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J Freedman

Publications and source records attributed to J Freedman.

224 records · Page 13Linked to original sources
PubMedDate not supplied

A cost-effectiveness evaluation of platelet crossmatching and HLA matching in the management of alloimmunized thrombocytopenic patients.

Effective platelet support for alloimmunized refractory thrombocytopenic patients may be provided by several potential strategies, the most common being HLA-matched single-donor platelets or crossmatch-compatible, pooled random- or single-donor platelets. This study used a detailed economic analysis to compare the cost-effectiveness of several techniques for platelet crossmatching and that of HLA-matched single-donor platelets. The crossmatch methods evaluated were a microlymphocytotoxicity test (LCT), an immunofluorescence technique (PSIFT), a radioactive antiglobulin test (PRAT), and an enzyme-linked immunosorbent assay (ELISA). The analysis was based on the need to support 100 refractory patients with acute leukemia with a presumed requirement of 500 transfusions. The relative costs for a successful crossmatch were: PRAT less than LCT less than LCT + PRAT less than PSIFT less than ELISA. In the comparison of the crossmatch methods, an increase in costs was generally associated with an increase in the number of successful transfusion episodes. However, decreasing marginal gains were seen. The HLA-matched single-donor platelets were relatively cost-inefficient in comparison to the crossmatch-compatible platelets. A theoretic sequence of tests for cost-effective provision of optimal platelet support in refractory patients was evaluated. Such considerations of cost are important in the selection of an optimal program for the management of alloimmunized refractory thrombocytopenic patients.

Blood Platelets↗
PubMedDate not supplied

Induction of a secondary human anti-HLA alloimmune response in severe combined immunodeficient mice engrafted with human lymphocytes.

BACKGROUND: Experimental manipulation of transfusion-induced alloimmunization is limited in humans by ethical considerations. Conversely, studies of alloimmunization in animal models may not reflect the human immune system closely enough to be of optimal benefit. The development of an in vivo model of human alloimmunization that is amenable to experimental manipulation is thus desirable. STUDY DESIGN AND METHODS: An in vivo model of human alloimmunization was evaluated by using mice with severe combined immunodeficiency (SCID). SCID mice underwent gamma-radiation (200 cGy) and received an intraperitoneal injection of human peripheral blood lymphocytes (PBLs) from donors immunized to HLA antigens by prior pregnancy (reconstitution). These Hu [human]-PBL-SCID mice were then challenged with HLA-mismatched PBLs. Alloantibodies were evaluated by flow cytometry and a standard two-stage microlymphocytotoxicity assay. RESULTS: Hu-PBL-SCID mice (n = 22) that were challenged with PBLs expressing the HLA antigens to which the donors had previously been immunized, made significantly more IgM and IgG alloantibodies than did the unchallenged mice. Responses were measurable by 1 week after reconstitution and challenge. Prior treatment of SCID mice with anti-asialo GM1, which depletes murine natural killer cells and macrophages, further increased the alloantibody response of challenged mice. The human alloantibodies generated were specific to the challenge HLA antigens as assessed by microlymphocytotoxicity assay. CONCLUSION: Hu-PBL-SCID mice are a useful model system in which to study and manipulate the induction of secondary human alloimmune responses against cellular HLA class I antigens. This model will be valuable for testing the in vivo effect of novel immunotherapies on the inhibition of the human alloantibody response.

Animals↗
PubMedDate not supplied

Unsaturated fatty acids enhance low density lipoprotein uptake and degradation by peripheral blood mononuclear cells.

The precise mechanism by which unsaturated fatty acids lower low density lipoprotein cholesterol is not known. Because cis-unsaturated fatty acids incorporated in cell membranes increase membrane fluidity and can thereby dramatically alter membrane-dependent cellular functions, we examined the effect of linoleate and oleate incorporation in peripheral blood mononuclear cell membranes on the physical properties of the membrane and concomitantly on low density lipoprotein uptake and degradation. We found that membrane enrichment with linoleate increased the rate of low density lipoprotein degradation in both freshly isolated and derepressed mononuclear cells. Enrichment with oleate led to similar increases in degradation. "Specific" low density lipoprotein uptake by derepressed cells was also enhanced by linoleate and oleate incorporation. Enrichment with both of these fatty acids produced an increase in membrane fluidity, as indicated by a reduction in the steady-state fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene incorporated in the membrane. In contrast, stearate enrichment had little effect on uptake or degradation of low density lipoprotein, nor did it affect membrane fluidity. These data point to a novel mechanism for the reduction in low density lipoprotein produced by unsaturated fatty acids that involves their physical effects on cell membranes as it relates to metabolism of the lipoprotein.

Cell Membrane↗