renal transplants performed in our single center from 1989 until 1993. The overall actuarial patient survival at 1 year and 5 years was 94.4% and 87.4%, respectively; the 1 year and 5 year graft survival rates were 88.3% and 77.8%, respectively. A total of 95 grafts were lost; death with function (35%) and chronic rejection (22%) were the major causes. Three variables (HLA-DR mismatch, delayed graft function, and prolonged cold ischemia time) had a significant detrimental effect on both short- and long-term graft survival. Zero HLA-DR mismatched grafts showed significantly enhanced survival over those with 1 HLA-DR mismatch both at 1 year (92.8% vs. 84.5%) and at 5 years (88.3% vs. 73.9%) only if cold ischemia time was less than 26 hours (P=0.0009). Occurrence of delayed graft function significantly lowered graft survival at both 1 year and 5 years (P=0.002), and the incidence was significantly associated with prolonged cold ischemia time (P<0.0001). HLA-A or HLA-B matching, percentage panel reactive antibodies (PRA), and anastomosis time showed no independent effect on long-term survival. The small number of 2 HLA-DR mismatched grafts (n=6) precluded separate analysis of this group. Acute rejection accounted for 12% of losses but had no statistically significant effect on graft survival, even though an increased frequency of rejection episodes was significantly associated with HLA-DR mismatch (P<0.0001). These results would suggest that significant survival benefits may be achieved by prospective HLA matching if cold ischemia times are limited. The efficiency of organ sharing must he improved to make optimal use of a limited resource.
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PMID:Importance of minimizing HLA-DR mismatch and cold preservation time in cadaveric renal transplantation. 860 72


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