摘要:

A group of 40 cadaveric kidneys was studied just prior to planned transplantation to further assess the applicability of31P-MRS in the analysis of clinical renal transplant viability. Renal intracellular high-energy phosphorus metabolites (ATP [or NADP], phosphomonoester [PME] and inorganic phosphate [Pi]) and pH were measured noninvasively with MRS surface coils external to cold storage containers.Pretransplant MRS parameters were correlated with subsequent renal function in recipient patients (measured one week postoperatively by the need of dialysis, drop in serum creatinine, urine output, and123I or131I Hippuran assessed renal tubular function).ATP and NADP was detected in eleven kidneys and was significantly (P<0.001) associated with the best renal function posttransplantation. These kidneys also had the highest PME/Piratios (1.66–0.54), while lower ratios (0.36–0.10) were associated with prolonged acute tubular necrosis. The PME/Piratios significantly (P<0.0001) correlated with subsequent clinical renal function, whereas cold storage times (37±10 hr) or intracellular renal pH (6.53–7.91) did not.These preliminary data suggest that MRS is a noninvasive, nondestructive and sterile method for assessing clinical viability during hypothermic storage of human cadaver kidneys and the subsequent recovery of renal function postrenal transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The evolution of HLA antibodies and autoantiidiotypic antibodies (AB2) were studied during an 18-month period in a patient who hyperacutely rejected an HLA-A2-positive kidney, but tolerated a second HLA-A2-positive kidney one year later. Following rejection of the first kidney, the patient's serum contained an HLA-A2 antibody that reacted with 100% of HLA-A2-positive panel cells. After several months, the HLA-A2 antibody activity was precipitously lost over a one-month period and could no longer be identified by sensitive lymphocytotoxicity procedures. Approximately one year later, the patient received a second HLA-A2-positive kidney that has survived for a 2-year period and was not associated with significant rejection episodes during the early posttransplantation period. Prior to and episodically following the second transplant, the patient's sera contained antiidiotypic-like antibodies that specifically inhibited HLA alloantibodies directed against HLA-A2. AB2, with specificity for a putative idiotype on HLA-A2 alloantibodies, existed concurrently with other HLA alloantibodies in the patient's serum that had not been lost over the course of several months.This case study demonstrates a temporal association between the loss of a specific HLA antibody and the development of an AB2 with inhibitory specificity for the antibody. The study also confirms that anamnestic responses to donor-specific antigens do not always occur in previously alloimmunized patients rechallenged with the same HLA antigens.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Multiple pretransplant sera obtained from aloimmunized renal transplant recipients were tested for the presence of antiidiotypic-like antibodies (AB2) that inhibit donor-specific HLA antibodies in the microlymphocytotoxicity assay. Fourteen patients received repetitive single-donor blood transfusions (SDT). In this patient group, sera were collected prior to each blood transfusion and prior to transplantation. Three additional patients were studied in whom prior donor-specific HLA antibodies had been lost over a period of 6 months preceding transplantation.Donor-specific AB2-like antibodies were found in the sera of 13/14 SDT patients who did not develop HLA antibodies, and in the 3 patients who had lost donor-specific HLA antibodies. All patients had received prior random blood transfusions in the year preceding the study. Five (38%) of the SDT patients had detectable donor-specific AB2 prior to the initiation of single-donor blood transfusion, presumably related to previous blood transfusions. In the remaining six SDT patients in whom complete serum sets were available, AB2 al ways appeared after the first blood transfusion. The specificity of HLA antibodies inhibited by AB2 was studied, and antibodies against HLA-A, -B, -C, -DR, and DQw were all identified. Thus, there was no predilection for patients to develop AB2 against locus-specific HLA gene products. This study also confirms the apparent polymorphism of putative crossreactive idiotypes. Approximately 25% of donor-specific HLA antibodies were not inhibited by relevant AB2.This study confirms and extends previous observations that alloimmunization is associated in many patients with the development of antiidiotypic-like antibodies that are capable of inhibiting the binding and cytotoxicity of HLA alloantibodies.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Class I and class II (HLA-DR, DP and DQ) MHC antigen expression and the phenotypic nature of the inflammatory infiltrate in gastric and duodenal biopsies in bone marrow transplantation patients with and without graft-versus-host disease were investigated. Increased expression of class I (P<0.016) and class II (HLA-DR,DP) antigens (P<0.002) was associated with GVHD. The epithelium in two GVHD-positive biopsies was HLA-DP-positive and HLA-DR-negative. None of the tissues expressed HLA-DQ. Association between MHC antigen expression and phenotype of infiltrating cell was then examined. The majority of GVHD biopsies showed an infiltrate composed of CD4+cells and CD8+cells. However, the two DP+, DR−biopsies were associated exclusively with CD8+intraepithelial cells, suggesting sequential events in GVHD, with CD8+cells infiltrating tissue first associated with HLA-DP expressions, followed by accumulation of CD4+as well as CD8+cells in association with expression of HLA-DR.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We evaluated relapse-free survival and the incidence and type of complications in 17 patients aged 40 or older with chronic myelogenous leukemia, acute myelogenous leukemia, or lymphoma who underwent allogeneic marrow transplantation following busulfan 16 mg/kg and cyclophosphamide 120 mg/kg. Nine patients are diseasefree survivors 5–38 months (median 26 months) following transplantation. The incidence of grades II-IV acute graft-versus-host disease was 35%. No significant difference was detected in the incidence of GVHD or interstitial pneumonia between patients aged 40 and older and a group of younger patients transplanted over the same time period. These observations should encourage consideration of allogeneic marrow transplantation in older patients and suggest that this busulfan-cyclophosphamide regimen is a promising alternative to regimens containing total-body irradiation in older individuals.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

This study was undertaken to evaluate the occurrence of VOD and other liver diseases following BMT in a patient population with a high incidence of hepatitis before conditioning regimen. We prospectively reviewed 186 consecutive patients undergoing BMT from 1976 to 1986 to determine incidence and type of liver disease after BMT and predisposing factors. Two of 186 patients experienced VOD (1.07%). Acute and chronic liver GVHD were found in 25.8% and 36% of the patients, respectively. Acute hepatitis (AH) was diagnosed in 29.4% and chronic hepatitis (CH) in 42.6% of the patients. Statistical analysis showed no influence of pre-transplant variables on the occurrence of acute GVHD and AH; there was a weak correlation (P=0.01) between pre-BMT abnormal transaminases and occurrence of chronic GVHD. Contingency table and Cox analysis showed a greater risk of CH for patients with abnormal pretransplant SGPT levels (P=0.0004 and P=0.0022). No other variables could be associated with posttransplant CH. Actuarial survival was 71% versus 69% for patients with normal versus abnormal transaminases (P= 0.2). As VOD was a rare event, despite 53% of patients having abnormal transaminase values before transplant, we suggest that a lower and slower TBI is more important than pretransplant normal transaminases in preventing this complication. We conclude that evidence of compensated hepatitis is not a relative contraindication for BMT.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Peripheral blood leukocyte samples (n=458) of 24 bone marrow transplant and 52 kidney transplant patients were examined weekly for the presence of human cytomegalovirus (HCMV) using an improved culture technique (DEAFF; detection of early antigen fluorescent foci). In total 5 (21%) bone marrow transplant and 11 (21%) kidney transplant patients developed a viremia. Patients' samples were investigated for the presence of HCMV DNA using an in vitro DNA amplification technique, the polymerase chain reaction (PCR). From the statistically evaluable viremic patients (n=13), 110 blood samples were analyzed. In 5 of these patients, the DEAFF and PCR led to identical results. In 8 patients however the PCR was more sensitive, i.e. HCMV DNA was detected for a longer period of time. Applying statistical analysis using the McNemar test, this result was significant (P<0.05). The PCR applied on leukocyte samples did not detect HCMV DNA in viruric patients without viremia. Moreover, the current PCR never led to positive results with peripheral blood leukocyte samples of healthy seropositive or seronegative controls. Since the PCR can be performed in 6 hr, this technique will contribute to rapid detection of HCMV DNA in peripheral blood leukocytes and therefore to optimal clinical management of HCMV-infected transplant recipients.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Idarubicin was conjugated to anti-Ly-2.1 and anti-L3T4 monoclonal antibodies. These conjugates were used to investigate their effects on skin graft survival in mice. Several donor and recepient combinations were used so that the effect of individual or mixtures of conjugates on class I and class II antigenic differences, as well as multiple H-2 and non-H-2 antigenic differences could be studied. Ida-anti-Ly-2.1 prolonged skin grafts for class I antigenic differences. A mixture of Ida-anti-L3T4 and Ida-anti-Ly-2.1 was more effective than either conjugate alone in prolonging the survival of skin grafts with class II antigenic differences. However, idarubicin conjugates alone or in combination were unable to prolong graft survival when multiple H-2 and non-H-2 differences existed. In all models free idarubicin or unconjugated monoclonal antibody did not prolong the skin grafts.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We have been investigating the effects of polyinosinic:polycytidylic acid (pI:C), an interferon inducer, on the graft-versus-host reaction. We have previously shown that pI:C treatment of C57BL/6×AF1(B6AF1) recipient mice immediately before injection of C57BL/6 (B6) parental lymphocytes inhibited the immunosuppression and pathological changes normally caused by the GVH reaction, by a mechanism apparently identical to that seen in F1hybrid resistance (HR) to hematopoietic grafts. We now demonstrate that delaying pI:C treatment by as little as 48 hr produces the opposite effect. Treatment of recipient B6AF1mice at different days after transfer of parental lymphocytes induced a marked increase in the severity of the GVH reaction, as measured by a decreased plaque-forming cell response to sheep erythrocytes; decreased proliferative response to the T and B cell mitogens PHA, Con A, and LPS; increased pathological changes in both lymphoid and nonlymphoid tissues; and increased GVH-associated mortality. This effect is unrelated to HR, as pI:C was able to augment the severity of the GVH reaction when A strain cells were injected into A×CBAF1recipients, which do not manifest HR. Early pI:C treatment (1 and 2 days after parental cell transfer) increased the severity of the GVH reaction much more than later pI:C treatment (7 and 8 days after parental cell transfer). This observation, along with the demonstration of altered pathology in GVH mice treated with pI:C, suggests that the effect of pI:C is not mediated through a direct suppressive effect of IF on the cells responding in either the PFC or mitogen assays, but rather by the ability of IF to activate or suppress mechanisms involved in the development of GVH-induced alterations.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To further define the role of arachidonic acid (AA) metabolites in transfusion-induced immunosuppression (TII), the effects of pharmacological manipulation of AA metabolism were examined in a rodent model. If the prostaglandins of the E series are mediators of TII, as has been recently hypothesized, then inhibition of cyclooxygenase (indomethacin) should abrogate whereas inhibition of lipoxygenase (nordihydroguaiaretic acid [NDGA]), or thromboxane synthetase (4–63557A) could potentiate the transfusion effect. Lewis rats received donor-specific transfusions from Buffalo rats in conjunction with one of the above inhibitors. Two weeks later they received intraabdominal Buffalo heart allografts or were used for one-way mixed lymphocyte reactions.Cyclooxygenase inhibition partially abrogated TII with shortened cardiac allograft survival. Lipoxygenase inhibition augmented TII, with depression of MLR and prolongation of allograft survival. Thromboxane synthetase inhibition had no effect. These results indicate that AA metabolites play a role in TII, and that immunoregulation via pharmacological manipulation of AA metabolism is possible.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID