Calculations of Bioelectric Potentials: III. Variation in Partition Coefficients and Ion Mobilities.
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Journal Article↗
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Results for “Mobilization potential”
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Mobility edge in a model one-dimensional potential.
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Journal Article↗
Mobility and invasiveness of metastatic esophageal cancer are potentiated by shear stress in a ROCK- and Ras-dependent manner.
To metastasize, tumor cells must adopt different morphological responses to resist shear forces encountered in circulating blood and invade through basement membranes. The Rho and Ras GTPases play a critical role in regulating this dynamic behavior. Recently, we demonstrated shear-induced activation of adherent esophageal metastatic cells, characterized by formation of dynamic membrane blebs. Although membrane blebbing has only recently been characterized as a rounded mode of cellular invasion promoted through Rho kinase (ROCK), the role of shear forces in modulating membrane blebbing activity is unknown. To further characterize membrane blebbing in esophageal metastatic cells (OC-1 cell line), we investigated the role of shear in cytoskeletal remodeling and signaling through ROCK and Ras. Our results show that actin and tubulin colocalize to the cortical ring of the OC-1 cell under static conditions. However, under shear, actin acquires a punctuate distribution and tubulin localizes to the leading edge of the OC-1 cell. We show for the first time that dynamic bleb formation is induced by shear alone independent of integrin-mediated adhesion (P < 0.001, compared with OC-1 cells). Y-27632, a specific inhibitor of ROCK, causes a significant reduction in shear-induced bleb formation and inhibits integrin alpha(v)beta(3)-Ras colocalization at the leading edge of the cell. Direct measurement of Ras activation shows that the level of GTP-bound Ras is elevated in sheared OC-1 cells and that the shear-induced increase in Ras activity is inhibited by Y-27632. Finally, we show that shear stress significantly increases OC-1 cell invasion (P < 0.007), an effect negated by the presence of Y-27632. Together our findings suggest a novel physiological role for ROCK and Ras in metastatic cell behavior.
Actins↗
Ku autoantigen is a potential major cause of nonspecific bands in electrophoretic mobility shift assays.
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Antigens, Nuclear↗
Cell surface charge in predicting metastatic potential of aspirated cells from the Dunning rat prostatic adenocarcinoma model.
The transplantable Dunning R-3327 rat prostatic adenocarcinoma model has provided a series of tumor variants with broad ranges of metastatic potential. We tested whether cell surface charge might be related to metastatic potential by measuring the electrophoretic mobility of live tumor cells obtained by needle aspiration. Cells were aspirated from tumors with low metastatic potential (following subcutaneous inoculation of 10(6) tumor cells the H, G and AT-1 variants had less than 5% metastases; AT-2 had 5-20%) and were compared to the electrophoretic mobility of cells aspirated from highly metastatic tumors (MAT-LyLu, MAT-Lu, AT-3 had greater than 90% metastases). Electrophoretic mobility expressed in mu/sec/volt/cm. was measured on 100 cells from each tumor subline, and the cell surface charge expressed as a zeta potential was calculated from electrophoretic mobility using the Helmholtz-Smoluchowski equation. The average zeta potential (+/- S.E.M.) for the four sublines with low metastatic potential was (-17.4 +/- 0.4 mV) compared to the three sublines with high metastatic potential (-26.5 +/- 0.7 mV), and the differences were significant (p less than .01) using the Mann-Whitney Wilcoxon test. Using a zeta potential of -20.5 mV as the cutoff between high and low metastatic potential, the sensitivity and specificity of zeta potential in predicting metastatic potential in 140 determinations on seven tumor lines were 92% and 82.5%, respectively. The predictive value of a positive test (value greater than -20.5 mV) was 80% and the predictive value of a negative test (value less than -20.5 mV) was 93%. The results support a difference in the cell surface charge between these metastatic and nonmetastatic tumors with increasing negativity at the cell surface correlating with increased metastatic potential, but not with tumor growth rates.
Adenocarcinoma↗
Recombinant rat stem cell factor synergizes with recombinant human granulocyte colony-stimulating factor in vivo in mice to mobilize peripheral blood progenitor cells that have enhanced repopulating potential.
Splenectomized mice treated for 7 days with pegylated recombinant rat stem cell factor (rrSCF-PEG) showed a dose-dependent increase in peripheral blood progenitor cells (PBPC) that have enhanced in vivo repopulating potential. A dose of rrSCF-PEG at 25 micrograms/kg/d for 7 days produced no significant increase in PBPC. However, when this dose of rrSCF-PEG was combined with an optimal dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 200 micrograms/kg/d), a synergistic increase in PBPC was observed. Compared with treatment with rhG-CSF alone, the combination of rrSCF-PEG plus rhG-CSF resulted in a synergistic increase in peripheral white blood cells, in the incidence and absolute numbers of PBPC, and in the incidence and absolute numbers of circulating cells with in vivo repopulating potential. These data suggest that low doses of SCF, which would have minimal, if any, effects in vivo, can synergize with optimal doses of rhG-CSF to enhance the mobilization of PBPC stimulated by rhG-CSF alone.
Animals↗
[Beta adrenergic agonists. Mechanisms of action: lipid mobilization and anabolism].
In this review, the results obtained in commercial livestock with certain beta-adrenergic agonists (clenbuterol and cimaterol) having an anabolic potential associated with lipid mobilizing properties are considered. The first chapter summarizes major data concerning the effects of beta-agonists on growth and carcass composition in cattle, sheep and pigs. The effect of clenbuterol and cimaterol on carcass quality is to increase the deposition of protein while reducing fat accretion. Then, we briefly consider the physiology and pharmacology of the sympathoadrenal system with a special attention to the distribution and properties of beta-adrenoceptors of various tissues which are putative targets for the beta-adrenergic agonists. Several mechanisms liable to be responsible for the anabolic action of these compounds are also discussed. This chapter includes the evaluation of the effects of beta-agonist on central nervous system and pancreas. A special attention is devoted to their metabolic impact on adipose tissue and muscle. In isolated fat cells, beta-agonists promote stimulation of lipolysis associated with reduction of lipogenesis and of insulin action. The in vitro effects on adipocytes are consistent with the in vivo effects of the compounds. Beta-agonist impact on protein synthesis and muscle accretion is also discussed with reference: 1) to the vascular effects of the compounds that should modify the nutrient flow into the muscle, 2) to a reduction of proteolysis mainly observed for the moment in in vitro studies, 3) to the possible beta-adrenergic-dependent enhancement of insulin action on the muscle. However, more direct experimental evidence is still needed to clearly assess the nature of the action(s) of such anabolic agents on muscle.
Adipose Tissue↗
Anomalous mobility of Brownian particles in a tilted symmetric sawtooth potential.
Overdamped motion of Brownian particles in a 1D periodic system with a simple symmetric sawtooth potential subjected to both unbiased thermal noise and spatially nonhomogeneous three-level colored noise is considered analytically. Upon application of a tilting force the particles exhibit anomalous transport properties, namely, absolute negative mobility, negative differential mobility, and the phenomenon of hypersensitive differential response. It is established that the mobility (differential mobility included) depends nonmonotonically on the parameters (switching rate, amplitude, and temperature) of nonequilibrium and thermal noises. The necessary conditions for various anomalous transport properties are found.
Journal Article↗
Hematopoietic potential and retroviral transduction of CD34+ Thy-1+ peripheral blood stem cells from asymptomatic human immunodeficiency virus type-1-infected individuals mobilized with granulocyte colony-stimulating factor.
The potential of hematopoietic stem cells (HSCs) from human immunodeficiency virus type-1 (HIV-1)-infected individuals, eg, self-renewal and multilineage differentiative capacity, might be perturbed due to the underlying disease. In this study, we assessed the HSC activity in the CD34+ Thy-1+ cell population of peripheral blood stem cells (PBSCs) of three asymptomatic HIV-1-infected individuals after granulocyte colony-stimulating factor (G-CSF; 10 microg/kg/d) mobilization. On day 4 of G-CSF treatment, 0.8% to 1% of the total blood mononuclear cells were CD34+. Leukapheresis followed by a two-step cell isolation process yielded a CD34+ Thy-1+ cell population of high purity (76% to 92% CD34+ Thy-1+ cells). This cell population showed no evidence of HIV-1-containing cells based on a semiquantitative HIV-1 DNA polymerase chain reaction. Furthermore, the purified cells showed normal hematopoietic potential in in vitro clonogenic assays. Successful gene transfer into committed progenitor cells (colony-forming units-cells) and more primitive stem/progenitor cells (long-term culture colony-forming cells) could be shown after amphotropic retroviral transduction. These data provide evidence that the CD34+ Thy-1+ stem cell compartment can be mobilized and enriched in early stage HIV-1-infected patients. Furthermore, successful transduction of this cell population as a prerequisite for stem cell-based clinical gene therapy protocols was demonstrated.
Adult↗
Phase I trial of recombinant fusion protein PIXY321 for mobilization of peripheral-blood cells.
PURPOSE: Mobilization of peripheral-blood cells (PBC) with cytokines alone results in rapid hematopoietic recovery and avoids the potential morbidity associated with mobilization by chemotherapy. PIXY321, a fusion protein that consists of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), has enhanced hematopoietic colony-forming activity as compared with individual or equimolar combinations of the two cytokines. A phase I trial of PIXY321 for mobilization of PBC in patients with malignant lymphoma was performed. PATIENTS AND METHODS: Thirteen patients with malignant lymphoma who were eligible for high-dose therapy (HDT) were enrolled onto the trial. All patients were ineligible for autologous bone marrow transplantation due to overt metastatic disease in the marrow or to severe marrow hypocellularity. PIXY321 was administered at three dose levels of 250, 500, and 750 micrograms/m2/d by continuous infusion until completion of PBC collections. Collections were initiated when the WBC count was greater than 10 x 10(9)/L or 4 days after the initiation of PIXY321, whichever came first. Collections were continued until a minimum of 6.5 x 10(8) mononuclear cells (MNC)/kg patient weight were obtained. RESULTS: PIXY321 was generally well tolerated. Side effects associated with PIXY321 administration did not exceed grade 2 and included fever (85%), chills/sweats (54%), myalgias (38%), fatigue (31%), nausea/vomiting (31%), headache (31%), edema (23%), and rhinorrhea (23%). The median numbers of colony-forming units-granulocyte/macrophage (CFU-GM) in the graft products for the three dose levels were 0.31, 2.94, and 2.88 x 10(4)/kg, respectively; the median numbers of burst-forming units-erythroid (BFU-e) were 0.20, 6.94, and 12.78 x 10(4)/kg, and the median numbers of CD34+ cells were 2.30, 0.74, and 0.39 x 10(6)/kg. Following transplantation, the median times to an absolute neutrophil count (ANC) > 0.5 x 10(9)/L were 12, 15, and 12 days, respectively, and the median times to platelet transfusion independence were 30, 19, and 15 days. CONCLUSION: PIXY321 can be safely administered and effectively mobilizes PBC in patients with bone marrow defects. PIXY321-mobilized PBC autotransplants result in rapid and sustained hematopoietic recovery.
Adult↗
CC chemokine receptor 3 mobilizes to the surface of human mast cells and potentiates immunoglobulin E-dependent generation of interleukin 13.
Eotaxins-1, -2, and -3 mediate the recruitment of blood-borne eosinophils to allergically inflamed tissues by binding CC chemokine receptor (CCR) 3. Mast cells (MCs) are resident tissue cells that also express CCR3. In the present study, we demonstrate that human (h) MCs in nasal polyps and cultured cord blood-derived hMCs express CCR3 not only on their surfaces but also in their secretory granules. Activation of hMCs mediated by the high-affinity Fc receptor for immunoglobulin (Ig)E (Fc epsilon RI) increased the surface presentation of CCR3 within 1 h, with a parallel decrease in intracellular CCR3 as determined by flow cytometry on saponin-permeabilized hMCs. Recombinant eotaxin-1 alone did not induce histamine release or cytokine generation, and did not significantly augment IgE-dependent histamine release by interleukin (IL)-4-primed hMCs. Nevertheless, stimulation of hMCs with eotaxin-1 2 h after Fc epsilon RI cross-linkage (concomitantly with maximal surface CCR3 expression) increased Fc epsilon RI-dependent IL-13 generation by hMCs, compared with their replicates stimulated simultaneously with both agonists. Thus, hMCs may store CCR3 and rapidly mobilize it to their surface with IgE-dependent activation, providing a novel potential mechanism for enhanced hMC effector function, including IL-13 production.
Cells, Cultured↗
The expansion of megakaryocyte progenitors from CD34+-enriched mobilized peripheral blood stem cells is inhibited by Flt3-L.
This study aimed to determine the optimal growth factor combination for expansion of megakaryocyte (Mk) progenitors with clonogenic potential from CD34+-enriched mobilized peripheral blood stem cells (PBSC). Mobilized PBSC were monocyte depleted and CD34+ enriched, then cultured with various combinations of interleukin-3 (IL-3), IL-6, IL-11, Flt3 ligand (Flt3-L), stem cell factor (SCF), granulocyte-macrophage colonystimulating factor (GM-CSF), and erythropoietin (EPO), using a 2(7-3) IV fractional factorial design. Expansion of Mk committed progenitors (CD41+) and primitive precursors (CD61+ CD34+) was determined using FACS and colony-forming assays. Amplification of Mk progenitor production was attributed to IL-3 (p < 0.002), SCF (p < 0.001), and GM-CSF (p < 0.05). Flt3-L inhibited the production of total CD61+ cells (p < 0.05), CD61+CD34+ cells (p < 0.03), and total CD41a+ cells (p < 0.01). Addition of Flt3-L to the optimum growth factor combination of megakaryocyte growth and development factor (MGDF), SCF, IL-3, and GM-CSF caused the greatest increase in total nucleated cells but reduced Mk progenitor expansion. There was also a 20% reduction in Mk+ colonies from cells expanded in the presence of Flt3-L. Factorial analysis identified the optimal combination of growth factors required to expand Mk precursors with clonogenic potential. The addition of Flt3-L to the optimal combination of MGDF, SCF, IL-3, and GM-CSF reduced both the fold expansion of Mk progenitors and Mk colony numbers.
Antigens, CD34↗
The effects of lyotropic anions on charge movement, calcium currents and calcium signals in frog skeletal muscle fibres.
1. Intramembrane charge movement and Ca2+ currents were monitored in voltage-clamped segments of frog skeletal muscle fibres using the triple-Vaseline-gap technique. Calcium signals were measured in current-clamped fibres using either of the indicators Arsenazo III or Antipyrylazo III. 2. Non-linear capacitative currents (charge 1) were obtained using a subtraction procedure which employed either a -20 mV control pulse from a holding potential of -100 mV or alternatively a control pulse to +80 mV in depolarized fibres. The amount of charge mobilized depended on voltage according to a two-state Boltzmann function. The total charge (Qmax) was increased by ca 100% and the steepness parameter (k) by ca 70% when a +80 mV control pulse was used. 3. Thiocyanate (SCN-) and other lyotropic anions reversibly shifted the voltage dependence of mobilized charge towards negative potentials. Qmax was not significantly affected. 'Off' charge tails were greatly prolonged by lyotropic anions. 4. Extracellularly applied lyotropic anions affected the dihydropyridine-sensitive Ca2+ current by shifting the I-V relation toward more negative voltages and delaying deactivation of the tail currents. 5. The effects of lyotropic anions did not depend on whether the anion was introduced intracellularly or extracellularly. 6. Extracellular SCN- reversibly increased the peak amplitude and rate of rise of Ca signals, and decreased the latent period between stimulation and onset of the Ca signal. 7. It is concluded that lyotropic anions have similar effects on Ca2+ currents and on charge movement.
Animals↗
Fatty acids and cyclooxygenase and lipoxygenase pathway inhibitors modulate inositol phosphate formation in pancreatic islets.
Isolated rat pancreatic islets prelabeled with myo-[3H]inositol respond to glucose and carbamylcholine with increased [3H] inositol phosphate (InsP) production. Prostaglandin E2 (PGE2) inhibits the effects of glucose and carbamylcholine on [3H]InsP production. Ionomycin reversed the effect of PGE2 on glucose-stimulated [3H]InsP production. The cyclooxygenase inhibitors indomethacin, ibuprofen, and eicosatetraynoic acid potentiated [3H]InsP production in response to 5 and 10 mM glucose but not to 17 mM glucose. Indomethacin did not affect the carbamylcholine response. Unsaturated fatty acids, including arachidonic acid, linolenic acid, eicosapentaenoic acid, oleic acid, and eicosatetraynoic acid, increased [3H]InsP production. Arachidonic acid potentiated [3H]InsP accumulation in response to low concentrations of glucose. Indomethacin potentiated the response to arachidonic acid. delta 9-Tetrahydrocannabinol, which mobilizes endogenous fatty acids, also potentiated glucose-stimulated [3H]InsP production. The lipoxygenase inhibitors BW755C and nordihydroguaiaretic acid inhibited [3H]InsP production in response to glucose, carbamylcholine, and fatty acids. Thus, PGE2 and endogenous cyclooxygenase products antagonize InsP production in islets, whereas fatty acids promote InsP accumulation.
4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
Electrophoretic mobility of a "soft particle" with a nonuniformly charged surface layer as a model for cells.
The electrophoretic mobility of a colloidal particle with a nonuniformly charged ion-penetrable surface layer in an electrolyte solution (as a model for a biological cell) is calculated for the case in which the surface charge layer consists of two oppositely charged sublayers. It is shown that the mobility and the surface potential (the latter of which is defined as the potential at the front surface of the surface charge layer) generally exhibit different behaviors, in contrast to the case of rigid particles, which is described by Smoluchowski's mobility formula. The mobility in some cases shows a minimum (or a maximum) when plotted as a function of the electrolyte concentration and alters its sign at a certain concentration, which is considered to be an isoelectric point of the mobility with respect to the electrolyte concentration. This isoelectric point is in general different from that of the surface potential.
Cell Membrane↗
Evaluation of potential aluminum chelators in vitro by aluminum solubilization ability, aluminum mobilization from transferrin and the octanol/aqueous distribution of the chelators and their complexes with aluminum.
Representative amino acids, carboxylic acids, a ketone, hydroxamic acids, 3-hydroxypyridinones and a linear catecholcarboxyamide were tested in vitro to estimate their aluminum (Al) chelation potential. Their ability to solubilize Al from insoluble Al borate in a previously described octanol/aqueous (o/a) system was tested. Salicylhydroxamic acid, rhodotorulic acid, the 3-hydroxypyridin-4-ones and a sulfonated linear polycatecholcarboxamide significantly increased solubilized Al, suggesting Al chelation potential. Some of the above compounds and some compounds previously shown to solubilize Al in the o/a system were tested for their ability to mobilize Al from the Al plasma binding protein transferrin. Chelators solubilizing Al in the o/a system were comparably effective in mobilizing Al from transferrin, supporting the utility of the o/a system as a screening method. The o/a distribution coefficient of each chelator was determined, when possible, to assess its hydrophilicity. When compared with the suggested desirable hydrophilicity of effective chelators, the o/a distribution coefficient of many of the 3-hydroxypyridin-4-ones and a sulfonated linear polycatecholcarboxamide suggest that they might be able to chelate intracellular Al. The o/a distribution coefficient of each Al-chelator complex was determined, when possible, to predict the likelihood of redistribution within or excretion from the intact animal of this complex. Complexation of chelators with Al usually increased chelator hydrophilicity. The results suggest several compounds that warrant further investigation as potential alternatives to desferrioxamine in the treatment of Al accumulation and toxicity.
1-Octanol↗
Myelopoietin, a chimeric agonist of human interleukin 3 and granulocyte colony-stimulating factor receptors, mobilizes CD34+ cells that rapidly engraft lethally x-irradiated nonhuman primates.
Myelopoietin (MPO), a multifunctional agonist of interleukin 3 and granulocyte colony-stimulating factor (G-CSF) receptors, was evaluated for its ability to mobilize hematopoietic colony-forming cells (CFC) and CD34+ cells relative to control cytokines in normal nonhuman primates. Additionally, the engraftment potential of MPO-mobilized CD34+ cells was assessed in lethally irradiated rhesus monkeys. Normal rhesus monkeys were administered either MPO (200 microg/kg/day), daniplestim (a high-affinity interleukin 3 receptor agonist) (100 microg/kg/day), G-CSF (100 microg/kg/day), or daniplestim coadministered with G-CSF (100 microg/kg/day each), subcutaneously for 10 consecutive days. The mobilization kinetics were characterized by peripheral blood (PB) complete blood counts, hematopoietic CFC [granulocyte-macrophage CFC (GM-CFC), megakaryocyte CFC (MK-CFC)], and the immunophenotype (CD34+ cells) of PB nucleated cells prior to and on day 3 to days 7, 10, 12, and 14, and at intervals up to day 28 following initiation of cytokine administration. A single large-volume leukapheresis was conducted on day 5 in an additional cohort (n = 10) of MPO-mobilized animals. Eight of these animals were transplanted with two doses of CD34+ cells/kg. A maximum 10-fold increase in PB leukocytes (white blood cells) (from baseline 7.8-12.3 x 10(3)/microL to approximately 90 x 10(3)/microL) was observed over day 7 to day 10 in the MPO, G-CSF, or daniplestim+G-CSF cohorts, whereas daniplestim alone stimulated a less than onefold increase. A sustained, maximal rise in PB-derived GM-CFC/mL was observed over day 4 to day 10 for the MPO-treated cohort, whereas the daniplestim+G-CSF, G-CSF alone, and daniplestim alone treated cohorts were characterized by a mean peak value on days 7, 6, and 18, respectively. Mean peak values for PB-derived GM-CFC/mL were greater for MPO (5,427/mL) than for daniplestim+G-CSF (3,534/mL), G-CSF alone (3,437/mL), or daniplestim alone (155/mL) treated cohorts. Mean peak values for CD34+ cells/mL were noted within day 4 to day 5 of cytokine administration: MPO (255/microL, day 5), daniplestim+G-CSF (47/microL, day 5), G-CSF (182/microL, day 4), and daniplestim (96/microL, day 5). Analysis of the mobilization data as area under the curve indicated that for total CFCs, GM-CFC, MK-CFC, or CD34+ cells, the MPO-treated areas under the curve were greater than those for all other experimental cohorts. A single, large-volume (3.0 x blood volume) leukapheresis at day 5 of MPO administration (PB: CD34+ cell/microL = 438 +/- 140, CFC/mL = 5,170 +/- 140) resulted in collection of sufficient CD34+ cells (4.31 x 10(6)/kg +/- 1.08) and/or total CFCs (33.8 x 10(4)/kg +/- 8.34) for autologous transplantation of the lethally irradiated host. The immunoselected CD34+ cells were transfused into autologous recipients (n = 8) at cell doses of 2 x 10(6)/kg (n = 5), and 4 x 10(6)/kg (n = 3) on the day of apheresis. Successful engraftment occurred with each cell dose. The data demonstrated that MPO is an effective and efficient mobilizer of PB progenitor cells and CD34+ cells, such that a single leukapheresis procedure results in collection of sufficient stem cells for transplantation and long term engraftment of lethally irradiated hosts.
Animals↗
Interleukin-1beta stimulates transendothelial mobilization of human peripheral blood mononuclear cells with a potential to differentiate into osteoclasts in the presence of osteoblasts.
There is accumulating evidence that interleukin-1 (IL-1) levels are increased locally at the site of active bone resorption in a variety of diseases including osteoporosis, periodontal disease and rheumatoid arthritis. However, the pathogenic role of IL-1 in bone loss remains to be fully elucidated. We present here additional evidence that IL-1beta enhances endothelial activation and thereby stimulates mobilization of peripheral blood mononuclear cells (PBMCs) from luminal to abluminal spaces across the endothelium. Furthermore, IL-1beta stimulates the differentiation of PBMCs into osteoclast-like cells with bone-resorbing activity in the presence of human osteoblastic SaOS-2 cells without systemic hormones. These findings provide circumstantial evidence for the hypothesis that IL-1beta generated in the bone microenviroment plays a stimulatory role in PBMC mobilization from the peripheral circulation and their subsequent differentiation into osteoclast-like cells in the bone tissue. In addition, the present study supports the notion that osteoclast progenitor cells might be derived from the peripheral circulating blood mononuclear cells in human.
Acid Phosphatase↗