AbstractB lymphocytes are a potential alternative to dendritic cell immunotherapy, with the advantages of relative abundance in peripheral blood and the ability to function as APCs. Although B cells express multiple receptors that induce costimulatory molecules, B cell vaccine studies have focused primarily on CD40 stimulation. To optimize the potential efficacy of B cell vaccines (Bvac), we compared the capacity of differentially stimulated B cells to induce Ag-specific CD8+ T cell responses in vivo. CD40- or TLR7-stimulated B cell APCs induced similar CD8+ T cell responses, but costimulation through the BCR and TLR7 produced a more effective Bvac as measured by T cell stimulation and the protection of mice from an infectious pathogen. This increased effectiveness depended upon enhanced production of IL-6 by BCR plus TLR7-stimulated B cells. These findings reveal alternative stimulation strategies for the production of effective Bvac and identify a key role for IL-6 in B cell Ag presentation and cellular vaccines.

1994-07-01·ASAIO Journal3区 · 工程技术

Automatic Control of Blood Volume Trends during Hemodialysis

3区 · 工程技术

Article

作者: Santoro, A ; Zucchelli, P ; Paolini, F ; Mancini, E ; Spongano, M

Dialysis induced hypovolemia plays an important role in triggering intradialytic hypotension. The authors developed an automatic system (BVAC) with feedback changes in the ultrafiltration rate (UFR) and dialysate conductivity (DC) to match blood volume (BV) intradialytic profiles with the desired trajectories. The system consists of three subunits: (1) an optical probe to continuously detect the BV changes derived from hemoglobin changes, and (2) a dialysis machine interfaced with (3), a personal computer in which a time-dependent model is implemented. The model is based on a dynamic regulator that can set the actual BV changes against the corresponding desired values. Any discrepancy is offset by changes in UFR and DC. To verify the efficacy of the BVAC system in reducing intradialytic cardiovascular instability, five hypotension-prone patients were studied during a three period protocol (A1-B-A2) that lasted six sessions per period per patient. During periods A1 and A2, the dialysis procedure was conventional hemodialysis (HD) with linear UFR and constant DC. During period B, both UFR and DC were automatically regulated by the BVAC system. Mean BV reduction and its variability were lower during period B than during periods A1 and A2 (-10.2%, -11.3%, and -11.5, respectively). Episodes of hypotension were significantly (P < 0.05) fewer during period B (n = 1) than during periods A1 (n = 8) and A2 (n = 5). The therapeutic interventions defined as infused milliliters of isotonic and hypertonic solution were fewer during period B compared with periods A1 and A2. Total UF and end-dialysis plasma sodium concentrations did not differ in the three study periods. BVAC was effective in improving cardiovascular tolerance to treatment.

1990-06-15·Blood1区 · 医学

BVAC ablative chemotherapy followed by autologous bone marrow transplantation for patients with advanced lymphoma

1区 · 医学

Article

作者: Burns, LJ ; Wen, BC ; Ginder, GD ; Fyfe, MA ; Gingrich, RD

Forty-one consecutive patients with lymphoma resistant to conventional combination chemotherapy have been entered into a study in which chemo- ablative therapy and autologous marrow rescue were used with curative intent. The actuarial proportion of 20 patients with Hodgkin's lymphoma remaining alive and free of recurrent disease is 49%, while that for 21 patients with non-Hodgkin's lymphoma is 41%. Our clinical approach to these patients involved a strategy whereby lymphomatous nodes greater than 2 cm in diameter that persisted despite salvage chemotherapy were given boost radiation therapy immediately before chemo-ablation. However, patients with this variable had a significantly lower survival due to septic complications rather than recurrent disease. We conclude that the treatment strategy used in this study with some modification may improve further on the already high probability of long-term disease-free survival experienced by this group of patients.

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