Search

Presents a study which examined the field dependence of magnetic transitions in magnetic superconductors. Discussion on the anisotropy of the magnetic transitions; Requirement for field-induced weak ferromagnetic transitions; Details of the experimental techniques used.

Presents a study which examined the systematic variation of anomalous praseodymium (Pr) antiferromagnetic ordering temperature for two-CuO[sub2]-layer cuprate systems. Details of the experimental techniques used; Discussion on the systematic of anomalous Pr ordering.

Focuses on a study which examined the magnetic ordering of praseodymium (Pr) ions in Pb[sub2]Sr[sub2]PrCu[sub3]O[sub8] using neturon diffraction and alternating current susceptibility measurements. Observations on the long-range ordering of Pr spins; Preparation of the sample; Isolation of magnetic signals.

The purpose of this study was to improve the transduction efficiency of adenoviral vectors (Ad) in human CD34+ hematopoietic progenitor cells. CD34+ cells from cord blood or mobilized peripheral blood were incubated with tumor necrosis factor-alpha (TNF-alpha). After removal of free TNF-alpha, the cells were infected with an Ad encoding green fluorescent protein (GFP). One day later, viable cells were counted and analyzed for GFP and CD34 by flow cytometry. To visualize vectoral trafficking, CD34+ cells were incubated with fluorophore-conjugated Ad. Plating efficiencies of hematopoietic progenitors before and after transduction were evaluated by methylcellulose assays. Pretreatment with TNF-alpha increased the transduction efficiency more than twofold (39.2% versus 15.5%) in a dose-dependent manner and strongly improved the survival of GFP-positive CD34+ cells. Time course experiments showed that TNF-alpha incubation times as short as 10 minutes were still effective. Neutralizing antibodies to TNF receptor II and RGD peptides diminished the TNF-alpha-dependent increase in transduction efficiency. No TNF-alpha-dependent increase in adenoviral receptors (coxsackie-adenovirus receptor, alphavbeta3-integrin) occurred. Analysis of viral binding demonstrated a significantly higher incidence of local concentrations of Ad along the cell surface (caps) in virus-positive cells of the TNF-alpha-treated group. Plating efficiency, especially the formation of granulocyte-macrophage colony forming units, was enhanced by TNF-alpha pretreatment. We conclude that brief incubation with TNF-alpha before addition of the Ad significantly increased the Ad transduction efficiency in CD34+ cells, and improved post-transduction survival of progenitors of the granulocyte-macrophage lineage. This finding correlates with increased Ad capping at the cell surface and suggests an alteration of Ad trafficking.

The chemokine, stromal cell-derived factor-1 (SDF1), is produced in the bone marrow and has been shown to modulate the homing of stem cells to this site by mediating chemokinesis and chemotaxis. Therefore, it was hypothesized that elevation of SDF1 level in the peripheral circulation would result in mobilization of primitive hematopoietic stem and progenitor cells. SDF1 plasma level was increased by intravenous injection of an adenoviral vector expressing SDF1alpha (AdSDF1) into severe combined immunodeficient mice. This resulted in a 10-fold increase in leukocyte count, a 3-fold increase in platelets, and mobilization of progenitors, including colony-forming units-granulocyte-macrophage to the peripheral circulation. In addition, AdSDF1 induced mobilization of cells with stem cell potential, including colony-forming units in spleen and long-term reconstituting cells. These data demonstrate that overexpression of SDF1 in the peripheral circulation results in the mobilization of hematopoietic cells with repopulating capacity, progenitor cells, and precursor cells. These studies lay the foundation for using SDF1 to induce mobilization of hematopoietic stem and progenitor cells in in vivo studies. (Blood. 2001;97:3354-3360)

In a carefully monitored pilot study, the in vivo biologic effects of filgrastim were investigated in eight patients with relapsed/refractory acute myelogenous leukemia. Within each patient, filgrastim was administered as a single agent prior to any chemotherapy in escalating doses of 0.12-6.0 micrograms/kg/day as a continuous intravenous infusion. The dose was increased every 14 days until an ANC of > or = 2500/mm3 had been achieved or there was evidence of proliferation of the leukemia. In patients who demonstrated growth of the leukemic clone, cytosine arabinoside was initiated at 200 mg/m2/day for 5 days. Through-out the course of therapy, the effects of filgrastim on maturation and proliferation were assessed by in vitro studies of bone marrow aspirates. Three patients demonstrated a sustained increase in ANC; one achieved a partial remission and remained on therapy for 31 weeks. Two of the three responding patients had hypocellular marrows at the time of initiating filgrastim and demonstrated a low but normal pattern of growth in CFU-GM assay early in the treatment course. This suggested that these two characteristics may define an environment in which filgrastim can induce a growth advantage for the normal residual hematopoietic elements. In this study of selected patients, filgrastim appeared safe.

Interleukin-1 (IL-1) modulation of cytokine receptors (human IL-1 receptor [hIL-1R], human granulocyte colony-stimulating factor [hG-CSFR], human granulocyte-macrophage CSF receptor [hGM-CSFR], and human tumor necrosis factor receptor [hTNFR]) on human neutrophils was studied both in vitro and in vivo. In vitro, incubation of neutrophils with IL-1 at 37 degrees C for 0.5 or 8 hours caused a reduction of IL-1 binding in a dose-dependent manner, but did not demonstrably affect binding of the other cytokines tested. In vivo, neutrophils from patients with gastrointestinal malignancies who were participating in a clinical trial of recombinant human IL-1 beta (rhIL-1 beta) demonstrated modulation of cytokine receptors in an IL-1 beta dose- and time-dependent manner. At the two highest dose levels of IL-1 beta (0.068 and 0.1 microgram/kg), reduction (> 40%) of G-CSF binding and elevation (twofold to sixfold) of IL-1 binding to neutrophils was observed after 1 hour and 4 to 8 hours, respectively. In addition, IL-1 beta rapidly elevated G-CSF and glucocorticoid levels in plasma. Patients at the lowest dose level (0.002 microgram/kg) had a less dramatic change in these parameters. Further in vitro studies showed that synthetic glucocorticoids and G-CSF synergistically up-modulated IL-1 binding to neutrophils in a dose- and time-dependent manner. Scatchard analysis of binding data showed that this in vitro synergistic modulation was due to an increase in receptor numbers, rather than an increase in binding affinity. In addition, both human umbilical cord blood and bone marrow neutrophils responded to G-CSF and dexamethasone (Dex) with a superadditive increase in IL-1 binding. Therefore, one of mechanisms for IL-1 up-modulation of IL-1R on human neutrophils in vivo was due to the fact that IL-1 rapidly elevates serum levels of G-CSF and glucocorticoids.

Colony-stimulating factor 1 (CSF-1) was purified from the serum-free conditioned medium of a human pancreatic carcinoma cell line (MIA PaCa-2) by a combination of conventional chromatography and high-performance liquid chromatography. The purity of human CSF-1 was demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with a diffuse single band of Mr 42,000-50,000 and by N-terminal amino acid analysis of glutamate residue. The CSF-1 was stable at 50 degrees C for 30 min. It is sensitive to treatment with trypsin, chymotrypsin, and subtilisin but less sensitive to papain digestion. Treatment of CSF-1 with different glycosidases did not affect the biological activity. Sulfhydryl reagents such as dithiothreitol (DTT), iodoacetic acid, and N-ethylmaleimide did not affect the biological activity at the concentration of 1 mM. However, CSF-1 activity was inhibited totally by the combination of 10 mM DTT and 1 mM SDS. Under denaturing and reducing conditions, CSF-1 appeared on SDS-PAGE as a single protein band of Mr 21,000-25,000 and concurrently lost its activity, indicating that human CSF-1 possibly consists of two similar subunits and that the intact quaternary structure is essential for the biological activity. When treated with neuraminidase and endo-beta-D-N-acetylglucosaminidase D, the molecular weight of CSF-1 was reduced to 36,000-40,000, and to 18,000-20,000 in the presence of mercaptoethanol. Because of the specificity of endo-beta-D-N-acetylglucosaminidase D, it is suggested that the carbohydrate moieties are Asn-linked "complex-type" units.

The formation of the cellular constituents of the blood is regulated by a series of endogenous polypeptides with largely paracrine function. A number of these hematopoietic growth factors (HGF's), which include colony stimulating factors, interleukins, and erythropoietin, have been purified to homogeneity and cloned, which in turn has led to extensive investigations of their biochemical properties and biological effects and functions. The HGF's act on target cells by binding to receptors. The kinetics and, to an even larger extent, dynamics of the factor/receptor associations display several intriguing characteristics, most of which are still poorly understood. Herein, the biochemical characteristics of HGF's receptors as well as the binding properties, post-receptor binding events and receptor modulation resulting from the association of HGF's and their target cells are reviewed.