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Zbigniew M Szczepiorkowski

Publications and source records attributed to Zbigniew M Szczepiorkowski.

9 recordsLinked to original sources

Method to assess fatty acid ethyl ester binding to albumin.

AIMS: To develop a method to assess the relative binding of fatty acid ethyl esters (FAEE) and free fatty acids (FFA) to albumin, and to determine if binding affinity is related to fatty acid chain length and or degree of saturation. METHODS: Radiolabelled ethyl-[14C] oleate bound to albumin was challenged with various ratios of FFA to FAEE. The displacement of ethyl-[14C] oleate by FFA was visualized and quantitated through a combination of native-PAGE, autoradiography, and liquid scintillation counting (LSC). RESULTS: As the ratio of FFA to FAEE increased from 0:1 to 12:1, for all fatty acids tested (myristate, palmitate, stearate, oleate, linoleate, and arachidonate), ethyl-[14C] oleate displacement increased, when expressed as radioactivity (in DPM) as a percentage of control. In contrast, ethyl oleate did not displace stearate or oleate from albumin at molar ratios up to 5:1 (FAEE:FFA). CONCLUSIONS: The method developed gave reproducible visualization of noncovalent binding of radiolabelled FAEE to albumin. The combination of native-PAGE and autoradiography LSC works well in assessing the binding properties of albumin and radiolabelled FAEE. The data indicate preferential binding of FFA over FAEE to albumin with six different FFA displacing FAEE to an approximately equal extent.

Albumins↗

Implementation of peripheral blood CD34 analyses to initiate leukapheresis: marked reduction in resource utilization.

BACKGROUND: Analysis of the peripheral blood (PB) C34 value may determine the optimal time to initiate leukapheresis. STUDY DESIGN AND METHODS: After selecting a threshold PB CD34 value of five CD34 + cells per microL to initiate leukapheresis procedure, a prospective analysis of 50 consecutive patients was initiated to identify the optimal time to initiate leukapheresis and its impact on costs and resource utilization. Clinical decisions were made to commence or to postpone leukapheresis with this PB CD34 threshold number. Based on PB CD34 values for each patient, the number of leukapheresis procedures, postponed or canceled, the number of CD34+ cells per kg, and the total number of cells collected were identified. Costs of mobilization were obtained from the hospital cost accounting system. RESULTS: In 13 months, 50 patients with a hematologic disorder underwent mobilization. There were 34 cancellations or postponements of collections due to a low PB CD34 value in 13 patients. By use of our identified costs per initial collection, this resulted in a savings of 67,660 US dollars. CONCLUSIONS: This prospective study defines how the implementation of the PB CD34 value results in costs savings. A low PB CD34 value canceled or postponed a significant number of leukapheresis procedures, resulting in a substantial cost savings. Use of the PB CD34 value should be the standard of care during mobilization and peripheral blood progenitor cell collection.

Adult↗

Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor.

During mammalian ontogeny, haematopoietic stem cells (HSCs) translocate from the fetal liver to the bone marrow, where haematopoiesis occurs throughout adulthood. Unique features of bone that contribute to a microenvironmental niche for stem cells might include the known high concentration of calcium ions at the HSC-enriched endosteal surface. Cells respond to extracellular ionic calcium concentrations through the seven-transmembrane-spanning calcium-sensing receptor (CaR), which we identified as being expressed on HSCs. Here we show that, through the CaR, the simple ionic mineral content of the niche may dictate the preferential localization of adult mammalian haematopoiesis in bone. Antenatal mice deficient in CaR had primitive haematopoietic cells in the circulation and spleen, whereas few were found in bone marrow. CaR-/- HSCs from fetal liver were normal in number, in proliferative and differentiative function, and in migration and homing to the bone marrow. Yet they were highly defective in localizing anatomically to the endosteal niche, behaviour that correlated with defective adhesion to the extracellular matrix protein, collagen I. CaR has a function in retaining HSCs in close physical proximity to the endosteal surface and the regulatory niche components associated with it.

Animals↗

Rituximab for TTP.

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ADAM Proteins↗

Red blood cell exchange transfusion in two patients with advanced erythropoietic protoporphyria.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare, autosomal dominant genetic disorder caused by the decreased or absent activity of ferrochelatase, the final enzyme in the heme biosynthetic pathway. This enzyme defect in peripheral blood progenitor cells leads to the accumulation of protoporphyrin deposits in multiple tissues. Plasmapheresis has been previously reported as an adjunctive therapy for patients with advanced hepatic EPP. Because the concentration of protoporphyrins is severalfold higher inside the red blood cell (RBC) compared to plasma, it was hypothesized that RBC exchange therapy might absorb excess protoporphyrins from the plasma and serve as an effective therapy to reduce protoporphyrin load in patients with advanced hepatic EPP. The effectiveness of RBC exchange plus hematin versus plasmapheresis plus hematin in two patients with advanced hepatic EPP is reported. STUDY DESIGN AND METHODS: Two patients with advanced hepatic EPP were treated with RBC exchange and plasmapheresis in the setting of recurrent disease in the graft (Patient 1) or preparation for liver transplantation (Patient 2). In vitro studies were performed to test transport of protoporphyrins from patients' plasma to normal RBCs. RESULTS: Compared with plasmapheresis, RBC exchange was more effective, for the duration of the therapy, in reducing blood levels of protoporphyrins. Liver function tests, however, showed only a modest improvement during therapy. In vitro extracellular protoporphyrin were rapidly adsorbed into normal RBCs. CONCLUSION: Neither RBC exchange nor plasmapheresis prevented progressive hepatic deterioration in advanced hepatic EPP despite a significant decrease in protoporphyrin levels.

Adult↗

Long-term transfusion of polymerized bovine hemoglobin in a Jehovah's Witness following chemotherapy for myeloid leukemia: a case report.

A 52-year-old female Jehovah's Witness presented with relapsed secondary acute myeloid leukemia. Because of chemotherapy-induced anemia, she was infused with the bovine hemoglobin (Hb)-based oxygen carrier HBOC-201 (Biopure) as the sole means of transfusion support. HBOC-201 has only been used for management of acute hemorrhage, and its utility in providing longer term transfusion support is unknown. Over a period of 18 days, a total dose of 1230 g of HBOC-201 was delivered. Although the patient succumbed to the disease after 18 days of treatment, this case documents our experience with the highest dose and duration of HBOC-201 ever used. Although possible renal toxicity could not be definitively excluded, the homogeneous extraction of oxygen by the brain in the presence of and perhaps from HBOC-201 was demonstrated.

Animals↗

Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers.

Containment of hepatitis C virus (HCV) and other chronic human viral infections is associated with persistence of virus-specific CD4 T cells, but ex vivo characterization of circulating CD4 T cells has not been achieved. To further define the phenotype and function of these cells, we developed a novel approach for the generation of tetrameric forms of MHC class II/peptide complexes that is based on the cellular peptide-exchange mechanism. HLA-DR molecules were expressed as precursors with a covalently linked CLIP peptide, which could be efficiently exchanged with viral peptides following linker cleavage. In subjects who spontaneously resolved HCV viremia, but not in those with chronic progressive infection, HCV tetramer-labeled cells could be isolated by magnetic bead capture despite very low frequencies (1:1,200 to 1:111,000) among circulating CD4 T cells. These T cells expressed a set of surface receptors (CCR7+CD45RA-CD27+) indicative of a surveillance function for secondary lymphoid structures and had undergone significant in vivo selection since they utilized a restricted Vbeta repertoire. These studies demonstrate a relationship between clinical outcome and the presence of circulating CD4 T cells directed against this virus. Moreover, they show that rare populations of memory CD4 T cells can be studied ex vivo in human diseases.

Animals↗

Treatment of recurrent allograft dysfunction with intravenous hematin after liver transplantation for erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is a rare inherited disorder of the heme biosynthetic pathway in which toxic levels of protoporphyrins often precipitate in the liver, leading to cirrhosis, liver failure, and the need for liver transplantation (OLT). Because the underlying enzyme defect in EPP is bone marrow derived, the risk for recurrent EPP allograft dysfunction is high. Although plasmapheresis may ameliorate acute allograft disease, strategies to maintain disease remission are needed. A 59-year-old man who underwent OLT for hepatic EPP experienced increased bilirubin and aminotransferases on postoperative day 700. Allograft biopsy demonstrated recurrent EPP. He was managed initially with plasmapheresis, hypertransfusion, and infusions of i.v. hematin. After normalization of liver tests, the hematin infusions have been given intermittently, are well tolerated, and associated with normal allograft function for nearly 2 years. This is the first case of the use of hematin given post-OLT to help achieve and maintain remission of allograft EPP disease.

Biopsy↗