摘要:

Background.Hepatitis G virus (HGV/GBV-C) RNA indicating current infection has been frequently isolated from the sera of transplant recipients and other multitransfused individuals. Lifetime exposure to the virus, however, is unknown. We carried out a study to determine the prevalence and risk factors of HGV antibodies and of HGV RNA among renal transplant recipients, and to investigate possible associations between HGV RNA and immunosuppressive treatment.Methods.HGV RNA was detected by reverse transcriptase-polymerase chain reaction, and HGV antibodies (anti-E2) by a newly developed immunoassay. To assess risk factors for HGV exposure, univariate and multivariate analysis was performed.Results.Of the 221 patients, 14% were HGV RNA positive and 40% had HGV antibodies. Both HGV RNA and anti-HGV were present in only two individuals. Thus, the overall HGV exposure prevalence was 53%. It increased significantly with the number of blood transfusions. In logistic regression, the adjusted HGV exposure prevalence odds ratio was 5.7 (95% confidence interval [CI]: 2.2-15) among patients with ≥10 transfusions (baseline: no transfusions). Other independent risk factors were a longer duration of hemodialysis and a longer time interval since transplantation. HGV viremia was not associated with the type of immunosuppressive treatment. Alanine aminotransferase levels were not significantly increased among HGV RNA-positive patients.Conclusions.Much higher proportions of renal transplant recipients were exposed to HGV than is suggested by HGV RNA detection alone. The majority of infected individuals apparently eliminate the virus over time. Contaminated blood transfusions have to be regarded as a main risk factor for HGV infection.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.The aim of the present study was to analyze the effect of HLA-DRB1* mismatches on graft function and graft survival in 92 patients who received serologically HLA-DR split antigen-matched cadaveric renal transplants.Methods.The polymorphic second exon of the HLA-DRB1 alleles was typed using the sequence-specific oligonucleotides technique.Results.The results show that in 26 of the 92 analyzed combinations, one or more HLA-DRB1* mismatches were found (28%). The analysis of the occurrence of treatable rejection episodes during the first 3 months after transplantation demonstrated a significantly higher incidence of rejection episodes in the HLA-DRB1*-mismatched group: 18 of 26 (69%) in the HLA-DRB1*-mismatched group against 23 of 66 (35%) in the HLA-DRB1*-matched group (Puncorr=0.0033). However, no effect of HLA-DRB1* mismatches on graft survival was found, although in general graft survival in the whole patient group was negatively influenced by the occurrence of rejection episodes during the first 3 months after transplantation (Puncorr=0.0008). In contrast, in the HLA-DR4-matched donor-recipient combinations (n=28), the effect of mismatching for the HLA-DRB1*04 alleles seemed to have a pronounced effect not only on the occurrence of rejection episodes but also in the form of diminished graft survival.Conclusions.Thus, this study indicates that the existence of HLA-DRB1* allele mismatches in renal transplant recipients, matched for the serologically defined HLA-DR split antigens, is not harmful for the transplant. The exception is the HLA-DRB1*04 mismatch, which seems to be deleterious for the grafted organ.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.In heart transplants, left ventricular function may be impaired in the absence of rejection or graft atherosclerosis. Matching between left ventricle and arterial receptor, i.e., ventriculoarterial coupling, and left ventricular efficiency have never been studied.Methods.Left ventricular pressure-volume loops and single beat analysis were used to determine effective arterial elastance (Ea) and the slope of the end-systolic pressure-volume relation (end-systolic elastance; Ees). Left ventricular efficiency was evaluated by determination of external work (EW), pressure-volume area (PVA), coronary blood flow (continuous thermodilution), and myocardial oxygen consumption (MVO2). Measurements were made at baseline in 11 control subjects and 9 heart transplant recipients (HTX) without rejection and were repeated after phenylephrine in the latter group.Results.At baseline, Ees, Ees/Ea, and work efficiency (EW/PVA) were lower in HTX than in control subjects (2.51±0.87 vs. 3.70±1.15 mmHg/ml/m2,P<0.01; 0.96±0.21 vs. 1.47±0.31,P<0.001; and 0.53±0.08 vs. 0.59±0.09,P<0.01, respectively). Energy conversion efficiency (PVA/MVO2) and mechanical efficiency (EW/MVO2) were higher in HTX (0.58±0.08 vs. 0.45±0.14,P<0.001; and 0.31±0.05 vs. 0.26±0.06,P<0.001, respectively). In HTX, phenylephrine infusion increased Ees, Ea, EW, PVA, and MVO2without modifying Ees/Ea, EW/PVA, PVA/MVO2, and EW/MVO2.Conclusions.In heart transplants, (1) left ventricular contractility is moderately depressed; (2) elevation of energy conversion efficiency compensates for the decrease in work efficiency, allowing normal mechanical efficiency; and (3) alpha 1 adrenergic stimulation does not impair ventriculoarterial coupling and mechanical efficiency.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.We have previously shown that MHC-mismatched fetal liver cells can durably engraft in 45% of nondefective fetal mice, although male donor cells were found in the blood in only 8% of female recipients. We postulated that adult bone marrow stem cells would engraft similarly to fetal liver cells and that postnatal administration of cytokines would recruit donor cells into the peripheral circulation.Methods.Bone marrow from C57BL/6 adult male mice was injected into allogeneic BALB/c or congenic C57BL/6 fetal recipients that were 11-13 days old. Engraftment was tested by quantitative polymerase chain reaction for the Y chromosome in female recipients (0.0001% sensitivity). Recipients were injected at 1-2 years of age with rat stem cell factor (SCF) and human granulocyte colony-stimulating factor (G-CSF) for 7 days and tested for donor cells in the blood.Results.The overall engraftment rate (in the blood, spleen, or liver) was 44% in both female allogeneic and congenic bone marrow recipients. Of 49 recipients of bone marrow or fetal liver cells with no evidence of donor cells in the blood before injection, 29 (59%) developed circulating donor cells at some time after cytokine injection for up to 2 months. Twenty-seven of 49 animals were negative in the blood, liver, and spleen before cytokine therapy; 14 of 27 (52%) became positive in the blood after stem cell factor/granulocyte colony-stimulating factor injection. Tolerance to donor skin grafts was not altered by the mobilization of donor cells into the circulation.Conclusions.Adult bone marrow durably engrafts in nondefective mice at a rate similar to that previously obtained with fetal liver. Engrafted donor cells can be mobilized with cytokines into the circulation for up to 2 months even in animals with no evidence of donor cells in the blood, liver, or spleen. Based on these results we estimate that 70-75% of hematopoietically nondefective fetal mice engraft with MHC-mismatched fetal liver or adult bone marrow stem cells.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.The precise mechanisms involved in islet xenograft rejection remain unknown. The purpose of the present study was to determine cellular mechanisms responsible for islet xenograft rejection in the liver to facilitate finding a procedure for prevention of immune rejection.Methods.Hepatic mononuclear cells (MNC) as well as splenocytes, peripheral blood MNC, and thymocytes from streptozotocin-induced diabetic mice (BALB/c) rejecting the intrahepatic rat (Lewis) islet xenografts were isolated and examined by two-color FACS analysis.Results.The characteristic finding of the hepatic MNC from the mice rejecting islet xenografts compared with mice receiving isografts was a significant increase in the yield as well as in the percentage of the cells expressing CD3+interleukin-2 receptor (IL-2R) α-β+, CD3+CD8α+β+, and T cell receptor (TCR) αβ+lymphocyte function-associated antigen-1+. The expression of CD3 and TCRαβ of these T cells was found to be of intermediate intensity (TCRintcells). The expansion of these TCRintcells occurred predominantly in the liver. There was no significant difference in the cells expressing CD3+IL-2Rα+, CD3+CD4+, CD3+TCRγδ+, CD3-IL-2Rβ+(natural killer cells), and B220+(B cells). In vivo administration of anti-IL-2Rβ monoclonal antibody directed to the expanded cells produced a prevention of rejection.Conclusions.These findings suggest that islet xenograft rejection in the liver from rat to mouse is an event for which the TCRintcells are responsible.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Genetically engineered structural variants of human β2-microglobulin (β2m) were produced by sequence exchange with mouse β2m for the purpose of examining species-specific antigenic determinant expression. For aggregate mapping, mouse and human β2m, which differ by 30% in their primary sequence of 99 amino acids, were prepared as chimeric (human X mouse) molecules and expressed in the FO-1 β2m-null human melanoma cell line. A chimera containing residues 1-69 from human β2m (and residues 70-99 from mouse β2m) induced expression of the epitopes defined by the anti-β2m monoclonal antibodies (mAb) BBM.1, NAMB-1, and L368; the reverse chimera did not, although HLA class I heavy chain was evident on the cell surface as determined with the TP25.99 mAb. For fine dissection of the epitopes defined by these mAbs, site-directed mutants of β2m were prepared by replacement of individual amino acids in human β2m with the dimorphic residue from mouse β2m. Substitutions were made at each divergent residue between positions 1 and 66 and, as controls for COOH-terminal modification, a series of residues between positions 75 and 94. Replacement of amino acids 38, 44, and 45, but not 16 other dimorphic residues in the linear stretch from residue 1 to residue 66, resulted in the loss of, or gross reduction in, binding by mAbs BBM.1 and NAMB-1. A reduction in binding was also observed for mAb L368. These data provide strong evidence that the antigenic epitopes defined by these mAb map to a region including S3 and its adjacent intra-β-strand turn of the three-stranded β-pleated sheet of β2m. The mapping of these epitopes is consistent with their accessibility in the assembled major histocompatibility complex class I molecule and indicates that the region from amino acid 38 to 45 is an important structural feature in the “foreignness” of human and mouse β2m.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.The aim of this article is to report our experience regarding the survival and the evolution of polyneuropathy of the extremities and autonomic dysfunction in 18 liver transplant patients with familial amyloidotic polyneuropathy type I after a mean follow-up of more than 2.5 years for 13 patients.Methods.The actuarial survival rate of the 18 patients is 72.2% and 60.1%, respectively, at 12 and 58 months.Results.In all the patients we noted clinical improvement of the polyneuropathy of the extremities and autonomic dysfunction during the first 6 months after transplant. The clinical data due to autonomic nervous system involvement showed an earlier improvement than those due to nervous motor involvement.Conclusions.In conclusion, our results suggest that liver transplant may be useful in the treatment of certain cases of familial amyloidotic polyneuropathy to stop the neurological deterioration of the patients and to avoid the fatal end of the disease.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

It was demonstrated by Bitter-Seurmann et al. that tolerance to subsequent skin allografts can be brought about, in some rat strain combinations, by heterotopic spleen allografts. We report here that in adult rats, tolerance can be also induced by vascularized spleen allografts using various strain combinations. DA (RT1av1) rats always accepted major histocompatible complex (MHC)-compatible but minor histocompatibility antigen (miH)-incompatible ACI (RT1av1) spleen grafts spontaneously, and further that those DA rats bearing ACI spleen grafts accepted subsequent ACI skin grafts indefinitely. In contrast, Fischer 344 (RT1lvl) rats always accepted not only the “weak” MHC-incompatible Lewis (RT1l) spleen grafts but also subsequent Lewis skin grafts indefinitely, when recipients were administered a short course of FK506 only at the time of primary spleen transplantation. Furthermore, in a number of MHC- and miH-incompatible strain combinations, recipients always accepted primary spleen grafts indefinitely when given a short course of FK506, but those recipients bearing donor spleens revealed split tolerance, that is, rejected subsequent donor-specific skin grafts but accepted heart grafts indefinitely. We conclude that the spleen seems to be a possible organ to induce transplantation tolerance, and that even if the MHC and miH are mismatched, unresponsiveness to at least heart grafts can be achieved by the administration of additional FK506 at the time of spleen transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Arterial reconstruction is essential in liver transplantation. In some patients there may be an inadequate flow as a result of stenosis, intimal dissection, or anomalies of the hepatic artery.Methods.This study analyzes our experience with 23 patients in whom arterial anastomosis was performed using the splenic artery due to the inadequacy of the hepatic artery. During the same period an aortoiliac conduit was used in 12 liver transplantations due to the same problem.Results.No splenic infarction, pancreatitis, or other related complications were found. Artery thrombosis developed in only two patients in the aortoiliac conduit group. One- and three-year patient actuarial survival were 78% vs. 80% and 72% vs. 80%, respectively, for the splenic artery group and the aortoiliac conduit group.Conclusions.Anastomosis with the splenic artery is an alternative in liver transplantation and is particularly suitable when splenomegaly is present.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Auxiliary liver transplantation offers an alternative method to conventional transplantation in acute liver failure. It is especially challenging for children because lifelong immunosuppression may be avoided. However, experience with this procedure is rare and there is controversy about whether to place the graft orthotopically or heterotopically.Methods.We present the case of a 3-year-old boy with acute liver failure due to non-ABC hepatitis complicated by aplastic anemia who underwent auxiliary liver transplantation. Segments 2 and 3 of the graft were implanted heterotopically in the right lower abdomen.Results.Good liver function was immediately restored. Aplastic anemia resolved 3 weeks after transplantation. Immunosuppressive therapy was discontinued after 14 months, and the graft was left to atrophy. Thirty-nine months after transplantation the boy is alive and well with normal liver function tests and normal blood cell counts.Conclusions.Heterotopic auxiliary liver transplantation allowed recovery of the native liver in a child with acute liver failure and aplastic anemia due to non-ABC hepatitis.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID