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J M Pater

Publications and source records attributed to J M Pater.

8 recordsLinked to original sources
PubMed2001

Functional characterization of minimal residual disease for P-glycoprotein and multidrug resistance protein activity in acute myeloid leukemia.

Relapse is common in acute myeloid leukemia (AML) due to persistence of residual leukemia cells: minimal residual disease (MRD). In 102 out of 127 patients (80%), cells at diagnosis displayed one or more leukemia-associated phenotypes (LAP), ie combinations of cell surface markers which are absent in normal cells and can thus be used to detect MRD at follow-up. Functional characterization of MRD cells for P-glycoprotein (Pgp) and multidrug resistance protein (MRP) activity is essential to investigate the role of these drug transport proteins in multidrug resistance in AML. A fluorescent probe assay using Syto16/PSC833 and calcein-AM/probenecid as substrate/modulator of the Pgp and MRP pump, respectively, and subsequent labeling of cells with monoclonal antibodies for LAP detection allowed simultaneous detection of LAP and Pgp or MRP activity. Validation of this assay is shown for 30 newly diagnosed AML and 11 MRD situations. In addition, no significant differences were found when comparing fresh and cryopreserved de novo AML for LAP expression (n = 43), Pgp (n = 30) and MRP (n = 24) function and for MRD samples for simultaneous LAP expression and Pgp/MRP activity (n = 10). This approach enables longitudinal and multicenter studies on the detection, quantification and functional characterisation of MRD cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Single expression of CD45RC and RT6 in correlation with T-helper 1 and T-helper 2 cytokine patterns in the rat.

Previous studies involving the function and development of peripheral T cells have proposed that, in the rat, CD4(+)CD45RC(+)RT6(-) and CD4(+)CD45RC(-)RT6(+) T-cell subsets may represent Th1 and Th2 cells, respectively. Here we tested this hypothesis directly by analyzing frequencies of IFN-gamma- and IL-4-producing cells in these two subpopulations using ELISPOT assays. We found that the CD4(+)CD45RC(-)RT6(+) subset showed higher numbers of IL-4-producing cells than the CD4(+)CD45RC(+)RT6(-) subset and, though less pronounced, that the latter demonstrated higher numbers of IFN-gamma producers. Therefore, we conclude that our results provide evidence for the existence of phenotypically defined Th1 and Th2 cells in the rat. This is supported by the finding that the ratios of IFN-gamma/IL-4 and CD45RC/RT6 correlated positively among various rat strains. Finally, rat strains susceptible to induction of a Th1-mediated autoimmune disease showed the highest CD45RC/RT6 ratio, whereas the reverse was true for strains susceptible to a Th2-mediated autoimmune disease.

ADP Ribose Transferases↗
PubMed1997

Post-thymic T-cell development in the rat.

The presence or absence of CD4, CD8, Thy-1, RT6 and CD45RC revealed a number of T-cell subpopulations in the rat. Vascular thymus transplantation was used in RT7 congenics to establish the lineage relationship between these subpopulations by following phenotypic changes after thymus emigration. We found that recent thymic emigrants exhibit the Thy-1+/RT6-/CD45RC- phenotype and express either CD4 or CD8. Within 11 days after emigration, these cells differentiated into Thy-1-/RT6+/CD45RC+ cells. From 33 to 76 days following transplantation, a proportion of the latter lost RT6 and/or CD45RC expression, suggesting further differentiation. The pathway of 'mature' T-cell differentiation could be reconstructed from these data and analysis of the differences between T-cell subsets in thymectomized and normal control rats. End-stages of post-thymic T-cell differentiation in the rat were most likely to be Thy-1-/RT6+/CD45RC- and Thy-1-/RT6-/CD45RC+ T cells.

Aging↗
PubMed1995

Simultaneous transplantation and intrathymic tolerance induction. A method with clinical potential.

It has been shown that donor-specific tolerance to cardiac allografts can be induced by pretreating the prospective recipient with injections of donor splenocytes (intrathymically) and antilymphocyte serum (intraperitoneally) weeks or days before the actual transplantation. This procedure, however, lacks clinical relevance in the case of cadaver donors due to the obligatory interval between the start of the tolerance induction protocol and transplantation. We have tried to devise a protocol in which this interval is eliminated, thus allowing allotransplantation simultaneously with tolerance induction. Our results show that simultaneous cardiac allotransplantation and intrathymic tolerance induction by intrathymic injection of donor splenocytes and treatment with antilymphocyte serum is indeed possible in the PVG to AO high-responder rat strain combination, provided that low doses of cyclosporine are given intramuscularly on day 1, 2, and 3 after transplantation. As we now are able to combine the start of tolerance induction with the actual allotransplantation, this procedure may indeed have clinical potential.

Animals↗