Blood
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Mononuclear cell preparations from peripheral blood after mobilization with hematopoietic growth factors have been shown to induce accelerated neutrophil and platelet recovery as compared with that induced by autologous bone marrow transplantation after myeloablative chemotherapy. Because these mononuclear cell products contain many immunocompetent cells other than hematopoietic progenitors, these accessory cells might contribute to the rapid immunohematopoietic reconstitution. We have monitored the concentrations of soluble CD4 (sCD4), sCD8, and sCD25; the recovery of the lymphocyte subsets and of natural killer (NK) cells; and the endogenous levels of granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3), IL-6, and granulocyte-macrophage-CSF (GM-CSF) in 12 patients who underwent high-dose chemotherapy supported by blood stem cells that were obtained by mobilization with chemotherapy and GM-CSF. ⋯ Statistically, the increases in sCD4, sCD8, sCD25, G-CSF, and IL-6 were highly significant, whereas there were no significant changes in IL-3 and GM-CSF. A rapid recovery of the NK activity was found in all 8 of the patients who could be monitored for this assay. Therefore, our study suggests that recovery of CD4+ cells, CD8+ cells, and NK activity coincided with that of neutrophils, which is preceded by a marked, but transient, elevation of IL-6 and G-CSF.
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Intracellular hemoglobin S (HbS) polymerization is most likely to be the primary determinant of the clinical and biologic manifestations of sickle cell disease (SCD). Fetal hemoglobin (HbF) does not enter the HbS polymer and its intracellular expression in sickle erythrocytes inhibits polymerization. HbF levels, high at birth but decreasing thereafter, protect the newborn from the clinical manifestations of this hemoglobinopathy. ⋯ In the non--F-cell population, polymerization was expected at birth at both oxygen saturation values. Three individuals had significantly greater predicted polymerization tendency than the remainder of the group because of early decreases in HbF. These individuals in particular, the remainder of the cohort, as well as other recruited newborns, will be studied prospectively to ascertain the relationship among hematologic parameters, which determine polymerization tendency and the various clinical manifestations of SCD.
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Clinical Trial Controlled Clinical Trial
Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma.
The B-cell antigen CD20 is expressed on normal B cells and by nearly all B-cell lymphomas. This nonmodulating antigen provides an excellent target for antibody-directed therapies. A chimeric anti-CD20 antibody (IDEC-C2B8), consisting of human IgG1-kappa constant regions and variable regions from the murine monoclonal anti-CD20 antibody IDEC-2B8, has been produced for clinical trials. ⋯ Two-week postinfusion tumor biopsies showed the chimeric antibody bound to tumor cells and a decrease in the percentage of B cells. Tumor regressions occurred in 6 of 15 patients (2 partial and 4 minor responses). The results of this single-dose trial have been used to design a multiple-dose phase I/II study.
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Protein tyrosine phosphorylation has been hypothesized to play a key role in the growth signaling induced by erythropoietin (Epo), although the Epo receptor (EpoR), a member of the cytokine receptor superfamily, lacks a tyrosine kinase domain. Recently, the JAK2 tyrosine kinase was shown to be activated on Epo stimulation and to bind to the cytoplasmic domain of EpoR in vitro. To further explore the mechanisms of activation of JAK2 in EpoR-mediated signal transduction, we assessed the conditions for association of JAK2 with EpoR in vivo. ⋯ By this approach, association also occurred with the mitogenically active H mutant but not with the mitogenically inactive PB or PM4 mutants. In the immune complex kinases assays, EpoR, JAK2, and a 150-kD protein were phosphorylated on tyrosine. Taken together, the results further support the hypothesis that, on Epo stimulation, JAK2 associates with the membrane-proximal cytoplasmic region of the EpoR to be activated and induces tyrosine phosphorylation of cellular substrates, including the EpoR, to transduce a growth signal.
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Editorial Review Comparative Study
Recombinant human erythropoietin and the anemia of cancer.