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A Zeevi

Publications and source records attributed to A Zeevi.

At least 163 records · Page 9Linked to original sources
PubMed1989

Multivisceral intestinal transplantation: surgical pathology.

We report the diagnostic surgical pathology of two children who underwent multivisceral abdominal transplantation and survived for 1 month and 6 months. There is little relevant literature, and diagnostic criteria for the various clinical possibilities are not established; this is made more complicated by the simultaneous occurrence of more than one process. We based our interpretations on conventional histology, augmented with immunohistology, including HLA staining that distinguished graft from host cells in situ. In some instances functional analysis of T cells propagated from the same biopsies was available and was used to corroborate morphological interpretations. A wide spectrum of changes was encountered. Graft-versus-host disease, a prime concern before surgery, was not seen. Rejection was severe in 1 patient, not present in the other, and both had evidence of lymphoproliferative disease, which was related to Epstein-Barr virus. Bacterial translocation through the gut wall was also a feature in both children. This paper documents and illustrates the various diagnostic possibilities.

Antigens, Viral↗
PubMed1989

Renal transplantation in baboons under FK 506.

FK 506 was tested in unrelated baboons submitted to renal transplantation and bilateral native nephrectomy. Untreated baboons died after 9.2 +/- 4.0 SD days. When FK 506 was given orally for 90 days, survival with the optimum dose was 74.6 +/- 28.9 days; this allowed maximum credit for each individual animal of 90 days. A 3-day course of intramuscular FK 506 started on postoperative day 4 allowed 1- to 2-month survival. Delayed rejection in these baboons as well as in those treated daily for 90 days with FK could sometimes be reversed temporarily with a second 3-day course. The doses required for a good therapeutic effect were 10 times greater in baboons than in dogs, a finding that may reflect a species difference of lymphocyte sensitivity to this drug. FK appeared to be relatively nontoxic in subhuman primates, and it remains a promising drug for clinical trial.

Animals↗
PubMed1989

Adherence of alloreactive lymphocytes to human arterial endothelial cell monolayers.

Early events of cellular infiltration during allograft rejection involve interactions between alloreactive lymphocytes and vascular endothelium. These interactions have been studied in an in vitro model of lymphocyte adherence to human arterial endothelial cell (HAEC) monolayers. Alloreactive lymphocytes primed against donor HLA antigens (DPL) or unrelated HLA antigens from a third party (TPL) were studied for their adherence to HAEC derived from organ transplant donors. DPL exhibited a degree of adherence to donor HAEC which was nearly twice that of the TPL population and developed a morphologically blastoid appearance. DPL adherence was dependent on the recognition of donor HLA antigens expressed on the HAEC surface and investigation of DPL and TPL adherence at various lymphocyte concentrations showed that the binding of DPL and TPL to HAEC was saturable. Monoclonal antibody (MoAb) directed against HLA class I antigens showed inhibition of only DPL adherence to HAEC monolayers expressing donor class I HLA antigens, whereas MoAb directed against other HAEC surface antigens failed to inhibit either the DPL or TPL populations. The results of this study suggest that in a transplant situation, lymphocyte activation and adherence to the graft endothelium is increased in the context of allorecognition.

Aorta↗
PubMed1989

In vitro studies of endomyocardial biopsies from heart transplant recipients on RATG and OKT3 immunoprophylaxis protocols.

Endomyocardial biopsy histology and the in vitro propagation of biopsy-infiltrating alloreactive T lymphocytes were analyzed in cardiac transplant patients on RATG (n = 24) and OKT3 (n = 9) immunoprophylaxis protocols. During the first three months posttransplant, 27% of the 167 biopsies in the RATG group showed histological grades of 2 or higher, significantly less than the 44% frequency of positive histology for biopsies in the OKT3 group (P = 0.035). For the histologically positive biopsies the frequency of lymphocyte growth, and the primed lymphocyte testing (PLT)* and CML activity of biopsy grown cells were similar in the RATG and OKT3 groups. However, for histologically negative biopsies, there was significantly more lymphocyte growth in the OKT3 than in the RATG groups (68% vs. 30%; P = 0.005). There was also significantly greater donor-specific CML activity of the biopsy-grown cultures in the OKT3 group. These data that suggest less cellular rejection is associated with RATG than with OKT3 immunoprophylaxis. They extend our previously reported clinical experience of a higher rejection-free survival in patients on the RATG protocol.

Adult↗
PubMed1988

A functional analysis of hematopoietic growth factor production from class I and class II human alloreactive T cell clones.

Class I and Class II human alloreactive T cell clones or their conditioned media were mixed with progenitor cell-enriched null cells to assess their ability to stimulate human hematopoietic progenitor cell (HPC) growth. Optimal release of erythroid, myeloid or megakaryocyte colony-stimulating factors occurred after 72 hours and required contact of cloned T cells with irradiated stimulator cells expressing the appropriate major histocompatibility complex (MHC) determinants recognized by the T cells. Individual clones were quite heterogeneous in their capacity to release hematopoietic growth factors. Clones that produced optimal levels of factors that stimulated granulocyte-macrophage colony growth did not always produce equivalent amounts of factors that stimulated erythroid colony growth and vice versa when tested against identical target cells. Class II clones released nearly twice as much interleukin 3 activity as Class I clones. Class II clones that lacked cell-mediated lympholytic (CML) activity against B or T lymphoblastoid targets were consistent stimulators of HPC growth. In contrast, Class I or Class II clones that contained CML activity either poorly stimulated or inhibited HPC growth. These CML-positive clones produced greater amounts of gamma interferon. Our findings may have important implications for HPC growth following allogeneic mismatched bone marrow transplantation.

Cell Division↗
PubMed1988

Sensitivity of activated human lymphocytes to cyclosporine and its metabolites.

Alloreactive T cells generated as clones from mixed lymphocyte cultures, or propagated from heart or liver transplant biopsies, were tested for secondary proliferation measured in the primed lymphocyte test in the presence of Cyclosporine A and metabolites fractionated from human bile. Significant differences were observed in Cyclosporine A sensitivity between various cell cultures ranging as high as 100-fold. The liver is the primary site of Cyclosporine A metabolism, which yields a number of hydroxylated and N-dimethylated derivatives that are eventually secreted into the bile. Bile was collected from adult liver transplant patients on Cyclosporine A therapy and following extraction with diethyl ether, separated by high pressure liquid chromatography. Thirteen fractions were tested for their effect on lymphocyte proliferation in concanavalin A activation, mixed lymphocyte cultures and primed lymphocyte test assays. The strongest immunosuppressive effect was found with fraction 8, which contained metabolite M17, which has a single hydroxylation in position 1. Only three other fractions 9, 10, and 13, which contained metabolites M1, M18, and M21, respectively, exhibited immunosuppressive activity, albeit much lower than that of Cyclosporine A. Differences in Cyclosporine A sensitivity among alloreactive T cells followed similar patterns with Cyclosporine A metabolites. Thus, the assessment of the Cyclosporine A effect must consider differences in drug sensitivity of lymphocytes involved in transplant immunity and the generation of metabolites with immunosuppressive activity.

Bile↗
PubMed1988

Immunologically mediated disease of the airways after pulmonary transplantation.

Obliterative bronchiolitis has occurred in eleven of 30 recipients of cardiopulmonary allografts who survived at least 4 months after transplantation, has caused significant morbidity, and has been associated with four of eleven late deaths in this series. Although some improvement, or at least stability, of pulmonary function has followed augmented immune suppression, it appears that once the process is recognized clinically, much of the damage to the airways is irreversible. The histopathology, response to therapy, and, most important, the response of donor specific alloreactivity in the lymphocytes from the lung (bronchoalveolar lavage and peripheral blood) suggest immune- mediated basis for bronchiolitis obliterans. The presence of donor specific alloreactivity detected by primed lymphocyte testing predicted obliterative bronchiolitis in five of six recipients (83% sensitivity, 91% specificity) was absent in ten of eleven recipients who have not as yet developed the process (negative predicted value of 91%). Currently, the presence of a positive primed lymphocyte test in the bronchoalveolar lavage of the cardiopulmonary recipient is an indication for early treatment by augmented immune suppression.

Bronchiolitis Obliterans↗
PubMed1988

HLA antigen expression on cultured human arterial endothelial cells.

Flow cytometric analysis and cellular assays were used to determine constitutive and induced expression of class I HLA antigens and class II antigens encoded by the HLA-DR, -DQ and -DP subregions on cultured human arterial endothelial cells (HAEC) derived from transplant donors. Class I but no or minimal quantities of class II HLA antigens were found on HAEC. Prior incubation of HAEC with gamma-IFN increased class I HLA antigen expression and induced class II HLA antigen expression on HAEC. The induced expression of HLA-DQ was lower than that of HLA-DR, but both were significantly reduced in comparison to the frequency of these antigens on EBV transformed lymphoblastoid cell lines derived from the same donor. In addition, supernatants from class I and class II alloreactive clones were shown to induce class II antigen expression on HAEC. By PLT analysis, it was shown that these antigens are functionally capable of generating a lymphocyte response. In this regard, HAEC have proved to be a helpful tool in designing in vitro lymphocyte-endothelial cell studies.

Cells, Cultured↗
PubMed1988

Unexpectedly high incidence of Pneumocystis carinii infection after lung-heart transplantation. Implications for lung defense and allograft survival.

Pneumonia due to Pneumocystis carinii (PCP) is regularly encountered in organ allograft recipients who are immunosuppressed to prevent rejection. Recipients of lung/heart allografts may be particularly prone to pulmonary infection due to systemic immunosuppression and the fact that defense mechanisms in the transplanted lung may be further impaired through tissue incompatibility and the effects of surgery. In this study, we monitored 16 lung transplant recipients for infection with Pneumocystis carinii using serial bronchoalveolar lavage (BAL) and found the prevalence of Pneumocystis infection of the lung to be 88%. Six episodes were associated with the usual symptoms of pneumonia, whereas 10 episodes were associated with minimal or no symptoms. In 3 of the 6 symptomatic episodes, a concurrent bacterial infection was also found. The total number of cells recovered from the lung by BAL, the proportion of T-lymphocytes, and the number of cytotoxic/suppressor and helper/inducer cells were elevated during infection with Pneumocystis compared to before and after. Spontaneous and interleukin-2-induced proliferation of BAL cells in vitro was also higher during infection, suggesting that there was an increased number of activated T-lymphocytes in the airspaces of the infected allograft. BAL cells cultured with irradiated spleen cells from the donor proliferated at higher levels when obtained after Pneumocystis infection than when obtained before or during infection even for subclinical infections. These results indicate that in the absence of prophylaxis, the prevalence of Pneumocystis infestation is very high after lung/heart transplantation. Impaired defense of the transplanted lung does not seem to stem from the inability of activated T-lymphocytes to accumulate in the allograft.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Lavage Fluid↗
PubMed1987

Alloreactive T-cell recognition of two DQ beta allelic specificities associated with DQw1.

Two sets of alloreactive T-cell clones from different original mixed lymphocyte reactions (MLR) discriminate between two DQ beta allelic forms when these are expressed in association with the same DQ alpha form. From these results we concluded that it is possible to guide a DQ specific response of alloreactive T-cell clones by setting up an appropriate responder-stimulator combination in the original MLR; DQw1 is associated with two allelic forms of the DQ molecule recognized as lymphocyte activating determinants by alloreactive T-cell clones; alloreactive T cells recognize specific alpha-beta chain combination of the DQ molecule; the allelic forms that differentiate the alpha or the beta chains of the DQ molecule from each other can also be recognized at the molecular level by DQ alpha and DQ beta RFLP analysis.

Alleles↗