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Search Results: 1 - 10 of 19765 matches for " Alexander Copelan "
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Divergent Pathways in COS-7 Cells Mediate Defective Internalization and Intracellular Routing of Truncated G-CSFR Forms in SCN/AML
Melissa G. Hunter, Morgan McLemore, Daniel C. Link, Megan Loveland, Alexander Copelan, Belinda R. Avalos
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0002452
Abstract: Background Expression of truncated G-CSFR forms in patients with SCN/AML induces hyperproliferation and prolonged cell survival. Previously, we showed that ligand internalization is delayed and degradation of truncated G-CSFR forms is defective in patients with SCN/AML. Methodology/Principal Findings In this study, we investigated the potential roles of dileucine and tyrosine-based motifs within the cytoplasmic domain of the G-CSFR in modulating ligand/receptor internalization. Using standard binding assays with radiolabeled ligand and COS-7 cells, substitutions in the dileucine motif or deletion of tyrosine residues in the G-CSFR did not alter internalization. Attachment of the transferrin receptor YTRF internalization motif to a truncated G-CSFR form from a patient with SCN/AML corrected defective internalization, but not receptor degradation suggesting that receptor internalization and degradation occur independently via distinct domains and/or processes. Conclusions Our data suggest that distinct domains within the G-CSFR mediate separate processes for receptor internalization and degradation. Our findings using standard binding assays differ from recently published data utilizing flow cytometry.
Neutrophil elastase downmodulates native G-CSFR expression and granulocyte-macrophage colony formation
Melissa G Piper, Pam R Massullo, Megan Loveland, Lawrence J Druhan, Tamila L Kindwall-Keller, Jing Ai, Alexander Copelan, Belinda R Avalos
Journal of Inflammation , 2010, DOI: 10.1186/1476-9255-7-5
Abstract: Human peripheral blood PMN isolated from healthy donors were incubated with NE. Expression of the G-CSFR was analyzed by flow cytometry and western blot analyses. Detection of G-CSFR cleavage products from the culture supernatants was also performed. Human bone marrow mononuclear cells were also cultured in the presence or absence of NE to determine its effects on the proliferation of granulocyte-macrophage colony forming units (CFU-GM).Treatment of PMN with NE induced a time-dependent decrease in G-CSFR expression that correlated with its degradation and the appearance of proteolytic cleavage fragments in conditioned media. Immunoblot analysis confirmed the G-CSFR was cleaved at its amino-terminus. Treatment of progenitor cells with NE prior to culture inhibited the growth of granulocyte-macrophage colony forming units.These findings indicate that in addition to transcriptional controls and ligand-induced internalization, direct proteolytic cleavage of the G-CSFR by NE also downregulates G-CSFR expression and inhibits G-CSFR-mediated granulopoiesis in vitro. Our results suggest that NE negatively regulates granulopoiesis through a novel negative feedback loop.Granulocyte colony-stimulating factor (G-CSF) is the major regulator of granulopoiesis and supports the survival, proliferation, and maturation of myeloid progenitor cells along the neutrophil (PMN) lineage [1]. G-CSF also activates certain functions of mature PMN and stimulates hematopoietic stem cell mobilization [2-6]. The growth of neutrophilic granulocytes in vitro from progenitor cells committed to neutrophils and monocytes (CFU-GM) is absolutely dependent upon G-CSF and sigmoidally increases with increasing G-CSF concentrations [2,5,7,8]. A critical role for G-CSF in regulating granulopoiesis in vivo has been demonstrated in G-CSF null mice who have chronic neutropenia and severely impaired granulopoietic responses to infection [6].The biological activities of G-CSF are mediated by the G-CSFR receptor (
Successful Hematopoietic Stem Cell Transplantation Following a Cyclophosphamide-Containing Preparative Regimen with Concomitant Phenobarbital Administration
Catherine Weber,Heather Kasberg,Edward Copelan
Case Reports in Transplantation , 2012, DOI: 10.1155/2012/721857
Abstract: Cyclophosphamide is an immunosuppressive agent and an anticancer prodrug which requires bioactivation catalyzed primarily by cytochrome P450 enzymes in order to be transformed into its active alkylating compounds. Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. Herein, we present the case of a chronically ill 21-year-old patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG), and total body irradiation (TBI) followed by an allogeneic hematopoietic stem cell transplant (HSCT) for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. The preparative regimen was tolerated well aside from a hypersensitivity reaction to eATG, and minimal cyclophosphamide-related toxicities. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management.
Successful Hematopoietic Stem Cell Transplantation Following a Cyclophosphamide-Containing Preparative Regimen with Concomitant Phenobarbital Administration
Catherine Weber,Heather Kasberg,Edward Copelan
Case Reports in Transplantation , 2012, DOI: 10.1155/2012/721857
Abstract: Cyclophosphamide is an immunosuppressive agent and an anticancer prodrug which requires bioactivation catalyzed primarily by cytochrome P450 enzymes in order to be transformed into its active alkylating compounds. Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. Herein, we present the case of a chronically ill 21-year-old patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG), and total body irradiation (TBI) followed by an allogeneic hematopoietic stem cell transplant (HSCT) for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. The preparative regimen was tolerated well aside from a hypersensitivity reaction to eATG, and minimal cyclophosphamide-related toxicities. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management. 1. Introduction Allogeneic hematopoietic stem cell transplantation is curative in most patients with aplastic anemia. This procedure is associated with toxicities from the preparative regimen and subsequent immunosuppressive therapy, as well as graft versus-host disease (GVHD) and graft failure. Cyclophosphamide is a standard component of preparative regimens for allotransplantation; however, the parent drug requires metabolism primarily by cytochrome P450 enzymes in order to produce its active alkylating compounds, and concomitant administration of interacting medications is of particular concern in the setting of HSCT due to the intensity of the preparative regimen administered. The activity of the relevant metabolic pathways is affected by a variety of drugs, including phenobarbital, an inducer of P450B and P450A enzymes [1]. Exposure to the active metabolites of cyclophosphamide is increased in the presence of concomitant phenobarbital administration. Although concern for a potential drug-drug interaction exists, the details surrounding this interaction have not yet been fully elucidated and to our knowledge, the only available literature published to date has not been among human subjects [1–6]. 2. Case Presentation A 19-year-old woman was in excellent health until she developed viral encephalitis and a prolonged coma requiring tracheostomy, percutaneous endoscopic gastrostomy (PEG) tube placement, and a long course of rehabilitation. The encephalopathy was
Sustained disease-free survival achieved with withdrawal of immunosuppression after rapid relapse of myelodysplastic syndrome following myeloablative allogeneic hematopoietic transplantation: a case report
Hamilton Betty K,Vereb Gregory,Copelan Edward A
Journal of Medical Case Reports , 2013, DOI: 10.1186/1752-1947-7-18
Abstract: Introduction Relapse after allogeneic hematopoietic stem cell transplantation in patients with myelodysplasia is a challenging problem with limited treatment options. Attempts to induce a graft-versus-leukemia effect have been used with limited success. In patients with myelodysplasia, sustained complete remissions have generally been limited to patients with long-term remission after transplant and those with low numbers of marrow blasts. Case presentation We report the case of a 41-year-old Caucasian woman with relapsed myelodysplastic syndrome and a high blast percentage six months after undergoing an allogeneic transplant who achieved a sustained complete remission after withdrawal of immunosuppression alone. Conclusion This case highlights the importance of a reasonable period of observation after withdrawing immunosuppression to induce graft-versus-leukemia, and the potential effectiveness of that approach.
Protection of Environment from Damaged Nuclear Station and Transparent Inflatable Blanket for Cities—Protection from Radioactive Dust and Chemical, Biological Weapons  [PDF]
Alexander Bolonkin
Journal of Environmental Protection (JEP) , 2011, DOI: 10.4236/jep.2011.24037
Abstract: The author, in a series of previous articles, designed the “AB Dome” made of transparent thin film supported by a small additional air overpressure for the purpose of covering a city or other important large installations or sub-regions. In present article the author offers a variation in which a damaged nuclear station can be quickly covered by such a cheap inflatable dome. By containing the radioactive dust from the damaged nuclear station, the danger zone is reduced to about 2 km2 rather than large regions which requires the resettlement of huge masses of people and which stops indus-try in large areas. If there is a big city (as Tokyo) near the nuclear disaster or there is already a dangerous amount of radioactive dust near a city, the city may also be covered by a large inflatable transparent Dome. The building of a gi-gantic inflatable AB Dome over an empty flat surface is not difficult. The cover is spread on a flat surface and a venti-lator (fan system) pumps air under the film cover and lifts the new dome into place but inflation takes many hours. However, to cover a city, garden, forest or other obstacle course in contrast to an empty, mowed field, the thin film cannot be easily deployed over building or trees without risking damage to it by snagging and other complications. This article proposes a new method which solves this problem. The design is a double film blanket filled by light gas such as, methane, hydrogen, or helium - although of these, methane will be the most practical and least likely to leak. Sections of this AB Blanket are lighter than air and will rise in the atmosphere. They can be made on a flat area serving as an as-sembly area and delivered by dirigible or helicopter to station at altitude over the city. Here they connect to the already assembled AB Blanket subassemblies, cover the city in an AB Dome and protect it from bad weather, chemical, bio-logical and radioactive fallout or particulates. After assembly of the dome is completed, the light gas can be replaced by (heavier but cheaper) air. Two projects for Tokyo (Japan) and Moscow (Russia) are used in this paper for sample computation.
Filters and Ultrafilters as Approximate Solutions in the Attainability Problems with Constraints of Asymptotic Character  [PDF]
Alexander Chentsov
Intelligent Information Management (IIM) , 2010, DOI: 10.4236/iim.2010.29062
Abstract: Abstract problems about attainability in topological spaces are considered. Some nonsequential version of the Warga approximate solutions is investigated: we use filters and ultrafilters of measurable spaces. Attrac- tion sets are constructed. AMS (MOS) subject classification. 46A, 49 K 40.
Using of High Altitude Wind Energy  [PDF]
Alexander Bolonkin
Smart Grid and Renewable Energy (SGRE) , 2011, DOI: 10.4236/sgre.2011.22010
Abstract: Ground based, wind energy extraction systems have reached their maximum capability. The limitations of current de-signs are: wind instability, high cost of installations, and small power output of a single unit. The wind energy industry needs of revolutionary ideas to increase the capabilities of wind installations. This article suggests a revolutionary innovation which produces a dramatic increase in power per unit and is independent of prevailing weather and at a lower cost per unit of energy extracted. The main innovation consists of large free-flying air rotors positioned at high altitude for power and air stream stability, and an energy cable transmission system between the air rotor and a ground based electric generator. The air rotor system flies at high altitude up to 14 km. A stability and control is provided and systems enable the changing of altitude. This article includes six examples having a high unit power output (up to 100 MW). The proposed examples provide the following main advantages: 1) Large power production capacity per unit—up to 5,000 - 10,000 times more than conventional ground-based rotor designs; 2) The rotor operates at high altitude of 1 - 14 km, where the wind flow is strong and steady; 3) Installation cost per unit energy is low; 4) The installation is environmentally friendly (no propeller noise).
Production of Freshwater and Energy from Earth’s Atmosphere  [PDF]
Alexander Bolonkin
Smart Grid and Renewable Energy (SGRE) , 2011, DOI: 10.4236/sgre.2011.22011
Abstract: The author offers a new, cheap method for the extraction of freshwater from the Earth’s atmosphere. The suggested method is fundamentally dictinct from all existing methods that extract freshwater from air. All other industrial methods extract water from a saline water source (in most cases from seawater). This new method may be used at any point in the Earth except the Polar Zones. It does not require long-distance freshwater transportation. If seawater is not utilized for increasing its productivity, this inexpensive new method is very environmentally-friendly. The author’s method has two working versions: 1) In the first variant warm (or hot) atmospheric air is lifted by the inflatable tube in a high altitude and atmospheric water vapor is condensed into freshwater: 2) in the second version, the warm air is pumped 20-30 meters under the sea-surface. In the first version, wind and solar heating of air are used for causing air flow. In version 2) wind and fans are used for causing air movment. The first method does not need energy, the second needs a small amount. Moreover, in variant 1) the freshwater has a high pressure (> 30 or more atm) and can be used for production of energy such as electricity and in that way the freshwater cost is lower. For increasing the productivity the seawater is injected into air and a solar air heater may be used. The solar air heater produces a huge amount of electricity as a very powerful electrical generation plant. The offered electricity installation is 100 - 200 times cheaper than any common electric plant of equivalent output.
Radial Electric Field in Tokamak Plasmas as a Physical Consequence of Ehrenfest’s Paradox  [PDF]
Romannikov Alexander
Journal of Modern Physics (JMP) , 2012, DOI: 10.4236/jmp.2012.330201
Abstract: A simplified form and some possible theoretical resolutions of the so-called Ehrenfest’s Paradox are described. A relation between physical consequences of this relativistic paradox and charge density ρ of tokamak plasma is shown. Plasma experiments which could resolve the Ehrenfest’s Paradox are presented.
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